For years, the default definitive treatment for patients with early-stage I non–small cell lung cancer (NSCLC) has been surgical resection, typically minimally invasive lobectomy with systematic lymph node dissection.

Guidelines from the National Comprehensive Cancer Network (NCCN), the American Society of Clinical Oncology, and the European Society for Medical Oncology all list surgery (in particular, lobectomy) as the primary local therapy for fit, operable patients with stage I NSCLC.

More recently, however, stereotactic body radiotherapy (SBRT), also called stereotactic ablative radiotherapy, has emerged as a definitive treatment option for stage I NSCLC, especially for older, less fit patients who are unsuitable or deemed high-risk for surgery.

“We see patients in our practice who cannot undergo surgery or who may not have adequate lung function to be able to tolerate surgery, and for these patients who are medically inoperable or surgically unresectable, radiation therapy may be a reasonable option,” Charu Aggarwal, MD, MPH, professor and lung cancer specialist, University of Pennsylvania, Philadelphia, told this news organization.

Given some encouraging data suggesting that SBRT could provide similar survival outcomes and be an alternative to surgery for operable disease, SBRT is also increasingly being considered in these early-stage patients. However, other evidence indicates that SBRT may be associated with higher rates of regional and distant recurrences and worse long-term survival, particularly in operable patients.

What may ultimately matter most is carefully selecting operable patients who undergo SBRT.

Aggarwal has encountered certain patients who are fit for surgery but would rather have radiation therapy. “This is an individual decision, and these patients are usually discussed at tumor board and in multidisciplinary discussions to really make sure that they’re making the right decision for themselves,” she explained.

 

The Pros and Cons of SBRT

SBRT is a nonsurgical approach in which precision high-dose radiation is delivered in just a few fractions — typically, 3, 5, or 8, depending on institutional protocols and tumor characteristics.

SBRT is performed on an outpatient basis, usually over 1-2 weeks, with most patients able to resume usual activities with minimal to no delay. Surgery, on the other hand, requires a hospital stay and takes most people about 2-6 weeks to return to regular activities. SBRT also avoids anesthesia and surgical incisions, both of which come with risks.

The data on SBRT in early-stage NSCLC are mixed. While some studies indicate that SBRT comes with promising survival outcomes, other research has reported worse survival and recurrence rates.

One potential reason for higher recurrence rates with SBRT is the lack of pathologic nodal staging, which only happens after surgery, as well as lower rates of nodal evaluation with endobronchial ultrasound or mediastinoscopy before surgery or SBRT. Without nodal assessments, clinicians may miss a more aggressive histology or more advanced nodal stage, which would go undertreated if patients received SBRT.

 

Latest Data in Large Cohort

A recent study published in Lung Cancer indicated that, when carefully selected, operable patients with early NSCLC have comparable survival with lobectomy or SBRT.

In the study, Dutch researchers took an in-depth look at survival and recurrence patterns in a retrospective cohort study of 2183 patients with clinical stage I NSCLC treated with minimally invasive lobectomy or SBRT. The study includes one of the largest cohorts to date, with robust data collection on baseline characteristics, comorbidities, tumor size, performance status, and follow-up.

Patients receiving SBRT were typically older (median age, 74 vs 67 years), had higher comorbidity burdens (Charlson index ≥ 5 in 57% of SBRT patients vs 23% of surgical patients), worse performance status, and lower lung function. To adjust for these differences, the researchers used propensity score weighting so the SBRT group’s baseline characteristics were comparable with those in the surgery group.

The surgery cohort had more invasive nodal evaluation: 21% underwent endobronchial ultrasound or mediastinoscopy vs only 12% in the SBRT group. The vast majority in both groups had PET-CT staging, reflecting modern imaging-based workups.

While 5-year local recurrence rates between the two groups were similar (13.1% for SBRT vs 12.1% for surgery), the 5-year regional recurrence rate was significantly higher after SBRT than lobectomy (18.1% vs 14.2%; hazard ratio [HR], 0.74), as was the distant metastasis rate (26.2% vs 20.2%; HR, 0.72).

Mortality at 30 days was higher after surgery than SBRT (1.0% vs 0.2%). And in the unadjusted analysis, 5-year overall survival was significantly better with lobectomy than SBRT (70.2% vs 40.3%).

However, when the analysis only included patients with similar baseline characteristics, overall survival was no longer significantly different in the two groups (HR, 0.89; 95% CI, 0.65-1.20). Lung cancer–specific mortality was also not significantly different between the two treatments (HR, 1.08), but the study was underpowered to detect significant differences in this outcome on the basis of a relatively low number of deaths from NSCLC.

Still, even after comparing similar patients, recurrence-free survival was notably better with surgery (HR, 0.70), due to fewer regional recurrences and distant metastases. Overall, 13% of the surgical cohort had nodal upstaging at pathology, meaning that even in clinically “node-negative” stage I disease, a subset of patients had unsuspected nodal involvement.

Patients receiving SBRT did not have pathologic nodal staging, raising the possibility of occult micrometastases. The authors noted that the proportion of SBRT patients with occult lymph node metastases is likely at least equal to that in the surgery group, but these metastases would go undetected without pathologic assessment.

Missing potential occult micrometastases in the SBRT group likely contributed to higher regional recurrence rates over time. By improving nodal staging, more patients with occult lymph node metastases who would be undertreated with SBRT may be identified before treatment, the authors said.

 

What Do Experts Say?

So, is SBRT an option for patients with stage I NSCLC?

Opinions vary.

“If you got one shot for a cure, then you want to do the surgery because that’s what results in a cure,” said Raja Flores, MD, chairman of Thoracic Surgery, Mount Sinai Health System, New York City.

Flores noted that the survival rate with surgery is high in this population. “There’s really nothing out there that can compare,” he said.

In his view, surgery “remains the gold standard.” However, “radiation could be considered in nonsurgical candidates,” he said.

The most recent NCCN guidelines align with Flores’ take. The guidelines say that SBRT is indicated for stage IA-IIA (N0) NSCLC in patients who are deemed “medically inoperable, high surgical risk as determined by thoracic surgeon, and those who decline surgery after thoracic surgical consultation.”

Clifford G. Robinson, MD, agreed. “In the United States, we largely treat patients with SBRT who are medically inoperable or high-risk operable and a much smaller proportion who decline surgery,” said Robinson, professor of radiation oncology and chief of SBRT at Washington University in St. Louis, St. Louis. “Many patients who are deemed operable are not offered SBRT.”

Still, for Robinson, determining which patients are best suited for surgery or SBRT remains unclear.

“Retrospective comparisons are fraught with problems because of confounding,” Robinson told this news organization. “That is, the healthier patients get surgery, and the less healthy ones get SBRT. No manner of fancy statistical manipulation can remove that fact.”

In fact, a recent meta-analysis found that the most significant variable predicting whether surgery or SBRT was superior in retrospective studies was whether the author was a surgeon or radiation oncologist.

Robinson noted that multiple randomized trials have attempted to randomize patients with medically operable early-stage NSCLC to surgery or SBRT and failed to accrue, largely due to patients’ “understandable unwillingness to be randomized between operative vs nonoperative interventions when most already prefer one or the other approach.”

Flores highlighted another point of caution about interpreting trial results: Not all early-stage NSCLC behaves similarly. “Some are slow-growing ‘turtles,’ and others are aggressive ‘rabbits’ — and the turtles are usually the ones that have been included in these radiotherapy trials, and that’s the danger,” he said.

While medical operability is the primary factor for deciding the treatment modality for early-stage NSCLC, there are other more subtle factors that can play into the decision.

These include prior surgery or radiotherapy to the chest, prior cancers, and social issues, such as the patient being a primary caregiver for another person and job insecurity, that might make recovery from surgery more challenging. And in rare instances, a patient may be medically fit to undergo surgery, but the cancer is technically challenging to resect due to anatomic issues or prior surgery to the chest, Robinson added.

 

A Winner?

Results from two ongoing, highly anticipated randomized trials expected in the next several years will hopefully provide additional insights and clarify ongoing uncertainties about the optimal treatment strategies for operable patients with stage I NSCLC.

STABLE-MATES is comparing outcomes after sublobar resection and SBRT in high-risk operable stage I NSCLC, and VALOR is evaluating outcomes after anatomic pulmonary resections and SBRT in patients with stage I NSCLC who have a long life expectancy and are fit enough to tolerate surgery.

But Robinson said his group believes that trying to decide on a winner is a “fool’s errand” and is instead running a pragmatic study across multiple academic and community centers around the United States and Canada where patients choose therapy based on their personal preferences and guidance from their physicians. The researchers will carefully track baseline comorbidity and frailty and assess serial quality-of-life changes over time.

“The goal is to create a calculator that a given patient might use in the future to determine what patients like them would have received, complete with expected outcomes and side effects,” Robinson said.

Robinson cautioned, however, that it “seems unlikely, given the existing literature, that one of the treatments will be truly ‘superior’ to the other one and lead to the ‘losing’ treatment fading away since both are excellent options with pros and cons.”

Aggarwal, Robinson, and Flores had no relevant disclosures.

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

For years, the default definitive treatment for patients with early-stage I non–small cell lung cancer (NSCLC) has been surgical resection, typically minimally invasive lobectomy with systematic lymph node dissection.

Guidelines from the National Comprehensive Cancer Network (NCCN), the American Society of Clinical Oncology, and the European Society for Medical Oncology all list surgery (in particular, lobectomy) as the primary local therapy for fit, operable patients with stage I NSCLC.

More recently, however, stereotactic body radiotherapy (SBRT), also called stereotactic ablative radiotherapy, has emerged as a definitive treatment option for stage I NSCLC, especially for older, less fit patients who are unsuitable or deemed high-risk for surgery.

“We see patients in our practice who cannot undergo surgery or who may not have adequate lung function to be able to tolerate surgery, and for these patients who are medically inoperable or surgically unresectable, radiation therapy may be a reasonable option,” Charu Aggarwal, MD, MPH, professor and lung cancer specialist, University of Pennsylvania, Philadelphia, told this news organization.

Given some encouraging data suggesting that SBRT could provide similar survival outcomes and be an alternative to surgery for operable disease, SBRT is also increasingly being considered in these early-stage patients. However, other evidence indicates that SBRT may be associated with higher rates of regional and distant recurrences and worse long-term survival, particularly in operable patients.

What may ultimately matter most is carefully selecting operable patients who undergo SBRT.

Aggarwal has encountered certain patients who are fit for surgery but would rather have radiation therapy. “This is an individual decision, and these patients are usually discussed at tumor board and in multidisciplinary discussions to really make sure that they’re making the right decision for themselves,” she explained.

 

The Pros and Cons of SBRT

SBRT is a nonsurgical approach in which precision high-dose radiation is delivered in just a few fractions — typically, 3, 5, or 8, depending on institutional protocols and tumor characteristics.

SBRT is performed on an outpatient basis, usually over 1-2 weeks, with most patients able to resume usual activities with minimal to no delay. Surgery, on the other hand, requires a hospital stay and takes most people about 2-6 weeks to return to regular activities. SBRT also avoids anesthesia and surgical incisions, both of which come with risks.

The data on SBRT in early-stage NSCLC are mixed. While some studies indicate that SBRT comes with promising survival outcomes, other research has reported worse survival and recurrence rates.

One potential reason for higher recurrence rates with SBRT is the lack of pathologic nodal staging, which only happens after surgery, as well as lower rates of nodal evaluation with endobronchial ultrasound or mediastinoscopy before surgery or SBRT. Without nodal assessments, clinicians may miss a more aggressive histology or more advanced nodal stage, which would go undertreated if patients received SBRT.

 

Latest Data in Large Cohort

A recent study published in Lung Cancer indicated that, when carefully selected, operable patients with early NSCLC have comparable survival with lobectomy or SBRT.

In the study, Dutch researchers took an in-depth look at survival and recurrence patterns in a retrospective cohort study of 2183 patients with clinical stage I NSCLC treated with minimally invasive lobectomy or SBRT. The study includes one of the largest cohorts to date, with robust data collection on baseline characteristics, comorbidities, tumor size, performance status, and follow-up.

Patients receiving SBRT were typically older (median age, 74 vs 67 years), had higher comorbidity burdens (Charlson index ≥ 5 in 57% of SBRT patients vs 23% of surgical patients), worse performance status, and lower lung function. To adjust for these differences, the researchers used propensity score weighting so the SBRT group’s baseline characteristics were comparable with those in the surgery group.

The surgery cohort had more invasive nodal evaluation: 21% underwent endobronchial ultrasound or mediastinoscopy vs only 12% in the SBRT group. The vast majority in both groups had PET-CT staging, reflecting modern imaging-based workups.

While 5-year local recurrence rates between the two groups were similar (13.1% for SBRT vs 12.1% for surgery), the 5-year regional recurrence rate was significantly higher after SBRT than lobectomy (18.1% vs 14.2%; hazard ratio [HR], 0.74), as was the distant metastasis rate (26.2% vs 20.2%; HR, 0.72).

Mortality at 30 days was higher after surgery than SBRT (1.0% vs 0.2%). And in the unadjusted analysis, 5-year overall survival was significantly better with lobectomy than SBRT (70.2% vs 40.3%).

However, when the analysis only included patients with similar baseline characteristics, overall survival was no longer significantly different in the two groups (HR, 0.89; 95% CI, 0.65-1.20). Lung cancer–specific mortality was also not significantly different between the two treatments (HR, 1.08), but the study was underpowered to detect significant differences in this outcome on the basis of a relatively low number of deaths from NSCLC.

Still, even after comparing similar patients, recurrence-free survival was notably better with surgery (HR, 0.70), due to fewer regional recurrences and distant metastases. Overall, 13% of the surgical cohort had nodal upstaging at pathology, meaning that even in clinically “node-negative” stage I disease, a subset of patients had unsuspected nodal involvement.

