Journal of Clinical Outcomes Management

Long-term results from the Dutch PREOPANC randomized, controlled trial confirm that neoadjuvant chemoradiotherapy conveys a survival advantage to patients with resectable and borderline resectable pancreatic cancer.

Neoadjuvant therapy remains controversial in this patient population, which makes up 15% of pancreatic cancer cases. Historically, these patients have been treated with surgery followed by adjuvant chemotherapy, but only about half of patients ever receive adjuvant chemotherapy due to early recurrence, surgical complication, or worsening disease. Neoadjuvant chemoradiotherapy is thought to increase the fraction of patients who receive chemotherapy. Improved exposure to chemotherapy could increase survival, and may also increase the rate of microscopically margin-negative resections.

Neoadjuvant chemoradiotherapy has become increasingly common, but the practice is based on retrospective analysis and small, phase II trials.

“This phase III, randomized trial demonstrates a long-term survival benefit with neoadjuvant treatment compared with upfront surgery in patients with resectable and borderline resectable pancreatic cancer,” the researchers wrote in the study, published online Jan. 27 in the Journal of Clinical Oncology. “The effect of neoadjuvant chemoradiotherapy was consistent across subgroups, including resectable and borderline resectable disease,” they added.

The new data represent long-term follow-up of 246 patients who had been randomized to neoadjuvant chemoradiotherapy or upfront surgery. Short-term data, published in 2020, showed trends toward improved survival but no statistically significant difference at a median of 27 months of follow-up. In the update, after a median follow-up of 59 months, patients in the neoadjuvant chemoradiotherapy group had better overall survival (hazard ratio [HR], 0.73; P = .025) and the 5-year overall survival was higher in the neoadjuvant chemoradiotherapy group (20.5%; 95% confidence interval [CI], 14.2%-29.8%) than the upfront surgery group (6.5%; 95% CI, 3.1%-13.7%).

Subgroup analyses found a survival advantage for upfront chemoradiotherapy among patients with borderline resectable tumors (HR, 0.67; P = .045), and a trend toward improved survival among patients with resectable tumors (HR, 0.79; P = .23). There was a trend toward more serious adverse events in the upfront chemoradiotherapy group (52% versus 41%; P = .096). There was no difference in major surgical complications or postoperative mortality.

The study found high progression rates within the first year in both the neoadjuvant chemoradiotherapy group and the upfront surgery group. “Apparently, our neoadjuvant schedule was not able to prevent many of these early progressions, and more effective schedules are warranted,” the authors wrote.

The survival outcomes were lower than those found in adjuvant trials, likely because of differences in patient populations. Adjuvant studies generally recruit patients who have recovered well from resection and have no early signs of recurrence, and therefore have a more favorable prognosis.

The long-term results from PREOPANC are in agreement with four previous studies that compared neoadjuvant chemoradiotherapy to upfront surgery.

A limitation of the study was that gemcitabine monotherapy was used in the adjuvant setting, and this regimen is now considered out of date.

The study was funded by the Dutch Cancer Foundation.

Long-term results from the Dutch PREOPANC randomized, controlled trial confirm that neoadjuvant chemoradiotherapy conveys a survival advantage to patients with resectable and borderline resectable pancreatic cancer.

Neoadjuvant therapy remains controversial in this patient population, which makes up 15% of pancreatic cancer cases. Historically, these patients have been treated with surgery followed by adjuvant chemotherapy, but only about half of patients ever receive adjuvant chemotherapy due to early recurrence, surgical complication, or worsening disease. Neoadjuvant chemoradiotherapy is thought to increase the fraction of patients who receive chemotherapy. Improved exposure to chemotherapy could increase survival, and may also increase the rate of microscopically margin-negative resections.

Neoadjuvant chemoradiotherapy has become increasingly common, but the practice is based on retrospective analysis and small, phase II trials.

“This phase III, randomized trial demonstrates a long-term survival benefit with neoadjuvant treatment compared with upfront surgery in patients with resectable and borderline resectable pancreatic cancer,” the researchers wrote in the study, published online Jan. 27 in the Journal of Clinical Oncology. “The effect of neoadjuvant chemoradiotherapy was consistent across subgroups, including resectable and borderline resectable disease,” they added.

The new data represent long-term follow-up of 246 patients who had been randomized to neoadjuvant chemoradiotherapy or upfront surgery. Short-term data, published in 2020, showed trends toward improved survival but no statistically significant difference at a median of 27 months of follow-up. In the update, after a median follow-up of 59 months, patients in the neoadjuvant chemoradiotherapy group had better overall survival (hazard ratio [HR], 0.73; P = .025) and the 5-year overall survival was higher in the neoadjuvant chemoradiotherapy group (20.5%; 95% confidence interval [CI], 14.2%-29.8%) than the upfront surgery group (6.5%; 95% CI, 3.1%-13.7%).

Subgroup analyses found a survival advantage for upfront chemoradiotherapy among patients with borderline resectable tumors (HR, 0.67; P = .045), and a trend toward improved survival among patients with resectable tumors (HR, 0.79; P = .23). There was a trend toward more serious adverse events in the upfront chemoradiotherapy group (52% versus 41%; P = .096). There was no difference in major surgical complications or postoperative mortality.

The study found high progression rates within the first year in both the neoadjuvant chemoradiotherapy group and the upfront surgery group. “Apparently, our neoadjuvant schedule was not able to prevent many of these early progressions, and more effective schedules are warranted,” the authors wrote.

The survival outcomes were lower than those found in adjuvant trials, likely because of differences in patient populations. Adjuvant studies generally recruit patients who have recovered well from resection and have no early signs of recurrence, and therefore have a more favorable prognosis.

The long-term results from PREOPANC are in agreement with four previous studies that compared neoadjuvant chemoradiotherapy to upfront surgery.

A limitation of the study was that gemcitabine monotherapy was used in the adjuvant setting, and this regimen is now considered out of date.

The study was funded by the Dutch Cancer Foundation.

Long-term results from the Dutch PREOPANC randomized, controlled trial confirm that neoadjuvant chemoradiotherapy conveys a survival advantage to patients with resectable and borderline resectable pancreatic cancer.

Neoadjuvant therapy remains controversial in this patient population, which makes up 15% of pancreatic cancer cases. Historically, these patients have been treated with surgery followed by adjuvant chemotherapy, but only about half of patients ever receive adjuvant chemotherapy due to early recurrence, surgical complication, or worsening disease. Neoadjuvant chemoradiotherapy is thought to increase the fraction of patients who receive chemotherapy. Improved exposure to chemotherapy could increase survival, and may also increase the rate of microscopically margin-negative resections.

Neoadjuvant chemoradiotherapy has become increasingly common, but the practice is based on retrospective analysis and small, phase II trials.

“This phase III, randomized trial demonstrates a long-term survival benefit with neoadjuvant treatment compared with upfront surgery in patients with resectable and borderline resectable pancreatic cancer,” the researchers wrote in the study, published online Jan. 27 in the Journal of Clinical Oncology. “The effect of neoadjuvant chemoradiotherapy was consistent across subgroups, including resectable and borderline resectable disease,” they added.

The new data represent long-term follow-up of 246 patients who had been randomized to neoadjuvant chemoradiotherapy or upfront surgery. Short-term data, published in 2020, showed trends toward improved survival but no statistically significant difference at a median of 27 months of follow-up. In the update, after a median follow-up of 59 months, patients in the neoadjuvant chemoradiotherapy group had better overall survival (hazard ratio [HR], 0.73; P = .025) and the 5-year overall survival was higher in the neoadjuvant chemoradiotherapy group (20.5%; 95% confidence interval [CI], 14.2%-29.8%) than the upfront surgery group (6.5%; 95% CI, 3.1%-13.7%).

Subgroup analyses found a survival advantage for upfront chemoradiotherapy among patients with borderline resectable tumors (HR, 0.67; P = .045), and a trend toward improved survival among patients with resectable tumors (HR, 0.79; P = .23). There was a trend toward more serious adverse events in the upfront chemoradiotherapy group (52% versus 41%; P = .096). There was no difference in major surgical complications or postoperative mortality.

The study found high progression rates within the first year in both the neoadjuvant chemoradiotherapy group and the upfront surgery group. “Apparently, our neoadjuvant schedule was not able to prevent many of these early progressions, and more effective schedules are warranted,” the authors wrote.

The survival outcomes were lower than those found in adjuvant trials, likely because of differences in patient populations. Adjuvant studies generally recruit patients who have recovered well from resection and have no early signs of recurrence, and therefore have a more favorable prognosis.

The long-term results from PREOPANC are in agreement with four previous studies that compared neoadjuvant chemoradiotherapy to upfront surgery.

A limitation of the study was that gemcitabine monotherapy was used in the adjuvant setting, and this regimen is now considered out of date.

The study was funded by the Dutch Cancer Foundation.

Computed tomographic angiography (CTA) appears preferable to standard cath-based angiography for the initial evaluation of most stable, intermediate-risk patients with angina-like symptoms, researchers say, based on their study conducted at centers across Europe.

Clinical outcomes over several years in the randomized trial – called DISCHARGE, with an enrollment of more than 3,500 – were statistically similar whether the patients were assigned to CTA or invasive coronary angiography (ICA) as their initial evaluation. Symptoms and quality-of-life measures were also similar.

But the patients assigned to the initial-CTA strategy, of whom fewer than a fourth went on to cardiac cath, showed far fewer procedure-related complications and less often went to coronary revascularization during the median follow-up of 3.5 years, the group reported March 4 in the New England Journal of Medicine.

Based on the findings, CTA “is a safe alternative to cardiac catheterization for patients with suspected CAD [coronary artery disease] that will likely change clinical practice worldwide by replacing invasive testing in patients with stable chest pain who can be expected to benefit” those with an intermediate pretest probability for obstructive disease, principal investigator Marc Dewey, MD, Charité – Universitätsmedizin Berlin, told this news organization.

None of the patient subgroups explored in the trial showed a significant clinical benefit from one strategy over the other, Dr. Dewey commented in an email.

The trial’s results don’t apply to patients unlike those entered, and in particular, he said, “ICA should remain the first test option in patients with high clinical pretest probability of obstructive CAD.”

Dr. Dewey is senior author on the study’s publication, which was timed to coincide with his presentation of the results at ECR 2022 Overture, an all-virtual scientific session of the European Congress of Radiology.

“This is the definitive study,” Matthew Budoff, MD, Lundquist Institute at Harbor-UCLA, Torrance, California, said in an interview. It suggests in a large population that the initial CTA strategy “is as good and maybe safer” in stable patients at intermediate risk compared with initial ICA. “I would say close to 75% or 80% of the patients that we see would fall into that range of risk” and be suitable for the testing algorithm used in the study, said Dr. Budoff, who was not part of the trial.

Invasive angiography would generally still be the initial approach for patients at greater than intermediate risk, such as those with breakthrough angina or electrocardiographic changes, he said. “I still think there’s a huge role for invasive angiography. It’s just a bit smaller now than it used to be for the lower-risk patient.”  

The DISCHARGE trial, agreed cardiothoracic radiology specialist Rozemarijn Vliegenthart, MD, PhD, University of Groningen, the Netherlands, “shows that in patients with intermediate pretest probability, CTA should be used as a gatekeeper before invasive coronary angiography, instead of directly referring for invasive coronary angiography.”

It shows that “a CT-first approach” is both safe and clinically effective and even a trend suggesting better clinical outcomes, compared with ICA. And it demonstrates that “still, many diagnostic invasive coronary angiographies are performed unnecessarily,” Dr. Vliegenthart said as the invited discussant following Dr. Dewey’s presentation.

DISCOVER is only the latest in a series of major studies to explore how CTA best fits in with ICA, stress imaging, and other tests for evaluating patients with chest pain. For example, “the PROMISE trial and the SCOT-HEART trial found that CT was as good as or even better than functional testing. DISCHARGE, I think, confirms the safety of the CT strategy” and reaffirms that it is “at least as good” as an ICA-first approach, cardiologist Klaus F. Kofoed, MD, PhD, DMSc, Rigshospitalet University of Copenhagen, said when co-presenting the trial’s results with Dr. Dewey.

“We can now say CT may be suitable in intermediate-risk patients referred for ICA, particularly those with a clinical constellation suggesting a higher event risk, with abnormal or inconclusive functional test results, or with persistent symptoms despite medical treatment,” said Dr. Kofoed, who is on the DISCOVER steering committee.

The trial’s 3,561 patients with stable chest pain – at 26 experienced centers in 16 countries – were randomly assigned to undergo CTA or ICA as their initial diagnostic imaging approach. Entry required them to be at intermediate risk, defined as an estimated 10% to 60% probability of having obstructive CAD. Of note, women made up about 56% of both groups.

Imaging was positive for obstructive disease in 26% of the 1,808 patients in the CTA group and in the same proportion of the 1,753 who were assigned to ICA. Nonobstructive CAD was identified in 36% and 22%, respectively.

Importantly, 404 (22.3%) patients in the CTA group then underwent ICA, which identified obstructive CAD in 293 (72.5%).

With a complete follow-up in about 99% of patients, the report notes, the rate of the primary endpoint of major adverse cardiac events, or MACE (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) was 2.1% in the CTA group and in 3.0% in the ICA group. The adjusted hazard ratio of 0.70 (95% confidence interval, 0.46-1.07; P = .10) fell short of significance.

The corresponding HR for an “expanded primary outcome” that also included transient ischemic attack or major procedure-related complications was 0.60 (95% CI, 0.42-0.85) in favor of the CTA group.

As a “pragmatic trial,” DISCHARGE relied on clinically identified events for the endpoint assessments and did not require, for example, laboratory biomarker or neurologic imaging for confirmation, the report notes.

Major procedure-related complications during the initial management phase occurred in 0.5% of the CTA group, and 1.9% of those assigned to initial ICA (HR, 0.26; 95% CI, 0.13-0.55).

Coronary revascularization was less common in the CTA group during the trial’s follow-up, 14.2% versus 18.0% for those assigned to ICA (HR, 0.76; 95% CI, 0.65-0.90).

But the prevalences of angina during the final 4 weeks of follow-up, the group reported, were statistically similar at 8.8% and 7.5% for patients assigned to CTA and ICA, respectively.

The trial showed “no material difference” between the initial CTA versus ICA strategies for its MACE primary endpoint, observed Joseph Loscalzo, MD, PhD, Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass., in an accompanying editorial.

“This result is probably a consequence of the lack of effect of revascularization on cardiovascular events among most patients with stable angina and the limited number of those with high-risk anatomy who would benefit from revascularization in the trial,” he writes.

That CTA was performed “significantly earlier than angiography, 3 days versus 12 days after enrollment,” may have led to earlier coronary revascularization in that group, and therefore is “a better outcome in patients whose anatomy would benefit from it.”

Dr. Loscalzo questioned several aspects of the trial design, which, for example, led to a more than 35% prevalence of patients with nonanginal chest pain among those randomized. Different criteria for classifying patients as “intermediate risk” might also have contributed to the fairly low prevalence of patients in either group ultimately identified with obstructive CAD, he proposes. That low prevalence “suggests that the overall trial population had a low risk of obstructive CAD rather than an intermediate risk.”

DISCHARGE was supported by grants from the European Union Seventh Framework Program, the Berlin Institute of Health, Rigshospitalet of the University of Copenhagen, the British Heart Foundation, and the German Research Foundation. Disclosures for the authors and editorialist are available at NEJM.org. Dr. Budoff has disclosed receiving grant support from General Electric. Dr. Vliegenthart discloses receiving grants from Siemens Healthineers and honorarium for speaking from Siemens Healthineers and Bayer.

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

Computed tomographic angiography (CTA) appears preferable to standard cath-based angiography for the initial evaluation of most stable, intermediate-risk patients with angina-like symptoms, researchers say, based on their study conducted at centers across Europe.

Clinical outcomes over several years in the randomized trial – called DISCHARGE, with an enrollment of more than 3,500 – were statistically similar whether the patients were assigned to CTA or invasive coronary angiography (ICA) as their initial evaluation. Symptoms and quality-of-life measures were also similar.

But the patients assigned to the initial-CTA strategy, of whom fewer than a fourth went on to cardiac cath, showed far fewer procedure-related complications and less often went to coronary revascularization during the median follow-up of 3.5 years, the group reported March 4 in the New England Journal of Medicine.

Based on the findings, CTA “is a safe alternative to cardiac catheterization for patients with suspected CAD [coronary artery disease] that will likely change clinical practice worldwide by replacing invasive testing in patients with stable chest pain who can be expected to benefit” those with an intermediate pretest probability for obstructive disease, principal investigator Marc Dewey, MD, Charité – Universitätsmedizin Berlin, told this news organization.

None of the patient subgroups explored in the trial showed a significant clinical benefit from one strategy over the other, Dr. Dewey commented in an email.

The trial’s results don’t apply to patients unlike those entered, and in particular, he said, “ICA should remain the first test option in patients with high clinical pretest probability of obstructive CAD.”

Dr. Dewey is senior author on the study’s publication, which was timed to coincide with his presentation of the results at ECR 2022 Overture, an all-virtual scientific session of the European Congress of Radiology.

“This is the definitive study,” Matthew Budoff, MD, Lundquist Institute at Harbor-UCLA, Torrance, California, said in an interview. It suggests in a large population that the initial CTA strategy “is as good and maybe safer” in stable patients at intermediate risk compared with initial ICA. “I would say close to 75% or 80% of the patients that we see would fall into that range of risk” and be suitable for the testing algorithm used in the study, said Dr. Budoff, who was not part of the trial.

Invasive angiography would generally still be the initial approach for patients at greater than intermediate risk, such as those with breakthrough angina or electrocardiographic changes, he said. “I still think there’s a huge role for invasive angiography. It’s just a bit smaller now than it used to be for the lower-risk patient.”  

The DISCHARGE trial, agreed cardiothoracic radiology specialist Rozemarijn Vliegenthart, MD, PhD, University of Groningen, the Netherlands, “shows that in patients with intermediate pretest probability, CTA should be used as a gatekeeper before invasive coronary angiography, instead of directly referring for invasive coronary angiography.”

It shows that “a CT-first approach” is both safe and clinically effective and even a trend suggesting better clinical outcomes, compared with ICA. And it demonstrates that “still, many diagnostic invasive coronary angiographies are performed unnecessarily,” Dr. Vliegenthart said as the invited discussant following Dr. Dewey’s presentation.

DISCOVER is only the latest in a series of major studies to explore how CTA best fits in with ICA, stress imaging, and other tests for evaluating patients with chest pain. For example, “the PROMISE trial and the SCOT-HEART trial found that CT was as good as or even better than functional testing. DISCHARGE, I think, confirms the safety of the CT strategy” and reaffirms that it is “at least as good” as an ICA-first approach, cardiologist Klaus F. Kofoed, MD, PhD, DMSc, Rigshospitalet University of Copenhagen, said when co-presenting the trial’s results with Dr. Dewey.

“We can now say CT may be suitable in intermediate-risk patients referred for ICA, particularly those with a clinical constellation suggesting a higher event risk, with abnormal or inconclusive functional test results, or with persistent symptoms despite medical treatment,” said Dr. Kofoed, who is on the DISCOVER steering committee.

The trial’s 3,561 patients with stable chest pain – at 26 experienced centers in 16 countries – were randomly assigned to undergo CTA or ICA as their initial diagnostic imaging approach. Entry required them to be at intermediate risk, defined as an estimated 10% to 60% probability of having obstructive CAD. Of note, women made up about 56% of both groups.

Imaging was positive for obstructive disease in 26% of the 1,808 patients in the CTA group and in the same proportion of the 1,753 who were assigned to ICA. Nonobstructive CAD was identified in 36% and 22%, respectively.

Importantly, 404 (22.3%) patients in the CTA group then underwent ICA, which identified obstructive CAD in 293 (72.5%).

With a complete follow-up in about 99% of patients, the report notes, the rate of the primary endpoint of major adverse cardiac events, or MACE (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) was 2.1% in the CTA group and in 3.0% in the ICA group. The adjusted hazard ratio of 0.70 (95% confidence interval, 0.46-1.07; P = .10) fell short of significance.

The corresponding HR for an “expanded primary outcome” that also included transient ischemic attack or major procedure-related complications was 0.60 (95% CI, 0.42-0.85) in favor of the CTA group.

As a “pragmatic trial,” DISCHARGE relied on clinically identified events for the endpoint assessments and did not require, for example, laboratory biomarker or neurologic imaging for confirmation, the report notes.

Major procedure-related complications during the initial management phase occurred in 0.5% of the CTA group, and 1.9% of those assigned to initial ICA (HR, 0.26; 95% CI, 0.13-0.55).

Coronary revascularization was less common in the CTA group during the trial’s follow-up, 14.2% versus 18.0% for those assigned to ICA (HR, 0.76; 95% CI, 0.65-0.90).

But the prevalences of angina during the final 4 weeks of follow-up, the group reported, were statistically similar at 8.8% and 7.5% for patients assigned to CTA and ICA, respectively.

The trial showed “no material difference” between the initial CTA versus ICA strategies for its MACE primary endpoint, observed Joseph Loscalzo, MD, PhD, Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass., in an accompanying editorial.

“This result is probably a consequence of the lack of effect of revascularization on cardiovascular events among most patients with stable angina and the limited number of those with high-risk anatomy who would benefit from revascularization in the trial,” he writes.

That CTA was performed “significantly earlier than angiography, 3 days versus 12 days after enrollment,” may have led to earlier coronary revascularization in that group, and therefore is “a better outcome in patients whose anatomy would benefit from it.”

Dr. Loscalzo questioned several aspects of the trial design, which, for example, led to a more than 35% prevalence of patients with nonanginal chest pain among those randomized. Different criteria for classifying patients as “intermediate risk” might also have contributed to the fairly low prevalence of patients in either group ultimately identified with obstructive CAD, he proposes. That low prevalence “suggests that the overall trial population had a low risk of obstructive CAD rather than an intermediate risk.”

DISCHARGE was supported by grants from the European Union Seventh Framework Program, the Berlin Institute of Health, Rigshospitalet of the University of Copenhagen, the British Heart Foundation, and the German Research Foundation. Disclosures for the authors and editorialist are available at NEJM.org. Dr. Budoff has disclosed receiving grant support from General Electric. Dr. Vliegenthart discloses receiving grants from Siemens Healthineers and honorarium for speaking from Siemens Healthineers and Bayer.

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

Computed tomographic angiography (CTA) appears preferable to standard cath-based angiography for the initial evaluation of most stable, intermediate-risk patients with angina-like symptoms, researchers say, based on their study conducted at centers across Europe.

Clinical outcomes over several years in the randomized trial – called DISCHARGE, with an enrollment of more than 3,500 – were statistically similar whether the patients were assigned to CTA or invasive coronary angiography (ICA) as their initial evaluation. Symptoms and quality-of-life measures were also similar.

But the patients assigned to the initial-CTA strategy, of whom fewer than a fourth went on to cardiac cath, showed far fewer procedure-related complications and less often went to coronary revascularization during the median follow-up of 3.5 years, the group reported March 4 in the New England Journal of Medicine.

Based on the findings, CTA “is a safe alternative to cardiac catheterization for patients with suspected CAD [coronary artery disease] that will likely change clinical practice worldwide by replacing invasive testing in patients with stable chest pain who can be expected to benefit” those with an intermediate pretest probability for obstructive disease, principal investigator Marc Dewey, MD, Charité – Universitätsmedizin Berlin, told this news organization.

None of the patient subgroups explored in the trial showed a significant clinical benefit from one strategy over the other, Dr. Dewey commented in an email.

The trial’s results don’t apply to patients unlike those entered, and in particular, he said, “ICA should remain the first test option in patients with high clinical pretest probability of obstructive CAD.”

Dr. Dewey is senior author on the study’s publication, which was timed to coincide with his presentation of the results at ECR 2022 Overture, an all-virtual scientific session of the European Congress of Radiology.

“This is the definitive study,” Matthew Budoff, MD, Lundquist Institute at Harbor-UCLA, Torrance, California, said in an interview. It suggests in a large population that the initial CTA strategy “is as good and maybe safer” in stable patients at intermediate risk compared with initial ICA. “I would say close to 75% or 80% of the patients that we see would fall into that range of risk” and be suitable for the testing algorithm used in the study, said Dr. Budoff, who was not part of the trial.

Invasive angiography would generally still be the initial approach for patients at greater than intermediate risk, such as those with breakthrough angina or electrocardiographic changes, he said. “I still think there’s a huge role for invasive angiography. It’s just a bit smaller now than it used to be for the lower-risk patient.”  

The DISCHARGE trial, agreed cardiothoracic radiology specialist Rozemarijn Vliegenthart, MD, PhD, University of Groningen, the Netherlands, “shows that in patients with intermediate pretest probability, CTA should be used as a gatekeeper before invasive coronary angiography, instead of directly referring for invasive coronary angiography.”

It shows that “a CT-first approach” is both safe and clinically effective and even a trend suggesting better clinical outcomes, compared with ICA. And it demonstrates that “still, many diagnostic invasive coronary angiographies are performed unnecessarily,” Dr. Vliegenthart said as the invited discussant following Dr. Dewey’s presentation.

DISCOVER is only the latest in a series of major studies to explore how CTA best fits in with ICA, stress imaging, and other tests for evaluating patients with chest pain. For example, “the PROMISE trial and the SCOT-HEART trial found that CT was as good as or even better than functional testing. DISCHARGE, I think, confirms the safety of the CT strategy” and reaffirms that it is “at least as good” as an ICA-first approach, cardiologist Klaus F. Kofoed, MD, PhD, DMSc, Rigshospitalet University of Copenhagen, said when co-presenting the trial’s results with Dr. Dewey.

“We can now say CT may be suitable in intermediate-risk patients referred for ICA, particularly those with a clinical constellation suggesting a higher event risk, with abnormal or inconclusive functional test results, or with persistent symptoms despite medical treatment,” said Dr. Kofoed, who is on the DISCOVER steering committee.

The trial’s 3,561 patients with stable chest pain – at 26 experienced centers in 16 countries – were randomly assigned to undergo CTA or ICA as their initial diagnostic imaging approach. Entry required them to be at intermediate risk, defined as an estimated 10% to 60% probability of having obstructive CAD. Of note, women made up about 56% of both groups.

Imaging was positive for obstructive disease in 26% of the 1,808 patients in the CTA group and in the same proportion of the 1,753 who were assigned to ICA. Nonobstructive CAD was identified in 36% and 22%, respectively.

Importantly, 404 (22.3%) patients in the CTA group then underwent ICA, which identified obstructive CAD in 293 (72.5%).

With a complete follow-up in about 99% of patients, the report notes, the rate of the primary endpoint of major adverse cardiac events, or MACE (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) was 2.1% in the CTA group and in 3.0% in the ICA group. The adjusted hazard ratio of 0.70 (95% confidence interval, 0.46-1.07; P = .10) fell short of significance.

The corresponding HR for an “expanded primary outcome” that also included transient ischemic attack or major procedure-related complications was 0.60 (95% CI, 0.42-0.85) in favor of the CTA group.

As a “pragmatic trial,” DISCHARGE relied on clinically identified events for the endpoint assessments and did not require, for example, laboratory biomarker or neurologic imaging for confirmation, the report notes.

Major procedure-related complications during the initial management phase occurred in 0.5% of the CTA group, and 1.9% of those assigned to initial ICA (HR, 0.26; 95% CI, 0.13-0.55).

Coronary revascularization was less common in the CTA group during the trial’s follow-up, 14.2% versus 18.0% for those assigned to ICA (HR, 0.76; 95% CI, 0.65-0.90).

But the prevalences of angina during the final 4 weeks of follow-up, the group reported, were statistically similar at 8.8% and 7.5% for patients assigned to CTA and ICA, respectively.

The trial showed “no material difference” between the initial CTA versus ICA strategies for its MACE primary endpoint, observed Joseph Loscalzo, MD, PhD, Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass., in an accompanying editorial.

“This result is probably a consequence of the lack of effect of revascularization on cardiovascular events among most patients with stable angina and the limited number of those with high-risk anatomy who would benefit from revascularization in the trial,” he writes.

That CTA was performed “significantly earlier than angiography, 3 days versus 12 days after enrollment,” may have led to earlier coronary revascularization in that group, and therefore is “a better outcome in patients whose anatomy would benefit from it.”

Dr. Loscalzo questioned several aspects of the trial design, which, for example, led to a more than 35% prevalence of patients with nonanginal chest pain among those randomized. Different criteria for classifying patients as “intermediate risk” might also have contributed to the fairly low prevalence of patients in either group ultimately identified with obstructive CAD, he proposes. That low prevalence “suggests that the overall trial population had a low risk of obstructive CAD rather than an intermediate risk.”

DISCHARGE was supported by grants from the European Union Seventh Framework Program, the Berlin Institute of Health, Rigshospitalet of the University of Copenhagen, the British Heart Foundation, and the German Research Foundation. Disclosures for the authors and editorialist are available at NEJM.org. Dr. Budoff has disclosed receiving grant support from General Electric. Dr. Vliegenthart discloses receiving grants from Siemens Healthineers and honorarium for speaking from Siemens Healthineers and Bayer.

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

New cases of COVID-19 in children continued their descent toward normalcy, falling below 100,000 in a week for the first time since early August 2021, according to the American Academy of Pediatrics and the Children’s Hospital Association.

The sixth consecutive week of declines saw just under 69,000 U.S. children test positive for COVID-19 from Feb. 25 to March 3, a drop of almost 46% from the previous week and 94% since the Omicron-fueled peak of 1.15 million during the week of Jan. 14-20, the AAP and CHA said in their weekly COVID report. The total number of child cases is 12.7 million since the pandemic began, with children representing 19% of all cases.

New admissions also stayed on a downward path, as the rate dropped to 0.24 per 100,000 children aged 0-17 years on March 5, a decline of nearly 81% since hitting 1.25 per 100,000 on Jan. 15. The latest 7-day average for daily admissions, 178 per day from Feb. 27 to March 5, was 29% lower than the previous week and almost 81% lower than the peak of 914 per day for Jan. 10-16, the Centers for Disease Control and Prevention reported.

The story is the same for emergency department visits with diagnosed COVID-19, which are reported as a percentage of all ED visits. On March 4, the 7-day average for children aged 0-11 years was 0.8%, compared with a high of 13.9% in mid-January, while 12- to 15-year-olds had dropped from 12.4% to 0.5% and 16- to 17-year-olds went from 12.6% down to 0.5%, the CDC said on its COVID Data Tracker.

Florida’s surgeon general says no to the vaccine

Vaccination, in the meantime, is struggling to maintain a foothold against the current of declining cases. Florida Surgeon General Joseph Ladapo said that “the Florida Department of Health is going to be the first state to officially recommend against the COVID-19 vaccines for healthy children,” NBC News reported March 7. With such a move, “Florida would become the first state to break from the CDC on vaccines for children,” CNN said in its report.

Vaccinations among children aged 5-11 years, which hit 1.6 million in 1 week shortly after emergency use was authorized in early November, declined quickly shorty thereafter and only rose slightly during the Omicron surge. Since mid-January, the number of children receiving an initial dose has declined for seven consecutive weeks and is now lower than ever, based on CDC data compiled by the AAP.

Just over one-third of children aged 5-11 have gotten at least one dose of COVID-19 vaccine, while 26.4% are fully vaccinated. Among children aged 12-17, just over two-thirds (67.8%) have received at least one dose, 57.8% have completed the vaccine regimen, and 21.9% have gotten a booster, the CDC reported.

As of March 2, “about 8.4 million children 12-17 have yet to receive their initial COVID-19 vaccine dose,” the AAP said. About 64,000 children aged 12-17 had received their first dose in the previous week, the group noted, which was the second-lowest weekly total since the vaccine was approved for children aged 12-15 in May of 2021.

New cases of COVID-19 in children continued their descent toward normalcy, falling below 100,000 in a week for the first time since early August 2021, according to the American Academy of Pediatrics and the Children’s Hospital Association.

The sixth consecutive week of declines saw just under 69,000 U.S. children test positive for COVID-19 from Feb. 25 to March 3, a drop of almost 46% from the previous week and 94% since the Omicron-fueled peak of 1.15 million during the week of Jan. 14-20, the AAP and CHA said in their weekly COVID report. The total number of child cases is 12.7 million since the pandemic began, with children representing 19% of all cases.

New admissions also stayed on a downward path, as the rate dropped to 0.24 per 100,000 children aged 0-17 years on March 5, a decline of nearly 81% since hitting 1.25 per 100,000 on Jan. 15. The latest 7-day average for daily admissions, 178 per day from Feb. 27 to March 5, was 29% lower than the previous week and almost 81% lower than the peak of 914 per day for Jan. 10-16, the Centers for Disease Control and Prevention reported.

The story is the same for emergency department visits with diagnosed COVID-19, which are reported as a percentage of all ED visits. On March 4, the 7-day average for children aged 0-11 years was 0.8%, compared with a high of 13.9% in mid-January, while 12- to 15-year-olds had dropped from 12.4% to 0.5% and 16- to 17-year-olds went from 12.6% down to 0.5%, the CDC said on its COVID Data Tracker.

Florida’s surgeon general says no to the vaccine

Vaccination, in the meantime, is struggling to maintain a foothold against the current of declining cases. Florida Surgeon General Joseph Ladapo said that “the Florida Department of Health is going to be the first state to officially recommend against the COVID-19 vaccines for healthy children,” NBC News reported March 7. With such a move, “Florida would become the first state to break from the CDC on vaccines for children,” CNN said in its report.

Vaccinations among children aged 5-11 years, which hit 1.6 million in 1 week shortly after emergency use was authorized in early November, declined quickly shorty thereafter and only rose slightly during the Omicron surge. Since mid-January, the number of children receiving an initial dose has declined for seven consecutive weeks and is now lower than ever, based on CDC data compiled by the AAP.

Just over one-third of children aged 5-11 have gotten at least one dose of COVID-19 vaccine, while 26.4% are fully vaccinated. Among children aged 12-17, just over two-thirds (67.8%) have received at least one dose, 57.8% have completed the vaccine regimen, and 21.9% have gotten a booster, the CDC reported.

As of March 2, “about 8.4 million children 12-17 have yet to receive their initial COVID-19 vaccine dose,” the AAP said. About 64,000 children aged 12-17 had received their first dose in the previous week, the group noted, which was the second-lowest weekly total since the vaccine was approved for children aged 12-15 in May of 2021.

New cases of COVID-19 in children continued their descent toward normalcy, falling below 100,000 in a week for the first time since early August 2021, according to the American Academy of Pediatrics and the Children’s Hospital Association.

The sixth consecutive week of declines saw just under 69,000 U.S. children test positive for COVID-19 from Feb. 25 to March 3, a drop of almost 46% from the previous week and 94% since the Omicron-fueled peak of 1.15 million during the week of Jan. 14-20, the AAP and CHA said in their weekly COVID report. The total number of child cases is 12.7 million since the pandemic began, with children representing 19% of all cases.

New admissions also stayed on a downward path, as the rate dropped to 0.24 per 100,000 children aged 0-17 years on March 5, a decline of nearly 81% since hitting 1.25 per 100,000 on Jan. 15. The latest 7-day average for daily admissions, 178 per day from Feb. 27 to March 5, was 29% lower than the previous week and almost 81% lower than the peak of 914 per day for Jan. 10-16, the Centers for Disease Control and Prevention reported.

The story is the same for emergency department visits with diagnosed COVID-19, which are reported as a percentage of all ED visits. On March 4, the 7-day average for children aged 0-11 years was 0.8%, compared with a high of 13.9% in mid-January, while 12- to 15-year-olds had dropped from 12.4% to 0.5% and 16- to 17-year-olds went from 12.6% down to 0.5%, the CDC said on its COVID Data Tracker.