Patients receiving SBRT did not have pathologic nodal staging, raising the possibility of occult micrometastases. The authors noted that the proportion of SBRT patients with occult lymph node metastases is likely at least equal to that in the surgery group, but these metastases would go undetected without pathologic assessment.

Missing potential occult micrometastases in the SBRT group likely contributed to higher regional recurrence rates over time. By improving nodal staging, more patients with occult lymph node metastases who would be undertreated with SBRT may be identified before treatment, the authors said.

 

What Do Experts Say?

So, is SBRT an option for patients with stage I NSCLC?

Opinions vary.

“If you got one shot for a cure, then you want to do the surgery because that’s what results in a cure,” said Raja Flores, MD, chairman of Thoracic Surgery, Mount Sinai Health System, New York City.

Flores noted that the survival rate with surgery is high in this population. “There’s really nothing out there that can compare,” he said.

In his view, surgery “remains the gold standard.” However, “radiation could be considered in nonsurgical candidates,” he said.

The most recent NCCN guidelines align with Flores’ take. The guidelines say that SBRT is indicated for stage IA-IIA (N0) NSCLC in patients who are deemed “medically inoperable, high surgical risk as determined by thoracic surgeon, and those who decline surgery after thoracic surgical consultation.”

Clifford G. Robinson, MD, agreed. “In the United States, we largely treat patients with SBRT who are medically inoperable or high-risk operable and a much smaller proportion who decline surgery,” said Robinson, professor of radiation oncology and chief of SBRT at Washington University in St. Louis, St. Louis. “Many patients who are deemed operable are not offered SBRT.”

Still, for Robinson, determining which patients are best suited for surgery or SBRT remains unclear.

“Retrospective comparisons are fraught with problems because of confounding,” Robinson told this news organization. “That is, the healthier patients get surgery, and the less healthy ones get SBRT. No manner of fancy statistical manipulation can remove that fact.”

In fact, a recent meta-analysis found that the most significant variable predicting whether surgery or SBRT was superior in retrospective studies was whether the author was a surgeon or radiation oncologist.

Robinson noted that multiple randomized trials have attempted to randomize patients with medically operable early-stage NSCLC to surgery or SBRT and failed to accrue, largely due to patients’ “understandable unwillingness to be randomized between operative vs nonoperative interventions when most already prefer one or the other approach.”

Flores highlighted another point of caution about interpreting trial results: Not all early-stage NSCLC behaves similarly. “Some are slow-growing ‘turtles,’ and others are aggressive ‘rabbits’ — and the turtles are usually the ones that have been included in these radiotherapy trials, and that’s the danger,” he said.

While medical operability is the primary factor for deciding the treatment modality for early-stage NSCLC, there are other more subtle factors that can play into the decision.

These include prior surgery or radiotherapy to the chest, prior cancers, and social issues, such as the patient being a primary caregiver for another person and job insecurity, that might make recovery from surgery more challenging. And in rare instances, a patient may be medically fit to undergo surgery, but the cancer is technically challenging to resect due to anatomic issues or prior surgery to the chest, Robinson added.

 

A Winner?

Results from two ongoing, highly anticipated randomized trials expected in the next several years will hopefully provide additional insights and clarify ongoing uncertainties about the optimal treatment strategies for operable patients with stage I NSCLC.

STABLE-MATES is comparing outcomes after sublobar resection and SBRT in high-risk operable stage I NSCLC, and VALOR is evaluating outcomes after anatomic pulmonary resections and SBRT in patients with stage I NSCLC who have a long life expectancy and are fit enough to tolerate surgery.

But Robinson said his group believes that trying to decide on a winner is a “fool’s errand” and is instead running a pragmatic study across multiple academic and community centers around the United States and Canada where patients choose therapy based on their personal preferences and guidance from their physicians. The researchers will carefully track baseline comorbidity and frailty and assess serial quality-of-life changes over time.

“The goal is to create a calculator that a given patient might use in the future to determine what patients like them would have received, complete with expected outcomes and side effects,” Robinson said.

Robinson cautioned, however, that it “seems unlikely, given the existing literature, that one of the treatments will be truly ‘superior’ to the other one and lead to the ‘losing’ treatment fading away since both are excellent options with pros and cons.”

Aggarwal, Robinson, and Flores had no relevant disclosures.

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

For years, the default definitive treatment for patients with early-stage I non–small cell lung cancer (NSCLC) has been surgical resection, typically minimally invasive lobectomy with systematic lymph node dissection.

Guidelines from the National Comprehensive Cancer Network (NCCN), the American Society of Clinical Oncology, and the European Society for Medical Oncology all list surgery (in particular, lobectomy) as the primary local therapy for fit, operable patients with stage I NSCLC.

More recently, however, stereotactic body radiotherapy (SBRT), also called stereotactic ablative radiotherapy, has emerged as a definitive treatment option for stage I NSCLC, especially for older, less fit patients who are unsuitable or deemed high-risk for surgery.

“We see patients in our practice who cannot undergo surgery or who may not have adequate lung function to be able to tolerate surgery, and for these patients who are medically inoperable or surgically unresectable, radiation therapy may be a reasonable option,” Charu Aggarwal, MD, MPH, professor and lung cancer specialist, University of Pennsylvania, Philadelphia, told this news organization.

Given some encouraging data suggesting that SBRT could provide similar survival outcomes and be an alternative to surgery for operable disease, SBRT is also increasingly being considered in these early-stage patients. However, other evidence indicates that SBRT may be associated with higher rates of regional and distant recurrences and worse long-term survival, particularly in operable patients.

What may ultimately matter most is carefully selecting operable patients who undergo SBRT.

Aggarwal has encountered certain patients who are fit for surgery but would rather have radiation therapy. “This is an individual decision, and these patients are usually discussed at tumor board and in multidisciplinary discussions to really make sure that they’re making the right decision for themselves,” she explained.

 

The Pros and Cons of SBRT

SBRT is a nonsurgical approach in which precision high-dose radiation is delivered in just a few fractions — typically, 3, 5, or 8, depending on institutional protocols and tumor characteristics.

SBRT is performed on an outpatient basis, usually over 1-2 weeks, with most patients able to resume usual activities with minimal to no delay. Surgery, on the other hand, requires a hospital stay and takes most people about 2-6 weeks to return to regular activities. SBRT also avoids anesthesia and surgical incisions, both of which come with risks.

The data on SBRT in early-stage NSCLC are mixed. While some studies indicate that SBRT comes with promising survival outcomes, other research has reported worse survival and recurrence rates.

One potential reason for higher recurrence rates with SBRT is the lack of pathologic nodal staging, which only happens after surgery, as well as lower rates of nodal evaluation with endobronchial ultrasound or mediastinoscopy before surgery or SBRT. Without nodal assessments, clinicians may miss a more aggressive histology or more advanced nodal stage, which would go undertreated if patients received SBRT.

 

Latest Data in Large Cohort

A recent study published in Lung Cancer indicated that, when carefully selected, operable patients with early NSCLC have comparable survival with lobectomy or SBRT.

In the study, Dutch researchers took an in-depth look at survival and recurrence patterns in a retrospective cohort study of 2183 patients with clinical stage I NSCLC treated with minimally invasive lobectomy or SBRT. The study includes one of the largest cohorts to date, with robust data collection on baseline characteristics, comorbidities, tumor size, performance status, and follow-up.

Patients receiving SBRT were typically older (median age, 74 vs 67 years), had higher comorbidity burdens (Charlson index ≥ 5 in 57% of SBRT patients vs 23% of surgical patients), worse performance status, and lower lung function. To adjust for these differences, the researchers used propensity score weighting so the SBRT group’s baseline characteristics were comparable with those in the surgery group.

The surgery cohort had more invasive nodal evaluation: 21% underwent endobronchial ultrasound or mediastinoscopy vs only 12% in the SBRT group. The vast majority in both groups had PET-CT staging, reflecting modern imaging-based workups.

While 5-year local recurrence rates between the two groups were similar (13.1% for SBRT vs 12.1% for surgery), the 5-year regional recurrence rate was significantly higher after SBRT than lobectomy (18.1% vs 14.2%; hazard ratio [HR], 0.74), as was the distant metastasis rate (26.2% vs 20.2%; HR, 0.72).

Mortality at 30 days was higher after surgery than SBRT (1.0% vs 0.2%). And in the unadjusted analysis, 5-year overall survival was significantly better with lobectomy than SBRT (70.2% vs 40.3%).

However, when the analysis only included patients with similar baseline characteristics, overall survival was no longer significantly different in the two groups (HR, 0.89; 95% CI, 0.65-1.20). Lung cancer–specific mortality was also not significantly different between the two treatments (HR, 1.08), but the study was underpowered to detect significant differences in this outcome on the basis of a relatively low number of deaths from NSCLC.

Still, even after comparing similar patients, recurrence-free survival was notably better with surgery (HR, 0.70), due to fewer regional recurrences and distant metastases. Overall, 13% of the surgical cohort had nodal upstaging at pathology, meaning that even in clinically “node-negative” stage I disease, a subset of patients had unsuspected nodal involvement.

Patients receiving SBRT did not have pathologic nodal staging, raising the possibility of occult micrometastases. The authors noted that the proportion of SBRT patients with occult lymph node metastases is likely at least equal to that in the surgery group, but these metastases would go undetected without pathologic assessment.

Missing potential occult micrometastases in the SBRT group likely contributed to higher regional recurrence rates over time. By improving nodal staging, more patients with occult lymph node metastases who would be undertreated with SBRT may be identified before treatment, the authors said.

 

What Do Experts Say?

So, is SBRT an option for patients with stage I NSCLC?

Opinions vary.

“If you got one shot for a cure, then you want to do the surgery because that’s what results in a cure,” said Raja Flores, MD, chairman of Thoracic Surgery, Mount Sinai Health System, New York City.

Flores noted that the survival rate with surgery is high in this population. “There’s really nothing out there that can compare,” he said.

In his view, surgery “remains the gold standard.” However, “radiation could be considered in nonsurgical candidates,” he said.

The most recent NCCN guidelines align with Flores’ take. The guidelines say that SBRT is indicated for stage IA-IIA (N0) NSCLC in patients who are deemed “medically inoperable, high surgical risk as determined by thoracic surgeon, and those who decline surgery after thoracic surgical consultation.”

Clifford G. Robinson, MD, agreed. “In the United States, we largely treat patients with SBRT who are medically inoperable or high-risk operable and a much smaller proportion who decline surgery,” said Robinson, professor of radiation oncology and chief of SBRT at Washington University in St. Louis, St. Louis. “Many patients who are deemed operable are not offered SBRT.”

Still, for Robinson, determining which patients are best suited for surgery or SBRT remains unclear.

“Retrospective comparisons are fraught with problems because of confounding,” Robinson told this news organization. “That is, the healthier patients get surgery, and the less healthy ones get SBRT. No manner of fancy statistical manipulation can remove that fact.”

In fact, a recent meta-analysis found that the most significant variable predicting whether surgery or SBRT was superior in retrospective studies was whether the author was a surgeon or radiation oncologist.

Robinson noted that multiple randomized trials have attempted to randomize patients with medically operable early-stage NSCLC to surgery or SBRT and failed to accrue, largely due to patients’ “understandable unwillingness to be randomized between operative vs nonoperative interventions when most already prefer one or the other approach.”

Flores highlighted another point of caution about interpreting trial results: Not all early-stage NSCLC behaves similarly. “Some are slow-growing ‘turtles,’ and others are aggressive ‘rabbits’ — and the turtles are usually the ones that have been included in these radiotherapy trials, and that’s the danger,” he said.

While medical operability is the primary factor for deciding the treatment modality for early-stage NSCLC, there are other more subtle factors that can play into the decision.

These include prior surgery or radiotherapy to the chest, prior cancers, and social issues, such as the patient being a primary caregiver for another person and job insecurity, that might make recovery from surgery more challenging. And in rare instances, a patient may be medically fit to undergo surgery, but the cancer is technically challenging to resect due to anatomic issues or prior surgery to the chest, Robinson added.

 

A Winner?

Results from two ongoing, highly anticipated randomized trials expected in the next several years will hopefully provide additional insights and clarify ongoing uncertainties about the optimal treatment strategies for operable patients with stage I NSCLC.

STABLE-MATES is comparing outcomes after sublobar resection and SBRT in high-risk operable stage I NSCLC, and VALOR is evaluating outcomes after anatomic pulmonary resections and SBRT in patients with stage I NSCLC who have a long life expectancy and are fit enough to tolerate surgery.

But Robinson said his group believes that trying to decide on a winner is a “fool’s errand” and is instead running a pragmatic study across multiple academic and community centers around the United States and Canada where patients choose therapy based on their personal preferences and guidance from their physicians. The researchers will carefully track baseline comorbidity and frailty and assess serial quality-of-life changes over time.

“The goal is to create a calculator that a given patient might use in the future to determine what patients like them would have received, complete with expected outcomes and side effects,” Robinson said.

Robinson cautioned, however, that it “seems unlikely, given the existing literature, that one of the treatments will be truly ‘superior’ to the other one and lead to the ‘losing’ treatment fading away since both are excellent options with pros and cons.”

Aggarwal, Robinson, and Flores had no relevant disclosures.

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

The United States Food and Drug Administration (FDA) approved guselkumab (Tremfya, Johnson & Johnson) for the treatment of adults with moderately to severely active Crohn’s disease (CD).

The approval marks the fourth indication for guselkumab, which was approved for moderate to severe plaque psoriasis in 2017, active psoriatic arthritis in 2020, and moderately to severely active ulcerative colitis in 2024. 

Guselkumab is the first and only interleukin-23 (IL-23) inhibitor that offers both subcutaneous (SC) and intravenous (IV) induction options for CD, the company said in a news release. 

“Despite the progress in the management of Crohn’s disease, many patients experience debilitating symptoms and are in need of new treatment options,” Remo Panaccione, MD, director of the Inflammatory Bowel Disease Unit at the University of Calgary, Calgary, Alberta, Canada, said in the release. 

“The approval of Tremfya offers an IL-23 inhibitor that has shown robust rates of endoscopic remission with both subcutaneous and intravenous induction regimens. Importantly, the fully subcutaneous regimen offers choice and flexibility for patients and providers not available before,” said Panaccione.

The FDA nod in CD was based on positive results from three phase 3 trials evaluating guselkumab in more than 1300 patients with moderately to severely active CD who failed or were intolerant to corticosteroids, immunomodulators, or biologics. 

The GRAVITI trial showed that guselkumab as SC induction and maintenance therapy was superior to placebo in clinical remission as well as endoscopic response and remission and deep remission. 

Results from GALAXI 2 and GALAXI 3 showed that guselkumab was superior to ustekinumab (Stelara) on all pooled endoscopic endpoints. 

Guselkumab is the only IL-23 inhibitor to demonstrate “clinical remission and endoscopic response, both at 1 year, with a fully subcutaneous induction regimen,” the company said. 

The recommended SC induction dose of guselkumab is 400 mg (given as two consecutive injections of 200 mg each, dispensed in one induction pack) at weeks 0, 4 and 8. The drug is also available in a 200 mg prefilled syringe. For the IV induction option, 200 mg IV infusions are administered at weeks 0, 4, and 8.

The recommended maintenance dosage is 100 mg administered by SC injection at week 16, and every 8 weeks thereafter, or 200 mg administered by SC injection at week 12, and every 4 weeks thereafter. 

Use of the lowest effective recommended dosage to maintain therapeutic response is recommended. 

Full prescribing information and medication guide are available online.

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

The United States Food and Drug Administration (FDA) approved guselkumab (Tremfya, Johnson & Johnson) for the treatment of adults with moderately to severely active Crohn’s disease (CD).

The approval marks the fourth indication for guselkumab, which was approved for moderate to severe plaque psoriasis in 2017, active psoriatic arthritis in 2020, and moderately to severely active ulcerative colitis in 2024. 

Guselkumab is the first and only interleukin-23 (IL-23) inhibitor that offers both subcutaneous (SC) and intravenous (IV) induction options for CD, the company said in a news release. 

“Despite the progress in the management of Crohn’s disease, many patients experience debilitating symptoms and are in need of new treatment options,” Remo Panaccione, MD, director of the Inflammatory Bowel Disease Unit at the University of Calgary, Calgary, Alberta, Canada, said in the release. 

“The approval of Tremfya offers an IL-23 inhibitor that has shown robust rates of endoscopic remission with both subcutaneous and intravenous induction regimens. Importantly, the fully subcutaneous regimen offers choice and flexibility for patients and providers not available before,” said Panaccione.

The FDA nod in CD was based on positive results from three phase 3 trials evaluating guselkumab in more than 1300 patients with moderately to severely active CD who failed or were intolerant to corticosteroids, immunomodulators, or biologics. 

The GRAVITI trial showed that guselkumab as SC induction and maintenance therapy was superior to placebo in clinical remission as well as endoscopic response and remission and deep remission. 

Results from GALAXI 2 and GALAXI 3 showed that guselkumab was superior to ustekinumab (Stelara) on all pooled endoscopic endpoints. 

Guselkumab is the only IL-23 inhibitor to demonstrate “clinical remission and endoscopic response, both at 1 year, with a fully subcutaneous induction regimen,” the company said. 

The recommended SC induction dose of guselkumab is 400 mg (given as two consecutive injections of 200 mg each, dispensed in one induction pack) at weeks 0, 4 and 8. The drug is also available in a 200 mg prefilled syringe. For the IV induction option, 200 mg IV infusions are administered at weeks 0, 4, and 8.

The recommended maintenance dosage is 100 mg administered by SC injection at week 16, and every 8 weeks thereafter, or 200 mg administered by SC injection at week 12, and every 4 weeks thereafter. 

Use of the lowest effective recommended dosage to maintain therapeutic response is recommended. 

Full prescribing information and medication guide are available online.

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

The United States Food and Drug Administration (FDA) approved guselkumab (Tremfya, Johnson & Johnson) for the treatment of adults with moderately to severely active Crohn’s disease (CD).

The approval marks the fourth indication for guselkumab, which was approved for moderate to severe plaque psoriasis in 2017, active psoriatic arthritis in 2020, and moderately to severely active ulcerative colitis in 2024. 

Guselkumab is the first and only interleukin-23 (IL-23) inhibitor that offers both subcutaneous (SC) and intravenous (IV) induction options for CD, the company said in a news release. 

“Despite the progress in the management of Crohn’s disease, many patients experience debilitating symptoms and are in need of new treatment options,” Remo Panaccione, MD, director of the Inflammatory Bowel Disease Unit at the University of Calgary, Calgary, Alberta, Canada, said in the release. 

“The approval of Tremfya offers an IL-23 inhibitor that has shown robust rates of endoscopic remission with both subcutaneous and intravenous induction regimens. Importantly, the fully subcutaneous regimen offers choice and flexibility for patients and providers not available before,” said Panaccione.

The FDA nod in CD was based on positive results from three phase 3 trials evaluating guselkumab in more than 1300 patients with moderately to severely active CD who failed or were intolerant to corticosteroids, immunomodulators, or biologics. 

The GRAVITI trial showed that guselkumab as SC induction and maintenance therapy was superior to placebo in clinical remission as well as endoscopic response and remission and deep remission. 

Results from GALAXI 2 and GALAXI 3 showed that guselkumab was superior to ustekinumab (Stelara) on all pooled endoscopic endpoints. 

Guselkumab is the only IL-23 inhibitor to demonstrate “clinical remission and endoscopic response, both at 1 year, with a fully subcutaneous induction regimen,” the company said. 

The recommended SC induction dose of guselkumab is 400 mg (given as two consecutive injections of 200 mg each, dispensed in one induction pack) at weeks 0, 4 and 8. The drug is also available in a 200 mg prefilled syringe. For the IV induction option, 200 mg IV infusions are administered at weeks 0, 4, and 8.

The recommended maintenance dosage is 100 mg administered by SC injection at week 16, and every 8 weeks thereafter, or 200 mg administered by SC injection at week 12, and every 4 weeks thereafter. 

Use of the lowest effective recommended dosage to maintain therapeutic response is recommended. 

Full prescribing information and medication guide are available online.

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

      Invasive pneumococcal disease (IPD) remains a serious health threat for infants and can result in hospitalizations, serious complications, or even death.^1-3 IPD rates peak at a critical stage in a child’s immune development, when maternal antibody protection wanes and the child has not yet received or is in the process of receiving their primary vaccination series.⁴ Pneumococcal vaccination is especially important during this vulnerable period to help protect against potentially severe consequences from IPD.^2,4,5                  

     Over the last 25 years, the widespread adoption of pneumococcal conjugate vaccines (PCVs) in children has led to a reduction in the spread of many different types of pneumococcal bacteria – referred to as serotypes.² Although these vaccines have helped reduce the burden of disease, pneumococcal disease remains an issue, with specific serotypes presenting a greater threat to children’s health.^6-10

Understanding the burden of IPD in children

     According to the Centers for Disease Control and Prevention (CDC), the incidence of IPD is highest in the first year of life,^3,* and the death rate due to IPD is higher in infants than in any other pediatric age group.^11,† Infants' immune systems are still developing in the first year of life; therefore, protection during this time is critical.^3,4,11 

     The CDC recommends routine pediatric pneumococcal vaccination as a four-dose series at months two, four, and six with a booster administered between 12-15 months.¹² Despite the risks associated with invasive pneumococcal disease, some children do not receive all four doses.^1-3,13 Many factors can contribute to incomplete childhood immunization coverage, including ethnicity, geographic location, and socioeconomic status.¹⁴ In fact, up to one in five babies within the Vaccines for Children Program have received only three of the four recommended PCV doses by two years of age, according to a CDC Morbidity and Mortality Weekly Report from 2021-2023.^12,13 The immune response generated after the third dose of a pneumococcal conjugate vaccine is important when evaluating protection against IPD, especially for the children who don't receive their fourth dose.^12,15,16                 

     Additionally, certain serotypes, like Serotype 3, are responsible for more IPD cases and are associated with higher morbidity and mortality rates in children.^7-10,a Despite being included in PCVs for over a decade, Serotype 3 continues to be a leading cause of IPD in children under five, as shown in a pooled analysis of national-level CDC data from 2018-2022.^7,17 This particular serotype has resisted antibody-mediated clearance and continues to be associated with adverse effects.¹⁸

What should pediatricians consider when it comes to protecting children from IPD?

     When it comes to protecting against IPD, it's important to consider factors in addition to the number of serotypes covered by a vaccine, such as early and robust protection against key serotypes that cause pediatric IPD in the first year of life.^2,7,10,19

     VAXNEUVANCE^® (Pneumococcal 15-valent Conjugate Vaccine) is a pediatric pneumococcal conjugate vaccine that can help deliver strong protection against key disease-causing serotypes during infancy, when the threat of IPD is the highest.^{2,3,7,10,19-21}

Indications and Usage           

     VAXNEUVANCE is indicated for active immunization for the prevention of invasive disease caused by Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F in individuals 6 weeks of age and older. 

Select Safety Information          

     Do not administer VAXNEUVANCE to individuals with a severe allergic reaction (eg, anaphylaxis) to any component of VAXNEUVANCE or to diphtheria toxoid.

     Some individuals with altered immunocompetence, including those receiving immunosuppressive therapy, may have a reduced immune response to VAXNEUVANCE.

     Apnea following intramuscular vaccination has been observed in some infants born prematurely. Vaccination of premature infants should be based on the infant’s medical status and the potential benefits and possible risks.

(Select Safety Information for VAXNEUVANCE continues below.)

     VAXNEUVANCE delivers robust immune responses at seven months, following the third dose, for three key disease-causing serotypes: 3, 22F and 33F.^7,10,19,b,c Clinical data showed that immune responses for VAXNEUVANCE were superior to PCV13 (pneumococcal 13-valent conjugate vaccine) for those three critical serotypes^2,7,10,19,d and were comparable for the 12 shared serotypes between the vaccines.¹⁹

     Further, VAXNEUVANCE showcased superior immune responses against Serotype 3 after the third dose with an immunoglobulin G (IgG) geometric mean concentrations (GMCs) response rate of 93.1% compared to PCV13, which demonstrated a 74% response rate.^19,b

     Although completing the full recommended immunization series remains the best way to help maximize protection,^12,22 many children still receive fewer than the recommended four doses of a PCV.^12,13 It is important to consider a vaccine that targets problematic serotypes and provides robust immune responses after three doses  – of the four dose series – to help protect this vulnerable population from IPD.^{3,4,7,10,11,19}

     VAXNEUVANCE can help prevent pediatric IPD in the first year of life and beyond and is an important option for pediatricians to consider for their appropriate patients.^7,19

###

Select Safety Information (continued)         

     The most commonly reported solicited adverse reactions in children vaccinated at 2, 4, 6, and 12 through 15 months of age, provided as a range across the 4-dose series, were: irritability (57.3% to 63.4%), somnolence (24.2% to 47.5%), injection-site pain (25.9% to 40.3%), fever ≥38.0°C (13.3% to 20.4%), decreased appetite (14.1% to 19.0%), injection-site induration (13.2% to 15.4%), injection-site erythema (13.7% to 21.4%) and injection-site swelling (11.3% to 13.4%).

     The most commonly reported solicited adverse reactions in children 2 through 17 years of age vaccinated with a single dose were: injection-site pain (54.8%), myalgia (23.7%), injection-site swelling (20.9%), injection-site erythema (19.2%), fatigue (15.8%), headache (11.9%) and injection-site induration (6.8%).

     Vaccination with VAXNEUVANCE may not protect all vaccine recipients.

Before administering VAXNEUVANCE, please read the accompanying Prescribing Information. The Patient Information also is available.