Florida’s surgeon general says no to the vaccine

Vaccination, in the meantime, is struggling to maintain a foothold against the current of declining cases. Florida Surgeon General Joseph Ladapo said that “the Florida Department of Health is going to be the first state to officially recommend against the COVID-19 vaccines for healthy children,” NBC News reported March 7. With such a move, “Florida would become the first state to break from the CDC on vaccines for children,” CNN said in its report.

Vaccinations among children aged 5-11 years, which hit 1.6 million in 1 week shortly after emergency use was authorized in early November, declined quickly shorty thereafter and only rose slightly during the Omicron surge. Since mid-January, the number of children receiving an initial dose has declined for seven consecutive weeks and is now lower than ever, based on CDC data compiled by the AAP.

Just over one-third of children aged 5-11 have gotten at least one dose of COVID-19 vaccine, while 26.4% are fully vaccinated. Among children aged 12-17, just over two-thirds (67.8%) have received at least one dose, 57.8% have completed the vaccine regimen, and 21.9% have gotten a booster, the CDC reported.

As of March 2, “about 8.4 million children 12-17 have yet to receive their initial COVID-19 vaccine dose,” the AAP said. About 64,000 children aged 12-17 had received their first dose in the previous week, the group noted, which was the second-lowest weekly total since the vaccine was approved for children aged 12-15 in May of 2021.

Sotorasib, an approved treatment for lung cancer, has demonstrated clinically meaningful anticancer activity and tolerability in patients with heavily pretreated KRASG12C-mutated advanced pancreatic cancer.

The findings were reported at the American Society of Clinical Oncology Genitourinary Cancers Symposium.

“This is clinically meaningful for patients because there is not an established standard therapy for these patients once they get to a third line of treatment,” said the study’s author John H Strickler, MD, of Duke University Medical Center, Durham, N.C.

The study, called CodeBreaK100, is an open-label global phase 1 and 2 trial. It consists of the largest dataset evaluating efficacy and safety of a KRASG12C inhibitor in patients with stage 4 pancreatic cancer.

Survival with Food and Drug Administration–approved second-line therapy in pancreatic ductal adenocarcinoma is 6 months with a 16% response rate. No therapies have demonstrated survival benefit after progression on first- and second-line chemotherapy. Among the 90% of pancreatic ductal adenocarcinoma tumors which harbor a KRAS mutation, 1%-2% are p.G12ac mutations. There are currently no approved treatments for KRASG12C-mutated PDAC.

The study included 38 patients (median age, 65.5 years; 76.3% male) with locally advanced or metastatic pancreatic malignancies who received oral sotorasib (960 mg once daily).

The patients in the trial received one or more prior systemic therapies (79% received two; range, one to eight) or were intolerant or ineligible for available therapies. The primary endpoint was complete plus partial response by blinded independent central review (RECIST 1.1).

Confirmed objective response were reported in 8 patients (21.1%; 95% confidence interval, 9.55%-37.22%) with disease control in 32 (84.2%; 95% CI, 68.75%-93.98%). The median duration of response was 5.7 months. After a median follow-up of 16.8 months, median progression-free survival was 4.0 months (95% CI, 2.8-5.6), and median overall survival was 6.9 months (95% CI, 5.0-9.1).

Once-daily sotorasib was well tolerated. The only treatment-related adverse events above grade 2 were six (15.8%) grade 3 events, with diarrhea in two and fatigue in two (each 5.3%), and single occurrences (2.6%) of abdominal pain, ALT/AST increase, pleural effusion and pulmonary embolism. Three adverse events were serious (7.9%), and no adverse events led to sotorasib discontinuation or were fatal.

Dr. Strickler described the case of a 64-year-old female with stage IV pancreatic cancer at diagnosis, who had baseline metastatic lesions in the liver, lymph nodes, lung and peritoneum. She received prior FOLFIRINOX first line until disease progression. With once-daily sotorasib, time to treatment response was 1.3 month, duration of response was 5.8 months, progression-free survival and overall were 7.1 months each.

Pointing to the centrally confirmed objective response rate of 21.1% and the disease control rate of 84.2%, Dr. Strickler observed in an interview that the CodeBreaK100 data support further exploration of sotorasib in this population with high unmet medical need and that based on these data, the CodeBreaK 100 clinical trial will be expanded to enroll more patients with pancreatic cancer and other tumor types.

The study was funded by Amgen.

Sotorasib, an approved treatment for lung cancer, has demonstrated clinically meaningful anticancer activity and tolerability in patients with heavily pretreated KRASG12C-mutated advanced pancreatic cancer.

The findings were reported at the American Society of Clinical Oncology Genitourinary Cancers Symposium.

“This is clinically meaningful for patients because there is not an established standard therapy for these patients once they get to a third line of treatment,” said the study’s author John H Strickler, MD, of Duke University Medical Center, Durham, N.C.

The study, called CodeBreaK100, is an open-label global phase 1 and 2 trial. It consists of the largest dataset evaluating efficacy and safety of a KRASG12C inhibitor in patients with stage 4 pancreatic cancer.

Survival with Food and Drug Administration–approved second-line therapy in pancreatic ductal adenocarcinoma is 6 months with a 16% response rate. No therapies have demonstrated survival benefit after progression on first- and second-line chemotherapy. Among the 90% of pancreatic ductal adenocarcinoma tumors which harbor a KRAS mutation, 1%-2% are p.G12ac mutations. There are currently no approved treatments for KRASG12C-mutated PDAC.

The study included 38 patients (median age, 65.5 years; 76.3% male) with locally advanced or metastatic pancreatic malignancies who received oral sotorasib (960 mg once daily).

The patients in the trial received one or more prior systemic therapies (79% received two; range, one to eight) or were intolerant or ineligible for available therapies. The primary endpoint was complete plus partial response by blinded independent central review (RECIST 1.1).

Confirmed objective response were reported in 8 patients (21.1%; 95% confidence interval, 9.55%-37.22%) with disease control in 32 (84.2%; 95% CI, 68.75%-93.98%). The median duration of response was 5.7 months. After a median follow-up of 16.8 months, median progression-free survival was 4.0 months (95% CI, 2.8-5.6), and median overall survival was 6.9 months (95% CI, 5.0-9.1).

Once-daily sotorasib was well tolerated. The only treatment-related adverse events above grade 2 were six (15.8%) grade 3 events, with diarrhea in two and fatigue in two (each 5.3%), and single occurrences (2.6%) of abdominal pain, ALT/AST increase, pleural effusion and pulmonary embolism. Three adverse events were serious (7.9%), and no adverse events led to sotorasib discontinuation or were fatal.

Dr. Strickler described the case of a 64-year-old female with stage IV pancreatic cancer at diagnosis, who had baseline metastatic lesions in the liver, lymph nodes, lung and peritoneum. She received prior FOLFIRINOX first line until disease progression. With once-daily sotorasib, time to treatment response was 1.3 month, duration of response was 5.8 months, progression-free survival and overall were 7.1 months each.

Pointing to the centrally confirmed objective response rate of 21.1% and the disease control rate of 84.2%, Dr. Strickler observed in an interview that the CodeBreaK100 data support further exploration of sotorasib in this population with high unmet medical need and that based on these data, the CodeBreaK 100 clinical trial will be expanded to enroll more patients with pancreatic cancer and other tumor types.

The study was funded by Amgen.

Sotorasib, an approved treatment for lung cancer, has demonstrated clinically meaningful anticancer activity and tolerability in patients with heavily pretreated KRASG12C-mutated advanced pancreatic cancer.

The findings were reported at the American Society of Clinical Oncology Genitourinary Cancers Symposium.

“This is clinically meaningful for patients because there is not an established standard therapy for these patients once they get to a third line of treatment,” said the study’s author John H Strickler, MD, of Duke University Medical Center, Durham, N.C.

The study, called CodeBreaK100, is an open-label global phase 1 and 2 trial. It consists of the largest dataset evaluating efficacy and safety of a KRASG12C inhibitor in patients with stage 4 pancreatic cancer.

Survival with Food and Drug Administration–approved second-line therapy in pancreatic ductal adenocarcinoma is 6 months with a 16% response rate. No therapies have demonstrated survival benefit after progression on first- and second-line chemotherapy. Among the 90% of pancreatic ductal adenocarcinoma tumors which harbor a KRAS mutation, 1%-2% are p.G12ac mutations. There are currently no approved treatments for KRASG12C-mutated PDAC.

The study included 38 patients (median age, 65.5 years; 76.3% male) with locally advanced or metastatic pancreatic malignancies who received oral sotorasib (960 mg once daily).

The patients in the trial received one or more prior systemic therapies (79% received two; range, one to eight) or were intolerant or ineligible for available therapies. The primary endpoint was complete plus partial response by blinded independent central review (RECIST 1.1).

Confirmed objective response were reported in 8 patients (21.1%; 95% confidence interval, 9.55%-37.22%) with disease control in 32 (84.2%; 95% CI, 68.75%-93.98%). The median duration of response was 5.7 months. After a median follow-up of 16.8 months, median progression-free survival was 4.0 months (95% CI, 2.8-5.6), and median overall survival was 6.9 months (95% CI, 5.0-9.1).

Once-daily sotorasib was well tolerated. The only treatment-related adverse events above grade 2 were six (15.8%) grade 3 events, with diarrhea in two and fatigue in two (each 5.3%), and single occurrences (2.6%) of abdominal pain, ALT/AST increase, pleural effusion and pulmonary embolism. Three adverse events were serious (7.9%), and no adverse events led to sotorasib discontinuation or were fatal.

Dr. Strickler described the case of a 64-year-old female with stage IV pancreatic cancer at diagnosis, who had baseline metastatic lesions in the liver, lymph nodes, lung and peritoneum. She received prior FOLFIRINOX first line until disease progression. With once-daily sotorasib, time to treatment response was 1.3 month, duration of response was 5.8 months, progression-free survival and overall were 7.1 months each.

Pointing to the centrally confirmed objective response rate of 21.1% and the disease control rate of 84.2%, Dr. Strickler observed in an interview that the CodeBreaK100 data support further exploration of sotorasib in this population with high unmet medical need and that based on these data, the CodeBreaK 100 clinical trial will be expanded to enroll more patients with pancreatic cancer and other tumor types.

The study was funded by Amgen.

Should patients with metastatic colorectal cancer (CRC) who respond to first-line treatment receive maintenance therapy, or are they better off on active surveillance?

In a recent trial designed to explore this question, British investigators made a strong case for active surveillance over maintenance therapy.

The researchers found that patients with metastatic CRC randomized to maintenance therapy with oral capecitabine (Xeloda) showed improved progression-free survival (PFS), compared with those being actively monitored – 3.88 versus 1.87 months.

But that benefit came at a cost. Patients on capecitabine experienced much worse toxicity and showed no overall survival benefit – 14.8 months in the capecitabine arm versus 15.2 in the surveillance arm.

The FOCUS4-N trial supports “the use of treatment breaks as safe management alternatives for patients” after induction, lead author Richard Adams, MD, an oncology professor at Cardiff University, Wales, and colleagues conclude in a study published in the Journal of Clinical Oncology.

Current treatment standards either require or recommend that patients with metastatic CRC receive maintenance therapy after induction chemotherapy, at least until they progress or experience excessive toxicity.

Although maintenance strategies have typically demonstrated a PFS benefit, that advantage may come at “the expense of ongoing ... toxicity.”

Dr. Adams and colleagues wanted to explore how patients would fare on an oral maintenance therapy with capecitabine, compared with active surveillance.

In the trial, researchers randomly assigned 254 patients who had responded to first-line therapy or had stable disease to either capecitabine (n = 127) or active monitoring (n = 127). Subjects were treated at 88 hospitals in the United Kingdom from 2014-2020. Most patients had widespread synchronous metastatic disease. About half had unresected primary tumors, and the majority had received doublet chemotherapy induction, which was irinotecan-based in 57%.

The authors found that patients receiving capecitabine maintenance therapy showed significant improvements in PFS (hazard ratio, 0.40; P < .0001), but also encountered considerably more toxicity than the surveillance group – including grade 2 or higher fatigue (25% vs. 12%), diarrhea (23% vs. 13%), and hand-foot skin reactions (26% vs. 3%).

Perhaps most notably, the treatment group did not experience an overall survival benefit (HR, 0.93; 95% confidence interval, 0.69-1.27; P = .66).

Overall, the authors noted, the main advantage of active maintenance was to delay the return of aggressive chemotherapy combinations for a few months.  

With previous trials reporting pretty much the same findings, there is now “overwhelming level-one evidence” that surveillance is an “appropriate” option with “less time on therapy, lower toxicity, and in a number of studies, better quality of life,” which are all important factors for patients, according to Dr. Adams and colleagues in a follow-up letter.   
 

A viable option

The current study pushes back on existing standards, which support maintenance therapy and can prevent patients from being offered active surveillance.

According to Dr. Adams and colleagues, “FOCUS4-N provides additional evidence to support the use of treatment breaks as safe management alternatives for patients who are stable or responding to first-line treatment for [metastatic] CRC.”

In addition, the FOCUS4-N trial suggests that oral capecitabine alone – instead of alongside intravenous bevacizumab (Avastin) every 3 weeks – is probably adequate for mCRC maintenance.

“It has been shown that single-agent bevacizumab is both ineffective and highly uneconomic” in the mCRC maintenance setting, “suggesting that it may be the capecitabine element of the combination that” provides the PFS benefit, the team noted.

An editorial accompanying the study also concluded that “treatment holidays are an equally viable and more cost-effective alternative” to maintenance and one of special interest to patients looking for a break after intensive induction.

“For patients, caregivers, and oncologists alike who are hesitant to ... stop therapy completely, it is important to note that” at least in trials, patients under surveillance “continue to be vigilantly monitored, including imaging every 8-12 weeks and symptom assessment every few weeks,” Pashtoon Murtaza Kasi, MD, medical oncologist at Weill Cornell Medicine/NewYork-Presbyterian, Manhattan, said in his editorial. 

Interestingly, Dr. Kasi pointed out, the trial found no difference in quality-of-life scores between the study arms in the FOCUS4-N trial.

The two groups scored similarly on mobility, self-care, usual activities, anxiety, and depression, and patients in the capecitabine group reported slightly less pain and discomfort, which may have occurred because of delayed disease progression.

“Although it is somewhat reassuring that maintenance approaches do not adversely affect overall quality of life and functioning, it does not mean that these regimens are free from side effects,” Dr. Kasi writes, adding that it’s possible the surveys missed the impacts of increased toxicity with maintenance therapy.
 

Caveats to the study

A letter published in the Journal of Clinical Oncology raises questions about the generalizability of the FOCUS4-N results.

In the letter, Annika Kurreck, MD, and colleagues from Charity-University Medicine Berlin, Germany, highlighted that the trial only included patients without actionable biomarkers, which likely meant the study population had particularly aggressive disease. This possibility is supported by the “dramatically short” PFS reported in FOCUS4-N compared with prior maintenance versus surveillance investigations.

In addition, the letter writers caution that the study was underpowered to detect an overall survival benefit.

“Therefore, it might be hypothesized that FOCUS4-N comprised a cohort of patients with a rather aggressive tumor biology and/or high tumor load, leading to a quick failure of any de-escalation treatment strategy,” Dr. Kurreck and colleagues write.

In a response letter, Dr. Adams and his team countered that there’s no consistent evidence from past trials suggesting that patients with poorer prognostic features are unfit for surveillance. “We believe that it is a common misrepresentation of the evidence that all patients with worse prognostic features need to be maintained on active but toxic combination therapies for longer,” they said.

Instead of a blanket approach, maintenance versus surveillance should be “an assessment guided by the clinician listening to and guiding the patient rather than a molecular or biologically measurable parameter,” they write.

Dr. Adams and colleagues agreed that identifying subgroups of patients who are more likely to benefit from maintenance versus surveillance is required research, which “we plan to undertake.”

The work was funded by Cancer Research UK and the National Institute for Health Research. Many of the investigators had industry ties, including Dr. Adams, who reported various relationships with and payments from Merck, Amgen, and others. Dr. Kasi also had ties to several companies, including Bristol Myers Squibb, Lilly, and AstraZeneca. Dr. Kurreck and the other letter writers had numerous company ties as well, including relationships and payments from Roche, the maker of bevacizumab.

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

Should patients with metastatic colorectal cancer (CRC) who respond to first-line treatment receive maintenance therapy, or are they better off on active surveillance?

In a recent trial designed to explore this question, British investigators made a strong case for active surveillance over maintenance therapy.

The researchers found that patients with metastatic CRC randomized to maintenance therapy with oral capecitabine (Xeloda) showed improved progression-free survival (PFS), compared with those being actively monitored – 3.88 versus 1.87 months.

But that benefit came at a cost. Patients on capecitabine experienced much worse toxicity and showed no overall survival benefit – 14.8 months in the capecitabine arm versus 15.2 in the surveillance arm.

The FOCUS4-N trial supports “the use of treatment breaks as safe management alternatives for patients” after induction, lead author Richard Adams, MD, an oncology professor at Cardiff University, Wales, and colleagues conclude in a study published in the Journal of Clinical Oncology.

Current treatment standards either require or recommend that patients with metastatic CRC receive maintenance therapy after induction chemotherapy, at least until they progress or experience excessive toxicity.

Although maintenance strategies have typically demonstrated a PFS benefit, that advantage may come at “the expense of ongoing ... toxicity.”

Dr. Adams and colleagues wanted to explore how patients would fare on an oral maintenance therapy with capecitabine, compared with active surveillance.

In the trial, researchers randomly assigned 254 patients who had responded to first-line therapy or had stable disease to either capecitabine (n = 127) or active monitoring (n = 127). Subjects were treated at 88 hospitals in the United Kingdom from 2014-2020. Most patients had widespread synchronous metastatic disease. About half had unresected primary tumors, and the majority had received doublet chemotherapy induction, which was irinotecan-based in 57%.

The authors found that patients receiving capecitabine maintenance therapy showed significant improvements in PFS (hazard ratio, 0.40; P < .0001), but also encountered considerably more toxicity than the surveillance group – including grade 2 or higher fatigue (25% vs. 12%), diarrhea (23% vs. 13%), and hand-foot skin reactions (26% vs. 3%).

Perhaps most notably, the treatment group did not experience an overall survival benefit (HR, 0.93; 95% confidence interval, 0.69-1.27; P = .66).

Overall, the authors noted, the main advantage of active maintenance was to delay the return of aggressive chemotherapy combinations for a few months.  

With previous trials reporting pretty much the same findings, there is now “overwhelming level-one evidence” that surveillance is an “appropriate” option with “less time on therapy, lower toxicity, and in a number of studies, better quality of life,” which are all important factors for patients, according to Dr. Adams and colleagues in a follow-up letter.   
 

A viable option

The current study pushes back on existing standards, which support maintenance therapy and can prevent patients from being offered active surveillance.

According to Dr. Adams and colleagues, “FOCUS4-N provides additional evidence to support the use of treatment breaks as safe management alternatives for patients who are stable or responding to first-line treatment for [metastatic] CRC.”

In addition, the FOCUS4-N trial suggests that oral capecitabine alone – instead of alongside intravenous bevacizumab (Avastin) every 3 weeks – is probably adequate for mCRC maintenance.

“It has been shown that single-agent bevacizumab is both ineffective and highly uneconomic” in the mCRC maintenance setting, “suggesting that it may be the capecitabine element of the combination that” provides the PFS benefit, the team noted.

An editorial accompanying the study also concluded that “treatment holidays are an equally viable and more cost-effective alternative” to maintenance and one of special interest to patients looking for a break after intensive induction.

“For patients, caregivers, and oncologists alike who are hesitant to ... stop therapy completely, it is important to note that” at least in trials, patients under surveillance “continue to be vigilantly monitored, including imaging every 8-12 weeks and symptom assessment every few weeks,” Pashtoon Murtaza Kasi, MD, medical oncologist at Weill Cornell Medicine/NewYork-Presbyterian, Manhattan, said in his editorial. 

Interestingly, Dr. Kasi pointed out, the trial found no difference in quality-of-life scores between the study arms in the FOCUS4-N trial.

The two groups scored similarly on mobility, self-care, usual activities, anxiety, and depression, and patients in the capecitabine group reported slightly less pain and discomfort, which may have occurred because of delayed disease progression.

“Although it is somewhat reassuring that maintenance approaches do not adversely affect overall quality of life and functioning, it does not mean that these regimens are free from side effects,” Dr. Kasi writes, adding that it’s possible the surveys missed the impacts of increased toxicity with maintenance therapy.
 

Caveats to the study

A letter published in the Journal of Clinical Oncology raises questions about the generalizability of the FOCUS4-N results.

In the letter, Annika Kurreck, MD, and colleagues from Charity-University Medicine Berlin, Germany, highlighted that the trial only included patients without actionable biomarkers, which likely meant the study population had particularly aggressive disease. This possibility is supported by the “dramatically short” PFS reported in FOCUS4-N compared with prior maintenance versus surveillance investigations.

In addition, the letter writers caution that the study was underpowered to detect an overall survival benefit.

“Therefore, it might be hypothesized that FOCUS4-N comprised a cohort of patients with a rather aggressive tumor biology and/or high tumor load, leading to a quick failure of any de-escalation treatment strategy,” Dr. Kurreck and colleagues write.

In a response letter, Dr. Adams and his team countered that there’s no consistent evidence from past trials suggesting that patients with poorer prognostic features are unfit for surveillance. “We believe that it is a common misrepresentation of the evidence that all patients with worse prognostic features need to be maintained on active but toxic combination therapies for longer,” they said.

Instead of a blanket approach, maintenance versus surveillance should be “an assessment guided by the clinician listening to and guiding the patient rather than a molecular or biologically measurable parameter,” they write.

Dr. Adams and colleagues agreed that identifying subgroups of patients who are more likely to benefit from maintenance versus surveillance is required research, which “we plan to undertake.”

The work was funded by Cancer Research UK and the National Institute for Health Research. Many of the investigators had industry ties, including Dr. Adams, who reported various relationships with and payments from Merck, Amgen, and others. Dr. Kasi also had ties to several companies, including Bristol Myers Squibb, Lilly, and AstraZeneca. Dr. Kurreck and the other letter writers had numerous company ties as well, including relationships and payments from Roche, the maker of bevacizumab.

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

Should patients with metastatic colorectal cancer (CRC) who respond to first-line treatment receive maintenance therapy, or are they better off on active surveillance?

In a recent trial designed to explore this question, British investigators made a strong case for active surveillance over maintenance therapy.

The researchers found that patients with metastatic CRC randomized to maintenance therapy with oral capecitabine (Xeloda) showed improved progression-free survival (PFS), compared with those being actively monitored – 3.88 versus 1.87 months.

But that benefit came at a cost. Patients on capecitabine experienced much worse toxicity and showed no overall survival benefit – 14.8 months in the capecitabine arm versus 15.2 in the surveillance arm.

The FOCUS4-N trial supports “the use of treatment breaks as safe management alternatives for patients” after induction, lead author Richard Adams, MD, an oncology professor at Cardiff University, Wales, and colleagues conclude in a study published in the Journal of Clinical Oncology.

Current treatment standards either require or recommend that patients with metastatic CRC receive maintenance therapy after induction chemotherapy, at least until they progress or experience excessive toxicity.

Although maintenance strategies have typically demonstrated a PFS benefit, that advantage may come at “the expense of ongoing ... toxicity.”

Dr. Adams and colleagues wanted to explore how patients would fare on an oral maintenance therapy with capecitabine, compared with active surveillance.

In the trial, researchers randomly assigned 254 patients who had responded to first-line therapy or had stable disease to either capecitabine (n = 127) or active monitoring (n = 127). Subjects were treated at 88 hospitals in the United Kingdom from 2014-2020. Most patients had widespread synchronous metastatic disease. About half had unresected primary tumors, and the majority had received doublet chemotherapy induction, which was irinotecan-based in 57%.

The authors found that patients receiving capecitabine maintenance therapy showed significant improvements in PFS (hazard ratio, 0.40; P < .0001), but also encountered considerably more toxicity than the surveillance group – including grade 2 or higher fatigue (25% vs. 12%), diarrhea (23% vs. 13%), and hand-foot skin reactions (26% vs. 3%).

Perhaps most notably, the treatment group did not experience an overall survival benefit (HR, 0.93; 95% confidence interval, 0.69-1.27; P = .66).

Overall, the authors noted, the main advantage of active maintenance was to delay the return of aggressive chemotherapy combinations for a few months.  

With previous trials reporting pretty much the same findings, there is now “overwhelming level-one evidence” that surveillance is an “appropriate” option with “less time on therapy, lower toxicity, and in a number of studies, better quality of life,” which are all important factors for patients, according to Dr. Adams and colleagues in a follow-up letter.   
 

A viable option

The current study pushes back on existing standards, which support maintenance therapy and can prevent patients from being offered active surveillance.

According to Dr. Adams and colleagues, “FOCUS4-N provides additional evidence to support the use of treatment breaks as safe management alternatives for patients who are stable or responding to first-line treatment for [metastatic] CRC.”

In addition, the FOCUS4-N trial suggests that oral capecitabine alone – instead of alongside intravenous bevacizumab (Avastin) every 3 weeks – is probably adequate for mCRC maintenance.

“It has been shown that single-agent bevacizumab is both ineffective and highly uneconomic” in the mCRC maintenance setting, “suggesting that it may be the capecitabine element of the combination that” provides the PFS benefit, the team noted.

An editorial accompanying the study also concluded that “treatment holidays are an equally viable and more cost-effective alternative” to maintenance and one of special interest to patients looking for a break after intensive induction.

“For patients, caregivers, and oncologists alike who are hesitant to ... stop therapy completely, it is important to note that” at least in trials, patients under surveillance “continue to be vigilantly monitored, including imaging every 8-12 weeks and symptom assessment every few weeks,” Pashtoon Murtaza Kasi, MD, medical oncologist at Weill Cornell Medicine/NewYork-Presbyterian, Manhattan, said in his editorial. 

Interestingly, Dr. Kasi pointed out, the trial found no difference in quality-of-life scores between the study arms in the FOCUS4-N trial.

The two groups scored similarly on mobility, self-care, usual activities, anxiety, and depression, and patients in the capecitabine group reported slightly less pain and discomfort, which may have occurred because of delayed disease progression.

“Although it is somewhat reassuring that maintenance approaches do not adversely affect overall quality of life and functioning, it does not mean that these regimens are free from side effects,” Dr. Kasi writes, adding that it’s possible the surveys missed the impacts of increased toxicity with maintenance therapy.
 

Caveats to the study

A letter published in the Journal of Clinical Oncology raises questions about the generalizability of the FOCUS4-N results.

In the letter, Annika Kurreck, MD, and colleagues from Charity-University Medicine Berlin, Germany, highlighted that the trial only included patients without actionable biomarkers, which likely meant the study population had particularly aggressive disease. This possibility is supported by the “dramatically short” PFS reported in FOCUS4-N compared with prior maintenance versus surveillance investigations.

In addition, the letter writers caution that the study was underpowered to detect an overall survival benefit.

“Therefore, it might be hypothesized that FOCUS4-N comprised a cohort of patients with a rather aggressive tumor biology and/or high tumor load, leading to a quick failure of any de-escalation treatment strategy,” Dr. Kurreck and colleagues write.

In a response letter, Dr. Adams and his team countered that there’s no consistent evidence from past trials suggesting that patients with poorer prognostic features are unfit for surveillance. “We believe that it is a common misrepresentation of the evidence that all patients with worse prognostic features need to be maintained on active but toxic combination therapies for longer,” they said.

Instead of a blanket approach, maintenance versus surveillance should be “an assessment guided by the clinician listening to and guiding the patient rather than a molecular or biologically measurable parameter,” they write.

Dr. Adams and colleagues agreed that identifying subgroups of patients who are more likely to benefit from maintenance versus surveillance is required research, which “we plan to undertake.”

The work was funded by Cancer Research UK and the National Institute for Health Research. Many of the investigators had industry ties, including Dr. Adams, who reported various relationships with and payments from Merck, Amgen, and others. Dr. Kasi also had ties to several companies, including Bristol Myers Squibb, Lilly, and AstraZeneca. Dr. Kurreck and the other letter writers had numerous company ties as well, including relationships and payments from Roche, the maker of bevacizumab.

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

As many in the world react with sanctions imposed on Russia after its invasion of Ukraine, the oncology community has now stepped into the fray.

All the large cancer organizations have put out statements in support of Ukraine, but one group has gone further and cut its ties with Russia.

“The international cancer specialist network, OncoAlert, severed all cooperation with doctors in Russia as part of the Western sanctions,” the group announced on its Twitter page, which is decorated with a blue and yellow ribbon and declares that it “stands with Ukraine.”

“The OncoAlert Network is nonpolitical but we cannot stand idle and not take a stand against this aggression toward our Ukrainian friends & colleagues,” the group said. “The network will be pulling out of ALL collaborations & congresses in Russia.”

Not surprisingly, the post was inundated with a barrage of inflammatory and politically laced tweets from Russian and Chinese users. Many of them repeated the same phrase about “violating the Hippocratic oath and the Geneva convention,” used foul language, and slammed the United States for past military actions in other parts of the world.

A prominent Russian oncologist also responded, posting a video in which he discussed the situation more coherently and without mudslinging or scripted phrases. Andrey Kaprin, MD, PhD, is chief oncologist of the Russian Federation as well as director general of the Federal State Budgetary Institution, NMRCC, of the Ministry of Health of the Russian Federation. He says they continue to maintain relations with the largest and best known oncologic organizations. “We haven’t felt any deterioration in our relationship yet, and of course, we hope that this won’t happen.”

Dr. Kaprin said he believes OncoAlert will return to cooperation with Russia, and that “reason will prevail.”

“No one is protected from cancer, not even doctors, and that is why there should be no politics here,” he said.

Dr. Kaprin was speaking from Russia state-affiliated media, so it was not an independent commentary. Several of the Twitter responses to his video, primarily from non-Russians, were less than complimentary.

One user replied: “Cancer is rife in the Kremlin.”

Another post pointed out the hypocrisy of Russians being upset that OncoAlert was cutting ties with them. “What about sick Ukrainian kids, having to shelter in hospital basement, not having lifesaving surgeries because Russia decided to invade a democratic country?”

And another post was not buying the story that “reason will prevail,” in that the doctor’s talk seemed to contradict the reality of the situation. “I guess for every child #Russia murders they get cut off a little more from the civilized world?”
 

Cancer patients vulnerable

The war in Ukraine is an “unfolding humanitarian emergency,” said the World Health Organization, and it has called on top-level officials involved in the Russian invasion to ensure access for delivery of essential medical, surgical, and trauma supplies to help the Ukrainian people and refugees in neighboring countries. A shortage of oxygen, insulin, cancer therapies, and other essential supplies will continue to grow more dire in the weeks and months ahead, WHO officials predict.

One of the more heartbreaking reports described how pediatric cancer patients have been moved to hospital basements that are serving as temporary bomb shelters. Hospital staff continue to try to provide limited treatment when possible, even though essential supplies are dwindling. 

“These children suffer more because they need to stay alive to fight with the cancer – and this fight cannot wait,” Lesia Lysytsia, MD, a doctor at Okhmatdyt, the country’s largest children’s hospital in Kyiv, said in an NBC news report.

For some children, the only treatment available is a basic form of chemotherapy, and at the Kyiv Regional Oncology Center, the situation became so dire for children in need of blood transfusions that physicians began to transfuse blood from parent to child.

“Our patients, they will die,” Dr. Lysytsia said. “We will calculate how many people or soldiers have died in attacks, but we will never calculate how many patients weren’t diagnosed of disease in time, how many patients died because they didn’t receive treatment. It’s an epic amount of people.”
 

Response from oncology community

Many of the large American oncology groups have issued strong statements expressing their support for Ukraine and offering assistance.

The American Cancer Society has partnered with the American Society of Clinical Oncology and the Sidney Kimmel Cancer Center–Jefferson Health to support all Ukrainian cancer patients and their families. The groups are engaging a network of oncologists and oncology nurses to provide support through the ACS Clinician Volunteer Corps.

The ACS and ASCO are making free cancer resources available in English, Ukrainian, Polish, and Russian through their patient information websites (available here and here), with additional patient education resources planned. 

The ACS noted that there are more than 179,000 newly diagnosed patients with cancer among the Ukrainian people “suffering from Russia’s unprovoked aggression.”

“Disruptions to cancer treatment pose a grave risk to the survival of Ukrainian patients with cancer,” commented Karen Knudsen, PhD, CEO at the ACS.

ASCO also issued its own statement, declaring that it stands with “our Ukrainian members, the worldwide oncology community, and health care providers around the globe in condemning Russia’s unprovoked war on Ukraine.”

The society notes that it represents oncology professionals in Ukraine and neighboring countries including Poland, Romania, Moldova, Slovakia, and Hungary, which are now receiving thousands of refugees from the Russian invasion.

“We are hearing daily reports of cancer treatment interrupted by acts of war, including damage to medical facilities and shortages of critical supplies. Countless patients now need to find cancer care in new and unfamiliar surroundings with limited medical records and minimal resources,” the society commented.

The American Association for Cancer Research also issued a statement by President David A. Tuveson, MD, PhD, and CEO Margaret Foti, PhD, MD (hc). The organization has more than 50,000 members around the world, and they “stand in solidarity with the citizens of Ukraine during the Russian attack on their country.”

“This abhorrent war, which has been instigated by Russia’s leaders, is isolating and interrupting the lifesaving work of scientists and clinicians in Ukraine and Russia, threatening years of effective research collaborations and community building,” the AACR comments. “Limiting the exchange of innovative ideas, practices, and data across borders will significantly retard cancer research and have an adverse effect on public health.”

Perhaps the most subdued statement came from the European Society of Medical Oncology, in a brief release entitled: “Against Any War.” The society expressed profound sadness about the unfolding tragedy in Ukraine and the suffering of people. “We would like to confirm our solidarity and unconditioned support to all oncology professionals and cancer patients, with no geographical boundaries.”

ESMO also said that they were reviewing possibilities “to be of concrete help for our members and their patients, in collaboration with national and transnational oncology societies, as well as the International Cancer Foundation.”

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

As many in the world react with sanctions imposed on Russia after its invasion of Ukraine, the oncology community has now stepped into the fray.

All the large cancer organizations have put out statements in support of Ukraine, but one group has gone further and cut its ties with Russia.

“The international cancer specialist network, OncoAlert, severed all cooperation with doctors in Russia as part of the Western sanctions,” the group announced on its Twitter page, which is decorated with a blue and yellow ribbon and declares that it “stands with Ukraine.”

“The OncoAlert Network is nonpolitical but we cannot stand idle and not take a stand against this aggression toward our Ukrainian friends & colleagues,” the group said. “The network will be pulling out of ALL collaborations & congresses in Russia.”

Not surprisingly, the post was inundated with a barrage of inflammatory and politically laced tweets from Russian and Chinese users. Many of them repeated the same phrase about “violating the Hippocratic oath and the Geneva convention,” used foul language, and slammed the United States for past military actions in other parts of the world.

A prominent Russian oncologist also responded, posting a video in which he discussed the situation more coherently and without mudslinging or scripted phrases. Andrey Kaprin, MD, PhD, is chief oncologist of the Russian Federation as well as director general of the Federal State Budgetary Institution, NMRCC, of the Ministry of Health of the Russian Federation. He says they continue to maintain relations with the largest and best known oncologic organizations. “We haven’t felt any deterioration in our relationship yet, and of course, we hope that this won’t happen.”

Dr. Kaprin said he believes OncoAlert will return to cooperation with Russia, and that “reason will prevail.”

“No one is protected from cancer, not even doctors, and that is why there should be no politics here,” he said.

Dr. Kaprin was speaking from Russia state-affiliated media, so it was not an independent commentary. Several of the Twitter responses to his video, primarily from non-Russians, were less than complimentary.

One user replied: “Cancer is rife in the Kremlin.”

Another post pointed out the hypocrisy of Russians being upset that OncoAlert was cutting ties with them. “What about sick Ukrainian kids, having to shelter in hospital basement, not having lifesaving surgeries because Russia decided to invade a democratic country?”