* Based on pooled analysis of national-level CDC ABC surveillance data from 2018–2022, representing ~35 million people surveyed annually in 10 states across the US. IPD incidence rates were 10.3 in <1 year, 8.2 in 1 year, 4.0 in 2–4 years, 5.0 in 1–4 years, and 1.3 in 5–17 years (Regional variations may exist).³

† Based on national-level CDC ABC surveillance data from 2022, representing ~35 million people in 10 states across the US (Regional variations may exist).¹¹ 

Key Study Details 

GMC Ratios Postdose 3^c

Primary endpoint: VAXNEUVANCE delivered comparable immune responses for 12 of the 13 shared serotypes found in PCV13. Shared Serotype 6A was just below the noninferiority criteria by a small margin, with the lower bound of the 2-sided 95% CI for the GMC ratio being 0.48 vs >0.5.^19,23

Study Design

Study 8 was a pivotal, double-blind, active comparator-controlled study in which participants were randomized to receive VAXNEUVANCE (N=860) or PCV13 (N=860) in a 4-dose series. The first 3 doses were administered to infants at 2, 4, and 6 months of age and the fourth dose was administered to children at 12 through 15 months of age. Participants also received other licensed pediatric vaccines concomitantly. Immune responses were measured by IgG response rates, IgG GMCs, and OPA GMTs for all 15 serotypes contained in VAXNEUVANCE.¹⁹

^aBased on a pooled analysis of national-level CDC data from 2018–2021, the top 6 IPD-causing serotypes in children under 5 years of age were 15C, 33F, 19F, 3, 23B, and 22F. Serotypes 15C and 23B are not included in any recommended pediatric PCV in the US.^{7,17,19,22,24           
b}Postdose 3 superiority was demonstrated based on measurements taken 30 days after the 6-month dose (at 7 months).^{19           
c}Measurements were taken 30 days postdose specified.^{19           
d}Secondary endpoint: Postdose 3 IgG response rate percentage point difference vs PCV13 (95% CI): for Serotype 3, 19.1 (14.4, 24.0); for Serotype 22F, 8.1 (5.1, 11.5); for Serotype 33F, -5.1 (-9.5, -0.7).^19,23

Randomized controlled trials assessing the clinical efficacy of VAXNEUVANCE compared to PCV13 have not been conducted.¹⁹

References:

¹Dalton M. Pneumoccal disease. National Foundation for Infectious Diseases. Published July 2024. https://www.nfid.org/infectious-disease/pneumococcal/     
²Gierke R, Wodi P, Kobayashi M. Epidemiology and Prevention of Vaccine-Preventable Diseases (Pink Book). 14th edition. Chapter 17: Pneumococcal disease. Epidemiology and Prevention of Vaccine-Preventable Diseases. Published May 1, 2024. Accessed December 10, 2024. https://www.cdc.gov/pinkbook/hcp/table-of-contents/chapter-17-pneumococcal-disease.html     
³Data available on request from the Merck National Service Center via email at [email protected]. Please specify information package US-PVC-02072.     
⁴Mohanty S, Done N, Liu Q, et al. Incidence of pneumococcal disease in children ≤48 months old in the United States: 1998–2019. Vaccine. Published online March 1, 2024. doi: 10.1016/j.vaccine.2024.03.013     
⁵Clinical overview of pneumococcal disease. Centers for Disease Control and Prevention. February 6, 2024. Accessed May 22, 2024. https://www.cdc.gov/pneumococcal/hcp/clinical-overview/     
⁶Wasserman MD, Perdrizet J, Grant L, et al. Clinical and economic burden of pneumococcal disease due to serotypes contained in current and investigational pneumococcal conjugate vaccines in children under five years of age. Infect Dis Ther. 2021;10(4):2701-2720. doi:10.1007/s40121-021-00544-1     
⁷Centers for Disease Control and Prevention (CDC). Visualization – Based on 1998-2022 serotype data for invasive pneumococcal disease cases by age group from Active Bacterial Core surveillance (ABCs). Updated July 22, 2024. Accessed August 30, 2024. https://data.cdc.gov/Public-Health-Surveillance/1998-2022-Serotype-Data-for-Invasive-Pneumococcal-/qvzb-qs6p/about_data     
⁸Varghese J, Chochua S, Tran T, et al. Multistate population and whole genome sequence-based strain surveillance of invasive pneumococci recovered in the USA during 2017. Clin Microbiol Infect. 2020;26(4):512.e1-512.e10. doi:10.1016/j.cmi.2019.09.008     
⁹Azarian T, Mitchell PK, Georgieva M, et al. Global emergence and population dynamics of divergent serotype 3 CC180 pneumococci. PLoS Pathog. 2018;14(11):e1007438. doi:10.1371/journal.ppat.1007438     
¹⁰Hu T, Weiss T, Owusu-Edusei K, Petigara T. Health and economic burden associated with 15-valent pneumococcal conjugate vaccine serotypes in children in the United States. J Med Econ. 2020;23(12):1653-1660. doi:10.1080/13696998.2020.184021613     
¹¹Active Bacterial Core surveillance (ABCs) report, Emerging Infections Program network, Streptococcus pneumoniae, 2022. Centers for Disease Control and Prevention. Updated July 5, 2024. Accessed October 15, 2024. https://www.cdc.gov/abcs/downloads/SPN_Surveillance_Report_2022.pdf     
¹²Recommended child and adolescent immunization schedule for ages 18 years or younger, United States, 2025. Centers for Disease Control and Prevention. Addendum updated November 21, 2024. Accessed November 25, 2024. https://www.cdc.gov/vaccines/hcp/imz-schedules/downloads/child/0-18yrs-child-combined-schedule.pdf     
¹³Hill HA, et al. Decline in Vaccination Coverage by Age 24 Months and Vaccination Inequities Among Children Born in 2020 and 2021 — National Immunization Survey-Child, United States, 2021–2023. MMWR Morb Mortal Wkly Rep, pages 844–853.   
¹⁴Feemster K, Weaver J, Buchwald U, Banniettis N, Cox KS, McIntosh ED, Spoulou V. Pneumococcal Vaccine Breakthrough and Failure in Infants and Children: A Narrative Review. Vaccines (Basel). 2023 Nov 24;11(12):1750. doi:10.3390/vaccines11121750. PMID: 38140155; PMCID: PMC10747311.     
¹⁵Recommendations to assure the quality, safety and efficacy of pneumoccoccal conjugate vaccines. Annex 3. TRS no 977. World Health Organization. October 19, 2013. Accessed October 31, 2024. https://www.who.int/publications/m/item/pneumococcal-conjugate-vaccines-annex3-trs-977
¹⁶Guidelines on clinical evaluation of vaccines: regulatory expectations. Annex 9. TRA No 924.World Health Organization. Last reviewed October 21, 2020. Accessed October 31, 2024. https://www.who.int/publications/m/item/WHO-TRS-1004-web-annex-9
¹⁷Prevnar 13. Prescribing Information. Pfizer; 2019.     
¹⁸Luck JN, Tettelin H, Orihuela CJ. Sugar-Coated Killer: Serotype 3 Pneumococcal Disease. Front Cell Infect Microbiol. 2020;10:613287. Published 2020 Dec 23. doi:10.3389/fcimb.2020.613287     
¹⁹VAXNEUVANCE. Prescribing Information. Merck & Co., Inc., 2024.     
²⁰Moraes-Pinto MI, Suano-Souza F, Aranda CS. Immune system: development and acquisition of immunological competence. J Pediatr (Rio J). 2021;97(S1):S59-S66. doi:10.1016/j.jped.2020.10.006     
²¹Wodi AP, Morelli V. Epidemiology and Prevention of Vaccine-Preventable Diseases (Pink Book). 14th edition. Chapter 1: Principles of vaccination. Centers for Disease Control and Prevention. Last reviewed March 2024. Accessed May 9, 2024. https://www.cdc.gov/pinkbook/hcp/table-of-contents/chapter-1-principles-of-vaccination.html     
²²Pneumococcal vaccination. Centers for Disease Control and Prevention. Last reviewed September 12, 2024. Accessed September 30, 2024. https://www.cdc.gov/pneumococcal/vaccines/index.html 
²³Lupinacci R, Rupp R, Wittawatmongkol O, et al. A phase 3, multicenter, randomized, double-blind, active-comparator-controlled study to evaluate the safety, tolerability, and immunogenicity of a 4-dose regimen of V114, a 15-valent pneumococcal conjugate vaccine, in healthy infants (PNEU-PED). Vaccine. 2023;41(5):1142-1152. doi:10.1016/j.vaccine.2022.12.054 
²⁴Prevnar 20. Prescribing Information. Pfizer; 2023. 

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Neither the editors of Pediatric News nor the Editorial Advisory Board nor the reporting staff contributed to this content.

US-PVC-01998 03/25

      Invasive pneumococcal disease (IPD) remains a serious health threat for infants and can result in hospitalizations, serious complications, or even death.^1-3 IPD rates peak at a critical stage in a child’s immune development, when maternal antibody protection wanes and the child has not yet received or is in the process of receiving their primary vaccination series.⁴ Pneumococcal vaccination is especially important during this vulnerable period to help protect against potentially severe consequences from IPD.^2,4,5                  

     Over the last 25 years, the widespread adoption of pneumococcal conjugate vaccines (PCVs) in children has led to a reduction in the spread of many different types of pneumococcal bacteria – referred to as serotypes.² Although these vaccines have helped reduce the burden of disease, pneumococcal disease remains an issue, with specific serotypes presenting a greater threat to children’s health.^6-10

Understanding the burden of IPD in children

     According to the Centers for Disease Control and Prevention (CDC), the incidence of IPD is highest in the first year of life,^3,* and the death rate due to IPD is higher in infants than in any other pediatric age group.^11,† Infants' immune systems are still developing in the first year of life; therefore, protection during this time is critical.^3,4,11 

     The CDC recommends routine pediatric pneumococcal vaccination as a four-dose series at months two, four, and six with a booster administered between 12-15 months.¹² Despite the risks associated with invasive pneumococcal disease, some children do not receive all four doses.^1-3,13 Many factors can contribute to incomplete childhood immunization coverage, including ethnicity, geographic location, and socioeconomic status.¹⁴ In fact, up to one in five babies within the Vaccines for Children Program have received only three of the four recommended PCV doses by two years of age, according to a CDC Morbidity and Mortality Weekly Report from 2021-2023.^12,13 The immune response generated after the third dose of a pneumococcal conjugate vaccine is important when evaluating protection against IPD, especially for the children who don't receive their fourth dose.^12,15,16                 

     Additionally, certain serotypes, like Serotype 3, are responsible for more IPD cases and are associated with higher morbidity and mortality rates in children.^7-10,a Despite being included in PCVs for over a decade, Serotype 3 continues to be a leading cause of IPD in children under five, as shown in a pooled analysis of national-level CDC data from 2018-2022.^7,17 This particular serotype has resisted antibody-mediated clearance and continues to be associated with adverse effects.¹⁸

What should pediatricians consider when it comes to protecting children from IPD?

     When it comes to protecting against IPD, it's important to consider factors in addition to the number of serotypes covered by a vaccine, such as early and robust protection against key serotypes that cause pediatric IPD in the first year of life.^2,7,10,19

     VAXNEUVANCE^® (Pneumococcal 15-valent Conjugate Vaccine) is a pediatric pneumococcal conjugate vaccine that can help deliver strong protection against key disease-causing serotypes during infancy, when the threat of IPD is the highest.^{2,3,7,10,19-21}

Indications and Usage           

     VAXNEUVANCE is indicated for active immunization for the prevention of invasive disease caused by Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F in individuals 6 weeks of age and older. 

Select Safety Information          

     Do not administer VAXNEUVANCE to individuals with a severe allergic reaction (eg, anaphylaxis) to any component of VAXNEUVANCE or to diphtheria toxoid.

     Some individuals with altered immunocompetence, including those receiving immunosuppressive therapy, may have a reduced immune response to VAXNEUVANCE.

     Apnea following intramuscular vaccination has been observed in some infants born prematurely. Vaccination of premature infants should be based on the infant’s medical status and the potential benefits and possible risks.

(Select Safety Information for VAXNEUVANCE continues below.)

     VAXNEUVANCE delivers robust immune responses at seven months, following the third dose, for three key disease-causing serotypes: 3, 22F and 33F.^7,10,19,b,c Clinical data showed that immune responses for VAXNEUVANCE were superior to PCV13 (pneumococcal 13-valent conjugate vaccine) for those three critical serotypes^2,7,10,19,d and were comparable for the 12 shared serotypes between the vaccines.¹⁹

     Further, VAXNEUVANCE showcased superior immune responses against Serotype 3 after the third dose with an immunoglobulin G (IgG) geometric mean concentrations (GMCs) response rate of 93.1% compared to PCV13, which demonstrated a 74% response rate.^19,b

     Although completing the full recommended immunization series remains the best way to help maximize protection,^12,22 many children still receive fewer than the recommended four doses of a PCV.^12,13 It is important to consider a vaccine that targets problematic serotypes and provides robust immune responses after three doses  – of the four dose series – to help protect this vulnerable population from IPD.^{3,4,7,10,11,19}

     VAXNEUVANCE can help prevent pediatric IPD in the first year of life and beyond and is an important option for pediatricians to consider for their appropriate patients.^7,19

###

Select Safety Information (continued)         

     The most commonly reported solicited adverse reactions in children vaccinated at 2, 4, 6, and 12 through 15 months of age, provided as a range across the 4-dose series, were: irritability (57.3% to 63.4%), somnolence (24.2% to 47.5%), injection-site pain (25.9% to 40.3%), fever ≥38.0°C (13.3% to 20.4%), decreased appetite (14.1% to 19.0%), injection-site induration (13.2% to 15.4%), injection-site erythema (13.7% to 21.4%) and injection-site swelling (11.3% to 13.4%).

     The most commonly reported solicited adverse reactions in children 2 through 17 years of age vaccinated with a single dose were: injection-site pain (54.8%), myalgia (23.7%), injection-site swelling (20.9%), injection-site erythema (19.2%), fatigue (15.8%), headache (11.9%) and injection-site induration (6.8%).

     Vaccination with VAXNEUVANCE may not protect all vaccine recipients.

Before administering VAXNEUVANCE, please read the accompanying Prescribing Information. The Patient Information also is available.

* Based on pooled analysis of national-level CDC ABC surveillance data from 2018–2022, representing ~35 million people surveyed annually in 10 states across the US. IPD incidence rates were 10.3 in <1 year, 8.2 in 1 year, 4.0 in 2–4 years, 5.0 in 1–4 years, and 1.3 in 5–17 years (Regional variations may exist).³

† Based on national-level CDC ABC surveillance data from 2022, representing ~35 million people in 10 states across the US (Regional variations may exist).¹¹ 

Key Study Details 

GMC Ratios Postdose 3^c

Primary endpoint: VAXNEUVANCE delivered comparable immune responses for 12 of the 13 shared serotypes found in PCV13. Shared Serotype 6A was just below the noninferiority criteria by a small margin, with the lower bound of the 2-sided 95% CI for the GMC ratio being 0.48 vs >0.5.^19,23

Study Design

Study 8 was a pivotal, double-blind, active comparator-controlled study in which participants were randomized to receive VAXNEUVANCE (N=860) or PCV13 (N=860) in a 4-dose series. The first 3 doses were administered to infants at 2, 4, and 6 months of age and the fourth dose was administered to children at 12 through 15 months of age. Participants also received other licensed pediatric vaccines concomitantly. Immune responses were measured by IgG response rates, IgG GMCs, and OPA GMTs for all 15 serotypes contained in VAXNEUVANCE.¹⁹

^aBased on a pooled analysis of national-level CDC data from 2018–2021, the top 6 IPD-causing serotypes in children under 5 years of age were 15C, 33F, 19F, 3, 23B, and 22F. Serotypes 15C and 23B are not included in any recommended pediatric PCV in the US.^{7,17,19,22,24           
b}Postdose 3 superiority was demonstrated based on measurements taken 30 days after the 6-month dose (at 7 months).^{19           
c}Measurements were taken 30 days postdose specified.^{19           
d}Secondary endpoint: Postdose 3 IgG response rate percentage point difference vs PCV13 (95% CI): for Serotype 3, 19.1 (14.4, 24.0); for Serotype 22F, 8.1 (5.1, 11.5); for Serotype 33F, -5.1 (-9.5, -0.7).^19,23

Randomized controlled trials assessing the clinical efficacy of VAXNEUVANCE compared to PCV13 have not been conducted.¹⁹

References:

¹Dalton M. Pneumoccal disease. National Foundation for Infectious Diseases. Published July 2024. https://www.nfid.org/infectious-disease/pneumococcal/     
²Gierke R, Wodi P, Kobayashi M. Epidemiology and Prevention of Vaccine-Preventable Diseases (Pink Book). 14th edition. Chapter 17: Pneumococcal disease. Epidemiology and Prevention of Vaccine-Preventable Diseases. Published May 1, 2024. Accessed December 10, 2024. https://www.cdc.gov/pinkbook/hcp/table-of-contents/chapter-17-pneumococcal-disease.html     
³Data available on request from the Merck National Service Center via email at [email protected]. Please specify information package US-PVC-02072.     
⁴Mohanty S, Done N, Liu Q, et al. Incidence of pneumococcal disease in children ≤48 months old in the United States: 1998–2019. Vaccine. Published online March 1, 2024. doi: 10.1016/j.vaccine.2024.03.013     
⁵Clinical overview of pneumococcal disease. Centers for Disease Control and Prevention. February 6, 2024. Accessed May 22, 2024. https://www.cdc.gov/pneumococcal/hcp/clinical-overview/     
⁶Wasserman MD, Perdrizet J, Grant L, et al. Clinical and economic burden of pneumococcal disease due to serotypes contained in current and investigational pneumococcal conjugate vaccines in children under five years of age. Infect Dis Ther. 2021;10(4):2701-2720. doi:10.1007/s40121-021-00544-1     
⁷Centers for Disease Control and Prevention (CDC). Visualization – Based on 1998-2022 serotype data for invasive pneumococcal disease cases by age group from Active Bacterial Core surveillance (ABCs). Updated July 22, 2024. Accessed August 30, 2024. https://data.cdc.gov/Public-Health-Surveillance/1998-2022-Serotype-Data-for-Invasive-Pneumococcal-/qvzb-qs6p/about_data     
⁸Varghese J, Chochua S, Tran T, et al. Multistate population and whole genome sequence-based strain surveillance of invasive pneumococci recovered in the USA during 2017. Clin Microbiol Infect. 2020;26(4):512.e1-512.e10. doi:10.1016/j.cmi.2019.09.008     
⁹Azarian T, Mitchell PK, Georgieva M, et al. Global emergence and population dynamics of divergent serotype 3 CC180 pneumococci. PLoS Pathog. 2018;14(11):e1007438. doi:10.1371/journal.ppat.1007438     
¹⁰Hu T, Weiss T, Owusu-Edusei K, Petigara T. Health and economic burden associated with 15-valent pneumococcal conjugate vaccine serotypes in children in the United States. J Med Econ. 2020;23(12):1653-1660. doi:10.1080/13696998.2020.184021613     
¹¹Active Bacterial Core surveillance (ABCs) report, Emerging Infections Program network, Streptococcus pneumoniae, 2022. Centers for Disease Control and Prevention. Updated July 5, 2024. Accessed October 15, 2024. https://www.cdc.gov/abcs/downloads/SPN_Surveillance_Report_2022.pdf     
¹²Recommended child and adolescent immunization schedule for ages 18 years or younger, United States, 2025. Centers for Disease Control and Prevention. Addendum updated November 21, 2024. Accessed November 25, 2024. https://www.cdc.gov/vaccines/hcp/imz-schedules/downloads/child/0-18yrs-child-combined-schedule.pdf     
¹³Hill HA, et al. Decline in Vaccination Coverage by Age 24 Months and Vaccination Inequities Among Children Born in 2020 and 2021 — National Immunization Survey-Child, United States, 2021–2023. MMWR Morb Mortal Wkly Rep, pages 844–853.   
¹⁴Feemster K, Weaver J, Buchwald U, Banniettis N, Cox KS, McIntosh ED, Spoulou V. Pneumococcal Vaccine Breakthrough and Failure in Infants and Children: A Narrative Review. Vaccines (Basel). 2023 Nov 24;11(12):1750. doi:10.3390/vaccines11121750. PMID: 38140155; PMCID: PMC10747311.     
¹⁵Recommendations to assure the quality, safety and efficacy of pneumoccoccal conjugate vaccines. Annex 3. TRS no 977. World Health Organization. October 19, 2013. Accessed October 31, 2024. https://www.who.int/publications/m/item/pneumococcal-conjugate-vaccines-annex3-trs-977
¹⁶Guidelines on clinical evaluation of vaccines: regulatory expectations. Annex 9. TRA No 924.World Health Organization. Last reviewed October 21, 2020. Accessed October 31, 2024. https://www.who.int/publications/m/item/WHO-TRS-1004-web-annex-9
¹⁷Prevnar 13. Prescribing Information. Pfizer; 2019.     
¹⁸Luck JN, Tettelin H, Orihuela CJ. Sugar-Coated Killer: Serotype 3 Pneumococcal Disease. Front Cell Infect Microbiol. 2020;10:613287. Published 2020 Dec 23. doi:10.3389/fcimb.2020.613287     
¹⁹VAXNEUVANCE. Prescribing Information. Merck & Co., Inc., 2024.     
²⁰Moraes-Pinto MI, Suano-Souza F, Aranda CS. Immune system: development and acquisition of immunological competence. J Pediatr (Rio J). 2021;97(S1):S59-S66. doi:10.1016/j.jped.2020.10.006     
²¹Wodi AP, Morelli V. Epidemiology and Prevention of Vaccine-Preventable Diseases (Pink Book). 14th edition. Chapter 1: Principles of vaccination. Centers for Disease Control and Prevention. Last reviewed March 2024. Accessed May 9, 2024. https://www.cdc.gov/pinkbook/hcp/table-of-contents/chapter-1-principles-of-vaccination.html     
²²Pneumococcal vaccination. Centers for Disease Control and Prevention. Last reviewed September 12, 2024. Accessed September 30, 2024. https://www.cdc.gov/pneumococcal/vaccines/index.html 
²³Lupinacci R, Rupp R, Wittawatmongkol O, et al. A phase 3, multicenter, randomized, double-blind, active-comparator-controlled study to evaluate the safety, tolerability, and immunogenicity of a 4-dose regimen of V114, a 15-valent pneumococcal conjugate vaccine, in healthy infants (PNEU-PED). Vaccine. 2023;41(5):1142-1152. doi:10.1016/j.vaccine.2022.12.054 
²⁴Prevnar 20. Prescribing Information. Pfizer; 2023. 

Copyright © 2025 Frontline Medical Communications Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form, by any means, without prior written permission of the Publisher. Frontline Medical Communications Inc. will not assume responsibility for damages, loss, or claims of any kind arising from or related to the information contained in this publication, including any claims related to the products, drugs, or services mentioned herein. The opinions expressed in this publication do not necessarily reflect the views of the Publisher. All other trademarks are property of their respective owners.

Neither the editors of Pediatric News nor the Editorial Advisory Board nor the reporting staff contributed to this content.

US-PVC-01998 03/25

      Invasive pneumococcal disease (IPD) remains a serious health threat for infants and can result in hospitalizations, serious complications, or even death.^1-3 IPD rates peak at a critical stage in a child’s immune development, when maternal antibody protection wanes and the child has not yet received or is in the process of receiving their primary vaccination series.⁴ Pneumococcal vaccination is especially important during this vulnerable period to help protect against potentially severe consequences from IPD.^2,4,5                  

     Over the last 25 years, the widespread adoption of pneumococcal conjugate vaccines (PCVs) in children has led to a reduction in the spread of many different types of pneumococcal bacteria – referred to as serotypes.² Although these vaccines have helped reduce the burden of disease, pneumococcal disease remains an issue, with specific serotypes presenting a greater threat to children’s health.^6-10

Understanding the burden of IPD in children

     According to the Centers for Disease Control and Prevention (CDC), the incidence of IPD is highest in the first year of life,^3,* and the death rate due to IPD is higher in infants than in any other pediatric age group.^11,† Infants' immune systems are still developing in the first year of life; therefore, protection during this time is critical.^3,4,11 

     The CDC recommends routine pediatric pneumococcal vaccination as a four-dose series at months two, four, and six with a booster administered between 12-15 months.¹² Despite the risks associated with invasive pneumococcal disease, some children do not receive all four doses.^1-3,13 Many factors can contribute to incomplete childhood immunization coverage, including ethnicity, geographic location, and socioeconomic status.¹⁴ In fact, up to one in five babies within the Vaccines for Children Program have received only three of the four recommended PCV doses by two years of age, according to a CDC Morbidity and Mortality Weekly Report from 2021-2023.^12,13 The immune response generated after the third dose of a pneumococcal conjugate vaccine is important when evaluating protection against IPD, especially for the children who don't receive their fourth dose.^12,15,16                 

     Additionally, certain serotypes, like Serotype 3, are responsible for more IPD cases and are associated with higher morbidity and mortality rates in children.^7-10,a Despite being included in PCVs for over a decade, Serotype 3 continues to be a leading cause of IPD in children under five, as shown in a pooled analysis of national-level CDC data from 2018-2022.^7,17 This particular serotype has resisted antibody-mediated clearance and continues to be associated with adverse effects.¹⁸

What should pediatricians consider when it comes to protecting children from IPD?

     When it comes to protecting against IPD, it's important to consider factors in addition to the number of serotypes covered by a vaccine, such as early and robust protection against key serotypes that cause pediatric IPD in the first year of life.^2,7,10,19

     VAXNEUVANCE^® (Pneumococcal 15-valent Conjugate Vaccine) is a pediatric pneumococcal conjugate vaccine that can help deliver strong protection against key disease-causing serotypes during infancy, when the threat of IPD is the highest.^{2,3,7,10,19-21}

Indications and Usage           

     VAXNEUVANCE is indicated for active immunization for the prevention of invasive disease caused by Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F in individuals 6 weeks of age and older. 

Select Safety Information          

     Do not administer VAXNEUVANCE to individuals with a severe allergic reaction (eg, anaphylaxis) to any component of VAXNEUVANCE or to diphtheria toxoid.

     Some individuals with altered immunocompetence, including those receiving immunosuppressive therapy, may have a reduced immune response to VAXNEUVANCE.

     Apnea following intramuscular vaccination has been observed in some infants born prematurely. Vaccination of premature infants should be based on the infant’s medical status and the potential benefits and possible risks.

(Select Safety Information for VAXNEUVANCE continues below.)

     VAXNEUVANCE delivers robust immune responses at seven months, following the third dose, for three key disease-causing serotypes: 3, 22F and 33F.^7,10,19,b,c Clinical data showed that immune responses for VAXNEUVANCE were superior to PCV13 (pneumococcal 13-valent conjugate vaccine) for those three critical serotypes^2,7,10,19,d and were comparable for the 12 shared serotypes between the vaccines.¹⁹

     Further, VAXNEUVANCE showcased superior immune responses against Serotype 3 after the third dose with an immunoglobulin G (IgG) geometric mean concentrations (GMCs) response rate of 93.1% compared to PCV13, which demonstrated a 74% response rate.^19,b

     Although completing the full recommended immunization series remains the best way to help maximize protection,^12,22 many children still receive fewer than the recommended four doses of a PCV.^12,13 It is important to consider a vaccine that targets problematic serotypes and provides robust immune responses after three doses  – of the four dose series – to help protect this vulnerable population from IPD.^{3,4,7,10,11,19}

     VAXNEUVANCE can help prevent pediatric IPD in the first year of life and beyond and is an important option for pediatricians to consider for their appropriate patients.^7,19

###

Select Safety Information (continued)         

     The most commonly reported solicited adverse reactions in children vaccinated at 2, 4, 6, and 12 through 15 months of age, provided as a range across the 4-dose series, were: irritability (57.3% to 63.4%), somnolence (24.2% to 47.5%), injection-site pain (25.9% to 40.3%), fever ≥38.0°C (13.3% to 20.4%), decreased appetite (14.1% to 19.0%), injection-site induration (13.2% to 15.4%), injection-site erythema (13.7% to 21.4%) and injection-site swelling (11.3% to 13.4%).

     The most commonly reported solicited adverse reactions in children 2 through 17 years of age vaccinated with a single dose were: injection-site pain (54.8%), myalgia (23.7%), injection-site swelling (20.9%), injection-site erythema (19.2%), fatigue (15.8%), headache (11.9%) and injection-site induration (6.8%).

     Vaccination with VAXNEUVANCE may not protect all vaccine recipients.

Before administering VAXNEUVANCE, please read the accompanying Prescribing Information. The Patient Information also is available.