And another post was not buying the story that “reason will prevail,” in that the doctor’s talk seemed to contradict the reality of the situation. “I guess for every child #Russia murders they get cut off a little more from the civilized world?”
 

Cancer patients vulnerable

The war in Ukraine is an “unfolding humanitarian emergency,” said the World Health Organization, and it has called on top-level officials involved in the Russian invasion to ensure access for delivery of essential medical, surgical, and trauma supplies to help the Ukrainian people and refugees in neighboring countries. A shortage of oxygen, insulin, cancer therapies, and other essential supplies will continue to grow more dire in the weeks and months ahead, WHO officials predict.

One of the more heartbreaking reports described how pediatric cancer patients have been moved to hospital basements that are serving as temporary bomb shelters. Hospital staff continue to try to provide limited treatment when possible, even though essential supplies are dwindling. 

“These children suffer more because they need to stay alive to fight with the cancer – and this fight cannot wait,” Lesia Lysytsia, MD, a doctor at Okhmatdyt, the country’s largest children’s hospital in Kyiv, said in an NBC news report.

For some children, the only treatment available is a basic form of chemotherapy, and at the Kyiv Regional Oncology Center, the situation became so dire for children in need of blood transfusions that physicians began to transfuse blood from parent to child.

“Our patients, they will die,” Dr. Lysytsia said. “We will calculate how many people or soldiers have died in attacks, but we will never calculate how many patients weren’t diagnosed of disease in time, how many patients died because they didn’t receive treatment. It’s an epic amount of people.”
 

Response from oncology community

Many of the large American oncology groups have issued strong statements expressing their support for Ukraine and offering assistance.

The American Cancer Society has partnered with the American Society of Clinical Oncology and the Sidney Kimmel Cancer Center–Jefferson Health to support all Ukrainian cancer patients and their families. The groups are engaging a network of oncologists and oncology nurses to provide support through the ACS Clinician Volunteer Corps.

The ACS and ASCO are making free cancer resources available in English, Ukrainian, Polish, and Russian through their patient information websites (available here and here), with additional patient education resources planned. 

The ACS noted that there are more than 179,000 newly diagnosed patients with cancer among the Ukrainian people “suffering from Russia’s unprovoked aggression.”

“Disruptions to cancer treatment pose a grave risk to the survival of Ukrainian patients with cancer,” commented Karen Knudsen, PhD, CEO at the ACS.

ASCO also issued its own statement, declaring that it stands with “our Ukrainian members, the worldwide oncology community, and health care providers around the globe in condemning Russia’s unprovoked war on Ukraine.”

The society notes that it represents oncology professionals in Ukraine and neighboring countries including Poland, Romania, Moldova, Slovakia, and Hungary, which are now receiving thousands of refugees from the Russian invasion.

“We are hearing daily reports of cancer treatment interrupted by acts of war, including damage to medical facilities and shortages of critical supplies. Countless patients now need to find cancer care in new and unfamiliar surroundings with limited medical records and minimal resources,” the society commented.

The American Association for Cancer Research also issued a statement by President David A. Tuveson, MD, PhD, and CEO Margaret Foti, PhD, MD (hc). The organization has more than 50,000 members around the world, and they “stand in solidarity with the citizens of Ukraine during the Russian attack on their country.”

“This abhorrent war, which has been instigated by Russia’s leaders, is isolating and interrupting the lifesaving work of scientists and clinicians in Ukraine and Russia, threatening years of effective research collaborations and community building,” the AACR comments. “Limiting the exchange of innovative ideas, practices, and data across borders will significantly retard cancer research and have an adverse effect on public health.”

Perhaps the most subdued statement came from the European Society of Medical Oncology, in a brief release entitled: “Against Any War.” The society expressed profound sadness about the unfolding tragedy in Ukraine and the suffering of people. “We would like to confirm our solidarity and unconditioned support to all oncology professionals and cancer patients, with no geographical boundaries.”

ESMO also said that they were reviewing possibilities “to be of concrete help for our members and their patients, in collaboration with national and transnational oncology societies, as well as the International Cancer Foundation.”

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

As many in the world react with sanctions imposed on Russia after its invasion of Ukraine, the oncology community has now stepped into the fray.

All the large cancer organizations have put out statements in support of Ukraine, but one group has gone further and cut its ties with Russia.

“The international cancer specialist network, OncoAlert, severed all cooperation with doctors in Russia as part of the Western sanctions,” the group announced on its Twitter page, which is decorated with a blue and yellow ribbon and declares that it “stands with Ukraine.”

“The OncoAlert Network is nonpolitical but we cannot stand idle and not take a stand against this aggression toward our Ukrainian friends & colleagues,” the group said. “The network will be pulling out of ALL collaborations & congresses in Russia.”

Not surprisingly, the post was inundated with a barrage of inflammatory and politically laced tweets from Russian and Chinese users. Many of them repeated the same phrase about “violating the Hippocratic oath and the Geneva convention,” used foul language, and slammed the United States for past military actions in other parts of the world.

A prominent Russian oncologist also responded, posting a video in which he discussed the situation more coherently and without mudslinging or scripted phrases. Andrey Kaprin, MD, PhD, is chief oncologist of the Russian Federation as well as director general of the Federal State Budgetary Institution, NMRCC, of the Ministry of Health of the Russian Federation. He says they continue to maintain relations with the largest and best known oncologic organizations. “We haven’t felt any deterioration in our relationship yet, and of course, we hope that this won’t happen.”

Dr. Kaprin said he believes OncoAlert will return to cooperation with Russia, and that “reason will prevail.”

“No one is protected from cancer, not even doctors, and that is why there should be no politics here,” he said.

Dr. Kaprin was speaking from Russia state-affiliated media, so it was not an independent commentary. Several of the Twitter responses to his video, primarily from non-Russians, were less than complimentary.

One user replied: “Cancer is rife in the Kremlin.”

Another post pointed out the hypocrisy of Russians being upset that OncoAlert was cutting ties with them. “What about sick Ukrainian kids, having to shelter in hospital basement, not having lifesaving surgeries because Russia decided to invade a democratic country?”

And another post was not buying the story that “reason will prevail,” in that the doctor’s talk seemed to contradict the reality of the situation. “I guess for every child #Russia murders they get cut off a little more from the civilized world?”
 

Cancer patients vulnerable

The war in Ukraine is an “unfolding humanitarian emergency,” said the World Health Organization, and it has called on top-level officials involved in the Russian invasion to ensure access for delivery of essential medical, surgical, and trauma supplies to help the Ukrainian people and refugees in neighboring countries. A shortage of oxygen, insulin, cancer therapies, and other essential supplies will continue to grow more dire in the weeks and months ahead, WHO officials predict.

One of the more heartbreaking reports described how pediatric cancer patients have been moved to hospital basements that are serving as temporary bomb shelters. Hospital staff continue to try to provide limited treatment when possible, even though essential supplies are dwindling. 

“These children suffer more because they need to stay alive to fight with the cancer – and this fight cannot wait,” Lesia Lysytsia, MD, a doctor at Okhmatdyt, the country’s largest children’s hospital in Kyiv, said in an NBC news report.

For some children, the only treatment available is a basic form of chemotherapy, and at the Kyiv Regional Oncology Center, the situation became so dire for children in need of blood transfusions that physicians began to transfuse blood from parent to child.

“Our patients, they will die,” Dr. Lysytsia said. “We will calculate how many people or soldiers have died in attacks, but we will never calculate how many patients weren’t diagnosed of disease in time, how many patients died because they didn’t receive treatment. It’s an epic amount of people.”
 

Response from oncology community

Many of the large American oncology groups have issued strong statements expressing their support for Ukraine and offering assistance.

The American Cancer Society has partnered with the American Society of Clinical Oncology and the Sidney Kimmel Cancer Center–Jefferson Health to support all Ukrainian cancer patients and their families. The groups are engaging a network of oncologists and oncology nurses to provide support through the ACS Clinician Volunteer Corps.

The ACS and ASCO are making free cancer resources available in English, Ukrainian, Polish, and Russian through their patient information websites (available here and here), with additional patient education resources planned. 

The ACS noted that there are more than 179,000 newly diagnosed patients with cancer among the Ukrainian people “suffering from Russia’s unprovoked aggression.”

“Disruptions to cancer treatment pose a grave risk to the survival of Ukrainian patients with cancer,” commented Karen Knudsen, PhD, CEO at the ACS.

ASCO also issued its own statement, declaring that it stands with “our Ukrainian members, the worldwide oncology community, and health care providers around the globe in condemning Russia’s unprovoked war on Ukraine.”

The society notes that it represents oncology professionals in Ukraine and neighboring countries including Poland, Romania, Moldova, Slovakia, and Hungary, which are now receiving thousands of refugees from the Russian invasion.

“We are hearing daily reports of cancer treatment interrupted by acts of war, including damage to medical facilities and shortages of critical supplies. Countless patients now need to find cancer care in new and unfamiliar surroundings with limited medical records and minimal resources,” the society commented.

The American Association for Cancer Research also issued a statement by President David A. Tuveson, MD, PhD, and CEO Margaret Foti, PhD, MD (hc). The organization has more than 50,000 members around the world, and they “stand in solidarity with the citizens of Ukraine during the Russian attack on their country.”

“This abhorrent war, which has been instigated by Russia’s leaders, is isolating and interrupting the lifesaving work of scientists and clinicians in Ukraine and Russia, threatening years of effective research collaborations and community building,” the AACR comments. “Limiting the exchange of innovative ideas, practices, and data across borders will significantly retard cancer research and have an adverse effect on public health.”

Perhaps the most subdued statement came from the European Society of Medical Oncology, in a brief release entitled: “Against Any War.” The society expressed profound sadness about the unfolding tragedy in Ukraine and the suffering of people. “We would like to confirm our solidarity and unconditioned support to all oncology professionals and cancer patients, with no geographical boundaries.”

ESMO also said that they were reviewing possibilities “to be of concrete help for our members and their patients, in collaboration with national and transnational oncology societies, as well as the International Cancer Foundation.”

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

A high-fiber diet, especially one rich in soluble fiber, is linked to a lower risk of incident disabling dementia, new research shows.

Investigators administered a dietary survey to 3,700 healthy adults at midlife and then followed them for up to 20 years. They found that participants who consumed the most fiber had approximately a 25% lower risk of developing dementia in later life.

“This study showed that people with a high intake of dietary fiber, especially soluble fiber, have a lower risk of dementia,” study investigator Kazumasa Yamagishi, MD, PhD, professor, department of public health medicine, faculty of medicine and health, Services Research and Development Center, University of Tsukuba, Japan, said in an interview.

CDC/Debora Cartagena

“There are still many unknowns about the causes of dementia, and it is not appropriate to determine causality based on the results of a single cohort study. However, the results of this study can be said to be one of the findings that will lead to the prevention of dementia,” Dr. Yamagishi said.

The study was published online Feb. 6 in Nutritional Neuroscience.
 

Brain-gut interaction

Brain-gut interaction has recently received attention for its potential involvement in the development of dementia. “The concept of brain-gut interaction emerged from the idea that the central nervous system communicates bidirectionally with the gastrointestinal tract, suggesting that the gut microbiome may influence brain plasticity and cognitive function,” the authors wrote.

A diet high in soluble fiber attenuates neuroinflammation in mouse models. Other animal studies have suggested that insoluble fiber might also have a beneficial effect on the microbiome.

The researchers wanted to see whether dietary fiber intake – especially soluble fiber – is associated with a reduced risk of dementia. They also investigated whether there was any difference between dementia in patients with vs. without a history of stroke.

In a previous study, these same researchers reported an inverse association between eating beans, which are high in fiber, and risk of disabling dementia. In the current study, the researchers extended the analyses to dietary fiber intake of total, soluble, and insoluble fibers, as well as other fiber-containing foods, such potatoes, vegetables, and fruits. However, they distinguished potatoes from other vegetables because the composition of starch in potatoes differs.

“Dietary fiber is a nutrient found in grains, potatoes, vegetables, and fruits and is known to affect intestinal bacteria,” Dr. Yamagishi said. “Recently, some experimental studies have shown that intestinal bacteria may be involved in cognitive functions as well as diseases of the digestive tract. However, there have been no studies that have actually examined the relationship between dietary fiber intake and the subsequent risk of dementia in large numbers of general people.”

The researchers turned to participants in the Circulatory Risk in Communities Study (CIRCS), an ongoing dynamic community cohort study involving five communities in Japan. The current study focused on communities where disabling dementia surveillance is conducted.

Participants (n = 3,739) ranged in age from 40 to 64 years (mean age, 51 years) at the time they completed the 24-hour dietary recall survey, and they participated in annual health checkups from 1985 to 1999. Potential risk factors for disabling dementia were measured at the time the dietary surveys were conducted. Participants were then followed for a median of 19.7 years (1999-2020) to confirm incident, disabling dementia.

“Disabling dementia” was defined as dementia that required care under the National Long-Term Care Insurance System and was further categorized on the basis of having a history or not having a history of stroke.

The researchers divided participants into quartiles, based on the amount of total, soluble, and insoluble intake reported in their surveys. They found that men tended to consume less total fiber compared to women.
 

Unclear mechanism

During follow-up, 670 participants developed disabling dementia.

Total fiber intake was “inversely and linearly” associated with risk of incident dementia, the authors reported, with each successive quartile associated with a lower risk compared to the lowest quartile (P for trend = .03).

The association remained after adjustment for potential factors that might affect dementia onset, such as body mass index, systolic blood pressure, antihypertensive medication use, serum total cholesterol, cholesterol-lowering medication, and diabetes (P for trend = .05).

“The inverse association was more evident for soluble fiber intake and was confined to dementia without a history of stroke,” the authors reported. Moreover, potatoes, not vegetables or fruits, showed a similar association.

“The mechanisms are currently unknown but might involve the interactions that take place between the gut and the brain,” Dr. Yamagishi said in a release.

“One possibility is that soluble fiber regulates the composition of gut bacteria. This composition may affect neuroinflammation, which plays a role in the onset of dementia,” he suggested. “It’s also possible that dietary fiber may reduce other risk factors for dementia, such as body weight, blood pressure, lipids, and glucose levels.”

The authors noted several limitations. For example, they did not distinguish between Alzheimer’s and non-Alzheimer’s dementia. Moreover, they classified dietary habits on the basis of a single survey, and participants’ dietary patterns might have changed over the study period.

In addition, Dr. Yamagishi noted, it is “important to confirm the association in other populations.”
 

Balance is key

In an interview, Uma Naidoo, MD, director of nutritional and lifestyle psychiatry, Massachusetts General Hospital, and nutrition educator at Harvard Medical School, both in Boston, said the study “adds to the growing pool of evidence suggesting that a diet rich in colorful, plant-based foods can benefit our neurological and psychiatric health, especially as we age.”

Dr. Naidoo, a chef and the author of “This Is Your Brain on Food,” who was not involved in the study, continued, “In nutritional psychiatry, balance is key and therefore consuming a well-rounded diet including ample amounts of fiber – particularly from sources like steel-cut oats, beans, lentils, and numerous other fruits and vegetables – can be part of a healthy lifestyle and prevention against cognitive decline in later years.

“While the study authors admit to limitations within the study, in my opinion, eating healthier has so many mental and physical health benefits that it’s a nutritional psychiatry no-brainer,” she added.

The study was partly supported by Health and Labour Science Research Grants for Dementia from the Ministry of Health, Labour and Welfare of Japan; JSPS Kakenhi; FULLHAP; and the Osaka University International Joint Research Promotion Programme with University College London. The authors and Dr. Naidoo report no relevant financial relationships.

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

A high-fiber diet, especially one rich in soluble fiber, is linked to a lower risk of incident disabling dementia, new research shows.

Investigators administered a dietary survey to 3,700 healthy adults at midlife and then followed them for up to 20 years. They found that participants who consumed the most fiber had approximately a 25% lower risk of developing dementia in later life.

“This study showed that people with a high intake of dietary fiber, especially soluble fiber, have a lower risk of dementia,” study investigator Kazumasa Yamagishi, MD, PhD, professor, department of public health medicine, faculty of medicine and health, Services Research and Development Center, University of Tsukuba, Japan, said in an interview.

CDC/Debora Cartagena

“There are still many unknowns about the causes of dementia, and it is not appropriate to determine causality based on the results of a single cohort study. However, the results of this study can be said to be one of the findings that will lead to the prevention of dementia,” Dr. Yamagishi said.

The study was published online Feb. 6 in Nutritional Neuroscience.
 

Brain-gut interaction

Brain-gut interaction has recently received attention for its potential involvement in the development of dementia. “The concept of brain-gut interaction emerged from the idea that the central nervous system communicates bidirectionally with the gastrointestinal tract, suggesting that the gut microbiome may influence brain plasticity and cognitive function,” the authors wrote.

A diet high in soluble fiber attenuates neuroinflammation in mouse models. Other animal studies have suggested that insoluble fiber might also have a beneficial effect on the microbiome.

The researchers wanted to see whether dietary fiber intake – especially soluble fiber – is associated with a reduced risk of dementia. They also investigated whether there was any difference between dementia in patients with vs. without a history of stroke.

In a previous study, these same researchers reported an inverse association between eating beans, which are high in fiber, and risk of disabling dementia. In the current study, the researchers extended the analyses to dietary fiber intake of total, soluble, and insoluble fibers, as well as other fiber-containing foods, such potatoes, vegetables, and fruits. However, they distinguished potatoes from other vegetables because the composition of starch in potatoes differs.

“Dietary fiber is a nutrient found in grains, potatoes, vegetables, and fruits and is known to affect intestinal bacteria,” Dr. Yamagishi said. “Recently, some experimental studies have shown that intestinal bacteria may be involved in cognitive functions as well as diseases of the digestive tract. However, there have been no studies that have actually examined the relationship between dietary fiber intake and the subsequent risk of dementia in large numbers of general people.”

The researchers turned to participants in the Circulatory Risk in Communities Study (CIRCS), an ongoing dynamic community cohort study involving five communities in Japan. The current study focused on communities where disabling dementia surveillance is conducted.

Participants (n = 3,739) ranged in age from 40 to 64 years (mean age, 51 years) at the time they completed the 24-hour dietary recall survey, and they participated in annual health checkups from 1985 to 1999. Potential risk factors for disabling dementia were measured at the time the dietary surveys were conducted. Participants were then followed for a median of 19.7 years (1999-2020) to confirm incident, disabling dementia.

“Disabling dementia” was defined as dementia that required care under the National Long-Term Care Insurance System and was further categorized on the basis of having a history or not having a history of stroke.

The researchers divided participants into quartiles, based on the amount of total, soluble, and insoluble intake reported in their surveys. They found that men tended to consume less total fiber compared to women.
 

Unclear mechanism

During follow-up, 670 participants developed disabling dementia.

Total fiber intake was “inversely and linearly” associated with risk of incident dementia, the authors reported, with each successive quartile associated with a lower risk compared to the lowest quartile (P for trend = .03).

The association remained after adjustment for potential factors that might affect dementia onset, such as body mass index, systolic blood pressure, antihypertensive medication use, serum total cholesterol, cholesterol-lowering medication, and diabetes (P for trend = .05).

“The inverse association was more evident for soluble fiber intake and was confined to dementia without a history of stroke,” the authors reported. Moreover, potatoes, not vegetables or fruits, showed a similar association.

“The mechanisms are currently unknown but might involve the interactions that take place between the gut and the brain,” Dr. Yamagishi said in a release.

“One possibility is that soluble fiber regulates the composition of gut bacteria. This composition may affect neuroinflammation, which plays a role in the onset of dementia,” he suggested. “It’s also possible that dietary fiber may reduce other risk factors for dementia, such as body weight, blood pressure, lipids, and glucose levels.”

The authors noted several limitations. For example, they did not distinguish between Alzheimer’s and non-Alzheimer’s dementia. Moreover, they classified dietary habits on the basis of a single survey, and participants’ dietary patterns might have changed over the study period.

In addition, Dr. Yamagishi noted, it is “important to confirm the association in other populations.”
 

Balance is key

In an interview, Uma Naidoo, MD, director of nutritional and lifestyle psychiatry, Massachusetts General Hospital, and nutrition educator at Harvard Medical School, both in Boston, said the study “adds to the growing pool of evidence suggesting that a diet rich in colorful, plant-based foods can benefit our neurological and psychiatric health, especially as we age.”

Dr. Naidoo, a chef and the author of “This Is Your Brain on Food,” who was not involved in the study, continued, “In nutritional psychiatry, balance is key and therefore consuming a well-rounded diet including ample amounts of fiber – particularly from sources like steel-cut oats, beans, lentils, and numerous other fruits and vegetables – can be part of a healthy lifestyle and prevention against cognitive decline in later years.

“While the study authors admit to limitations within the study, in my opinion, eating healthier has so many mental and physical health benefits that it’s a nutritional psychiatry no-brainer,” she added.

The study was partly supported by Health and Labour Science Research Grants for Dementia from the Ministry of Health, Labour and Welfare of Japan; JSPS Kakenhi; FULLHAP; and the Osaka University International Joint Research Promotion Programme with University College London. The authors and Dr. Naidoo report no relevant financial relationships.

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

A high-fiber diet, especially one rich in soluble fiber, is linked to a lower risk of incident disabling dementia, new research shows.

Investigators administered a dietary survey to 3,700 healthy adults at midlife and then followed them for up to 20 years. They found that participants who consumed the most fiber had approximately a 25% lower risk of developing dementia in later life.

“This study showed that people with a high intake of dietary fiber, especially soluble fiber, have a lower risk of dementia,” study investigator Kazumasa Yamagishi, MD, PhD, professor, department of public health medicine, faculty of medicine and health, Services Research and Development Center, University of Tsukuba, Japan, said in an interview.

CDC/Debora Cartagena

“There are still many unknowns about the causes of dementia, and it is not appropriate to determine causality based on the results of a single cohort study. However, the results of this study can be said to be one of the findings that will lead to the prevention of dementia,” Dr. Yamagishi said.

The study was published online Feb. 6 in Nutritional Neuroscience.
 

Brain-gut interaction

Brain-gut interaction has recently received attention for its potential involvement in the development of dementia. “The concept of brain-gut interaction emerged from the idea that the central nervous system communicates bidirectionally with the gastrointestinal tract, suggesting that the gut microbiome may influence brain plasticity and cognitive function,” the authors wrote.

A diet high in soluble fiber attenuates neuroinflammation in mouse models. Other animal studies have suggested that insoluble fiber might also have a beneficial effect on the microbiome.

The researchers wanted to see whether dietary fiber intake – especially soluble fiber – is associated with a reduced risk of dementia. They also investigated whether there was any difference between dementia in patients with vs. without a history of stroke.

In a previous study, these same researchers reported an inverse association between eating beans, which are high in fiber, and risk of disabling dementia. In the current study, the researchers extended the analyses to dietary fiber intake of total, soluble, and insoluble fibers, as well as other fiber-containing foods, such potatoes, vegetables, and fruits. However, they distinguished potatoes from other vegetables because the composition of starch in potatoes differs.

“Dietary fiber is a nutrient found in grains, potatoes, vegetables, and fruits and is known to affect intestinal bacteria,” Dr. Yamagishi said. “Recently, some experimental studies have shown that intestinal bacteria may be involved in cognitive functions as well as diseases of the digestive tract. However, there have been no studies that have actually examined the relationship between dietary fiber intake and the subsequent risk of dementia in large numbers of general people.”

The researchers turned to participants in the Circulatory Risk in Communities Study (CIRCS), an ongoing dynamic community cohort study involving five communities in Japan. The current study focused on communities where disabling dementia surveillance is conducted.

Participants (n = 3,739) ranged in age from 40 to 64 years (mean age, 51 years) at the time they completed the 24-hour dietary recall survey, and they participated in annual health checkups from 1985 to 1999. Potential risk factors for disabling dementia were measured at the time the dietary surveys were conducted. Participants were then followed for a median of 19.7 years (1999-2020) to confirm incident, disabling dementia.

“Disabling dementia” was defined as dementia that required care under the National Long-Term Care Insurance System and was further categorized on the basis of having a history or not having a history of stroke.

The researchers divided participants into quartiles, based on the amount of total, soluble, and insoluble intake reported in their surveys. They found that men tended to consume less total fiber compared to women.
 

Unclear mechanism

During follow-up, 670 participants developed disabling dementia.

Total fiber intake was “inversely and linearly” associated with risk of incident dementia, the authors reported, with each successive quartile associated with a lower risk compared to the lowest quartile (P for trend = .03).

The association remained after adjustment for potential factors that might affect dementia onset, such as body mass index, systolic blood pressure, antihypertensive medication use, serum total cholesterol, cholesterol-lowering medication, and diabetes (P for trend = .05).

“The inverse association was more evident for soluble fiber intake and was confined to dementia without a history of stroke,” the authors reported. Moreover, potatoes, not vegetables or fruits, showed a similar association.

“The mechanisms are currently unknown but might involve the interactions that take place between the gut and the brain,” Dr. Yamagishi said in a release.

“One possibility is that soluble fiber regulates the composition of gut bacteria. This composition may affect neuroinflammation, which plays a role in the onset of dementia,” he suggested. “It’s also possible that dietary fiber may reduce other risk factors for dementia, such as body weight, blood pressure, lipids, and glucose levels.”

The authors noted several limitations. For example, they did not distinguish between Alzheimer’s and non-Alzheimer’s dementia. Moreover, they classified dietary habits on the basis of a single survey, and participants’ dietary patterns might have changed over the study period.

In addition, Dr. Yamagishi noted, it is “important to confirm the association in other populations.”
 

Balance is key

In an interview, Uma Naidoo, MD, director of nutritional and lifestyle psychiatry, Massachusetts General Hospital, and nutrition educator at Harvard Medical School, both in Boston, said the study “adds to the growing pool of evidence suggesting that a diet rich in colorful, plant-based foods can benefit our neurological and psychiatric health, especially as we age.”

Dr. Naidoo, a chef and the author of “This Is Your Brain on Food,” who was not involved in the study, continued, “In nutritional psychiatry, balance is key and therefore consuming a well-rounded diet including ample amounts of fiber – particularly from sources like steel-cut oats, beans, lentils, and numerous other fruits and vegetables – can be part of a healthy lifestyle and prevention against cognitive decline in later years.

“While the study authors admit to limitations within the study, in my opinion, eating healthier has so many mental and physical health benefits that it’s a nutritional psychiatry no-brainer,” she added.

The study was partly supported by Health and Labour Science Research Grants for Dementia from the Ministry of Health, Labour and Welfare of Japan; JSPS Kakenhi; FULLHAP; and the Osaka University International Joint Research Promotion Programme with University College London. The authors and Dr. Naidoo report no relevant financial relationships.

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

Six key bacterial species of the gut microbiome have been identified as predictors of the development of type 2 diabetes, according to results from a 15-year follow-up study of more than 5,000 people in Finland.

“We are not aware of previous long-term prospective studies of the associations between type 2 diabetes and the gut microbiome similar to the current study,” stated the authors of the study, published online Jan. 31, 2022, in Diabetes Care.

Though requiring further validation, the results “build on and extend previous mainly cross-sectional evidence and further support links between dietary habits, metabolic diseases, and type 2 diabetes that are modulated by the gut microbiome,” the authors wrote.

The findings are from a prospective study of data on fecal samples from 5,572 people in Finland in 2002 in the FINRISK 2002 population cohort. In 2017, the samples were sent for sequencing as follow-up.

Of note, the study excluded people with prevalent diabetes at baseline, including those being treated with antidiabetic drugs such as metformin.
 

Four species, two clusters associated with type 2 diabetes development

Over a median follow-up of 15.8 years, 432 (7.8%) participants went on to have a diagnosis of type 2 diabetes, and the presence of four species and two clusters at baseline were significantly associated with the development of type 2 diabetes.

The four species include Clostridium citroniae (hazard ratio, 1.21; unadjusted P = .02), C. bolteae (HR, 1.20; unadjusted P = .01), Tyzzerella nexilis (HR, 1.17; unadjusted P = .03), and Ruminococcus gnavus (HR, 1.17; P = .04).

And the two positively associated clusters mostly consisted of the same species (both HR, 1.18).

Importantly, the associations were nearly the same among participants in eastern and western Finland, which are known for having unique genetic as well as lifestyle differences that impact morbidity and mortality.

“Three of these taxa could be clustered together by proportional abundance in both geographic areas, and combined abundance of the four taxa was also predictive of incident type 2 diabetes,” the authors wrote.

They noted that the identified species have been previously associated with type 2 diabetes and appear to be linked in some ways to the quality of diet and with other metabolic diseases, such as fatty liver disease.

C. citroniae, for instance, has been associated with trimethylamine N-oxide (TMAO), a compound likely linked to the intake of red meat, and the authors noted that a direct association between red meat intake and type 2 diabetes risk has been known for more than 15 years.

TMAO has also been associated with adipose tissue inflammation and impeded hepatic insulin signaling, which are all involved in increased insulin resistance, high blood glucose levels, and type 2 diabetes, the authors explained.

R. gnavus has been previously associated with obesity in humans and animals. And the bacterial species is also “potentially related to glucose metabolism regulation and linked to increases in inflammatory cytokines, both of which are related to type 2 diabetes pathophysiology,” the authors reported.
 

Stepping stone toward improved prediction

Coauthor Teemu J. Niiranen, MD, PhD, of the division of medicine, Turku (Finland) University Hospital, noted that, while prior studies have linked type 2 diabetes with distinctive characteristics of gut microbiome composition, most studies have not included prospective data, and long-term studies have been lacking.

Furthermore, many of the studies could have been confounded by the use of antidiabetic drugs that could influence gut microbiome composition, including metformin, which was excluded in the current study.

“We avoid several of the biases related to cross-sectional studies, such as the confounding effects of diabetes medications,” Dr. Niiranen said in an interview.

“We also know the temporal sequence of the exposure and the outcome, and that the changes in the gut microbiome preceded the development of diabetes,” he said. “All in all, a cohort study like this provides a much greater level of evidence than cross-sectional studies.”

Dr. Niiranen noted, however, that “although we demonstrate that certain gut microbiome changes are associated with greater risk of future diabetes, we are still quite far from clinical use.”

In addition to needing to replicate the results in other ethnic groups and locations, “we would need to find optimal clinical cutoffs for clinical decision-making and demonstrate the amount increase in predictive ability, compared with conventional diabetes risk factors,” he said.

The study nevertheless “serves as a stepping stone toward the goal of improved prediction and the development of effective treatments for type 2 diabetes through modification of the gut microbiome,” the authors wrote.

Other research has shed light on gut bacteria that appear to be linked to the prevention rather than the development of diabetes, identifying species that help produce butyrate, a short-chain fatty acid that may in fact provide protection against type 2 diabetes.

And additional research does suggest potential clinical implications. Efforts to improve insulin sensitivity via the gut through fecal microbial transplantation are also making headway, with an oral capsule formulation showing benefit among patients with severe obesity.

The research was funded in part by grants from the Finnish Cultural Foundation, the Finnish Foundation for Cardiovascular Research, the Emil Aaltonen Foundation, the Finnish Medical Foundation, the Sigrid Jusélius Foundation, and the Academy of Finland.

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

Six key bacterial species of the gut microbiome have been identified as predictors of the development of type 2 diabetes, according to results from a 15-year follow-up study of more than 5,000 people in Finland.

“We are not aware of previous long-term prospective studies of the associations between type 2 diabetes and the gut microbiome similar to the current study,” stated the authors of the study, published online Jan. 31, 2022, in Diabetes Care.

Though requiring further validation, the results “build on and extend previous mainly cross-sectional evidence and further support links between dietary habits, metabolic diseases, and type 2 diabetes that are modulated by the gut microbiome,” the authors wrote.

The findings are from a prospective study of data on fecal samples from 5,572 people in Finland in 2002 in the FINRISK 2002 population cohort. In 2017, the samples were sent for sequencing as follow-up.

Of note, the study excluded people with prevalent diabetes at baseline, including those being treated with antidiabetic drugs such as metformin.
 

Four species, two clusters associated with type 2 diabetes development

Over a median follow-up of 15.8 years, 432 (7.8%) participants went on to have a diagnosis of type 2 diabetes, and the presence of four species and two clusters at baseline were significantly associated with the development of type 2 diabetes.

The four species include Clostridium citroniae (hazard ratio, 1.21; unadjusted P = .02), C. bolteae (HR, 1.20; unadjusted P = .01), Tyzzerella nexilis (HR, 1.17; unadjusted P = .03), and Ruminococcus gnavus (HR, 1.17; P = .04).

And the two positively associated clusters mostly consisted of the same species (both HR, 1.18).

Importantly, the associations were nearly the same among participants in eastern and western Finland, which are known for having unique genetic as well as lifestyle differences that impact morbidity and mortality.

“Three of these taxa could be clustered together by proportional abundance in both geographic areas, and combined abundance of the four taxa was also predictive of incident type 2 diabetes,” the authors wrote.

They noted that the identified species have been previously associated with type 2 diabetes and appear to be linked in some ways to the quality of diet and with other metabolic diseases, such as fatty liver disease.

C. citroniae, for instance, has been associated with trimethylamine N-oxide (TMAO), a compound likely linked to the intake of red meat, and the authors noted that a direct association between red meat intake and type 2 diabetes risk has been known for more than 15 years.

TMAO has also been associated with adipose tissue inflammation and impeded hepatic insulin signaling, which are all involved in increased insulin resistance, high blood glucose levels, and type 2 diabetes, the authors explained.

R. gnavus has been previously associated with obesity in humans and animals. And the bacterial species is also “potentially related to glucose metabolism regulation and linked to increases in inflammatory cytokines, both of which are related to type 2 diabetes pathophysiology,” the authors reported.
 

Stepping stone toward improved prediction

Coauthor Teemu J. Niiranen, MD, PhD, of the division of medicine, Turku (Finland) University Hospital, noted that, while prior studies have linked type 2 diabetes with distinctive characteristics of gut microbiome composition, most studies have not included prospective data, and long-term studies have been lacking.

Furthermore, many of the studies could have been confounded by the use of antidiabetic drugs that could influence gut microbiome composition, including metformin, which was excluded in the current study.

“We avoid several of the biases related to cross-sectional studies, such as the confounding effects of diabetes medications,” Dr. Niiranen said in an interview.

“We also know the temporal sequence of the exposure and the outcome, and that the changes in the gut microbiome preceded the development of diabetes,” he said. “All in all, a cohort study like this provides a much greater level of evidence than cross-sectional studies.”

Dr. Niiranen noted, however, that “although we demonstrate that certain gut microbiome changes are associated with greater risk of future diabetes, we are still quite far from clinical use.”

In addition to needing to replicate the results in other ethnic groups and locations, “we would need to find optimal clinical cutoffs for clinical decision-making and demonstrate the amount increase in predictive ability, compared with conventional diabetes risk factors,” he said.

The study nevertheless “serves as a stepping stone toward the goal of improved prediction and the development of effective treatments for type 2 diabetes through modification of the gut microbiome,” the authors wrote.

Other research has shed light on gut bacteria that appear to be linked to the prevention rather than the development of diabetes, identifying species that help produce butyrate, a short-chain fatty acid that may in fact provide protection against type 2 diabetes.

And additional research does suggest potential clinical implications. Efforts to improve insulin sensitivity via the gut through fecal microbial transplantation are also making headway, with an oral capsule formulation showing benefit among patients with severe obesity.

The research was funded in part by grants from the Finnish Cultural Foundation, the Finnish Foundation for Cardiovascular Research, the Emil Aaltonen Foundation, the Finnish Medical Foundation, the Sigrid Jusélius Foundation, and the Academy of Finland.

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

Six key bacterial species of the gut microbiome have been identified as predictors of the development of type 2 diabetes, according to results from a 15-year follow-up study of more than 5,000 people in Finland.