* Based on pooled analysis of national-level CDC ABC surveillance data from 2018–2022, representing ~35 million people surveyed annually in 10 states across the US. IPD incidence rates were 10.3 in <1 year, 8.2 in 1 year, 4.0 in 2–4 years, 5.0 in 1–4 years, and 1.3 in 5–17 years (Regional variations may exist).³

† Based on national-level CDC ABC surveillance data from 2022, representing ~35 million people in 10 states across the US (Regional variations may exist).¹¹ 

Key Study Details 

GMC Ratios Postdose 3^c

Primary endpoint: VAXNEUVANCE delivered comparable immune responses for 12 of the 13 shared serotypes found in PCV13. Shared Serotype 6A was just below the noninferiority criteria by a small margin, with the lower bound of the 2-sided 95% CI for the GMC ratio being 0.48 vs >0.5.^19,23

Study Design

Study 8 was a pivotal, double-blind, active comparator-controlled study in which participants were randomized to receive VAXNEUVANCE (N=860) or PCV13 (N=860) in a 4-dose series. The first 3 doses were administered to infants at 2, 4, and 6 months of age and the fourth dose was administered to children at 12 through 15 months of age. Participants also received other licensed pediatric vaccines concomitantly. Immune responses were measured by IgG response rates, IgG GMCs, and OPA GMTs for all 15 serotypes contained in VAXNEUVANCE.¹⁹

^aBased on a pooled analysis of national-level CDC data from 2018–2021, the top 6 IPD-causing serotypes in children under 5 years of age were 15C, 33F, 19F, 3, 23B, and 22F. Serotypes 15C and 23B are not included in any recommended pediatric PCV in the US.^{7,17,19,22,24           
b}Postdose 3 superiority was demonstrated based on measurements taken 30 days after the 6-month dose (at 7 months).^{19           
c}Measurements were taken 30 days postdose specified.^{19           
d}Secondary endpoint: Postdose 3 IgG response rate percentage point difference vs PCV13 (95% CI): for Serotype 3, 19.1 (14.4, 24.0); for Serotype 22F, 8.1 (5.1, 11.5); for Serotype 33F, -5.1 (-9.5, -0.7).^19,23

Randomized controlled trials assessing the clinical efficacy of VAXNEUVANCE compared to PCV13 have not been conducted.¹⁹

References:

¹Dalton M. Pneumoccal disease. National Foundation for Infectious Diseases. Published July 2024. https://www.nfid.org/infectious-disease/pneumococcal/     
²Gierke R, Wodi P, Kobayashi M. Epidemiology and Prevention of Vaccine-Preventable Diseases (Pink Book). 14th edition. Chapter 17: Pneumococcal disease. Epidemiology and Prevention of Vaccine-Preventable Diseases. Published May 1, 2024. Accessed December 10, 2024. https://www.cdc.gov/pinkbook/hcp/table-of-contents/chapter-17-pneumococcal-disease.html     
³Data available on request from the Merck National Service Center via email at [email protected]. Please specify information package US-PVC-02072.     
⁴Mohanty S, Done N, Liu Q, et al. Incidence of pneumococcal disease in children ≤48 months old in the United States: 1998–2019. Vaccine. Published online March 1, 2024. doi: 10.1016/j.vaccine.2024.03.013     
⁵Clinical overview of pneumococcal disease. Centers for Disease Control and Prevention. February 6, 2024. Accessed May 22, 2024. https://www.cdc.gov/pneumococcal/hcp/clinical-overview/     
⁶Wasserman MD, Perdrizet J, Grant L, et al. Clinical and economic burden of pneumococcal disease due to serotypes contained in current and investigational pneumococcal conjugate vaccines in children under five years of age. Infect Dis Ther. 2021;10(4):2701-2720. doi:10.1007/s40121-021-00544-1     
⁷Centers for Disease Control and Prevention (CDC). Visualization – Based on 1998-2022 serotype data for invasive pneumococcal disease cases by age group from Active Bacterial Core surveillance (ABCs). Updated July 22, 2024. Accessed August 30, 2024. https://data.cdc.gov/Public-Health-Surveillance/1998-2022-Serotype-Data-for-Invasive-Pneumococcal-/qvzb-qs6p/about_data     
⁸Varghese J, Chochua S, Tran T, et al. Multistate population and whole genome sequence-based strain surveillance of invasive pneumococci recovered in the USA during 2017. Clin Microbiol Infect. 2020;26(4):512.e1-512.e10. doi:10.1016/j.cmi.2019.09.008     
⁹Azarian T, Mitchell PK, Georgieva M, et al. Global emergence and population dynamics of divergent serotype 3 CC180 pneumococci. PLoS Pathog. 2018;14(11):e1007438. doi:10.1371/journal.ppat.1007438     
¹⁰Hu T, Weiss T, Owusu-Edusei K, Petigara T. Health and economic burden associated with 15-valent pneumococcal conjugate vaccine serotypes in children in the United States. J Med Econ. 2020;23(12):1653-1660. doi:10.1080/13696998.2020.184021613     
¹¹Active Bacterial Core surveillance (ABCs) report, Emerging Infections Program network, Streptococcus pneumoniae, 2022. Centers for Disease Control and Prevention. Updated July 5, 2024. Accessed October 15, 2024. https://www.cdc.gov/abcs/downloads/SPN_Surveillance_Report_2022.pdf     
¹²Recommended child and adolescent immunization schedule for ages 18 years or younger, United States, 2025. Centers for Disease Control and Prevention. Addendum updated November 21, 2024. Accessed November 25, 2024. https://www.cdc.gov/vaccines/hcp/imz-schedules/downloads/child/0-18yrs-child-combined-schedule.pdf     
¹³Hill HA, et al. Decline in Vaccination Coverage by Age 24 Months and Vaccination Inequities Among Children Born in 2020 and 2021 — National Immunization Survey-Child, United States, 2021–2023. MMWR Morb Mortal Wkly Rep, pages 844–853.   
¹⁴Feemster K, Weaver J, Buchwald U, Banniettis N, Cox KS, McIntosh ED, Spoulou V. Pneumococcal Vaccine Breakthrough and Failure in Infants and Children: A Narrative Review. Vaccines (Basel). 2023 Nov 24;11(12):1750. doi:10.3390/vaccines11121750. PMID: 38140155; PMCID: PMC10747311.     
¹⁵Recommendations to assure the quality, safety and efficacy of pneumoccoccal conjugate vaccines. Annex 3. TRS no 977. World Health Organization. October 19, 2013. Accessed October 31, 2024. https://www.who.int/publications/m/item/pneumococcal-conjugate-vaccines-annex3-trs-977
¹⁶Guidelines on clinical evaluation of vaccines: regulatory expectations. Annex 9. TRA No 924.World Health Organization. Last reviewed October 21, 2020. Accessed October 31, 2024. https://www.who.int/publications/m/item/WHO-TRS-1004-web-annex-9
¹⁷Prevnar 13. Prescribing Information. Pfizer; 2019.     
¹⁸Luck JN, Tettelin H, Orihuela CJ. Sugar-Coated Killer: Serotype 3 Pneumococcal Disease. Front Cell Infect Microbiol. 2020;10:613287. Published 2020 Dec 23. doi:10.3389/fcimb.2020.613287     
¹⁹VAXNEUVANCE. Prescribing Information. Merck & Co., Inc., 2024.     
²⁰Moraes-Pinto MI, Suano-Souza F, Aranda CS. Immune system: development and acquisition of immunological competence. J Pediatr (Rio J). 2021;97(S1):S59-S66. doi:10.1016/j.jped.2020.10.006     
²¹Wodi AP, Morelli V. Epidemiology and Prevention of Vaccine-Preventable Diseases (Pink Book). 14th edition. Chapter 1: Principles of vaccination. Centers for Disease Control and Prevention. Last reviewed March 2024. Accessed May 9, 2024. https://www.cdc.gov/pinkbook/hcp/table-of-contents/chapter-1-principles-of-vaccination.html     
²²Pneumococcal vaccination. Centers for Disease Control and Prevention. Last reviewed September 12, 2024. Accessed September 30, 2024. https://www.cdc.gov/pneumococcal/vaccines/index.html 
²³Lupinacci R, Rupp R, Wittawatmongkol O, et al. A phase 3, multicenter, randomized, double-blind, active-comparator-controlled study to evaluate the safety, tolerability, and immunogenicity of a 4-dose regimen of V114, a 15-valent pneumococcal conjugate vaccine, in healthy infants (PNEU-PED). Vaccine. 2023;41(5):1142-1152. doi:10.1016/j.vaccine.2022.12.054 
²⁴Prevnar 20. Prescribing Information. Pfizer; 2023. 

Copyright © 2025 Frontline Medical Communications Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form, by any means, without prior written permission of the Publisher. Frontline Medical Communications Inc. will not assume responsibility for damages, loss, or claims of any kind arising from or related to the information contained in this publication, including any claims related to the products, drugs, or services mentioned herein. The opinions expressed in this publication do not necessarily reflect the views of the Publisher. All other trademarks are property of their respective owners.

Neither the editors of Pediatric News nor the Editorial Advisory Board nor the reporting staff contributed to this content.

US-PVC-01998 03/25

In patients with gastroesophageal reflux (GERD) symptoms undergoing screening upper endoscopy, adjunctive use of wide-area transepithelial sampling with 3D computer-assisted analysis (WATS-3D) increases detection of Barrett’s esophagus (BE) and dysplasia, new research showed. 

Compared with forceps biopsies (FB) alone, the addition of WATS-3D led to confirmation of BE in an additional one fifth of patients, roughly doubled dysplasia diagnoses, and influenced clinical management in the majority of patients. 

“The big take-home point here is that the use of WATS-3D brushing along with conventional biopsies increases the likelihood that intestinal metaplasia will be identified,” first author Nicholas Shaheen, MD, MPH, AGAF, with the Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine at Chapel Hill, North Carolina, told GI & Hepatology News. 

“Almost 20% of patients who harbor BE were only identified by WATS-3D and might have otherwise gone undiagnosed had only forceps biopsies been performed,” Shaheen said. 

The study was published in The American Journal of Gastroenterology.

 

Beyond Traditional Biopsies

BE develops as a complication of chronic GERD and is the chief precursor to esophageal adenocarcinoma. Early detection of BE and dysplasia is crucial to enable timely intervention. 

The current gold standard for BE screening involves upper endoscopy with FB following the Seattle protocol, which consists of four-quadrant biopsies from every 1-2 cm of areas of columnar-lined epithelium (CLE) to confirm the presence of intestinal metaplasia. However, this protocol is prone to sampling errors and high false-negative rates, leading to repeat endoscopy, the study team pointed out. 

WATS-3D (CDx Diagnostics) is a complementary technique designed to improve diagnostic yield by using brush biopsy to sample more tissue than routine biopsies.

WATS-3D has been shown to increase detection of dysplasia in patients with BE undergoing surveillance for BE, but less is known about the value of WATS-3D for BE screening in a community-based cohort of patients with GERD. 

To investigate, Shaheen and colleagues studied 23,933 consecutive patients enrolled in a prospective observational registry assessing the utility of WATS-3D in the screening of symptomatic GERD patients for BE. 

Patients had both WATS-3D and FB in the same endoscopic session. No patient had a history of BE, intestinal metaplasia or dysplasia in esophageal mucosa, or esophageal surgery, endoscopic ablation or endoscopic mucosal resection prior to enrollment. 

Overall, 6829 patients (29%) met endoscopic criteria for BE (≥ 1 cm esophageal CLE with accompanying biopsies showing intestinal metaplasia). 

Of these, 2878 (42%) had intestinal metaplasia identified by either FB or WATS-3D, but 19.3% had their BE diagnosis confirmed solely on the basis of WATS-3D findings. 

Among patients who fulfilled the endoscopic criteria for BE, the adjunctive yield of WATS-3D was 76.5% and the absolute yield was 18.1%.

Of the 240 (1.0%) patients with dysplasia, 107 (45%) were found solely by WATS-3D.

 

‘Clinically Valuable Adjunct’

Among patients with positive WATS-3D but negative FB results, clinical management changed in 90.7% of cases, mostly involving initiation or modification of surveillance and proton pump inhibitor therapy. 

These results suggest that WATS-3D is a “clinically valuable adjunct” to FB for the diagnosis of BE when used as a screening tool in symptomatic GERD patients and particularly in patients with endoscopic evidence of > 1 cm esophageal columnar-lined epithelium, the study team wrote. 

Adjunctive use of WATS-3D when BE is suspected “may save endoscopies and lead to quicker, more accurate diagnoses,” they added. 

The investigators said a limitation of the study is the lack of central pathology review, potentially leading to diagnostic variability. They also noted that over half of the detected dysplasia cases were crypt dysplasia or indefinite for dysplasia, raising concerns about clinical significance. 

Reached for comment, Philip O. Katz, MD, AGAF, professor of medicine and director of the GI Function Laboratories, Weill Cornell Medicine in New York, said he’s been using WATS for more than a decade as an adjunct to standard biopsy in patients undergoing screening and surveillance for BE and finds it clinically helpful in managing his patients.

This new study provides “further information that WATS added to biopsy that has been traditionally done with the Seattle protocol increases the yield of intestinal metaplasia and likely dysplasia in patients being screened for Barrett’s,” Katz, who wasn’t involved in the study, told GI & Hepatology News.

Funding for the study was provided by CDx Diagnostics. Shaheen and several coauthors disclosed relationships with the company. Katz disclosed relationships (consultant/advisor) for Phathom Pharmaceuticals and Sebella.

A version of this article appeared on Medscape.com.

In patients with gastroesophageal reflux (GERD) symptoms undergoing screening upper endoscopy, adjunctive use of wide-area transepithelial sampling with 3D computer-assisted analysis (WATS-3D) increases detection of Barrett’s esophagus (BE) and dysplasia, new research showed. 