“We are not aware of previous long-term prospective studies of the associations between type 2 diabetes and the gut microbiome similar to the current study,” stated the authors of the study, published online Jan. 31, 2022, in Diabetes Care.

Though requiring further validation, the results “build on and extend previous mainly cross-sectional evidence and further support links between dietary habits, metabolic diseases, and type 2 diabetes that are modulated by the gut microbiome,” the authors wrote.

The findings are from a prospective study of data on fecal samples from 5,572 people in Finland in 2002 in the FINRISK 2002 population cohort. In 2017, the samples were sent for sequencing as follow-up.

Of note, the study excluded people with prevalent diabetes at baseline, including those being treated with antidiabetic drugs such as metformin.
 

Four species, two clusters associated with type 2 diabetes development

Over a median follow-up of 15.8 years, 432 (7.8%) participants went on to have a diagnosis of type 2 diabetes, and the presence of four species and two clusters at baseline were significantly associated with the development of type 2 diabetes.

The four species include Clostridium citroniae (hazard ratio, 1.21; unadjusted P = .02), C. bolteae (HR, 1.20; unadjusted P = .01), Tyzzerella nexilis (HR, 1.17; unadjusted P = .03), and Ruminococcus gnavus (HR, 1.17; P = .04).

And the two positively associated clusters mostly consisted of the same species (both HR, 1.18).

Importantly, the associations were nearly the same among participants in eastern and western Finland, which are known for having unique genetic as well as lifestyle differences that impact morbidity and mortality.

“Three of these taxa could be clustered together by proportional abundance in both geographic areas, and combined abundance of the four taxa was also predictive of incident type 2 diabetes,” the authors wrote.

They noted that the identified species have been previously associated with type 2 diabetes and appear to be linked in some ways to the quality of diet and with other metabolic diseases, such as fatty liver disease.

C. citroniae, for instance, has been associated with trimethylamine N-oxide (TMAO), a compound likely linked to the intake of red meat, and the authors noted that a direct association between red meat intake and type 2 diabetes risk has been known for more than 15 years.

TMAO has also been associated with adipose tissue inflammation and impeded hepatic insulin signaling, which are all involved in increased insulin resistance, high blood glucose levels, and type 2 diabetes, the authors explained.

R. gnavus has been previously associated with obesity in humans and animals. And the bacterial species is also “potentially related to glucose metabolism regulation and linked to increases in inflammatory cytokines, both of which are related to type 2 diabetes pathophysiology,” the authors reported.
 

Stepping stone toward improved prediction

Coauthor Teemu J. Niiranen, MD, PhD, of the division of medicine, Turku (Finland) University Hospital, noted that, while prior studies have linked type 2 diabetes with distinctive characteristics of gut microbiome composition, most studies have not included prospective data, and long-term studies have been lacking.

Furthermore, many of the studies could have been confounded by the use of antidiabetic drugs that could influence gut microbiome composition, including metformin, which was excluded in the current study.

“We avoid several of the biases related to cross-sectional studies, such as the confounding effects of diabetes medications,” Dr. Niiranen said in an interview.

“We also know the temporal sequence of the exposure and the outcome, and that the changes in the gut microbiome preceded the development of diabetes,” he said. “All in all, a cohort study like this provides a much greater level of evidence than cross-sectional studies.”

Dr. Niiranen noted, however, that “although we demonstrate that certain gut microbiome changes are associated with greater risk of future diabetes, we are still quite far from clinical use.”

In addition to needing to replicate the results in other ethnic groups and locations, “we would need to find optimal clinical cutoffs for clinical decision-making and demonstrate the amount increase in predictive ability, compared with conventional diabetes risk factors,” he said.

The study nevertheless “serves as a stepping stone toward the goal of improved prediction and the development of effective treatments for type 2 diabetes through modification of the gut microbiome,” the authors wrote.

Other research has shed light on gut bacteria that appear to be linked to the prevention rather than the development of diabetes, identifying species that help produce butyrate, a short-chain fatty acid that may in fact provide protection against type 2 diabetes.

And additional research does suggest potential clinical implications. Efforts to improve insulin sensitivity via the gut through fecal microbial transplantation are also making headway, with an oral capsule formulation showing benefit among patients with severe obesity.

The research was funded in part by grants from the Finnish Cultural Foundation, the Finnish Foundation for Cardiovascular Research, the Emil Aaltonen Foundation, the Finnish Medical Foundation, the Sigrid Jusélius Foundation, and the Academy of Finland.

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

The currently available two-dose COVID-19 vaccines were not effective in preventing symptomatic disease caused by the Omicron variant, as determined on the basis of data from more than 800,000 Omicron-infected individuals.

Early laboratory data suggested a substantially lower neutralizing antibody response to the Omicron variant, compared with both the original COVID-19 strain and the Delta variant, write Nick Andrews, PhD, of the United Kingdom Health Security Agency, London, and colleagues.

Vaccines have shown high levels of effectiveness against symptomatic disease and severe disease and death resulting from the original COVID-19 virus and the Alpha variant and modest effectiveness against the Beta and Delta variants, they say.

“Neutralizing antibodies correlate with protection against reinfection and vaccine effectiveness against infection; therefore, reduced vaccine effectiveness against the omicron variant is anticipated on the basis of these early laboratory findings,” they explain.

In a study published in the New England Journal of Medicine, the researchers identified 886,774 adults aged 18 years and older who had been infected with the Omicron variant, 204,154 who had been infected with the Delta variant, and 1,572,621 symptomatic control patients who tested negative for COVID-19 between Nov. 27, 2021, and Jan. 12, 2022. The participants had been vaccinated with two doses of BNT162b2 (Pfizer–BioNTech), ChAdOx1 nCoV-19 (AstraZeneca), or mRNA-1273 (Moderna) vaccine, plus a booster given at least 175 days after a second dose, after Sept. 13, 2021.

Vaccine effectiveness was calculated after primary immunization at weeks 2-4, 5-9, 10-14, 15-19, 20-24, and 25 or longer after the second dose, and at 2-4, 5-9, and 10 or more weeks after boosters.

Omicron infections that occurred starting 14 or more days after a booster occurred a median of 39 days after the booster.

“Vaccine effectiveness was lower for the Omicron variant than for the Delta variant at all intervals after vaccination and for all combinations of primary courses and booster doses investigated,” the researchers write.

Individuals who received two doses of ChAdOx1 nCoV-19 had almost no protection against symptomatic disease caused by Omicron from 20-24 weeks after the second dose. For individuals who received two doses of BNT162b2, effectiveness was 65.5% 2-4 weeks after the second dose, but effectiveness declined to 15.4% after 15-19 weeks and to 8.8% after 25 or more weeks. For individuals who received two doses of mRNA-1273, vaccine effectiveness was 75.1% after 2-4 weeks, but effectiveness declined to 14.9% after 25 or more weeks.

Boosters created a short-term improvement in vaccine effectiveness against the Omicron variant, but this effect also declined over time.

Among individuals who received primary doses of ChAdOx1 nCoV-19, vaccine effectiveness increased to 62.4% 2-4 weeks after a BNT162b2 booster, then declined to 39.6% after 10 or more weeks. After an mRNA-1273 booster, vaccine effectiveness increased to 70.1% at 2-4 weeks and decreased to 60.9% at 5-9 weeks.

Among individuals who received primary doses of BNT162b2, vaccine effectiveness increased to 67.2% 2-4 weeks after a BNT162b2 booster, then declined to 45.7% at 10 or more weeks. After an mRNA-1273 booster, vaccine effectiveness increased to 73.9% at 2-4 weeks, then declined to 64.4% at 5-9 weeks.

Among individuals who received primary doses of mRNA-1273, vaccine effectiveness increased to 64.9% 2-4 weeks after a BNT162b2 booster and 66.3% 2-4 weeks after an mRNA-1273 booster.

The study findings were limited by potential confounding from study participants who had traveled and may have had different levels of vaccine coverage and by the inability to break down estimates on the basis of age and clinical risk that might affect vaccine effectiveness, the researchers note. Other limitations include a lack of data on vaccine effectiveness for a longer period after boosters, they say.

However, the results are consistent with neutralization data for the Omicron variant in studies from the United Kingdom, South Africa, and Germany, they write. “Our findings support maximizing coverage with third doses of vaccine in highly vaccinated populations such as in the United Kingdom. Further follow-up will be needed to assess protection against severe disease and the duration of protection after booster vaccination,” they conclude.
 

Focus on severe disease prevention

Paul Offit, MD, of the University of Pennsylvania, Philadelphia, addressed the topic of vaccine effectiveness in an op-ed published on March 4 in The Philadelphia Inquirer. The following is adapted from the op-ed, with his permission.

“The goal of the COVID vaccine – as is true for all vaccines – is to prevent serious illness,” Dr. Offit wrote.

“For most people with normal immune systems, two doses of mRNA vaccines appear to do exactly that. But not everyone,” wrote Dr. Offit, who serves as director of the Vaccine Education Center at the Children’s Hospital of Philadelphia and also serves on the Food and Drug Administration’s Vaccine Advisory Committee. “Three doses are required to induce high levels of protection against serious illness for people over 65 years of age or for people with other conditions that make them vulnerable, which can be anything from being overweight to having cancer. For people who are immune compromised, four doses might be required,” he noted.

Frequent vaccine boosting, although it may help prevent milder cases of COVID-19, such as those seen with the Omicron variant, is impractical, Dr. Offit emphasized. Instead, a newer, variant-specific vaccine might be needed if a variant emerges that overrides the protection against severe disease currently afforded by the available vaccines, he said. “But we’re not there yet. For now, we are going to have to realize that it is virtually impossible to prevent mild COVID without frequent boosting. So, let’s learn to accept that the goal of COVID vaccines is to prevent severe and not mild illness and stop talking about frequent boosting. Otherwise, we will never be able to live our lives as before,” he wrote.

The study was supported by the U.K. Health Security Agency. The researchers and Dr. Offit have disclosed no relevant financial relationships.

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

The currently available two-dose COVID-19 vaccines were not effective in preventing symptomatic disease caused by the Omicron variant, as determined on the basis of data from more than 800,000 Omicron-infected individuals.

Early laboratory data suggested a substantially lower neutralizing antibody response to the Omicron variant, compared with both the original COVID-19 strain and the Delta variant, write Nick Andrews, PhD, of the United Kingdom Health Security Agency, London, and colleagues.

Vaccines have shown high levels of effectiveness against symptomatic disease and severe disease and death resulting from the original COVID-19 virus and the Alpha variant and modest effectiveness against the Beta and Delta variants, they say.

“Neutralizing antibodies correlate with protection against reinfection and vaccine effectiveness against infection; therefore, reduced vaccine effectiveness against the omicron variant is anticipated on the basis of these early laboratory findings,” they explain.

In a study published in the New England Journal of Medicine, the researchers identified 886,774 adults aged 18 years and older who had been infected with the Omicron variant, 204,154 who had been infected with the Delta variant, and 1,572,621 symptomatic control patients who tested negative for COVID-19 between Nov. 27, 2021, and Jan. 12, 2022. The participants had been vaccinated with two doses of BNT162b2 (Pfizer–BioNTech), ChAdOx1 nCoV-19 (AstraZeneca), or mRNA-1273 (Moderna) vaccine, plus a booster given at least 175 days after a second dose, after Sept. 13, 2021.

Vaccine effectiveness was calculated after primary immunization at weeks 2-4, 5-9, 10-14, 15-19, 20-24, and 25 or longer after the second dose, and at 2-4, 5-9, and 10 or more weeks after boosters.

Omicron infections that occurred starting 14 or more days after a booster occurred a median of 39 days after the booster.

“Vaccine effectiveness was lower for the Omicron variant than for the Delta variant at all intervals after vaccination and for all combinations of primary courses and booster doses investigated,” the researchers write.

Individuals who received two doses of ChAdOx1 nCoV-19 had almost no protection against symptomatic disease caused by Omicron from 20-24 weeks after the second dose. For individuals who received two doses of BNT162b2, effectiveness was 65.5% 2-4 weeks after the second dose, but effectiveness declined to 15.4% after 15-19 weeks and to 8.8% after 25 or more weeks. For individuals who received two doses of mRNA-1273, vaccine effectiveness was 75.1% after 2-4 weeks, but effectiveness declined to 14.9% after 25 or more weeks.

Boosters created a short-term improvement in vaccine effectiveness against the Omicron variant, but this effect also declined over time.

Among individuals who received primary doses of ChAdOx1 nCoV-19, vaccine effectiveness increased to 62.4% 2-4 weeks after a BNT162b2 booster, then declined to 39.6% after 10 or more weeks. After an mRNA-1273 booster, vaccine effectiveness increased to 70.1% at 2-4 weeks and decreased to 60.9% at 5-9 weeks.

Among individuals who received primary doses of BNT162b2, vaccine effectiveness increased to 67.2% 2-4 weeks after a BNT162b2 booster, then declined to 45.7% at 10 or more weeks. After an mRNA-1273 booster, vaccine effectiveness increased to 73.9% at 2-4 weeks, then declined to 64.4% at 5-9 weeks.

Among individuals who received primary doses of mRNA-1273, vaccine effectiveness increased to 64.9% 2-4 weeks after a BNT162b2 booster and 66.3% 2-4 weeks after an mRNA-1273 booster.

The study findings were limited by potential confounding from study participants who had traveled and may have had different levels of vaccine coverage and by the inability to break down estimates on the basis of age and clinical risk that might affect vaccine effectiveness, the researchers note. Other limitations include a lack of data on vaccine effectiveness for a longer period after boosters, they say.

However, the results are consistent with neutralization data for the Omicron variant in studies from the United Kingdom, South Africa, and Germany, they write. “Our findings support maximizing coverage with third doses of vaccine in highly vaccinated populations such as in the United Kingdom. Further follow-up will be needed to assess protection against severe disease and the duration of protection after booster vaccination,” they conclude.
 

Focus on severe disease prevention

Paul Offit, MD, of the University of Pennsylvania, Philadelphia, addressed the topic of vaccine effectiveness in an op-ed published on March 4 in The Philadelphia Inquirer. The following is adapted from the op-ed, with his permission.

“The goal of the COVID vaccine – as is true for all vaccines – is to prevent serious illness,” Dr. Offit wrote.

“For most people with normal immune systems, two doses of mRNA vaccines appear to do exactly that. But not everyone,” wrote Dr. Offit, who serves as director of the Vaccine Education Center at the Children’s Hospital of Philadelphia and also serves on the Food and Drug Administration’s Vaccine Advisory Committee. “Three doses are required to induce high levels of protection against serious illness for people over 65 years of age or for people with other conditions that make them vulnerable, which can be anything from being overweight to having cancer. For people who are immune compromised, four doses might be required,” he noted.

Frequent vaccine boosting, although it may help prevent milder cases of COVID-19, such as those seen with the Omicron variant, is impractical, Dr. Offit emphasized. Instead, a newer, variant-specific vaccine might be needed if a variant emerges that overrides the protection against severe disease currently afforded by the available vaccines, he said. “But we’re not there yet. For now, we are going to have to realize that it is virtually impossible to prevent mild COVID without frequent boosting. So, let’s learn to accept that the goal of COVID vaccines is to prevent severe and not mild illness and stop talking about frequent boosting. Otherwise, we will never be able to live our lives as before,” he wrote.

The study was supported by the U.K. Health Security Agency. The researchers and Dr. Offit have disclosed no relevant financial relationships.

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

The currently available two-dose COVID-19 vaccines were not effective in preventing symptomatic disease caused by the Omicron variant, as determined on the basis of data from more than 800,000 Omicron-infected individuals.

Early laboratory data suggested a substantially lower neutralizing antibody response to the Omicron variant, compared with both the original COVID-19 strain and the Delta variant, write Nick Andrews, PhD, of the United Kingdom Health Security Agency, London, and colleagues.

Vaccines have shown high levels of effectiveness against symptomatic disease and severe disease and death resulting from the original COVID-19 virus and the Alpha variant and modest effectiveness against the Beta and Delta variants, they say.

“Neutralizing antibodies correlate with protection against reinfection and vaccine effectiveness against infection; therefore, reduced vaccine effectiveness against the omicron variant is anticipated on the basis of these early laboratory findings,” they explain.

In a study published in the New England Journal of Medicine, the researchers identified 886,774 adults aged 18 years and older who had been infected with the Omicron variant, 204,154 who had been infected with the Delta variant, and 1,572,621 symptomatic control patients who tested negative for COVID-19 between Nov. 27, 2021, and Jan. 12, 2022. The participants had been vaccinated with two doses of BNT162b2 (Pfizer–BioNTech), ChAdOx1 nCoV-19 (AstraZeneca), or mRNA-1273 (Moderna) vaccine, plus a booster given at least 175 days after a second dose, after Sept. 13, 2021.

Vaccine effectiveness was calculated after primary immunization at weeks 2-4, 5-9, 10-14, 15-19, 20-24, and 25 or longer after the second dose, and at 2-4, 5-9, and 10 or more weeks after boosters.

Omicron infections that occurred starting 14 or more days after a booster occurred a median of 39 days after the booster.

“Vaccine effectiveness was lower for the Omicron variant than for the Delta variant at all intervals after vaccination and for all combinations of primary courses and booster doses investigated,” the researchers write.

Individuals who received two doses of ChAdOx1 nCoV-19 had almost no protection against symptomatic disease caused by Omicron from 20-24 weeks after the second dose. For individuals who received two doses of BNT162b2, effectiveness was 65.5% 2-4 weeks after the second dose, but effectiveness declined to 15.4% after 15-19 weeks and to 8.8% after 25 or more weeks. For individuals who received two doses of mRNA-1273, vaccine effectiveness was 75.1% after 2-4 weeks, but effectiveness declined to 14.9% after 25 or more weeks.

Boosters created a short-term improvement in vaccine effectiveness against the Omicron variant, but this effect also declined over time.

Among individuals who received primary doses of ChAdOx1 nCoV-19, vaccine effectiveness increased to 62.4% 2-4 weeks after a BNT162b2 booster, then declined to 39.6% after 10 or more weeks. After an mRNA-1273 booster, vaccine effectiveness increased to 70.1% at 2-4 weeks and decreased to 60.9% at 5-9 weeks.