Compared with forceps biopsies (FB) alone, the addition of WATS-3D led to confirmation of BE in an additional one fifth of patients, roughly doubled dysplasia diagnoses, and influenced clinical management in the majority of patients. 

“The big take-home point here is that the use of WATS-3D brushing along with conventional biopsies increases the likelihood that intestinal metaplasia will be identified,” first author Nicholas Shaheen, MD, MPH, AGAF, with the Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine at Chapel Hill, North Carolina, told GI & Hepatology News. 

“Almost 20% of patients who harbor BE were only identified by WATS-3D and might have otherwise gone undiagnosed had only forceps biopsies been performed,” Shaheen said. 

The study was published in The American Journal of Gastroenterology.

 

Beyond Traditional Biopsies

BE develops as a complication of chronic GERD and is the chief precursor to esophageal adenocarcinoma. Early detection of BE and dysplasia is crucial to enable timely intervention. 

The current gold standard for BE screening involves upper endoscopy with FB following the Seattle protocol, which consists of four-quadrant biopsies from every 1-2 cm of areas of columnar-lined epithelium (CLE) to confirm the presence of intestinal metaplasia. However, this protocol is prone to sampling errors and high false-negative rates, leading to repeat endoscopy, the study team pointed out. 

WATS-3D (CDx Diagnostics) is a complementary technique designed to improve diagnostic yield by using brush biopsy to sample more tissue than routine biopsies.

WATS-3D has been shown to increase detection of dysplasia in patients with BE undergoing surveillance for BE, but less is known about the value of WATS-3D for BE screening in a community-based cohort of patients with GERD. 

To investigate, Shaheen and colleagues studied 23,933 consecutive patients enrolled in a prospective observational registry assessing the utility of WATS-3D in the screening of symptomatic GERD patients for BE. 

Patients had both WATS-3D and FB in the same endoscopic session. No patient had a history of BE, intestinal metaplasia or dysplasia in esophageal mucosa, or esophageal surgery, endoscopic ablation or endoscopic mucosal resection prior to enrollment. 

Overall, 6829 patients (29%) met endoscopic criteria for BE (≥ 1 cm esophageal CLE with accompanying biopsies showing intestinal metaplasia). 

Of these, 2878 (42%) had intestinal metaplasia identified by either FB or WATS-3D, but 19.3% had their BE diagnosis confirmed solely on the basis of WATS-3D findings. 

Among patients who fulfilled the endoscopic criteria for BE, the adjunctive yield of WATS-3D was 76.5% and the absolute yield was 18.1%.

Of the 240 (1.0%) patients with dysplasia, 107 (45%) were found solely by WATS-3D.

 

‘Clinically Valuable Adjunct’

Among patients with positive WATS-3D but negative FB results, clinical management changed in 90.7% of cases, mostly involving initiation or modification of surveillance and proton pump inhibitor therapy. 

These results suggest that WATS-3D is a “clinically valuable adjunct” to FB for the diagnosis of BE when used as a screening tool in symptomatic GERD patients and particularly in patients with endoscopic evidence of > 1 cm esophageal columnar-lined epithelium, the study team wrote. 

Adjunctive use of WATS-3D when BE is suspected “may save endoscopies and lead to quicker, more accurate diagnoses,” they added. 

The investigators said a limitation of the study is the lack of central pathology review, potentially leading to diagnostic variability. They also noted that over half of the detected dysplasia cases were crypt dysplasia or indefinite for dysplasia, raising concerns about clinical significance. 

Reached for comment, Philip O. Katz, MD, AGAF, professor of medicine and director of the GI Function Laboratories, Weill Cornell Medicine in New York, said he’s been using WATS for more than a decade as an adjunct to standard biopsy in patients undergoing screening and surveillance for BE and finds it clinically helpful in managing his patients.

This new study provides “further information that WATS added to biopsy that has been traditionally done with the Seattle protocol increases the yield of intestinal metaplasia and likely dysplasia in patients being screened for Barrett’s,” Katz, who wasn’t involved in the study, told GI & Hepatology News.

Funding for the study was provided by CDx Diagnostics. Shaheen and several coauthors disclosed relationships with the company. Katz disclosed relationships (consultant/advisor) for Phathom Pharmaceuticals and Sebella.

A version of this article appeared on Medscape.com.

In patients with gastroesophageal reflux (GERD) symptoms undergoing screening upper endoscopy, adjunctive use of wide-area transepithelial sampling with 3D computer-assisted analysis (WATS-3D) increases detection of Barrett’s esophagus (BE) and dysplasia, new research showed. 

Compared with forceps biopsies (FB) alone, the addition of WATS-3D led to confirmation of BE in an additional one fifth of patients, roughly doubled dysplasia diagnoses, and influenced clinical management in the majority of patients. 

“The big take-home point here is that the use of WATS-3D brushing along with conventional biopsies increases the likelihood that intestinal metaplasia will be identified,” first author Nicholas Shaheen, MD, MPH, AGAF, with the Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine at Chapel Hill, North Carolina, told GI & Hepatology News. 

“Almost 20% of patients who harbor BE were only identified by WATS-3D and might have otherwise gone undiagnosed had only forceps biopsies been performed,” Shaheen said. 

The study was published in The American Journal of Gastroenterology.

 

Beyond Traditional Biopsies

BE develops as a complication of chronic GERD and is the chief precursor to esophageal adenocarcinoma. Early detection of BE and dysplasia is crucial to enable timely intervention. 

The current gold standard for BE screening involves upper endoscopy with FB following the Seattle protocol, which consists of four-quadrant biopsies from every 1-2 cm of areas of columnar-lined epithelium (CLE) to confirm the presence of intestinal metaplasia. However, this protocol is prone to sampling errors and high false-negative rates, leading to repeat endoscopy, the study team pointed out. 

WATS-3D (CDx Diagnostics) is a complementary technique designed to improve diagnostic yield by using brush biopsy to sample more tissue than routine biopsies.

WATS-3D has been shown to increase detection of dysplasia in patients with BE undergoing surveillance for BE, but less is known about the value of WATS-3D for BE screening in a community-based cohort of patients with GERD. 

To investigate, Shaheen and colleagues studied 23,933 consecutive patients enrolled in a prospective observational registry assessing the utility of WATS-3D in the screening of symptomatic GERD patients for BE. 

Patients had both WATS-3D and FB in the same endoscopic session. No patient had a history of BE, intestinal metaplasia or dysplasia in esophageal mucosa, or esophageal surgery, endoscopic ablation or endoscopic mucosal resection prior to enrollment. 

Overall, 6829 patients (29%) met endoscopic criteria for BE (≥ 1 cm esophageal CLE with accompanying biopsies showing intestinal metaplasia). 

Of these, 2878 (42%) had intestinal metaplasia identified by either FB or WATS-3D, but 19.3% had their BE diagnosis confirmed solely on the basis of WATS-3D findings. 

Among patients who fulfilled the endoscopic criteria for BE, the adjunctive yield of WATS-3D was 76.5% and the absolute yield was 18.1%.

Of the 240 (1.0%) patients with dysplasia, 107 (45%) were found solely by WATS-3D.

 

‘Clinically Valuable Adjunct’

Among patients with positive WATS-3D but negative FB results, clinical management changed in 90.7% of cases, mostly involving initiation or modification of surveillance and proton pump inhibitor therapy. 

These results suggest that WATS-3D is a “clinically valuable adjunct” to FB for the diagnosis of BE when used as a screening tool in symptomatic GERD patients and particularly in patients with endoscopic evidence of > 1 cm esophageal columnar-lined epithelium, the study team wrote. 

Adjunctive use of WATS-3D when BE is suspected “may save endoscopies and lead to quicker, more accurate diagnoses,” they added. 

The investigators said a limitation of the study is the lack of central pathology review, potentially leading to diagnostic variability. They also noted that over half of the detected dysplasia cases were crypt dysplasia or indefinite for dysplasia, raising concerns about clinical significance. 

Reached for comment, Philip O. Katz, MD, AGAF, professor of medicine and director of the GI Function Laboratories, Weill Cornell Medicine in New York, said he’s been using WATS for more than a decade as an adjunct to standard biopsy in patients undergoing screening and surveillance for BE and finds it clinically helpful in managing his patients.

This new study provides “further information that WATS added to biopsy that has been traditionally done with the Seattle protocol increases the yield of intestinal metaplasia and likely dysplasia in patients being screened for Barrett’s,” Katz, who wasn’t involved in the study, told GI & Hepatology News.

Funding for the study was provided by CDx Diagnostics. Shaheen and several coauthors disclosed relationships with the company. Katz disclosed relationships (consultant/advisor) for Phathom Pharmaceuticals and Sebella.

A version of this article appeared on Medscape.com.

A recent study supports the importance of intensive nutrition therapy in managing patients with alcohol-related acute-on-chronic liver failure (ACLF).

In a randomized controlled trial, compared with standard care, dietitian-supported, intensive nutritional therapy improved survival, reduced frailty, and lowered hospitalization rates in men with alcohol-related ACLF.

The study, performed by a team from the Postgraduate Institute of Medical Education and Research, Chandigarh, India, was published in Clinical Gastroenterology and Hepatology.

ACLF related to alcohol use is associated with poor outcomes due to poor nutritional intake and frailty. Frail patients with ACLF face higher morbidity, mortality, and hospitalization rates than their nonfrail counterparts. However, research on the role of structured nutritional interventions in improving these outcomes is limited.

Patal Giri, MBBS, MD, and colleagues enrolled 70 men with alcohol-related ACLF and frailty (liver frailty index [LFI] > 4.5) in a single-center, open-label study. Half were randomly allocated to an intervention group receiving outpatient intensive nutrition therapy (OINT) plus standard medical treatment (SMT) and half to a control group receiving SMT alone for 3 months.

The intervention group received a monitored high-calorie, high-protein, and salt-restricted diet as prescribed by a dedicated senior liver dietitian. The control group received regular nutritional recommendations and were managed for the ACLF-associated complications, without intervention or guidance by the study team.

After 3 months follow-up, overall survival (the primary outcome) was significantly improved in the OINT group compared with the control group (91.4% vs 57.1%), “suggesting that the improvement in nutrition status is associated with better survival,” the study team noted. Three patients died in the OINT group vs 15 in the SMT group.

OINT also led to a significant improvement in frailty, with LFI scores decreasing by an average of 0.93 in the intervention group vs 0.33 in the control group; 97% of patients improved from frail to prefrail status in the OINT group, whereas only 20% of patients improved in the SMT group.

The mean change in LFI of 0.93 with OINT is “well above the substantially clinically important difference” (change of 0.8) established in a previous study, the authors noted.

Significant improvements in weight and body mass index were also observed in the OINT group relative to the control group.

Liver disease severity, including model for end-stage liver disease (MELD) scores, showed greater improvement in the OINT group than in the control group (−8.7 vs −6.3 points from baseline to 3 months).

During the follow-up period, fewer patients in the intervention group than in the control group required a hospital stay (17% vs 45.7%).

Limitations of the study include the single-center design and the short follow-up period of 3 months, which limits long-term outcome assessment. Further, the study only included patients meeting Asia Pacific Association for Study of Liver criteria for ACLF, which does not include the patients with organ failure as defined by European Association for the Study of the Liver-Chronic Liver Failure Consortium criteria. Patients with ACLF who had more severe disease (MELD score > 30 or AARC > 10) were also not included.

Despite these limitations, the authors said their study showed that “dietician-monitored goal-directed nutrition therapy is very important in the management of patients with alcohol-related ACLF along with SMT.”

 

Confirmatory Data 

Reached for comment, Katherine Patton, MEd, RD, a registered dietitian with the Center for Human Nutrition at Cleveland Clinic, Cleveland, Ohio, said it’s well known that the ACLF patient population has a “very high rate of morbidity and mortality and their quality of life tends to be poor due to their frailty. It is also fairly well-known that proper nutrition therapy can improve outcomes, however barriers to adequate nutrition include decreased appetite, nausea, pain, altered taste, and early satiety from ascites.”

“Hepatologists are likely stressing the importance of adequate protein energy intake and doctors may refer patients to an outpatient dietitian, but it is up to the patient to make that appointment and act on the recommendations,” Patton told GI & Hepatology News.

“If a dietitian works in the same clinic as the hepatologist and patients can be referred and seen the same day, this is ideal. During a hospital admission, protein/calorie intake can be more closely monitored and encouraged by a multi-disciplinary team,” Patton explained.

She cautioned that “the average patient is not familiar with how to apply general calorie and protein goals to their everyday eating habits. This study amplifies the role of a dietitian and what consistent education and resources can do to improve a patient’s quality of life and survival.”

This study had no specific funding. The authors have declared no relevant conflicts of interest. Patton had no relevant disclosures.

A version of this article appeared on Medscape.com.

A recent study supports the importance of intensive nutrition therapy in managing patients with alcohol-related acute-on-chronic liver failure (ACLF).

In a randomized controlled trial, compared with standard care, dietitian-supported, intensive nutritional therapy improved survival, reduced frailty, and lowered hospitalization rates in men with alcohol-related ACLF.

The study, performed by a team from the Postgraduate Institute of Medical Education and Research, Chandigarh, India, was published in Clinical Gastroenterology and Hepatology.

ACLF related to alcohol use is associated with poor outcomes due to poor nutritional intake and frailty. Frail patients with ACLF face higher morbidity, mortality, and hospitalization rates than their nonfrail counterparts. However, research on the role of structured nutritional interventions in improving these outcomes is limited.