Among individuals who received primary doses of BNT162b2, vaccine effectiveness increased to 67.2% 2-4 weeks after a BNT162b2 booster, then declined to 45.7% at 10 or more weeks. After an mRNA-1273 booster, vaccine effectiveness increased to 73.9% at 2-4 weeks, then declined to 64.4% at 5-9 weeks.

Among individuals who received primary doses of mRNA-1273, vaccine effectiveness increased to 64.9% 2-4 weeks after a BNT162b2 booster and 66.3% 2-4 weeks after an mRNA-1273 booster.

The study findings were limited by potential confounding from study participants who had traveled and may have had different levels of vaccine coverage and by the inability to break down estimates on the basis of age and clinical risk that might affect vaccine effectiveness, the researchers note. Other limitations include a lack of data on vaccine effectiveness for a longer period after boosters, they say.

However, the results are consistent with neutralization data for the Omicron variant in studies from the United Kingdom, South Africa, and Germany, they write. “Our findings support maximizing coverage with third doses of vaccine in highly vaccinated populations such as in the United Kingdom. Further follow-up will be needed to assess protection against severe disease and the duration of protection after booster vaccination,” they conclude.
 

Focus on severe disease prevention

Paul Offit, MD, of the University of Pennsylvania, Philadelphia, addressed the topic of vaccine effectiveness in an op-ed published on March 4 in The Philadelphia Inquirer. The following is adapted from the op-ed, with his permission.

“The goal of the COVID vaccine – as is true for all vaccines – is to prevent serious illness,” Dr. Offit wrote.

“For most people with normal immune systems, two doses of mRNA vaccines appear to do exactly that. But not everyone,” wrote Dr. Offit, who serves as director of the Vaccine Education Center at the Children’s Hospital of Philadelphia and also serves on the Food and Drug Administration’s Vaccine Advisory Committee. “Three doses are required to induce high levels of protection against serious illness for people over 65 years of age or for people with other conditions that make them vulnerable, which can be anything from being overweight to having cancer. For people who are immune compromised, four doses might be required,” he noted.

Frequent vaccine boosting, although it may help prevent milder cases of COVID-19, such as those seen with the Omicron variant, is impractical, Dr. Offit emphasized. Instead, a newer, variant-specific vaccine might be needed if a variant emerges that overrides the protection against severe disease currently afforded by the available vaccines, he said. “But we’re not there yet. For now, we are going to have to realize that it is virtually impossible to prevent mild COVID without frequent boosting. So, let’s learn to accept that the goal of COVID vaccines is to prevent severe and not mild illness and stop talking about frequent boosting. Otherwise, we will never be able to live our lives as before,” he wrote.

The study was supported by the U.K. Health Security Agency. The researchers and Dr. Offit have disclosed no relevant financial relationships.

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

The Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee has chosen the influenza vaccine strains for the 2022-2023 season in the northern hemisphere, which begins in the fall of 2022.

On March 3, the committee unanimously voted to endorse the World Health Organization’s recommendations as to which influenza strains to include for coverage by vaccines for the upcoming flu season. Two of the four recommended strains are different from last season.

The committee also heard updates on flu activity this season. So far, data from the U.S. Flu Vaccine Effectiveness (VE) network, which consists of seven study sites, have not shown that the vaccine is protective against influenza A. “We can say that it is not highly effective,” Brendan Flannery, PhD, who leads the U.S. Flu VE network for the Centers for Disease Control and Prevention, said in an interview. He was not involved with the advisory committee meeting. Flu activity this season has been low, he explained, so there are fewer cases his team can use to estimate vaccine efficacy. “If there’s some benefit, it’s hard for us to show that now,” he said.
 

Vaccine strains

The panel voted to include a A/Darwin/9/2021-like strain for the H3N2 component of the vaccine; this is changed from A/Cambodia/e0826360/2020. For the influenza B Victoria lineage component, the committee voted to include a B/Austria/1359417/2021-like virus, a swap from this year’s B/Washington/02/2019-like virus. These changes apply to the egg-based, cell-culture, and recombinant vaccines. Both new strains were included in WHO’s 2022 influenza vaccine strain recommendations for the southern hemisphere.

For the influenza A H1N1 component, the group also agreed to include a A/Victoria/2570/2019 (H1N1) pdm09-like virus for the egg-based vaccine and the A/Wisconsin/588/2019 (H1N1) pdm09-like virus for cell culture or recombinant vaccines. These strains were included for the 2021-2022 season. The panel also voted for the inclusion of a B/Phuket/3073/2013-like virus (B/Yamagata lineage) as the second influenza B strain for the quadrivalent egg-based, cell culture, or recombinant vaccines, which is unchanged from this flu season.
 

‘Sporadic’ flu activity

While there was an uptick in influenza activity this year compared to the 2020-2021 season, hospitalization rates are lower than in the four seasons preceding the pandemic (from 2016-2017 to 2019-2020). As of Feb. 26, the cumulative hospitalization rate for this flu season was 5.2 hospitalizations per 100,000 individuals. There have been eight pediatric deaths due to influenza so far this season, compared to one pediatric death reported to the CDC during the 2020-2021 flu season.

About 4.1% of specimens tested at clinical laboratories were positive for flu. Since Oct. 30, 2.7% of specimens have been positive for influenza this season. Nearly all viruses detected (97.7%) have been influenza A.

Lisa Grohskopf, MD, MPH, a medical officer in the influenza division at the CDC who presented the data at the meeting, described flu activity this season as “sporadic” and noted that activity is increasing in some areas of the country. According to CDC’s weekly influenza surveillance report, most states had minimal influenza-like illness (ILI) activity, although Arkansas, Idaho, Iowa, Kansas, Minnesota, and Utah had slightly higher ILI activity as of Feb. 26. Champaign-Urbana, Illinois; St. Cloud, Minnesota; and Brownwood, Texas, had the highest levels of flu activity in the country.
 

Low vaccine effectiveness

As of Jan. 22, results from the U.S. Flu VE network do not show statistically significant evidence that the flu vaccine is effective. Currently, the vaccine is estimated to be 8% effective against preventing influenza A infection (95% confidence interval, –31% to 36%) and 14% effective against preventing A/H3N2 infection (95% CI, –28% to 43%) for people aged 6 months and older.

The network did not have enough data to provide age-specific VE estimates or estimates of effectiveness against influenza B. This could be due to low flu activity relative to prepandemic years, Dr. Flannery said. Of the 2,758 individuals enrolled in the VE flu network this season, just 147 (5%) tested positive for the flu this season. This is the lowest positivity rate observed in the Flu VE network participants with respiratory illness over the past 10 flu seasons, Dr. Grohskopf noted. In comparison, estimates from the 2019 to 2020 season included 4,112 individuals, and 1,060 tested positive for flu.

“We are really at the bare minimum of what we can use for a flu vaccine effectiveness estimate,” Dr. Flannery said about the more recent data. The network was not able to produce any estimates about flu vaccine effectiveness for the 2020-2021 season because of historically low flu activity.

The Department of Defense also presented vaccine efficacy estimates for the 2021–2022 season. The vaccine has been 36% effective (95% CI, 28%-44%) against all strains of the virus, 33% effective against influenza A (95% CI, 24%-41%), 32% effective against A/H3N2 (95% CI, 3%-53%), and 59% effective against influenza B (95% CI, 42%-71%). These results are from a young, healthy adult population, Lieutenant Commander Courtney Gustin, DrPH, MSN, told the panel, and they may not be reflective of efficacy rates across all age groups.

Though these findings suggest there is low to no measurable benefit against influenza A, Dr. Flannery said the CDC still recommends getting the flu vaccine, as it can be protective against other circulating flu strains. “We have been able to demonstrate protection against other H3 [viruses], B viruses, and H1 viruses in the past,” he said. And as these results only show protection against mild disease, “there is still possibility that there’s benefit against more severe disease,” he added. Studies measuring effectiveness against more severe outcomes are not yet available.

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

The Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee has chosen the influenza vaccine strains for the 2022-2023 season in the northern hemisphere, which begins in the fall of 2022.

On March 3, the committee unanimously voted to endorse the World Health Organization’s recommendations as to which influenza strains to include for coverage by vaccines for the upcoming flu season. Two of the four recommended strains are different from last season.

The committee also heard updates on flu activity this season. So far, data from the U.S. Flu Vaccine Effectiveness (VE) network, which consists of seven study sites, have not shown that the vaccine is protective against influenza A. “We can say that it is not highly effective,” Brendan Flannery, PhD, who leads the U.S. Flu VE network for the Centers for Disease Control and Prevention, said in an interview. He was not involved with the advisory committee meeting. Flu activity this season has been low, he explained, so there are fewer cases his team can use to estimate vaccine efficacy. “If there’s some benefit, it’s hard for us to show that now,” he said.
 

Vaccine strains

The panel voted to include a A/Darwin/9/2021-like strain for the H3N2 component of the vaccine; this is changed from A/Cambodia/e0826360/2020. For the influenza B Victoria lineage component, the committee voted to include a B/Austria/1359417/2021-like virus, a swap from this year’s B/Washington/02/2019-like virus. These changes apply to the egg-based, cell-culture, and recombinant vaccines. Both new strains were included in WHO’s 2022 influenza vaccine strain recommendations for the southern hemisphere.

For the influenza A H1N1 component, the group also agreed to include a A/Victoria/2570/2019 (H1N1) pdm09-like virus for the egg-based vaccine and the A/Wisconsin/588/2019 (H1N1) pdm09-like virus for cell culture or recombinant vaccines. These strains were included for the 2021-2022 season. The panel also voted for the inclusion of a B/Phuket/3073/2013-like virus (B/Yamagata lineage) as the second influenza B strain for the quadrivalent egg-based, cell culture, or recombinant vaccines, which is unchanged from this flu season.
 

‘Sporadic’ flu activity

While there was an uptick in influenza activity this year compared to the 2020-2021 season, hospitalization rates are lower than in the four seasons preceding the pandemic (from 2016-2017 to 2019-2020). As of Feb. 26, the cumulative hospitalization rate for this flu season was 5.2 hospitalizations per 100,000 individuals. There have been eight pediatric deaths due to influenza so far this season, compared to one pediatric death reported to the CDC during the 2020-2021 flu season.

About 4.1% of specimens tested at clinical laboratories were positive for flu. Since Oct. 30, 2.7% of specimens have been positive for influenza this season. Nearly all viruses detected (97.7%) have been influenza A.

Lisa Grohskopf, MD, MPH, a medical officer in the influenza division at the CDC who presented the data at the meeting, described flu activity this season as “sporadic” and noted that activity is increasing in some areas of the country. According to CDC’s weekly influenza surveillance report, most states had minimal influenza-like illness (ILI) activity, although Arkansas, Idaho, Iowa, Kansas, Minnesota, and Utah had slightly higher ILI activity as of Feb. 26. Champaign-Urbana, Illinois; St. Cloud, Minnesota; and Brownwood, Texas, had the highest levels of flu activity in the country.
 

Low vaccine effectiveness

As of Jan. 22, results from the U.S. Flu VE network do not show statistically significant evidence that the flu vaccine is effective. Currently, the vaccine is estimated to be 8% effective against preventing influenza A infection (95% confidence interval, –31% to 36%) and 14% effective against preventing A/H3N2 infection (95% CI, –28% to 43%) for people aged 6 months and older.

The network did not have enough data to provide age-specific VE estimates or estimates of effectiveness against influenza B. This could be due to low flu activity relative to prepandemic years, Dr. Flannery said. Of the 2,758 individuals enrolled in the VE flu network this season, just 147 (5%) tested positive for the flu this season. This is the lowest positivity rate observed in the Flu VE network participants with respiratory illness over the past 10 flu seasons, Dr. Grohskopf noted. In comparison, estimates from the 2019 to 2020 season included 4,112 individuals, and 1,060 tested positive for flu.

“We are really at the bare minimum of what we can use for a flu vaccine effectiveness estimate,” Dr. Flannery said about the more recent data. The network was not able to produce any estimates about flu vaccine effectiveness for the 2020-2021 season because of historically low flu activity.

The Department of Defense also presented vaccine efficacy estimates for the 2021–2022 season. The vaccine has been 36% effective (95% CI, 28%-44%) against all strains of the virus, 33% effective against influenza A (95% CI, 24%-41%), 32% effective against A/H3N2 (95% CI, 3%-53%), and 59% effective against influenza B (95% CI, 42%-71%). These results are from a young, healthy adult population, Lieutenant Commander Courtney Gustin, DrPH, MSN, told the panel, and they may not be reflective of efficacy rates across all age groups.

Though these findings suggest there is low to no measurable benefit against influenza A, Dr. Flannery said the CDC still recommends getting the flu vaccine, as it can be protective against other circulating flu strains. “We have been able to demonstrate protection against other H3 [viruses], B viruses, and H1 viruses in the past,” he said. And as these results only show protection against mild disease, “there is still possibility that there’s benefit against more severe disease,” he added. Studies measuring effectiveness against more severe outcomes are not yet available.

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

The Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee has chosen the influenza vaccine strains for the 2022-2023 season in the northern hemisphere, which begins in the fall of 2022.

On March 3, the committee unanimously voted to endorse the World Health Organization’s recommendations as to which influenza strains to include for coverage by vaccines for the upcoming flu season. Two of the four recommended strains are different from last season.

The committee also heard updates on flu activity this season. So far, data from the U.S. Flu Vaccine Effectiveness (VE) network, which consists of seven study sites, have not shown that the vaccine is protective against influenza A. “We can say that it is not highly effective,” Brendan Flannery, PhD, who leads the U.S. Flu VE network for the Centers for Disease Control and Prevention, said in an interview. He was not involved with the advisory committee meeting. Flu activity this season has been low, he explained, so there are fewer cases his team can use to estimate vaccine efficacy. “If there’s some benefit, it’s hard for us to show that now,” he said.
 

Vaccine strains

The panel voted to include a A/Darwin/9/2021-like strain for the H3N2 component of the vaccine; this is changed from A/Cambodia/e0826360/2020. For the influenza B Victoria lineage component, the committee voted to include a B/Austria/1359417/2021-like virus, a swap from this year’s B/Washington/02/2019-like virus. These changes apply to the egg-based, cell-culture, and recombinant vaccines. Both new strains were included in WHO’s 2022 influenza vaccine strain recommendations for the southern hemisphere.

For the influenza A H1N1 component, the group also agreed to include a A/Victoria/2570/2019 (H1N1) pdm09-like virus for the egg-based vaccine and the A/Wisconsin/588/2019 (H1N1) pdm09-like virus for cell culture or recombinant vaccines. These strains were included for the 2021-2022 season. The panel also voted for the inclusion of a B/Phuket/3073/2013-like virus (B/Yamagata lineage) as the second influenza B strain for the quadrivalent egg-based, cell culture, or recombinant vaccines, which is unchanged from this flu season.
 

‘Sporadic’ flu activity

While there was an uptick in influenza activity this year compared to the 2020-2021 season, hospitalization rates are lower than in the four seasons preceding the pandemic (from 2016-2017 to 2019-2020). As of Feb. 26, the cumulative hospitalization rate for this flu season was 5.2 hospitalizations per 100,000 individuals. There have been eight pediatric deaths due to influenza so far this season, compared to one pediatric death reported to the CDC during the 2020-2021 flu season.

About 4.1% of specimens tested at clinical laboratories were positive for flu. Since Oct. 30, 2.7% of specimens have been positive for influenza this season. Nearly all viruses detected (97.7%) have been influenza A.

Lisa Grohskopf, MD, MPH, a medical officer in the influenza division at the CDC who presented the data at the meeting, described flu activity this season as “sporadic” and noted that activity is increasing in some areas of the country. According to CDC’s weekly influenza surveillance report, most states had minimal influenza-like illness (ILI) activity, although Arkansas, Idaho, Iowa, Kansas, Minnesota, and Utah had slightly higher ILI activity as of Feb. 26. Champaign-Urbana, Illinois; St. Cloud, Minnesota; and Brownwood, Texas, had the highest levels of flu activity in the country.
 

Low vaccine effectiveness

As of Jan. 22, results from the U.S. Flu VE network do not show statistically significant evidence that the flu vaccine is effective. Currently, the vaccine is estimated to be 8% effective against preventing influenza A infection (95% confidence interval, –31% to 36%) and 14% effective against preventing A/H3N2 infection (95% CI, –28% to 43%) for people aged 6 months and older.

The network did not have enough data to provide age-specific VE estimates or estimates of effectiveness against influenza B. This could be due to low flu activity relative to prepandemic years, Dr. Flannery said. Of the 2,758 individuals enrolled in the VE flu network this season, just 147 (5%) tested positive for the flu this season. This is the lowest positivity rate observed in the Flu VE network participants with respiratory illness over the past 10 flu seasons, Dr. Grohskopf noted. In comparison, estimates from the 2019 to 2020 season included 4,112 individuals, and 1,060 tested positive for flu.

“We are really at the bare minimum of what we can use for a flu vaccine effectiveness estimate,” Dr. Flannery said about the more recent data. The network was not able to produce any estimates about flu vaccine effectiveness for the 2020-2021 season because of historically low flu activity.

The Department of Defense also presented vaccine efficacy estimates for the 2021–2022 season. The vaccine has been 36% effective (95% CI, 28%-44%) against all strains of the virus, 33% effective against influenza A (95% CI, 24%-41%), 32% effective against A/H3N2 (95% CI, 3%-53%), and 59% effective against influenza B (95% CI, 42%-71%). These results are from a young, healthy adult population, Lieutenant Commander Courtney Gustin, DrPH, MSN, told the panel, and they may not be reflective of efficacy rates across all age groups.

Though these findings suggest there is low to no measurable benefit against influenza A, Dr. Flannery said the CDC still recommends getting the flu vaccine, as it can be protective against other circulating flu strains. “We have been able to demonstrate protection against other H3 [viruses], B viruses, and H1 viruses in the past,” he said. And as these results only show protection against mild disease, “there is still possibility that there’s benefit against more severe disease,” he added. Studies measuring effectiveness against more severe outcomes are not yet available.

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