Patal Giri, MBBS, MD, and colleagues enrolled 70 men with alcohol-related ACLF and frailty (liver frailty index [LFI] > 4.5) in a single-center, open-label study. Half were randomly allocated to an intervention group receiving outpatient intensive nutrition therapy (OINT) plus standard medical treatment (SMT) and half to a control group receiving SMT alone for 3 months.

The intervention group received a monitored high-calorie, high-protein, and salt-restricted diet as prescribed by a dedicated senior liver dietitian. The control group received regular nutritional recommendations and were managed for the ACLF-associated complications, without intervention or guidance by the study team.

After 3 months follow-up, overall survival (the primary outcome) was significantly improved in the OINT group compared with the control group (91.4% vs 57.1%), “suggesting that the improvement in nutrition status is associated with better survival,” the study team noted. Three patients died in the OINT group vs 15 in the SMT group.

OINT also led to a significant improvement in frailty, with LFI scores decreasing by an average of 0.93 in the intervention group vs 0.33 in the control group; 97% of patients improved from frail to prefrail status in the OINT group, whereas only 20% of patients improved in the SMT group.

The mean change in LFI of 0.93 with OINT is “well above the substantially clinically important difference” (change of 0.8) established in a previous study, the authors noted.

Significant improvements in weight and body mass index were also observed in the OINT group relative to the control group.

Liver disease severity, including model for end-stage liver disease (MELD) scores, showed greater improvement in the OINT group than in the control group (−8.7 vs −6.3 points from baseline to 3 months).

During the follow-up period, fewer patients in the intervention group than in the control group required a hospital stay (17% vs 45.7%).

Limitations of the study include the single-center design and the short follow-up period of 3 months, which limits long-term outcome assessment. Further, the study only included patients meeting Asia Pacific Association for Study of Liver criteria for ACLF, which does not include the patients with organ failure as defined by European Association for the Study of the Liver-Chronic Liver Failure Consortium criteria. Patients with ACLF who had more severe disease (MELD score > 30 or AARC > 10) were also not included.

Despite these limitations, the authors said their study showed that “dietician-monitored goal-directed nutrition therapy is very important in the management of patients with alcohol-related ACLF along with SMT.”

 

Confirmatory Data 

Reached for comment, Katherine Patton, MEd, RD, a registered dietitian with the Center for Human Nutrition at Cleveland Clinic, Cleveland, Ohio, said it’s well known that the ACLF patient population has a “very high rate of morbidity and mortality and their quality of life tends to be poor due to their frailty. It is also fairly well-known that proper nutrition therapy can improve outcomes, however barriers to adequate nutrition include decreased appetite, nausea, pain, altered taste, and early satiety from ascites.”

“Hepatologists are likely stressing the importance of adequate protein energy intake and doctors may refer patients to an outpatient dietitian, but it is up to the patient to make that appointment and act on the recommendations,” Patton told GI & Hepatology News.

“If a dietitian works in the same clinic as the hepatologist and patients can be referred and seen the same day, this is ideal. During a hospital admission, protein/calorie intake can be more closely monitored and encouraged by a multi-disciplinary team,” Patton explained.

She cautioned that “the average patient is not familiar with how to apply general calorie and protein goals to their everyday eating habits. This study amplifies the role of a dietitian and what consistent education and resources can do to improve a patient’s quality of life and survival.”

This study had no specific funding. The authors have declared no relevant conflicts of interest. Patton had no relevant disclosures.

A version of this article appeared on Medscape.com.

A recent study supports the importance of intensive nutrition therapy in managing patients with alcohol-related acute-on-chronic liver failure (ACLF).

In a randomized controlled trial, compared with standard care, dietitian-supported, intensive nutritional therapy improved survival, reduced frailty, and lowered hospitalization rates in men with alcohol-related ACLF.

The study, performed by a team from the Postgraduate Institute of Medical Education and Research, Chandigarh, India, was published in Clinical Gastroenterology and Hepatology.

ACLF related to alcohol use is associated with poor outcomes due to poor nutritional intake and frailty. Frail patients with ACLF face higher morbidity, mortality, and hospitalization rates than their nonfrail counterparts. However, research on the role of structured nutritional interventions in improving these outcomes is limited.

Patal Giri, MBBS, MD, and colleagues enrolled 70 men with alcohol-related ACLF and frailty (liver frailty index [LFI] > 4.5) in a single-center, open-label study. Half were randomly allocated to an intervention group receiving outpatient intensive nutrition therapy (OINT) plus standard medical treatment (SMT) and half to a control group receiving SMT alone for 3 months.

The intervention group received a monitored high-calorie, high-protein, and salt-restricted diet as prescribed by a dedicated senior liver dietitian. The control group received regular nutritional recommendations and were managed for the ACLF-associated complications, without intervention or guidance by the study team.

After 3 months follow-up, overall survival (the primary outcome) was significantly improved in the OINT group compared with the control group (91.4% vs 57.1%), “suggesting that the improvement in nutrition status is associated with better survival,” the study team noted. Three patients died in the OINT group vs 15 in the SMT group.

OINT also led to a significant improvement in frailty, with LFI scores decreasing by an average of 0.93 in the intervention group vs 0.33 in the control group; 97% of patients improved from frail to prefrail status in the OINT group, whereas only 20% of patients improved in the SMT group.

The mean change in LFI of 0.93 with OINT is “well above the substantially clinically important difference” (change of 0.8) established in a previous study, the authors noted.

Significant improvements in weight and body mass index were also observed in the OINT group relative to the control group.

Liver disease severity, including model for end-stage liver disease (MELD) scores, showed greater improvement in the OINT group than in the control group (−8.7 vs −6.3 points from baseline to 3 months).

During the follow-up period, fewer patients in the intervention group than in the control group required a hospital stay (17% vs 45.7%).

Limitations of the study include the single-center design and the short follow-up period of 3 months, which limits long-term outcome assessment. Further, the study only included patients meeting Asia Pacific Association for Study of Liver criteria for ACLF, which does not include the patients with organ failure as defined by European Association for the Study of the Liver-Chronic Liver Failure Consortium criteria. Patients with ACLF who had more severe disease (MELD score > 30 or AARC > 10) were also not included.

Despite these limitations, the authors said their study showed that “dietician-monitored goal-directed nutrition therapy is very important in the management of patients with alcohol-related ACLF along with SMT.”

 

Confirmatory Data 

Reached for comment, Katherine Patton, MEd, RD, a registered dietitian with the Center for Human Nutrition at Cleveland Clinic, Cleveland, Ohio, said it’s well known that the ACLF patient population has a “very high rate of morbidity and mortality and their quality of life tends to be poor due to their frailty. It is also fairly well-known that proper nutrition therapy can improve outcomes, however barriers to adequate nutrition include decreased appetite, nausea, pain, altered taste, and early satiety from ascites.”

“Hepatologists are likely stressing the importance of adequate protein energy intake and doctors may refer patients to an outpatient dietitian, but it is up to the patient to make that appointment and act on the recommendations,” Patton told GI & Hepatology News.

“If a dietitian works in the same clinic as the hepatologist and patients can be referred and seen the same day, this is ideal. During a hospital admission, protein/calorie intake can be more closely monitored and encouraged by a multi-disciplinary team,” Patton explained.

She cautioned that “the average patient is not familiar with how to apply general calorie and protein goals to their everyday eating habits. This study amplifies the role of a dietitian and what consistent education and resources can do to improve a patient’s quality of life and survival.”

This study had no specific funding. The authors have declared no relevant conflicts of interest. Patton had no relevant disclosures.

A version of this article appeared on Medscape.com.

Results from the PHENIX-I trial support skipping pelvic lymphadenectomy in women with early cervical cancer who have a negative sentinel lymph node biopsy.

Omitting pelvic lymphadenectomy in these patients “did not compromise disease-free survival and potentially [led to] improved overall survival,” reported lead investigator Jihong Liu, MD, gynecologic oncologist, Sun Yat-sen University Cancer Center, Guangzhou, China.

Forgoing the additional procedure also decreased the incidence of retroperitoneal lymph node recurrence and adverse events and demonstrated superior surgical outcomes including shorter operative duration, reduced blood loss, and a lower morbidity.

Liu reported the PHENIX-I results at this year’s Society of Gynecologic Oncology Annual Meeting on Women’s Cancers (SGO) 2025.

Pelvic lymphadenectomy has been part of standard care for early-stage cervical cancer for over a century, even though the incidence of lymph node metastasis in early-stage cervical cancer is relatively low. Overtreatment and increased morbidity have been notable drawbacks of the procedure.

It may be possible to forgo pelvic lymphadenectomy in early-stage cervical cancer when sentinel lymph node biopsy findings are negative, but evidence from randomized controlled trials are lacking, Liu explained.

The PHENIX-I trial prospectively assessed survival outcomes among patients who received pelvic lymphadenectomy and those who did not. More specifically, all patients underwent sentinel lymph node biopsy and patients with negative lymph nodes were then intraoperatively randomized (1:1) to undergo pelvic lymphadenectomy (417 patients) or not (416 patients).

The multicenter, randomized controlled trial involved patients undergoing radical hysterectomy for stage IA1 (lymphovascular invasion), IA2, IB1, IB2 or IIA1 cervical cancer with tumor size not exceeding 3 cm.

“The only difference between the two groups was that patients in the experimental arm did not have pelvic lymphadenectomy,” Liu said.

Liu and colleagues reported that 23 patients (2.8%) had a positive lymph node on postoperative pathology examination. The rate of false-negative sentinel lymph node biopsy was < 1%. About half the patients in both groups received postoperative adjuvant therapy, and there was no significant between-group difference in the rates and time to initiate adjuvant therapy.

Overall, about 3.85% of patients (n = 16) in the biopsy-only group had a recurrence compared with 6.24% (n = 26) in the pelvic lymphadenectomy group at a median follow-up of 50 months.

But no patients in the biopsy-only group had a recurrence in the retroperitoneal lymph nodes compared with 9 patients in the pelvic lymphadenectomy group.

The 3-year disease-free survival (primary endpoint) rates were similar between the two groups — 96.8% in the biopsy-only group and 94.5% in the lymphadenectomy group (hazard ratio [HR], 0.61; P = .12). However, the 3-year overall survival was significantly higher in biopsy-only group — 100% vs 97.8% in the lymphadenectomy group (HR, 0.21; P = .007). Overall, three patients (19%) in the biopsy-only group died from cervical cancer vs 14 (54%) in the lymphadenectomy group.

As for surgical complications, pelvic lymphadenectomy was associated with a higher incidence of pain (5.8% vs 1.7%), lymphocyst (22.1% vs 8.4%), and lymphedema (10.1% vs 2.4%), as well as longer operating time and more blood loss.

Offering perspective on PHENIX-I, discussant Premal Thaker, MD, noted that this is the first randomized trial to report on the use of sentinel lymph node biopsy alone vs biopsy plus pelvic lymphadenectomy after radical hysterectomy.

Key takeaways are the “equivalent” 3-year disease-free outcomes but “lower” overall survival in the pelvic lymphadenectomy group as well as more adverse events, said Thaker, gynecologic oncologist and surgeon, Siteman Cancer Center, Washington University, St Louis.

Although quality of life data was not presented in the trial, patients who skipped pelvic lymphadenectomy had fewer adverse events, “which is very important for our patients,” Thaker added.

This study had no commercial funding. Liu and Thaker had no relevant disclosures.

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

Results from the PHENIX-I trial support skipping pelvic lymphadenectomy in women with early cervical cancer who have a negative sentinel lymph node biopsy.

Omitting pelvic lymphadenectomy in these patients “did not compromise disease-free survival and potentially [led to] improved overall survival,” reported lead investigator Jihong Liu, MD, gynecologic oncologist, Sun Yat-sen University Cancer Center, Guangzhou, China.

Forgoing the additional procedure also decreased the incidence of retroperitoneal lymph node recurrence and adverse events and demonstrated superior surgical outcomes including shorter operative duration, reduced blood loss, and a lower morbidity.

Liu reported the PHENIX-I results at this year’s Society of Gynecologic Oncology Annual Meeting on Women’s Cancers (SGO) 2025.

Pelvic lymphadenectomy has been part of standard care for early-stage cervical cancer for over a century, even though the incidence of lymph node metastasis in early-stage cervical cancer is relatively low. Overtreatment and increased morbidity have been notable drawbacks of the procedure.

It may be possible to forgo pelvic lymphadenectomy in early-stage cervical cancer when sentinel lymph node biopsy findings are negative, but evidence from randomized controlled trials are lacking, Liu explained.

The PHENIX-I trial prospectively assessed survival outcomes among patients who received pelvic lymphadenectomy and those who did not. More specifically, all patients underwent sentinel lymph node biopsy and patients with negative lymph nodes were then intraoperatively randomized (1:1) to undergo pelvic lymphadenectomy (417 patients) or not (416 patients).

The multicenter, randomized controlled trial involved patients undergoing radical hysterectomy for stage IA1 (lymphovascular invasion), IA2, IB1, IB2 or IIA1 cervical cancer with tumor size not exceeding 3 cm.

“The only difference between the two groups was that patients in the experimental arm did not have pelvic lymphadenectomy,” Liu said.

Liu and colleagues reported that 23 patients (2.8%) had a positive lymph node on postoperative pathology examination. The rate of false-negative sentinel lymph node biopsy was < 1%. About half the patients in both groups received postoperative adjuvant therapy, and there was no significant between-group difference in the rates and time to initiate adjuvant therapy.

Overall, about 3.85% of patients (n = 16) in the biopsy-only group had a recurrence compared with 6.24% (n = 26) in the pelvic lymphadenectomy group at a median follow-up of 50 months.

But no patients in the biopsy-only group had a recurrence in the retroperitoneal lymph nodes compared with 9 patients in the pelvic lymphadenectomy group.

The 3-year disease-free survival (primary endpoint) rates were similar between the two groups — 96.8% in the biopsy-only group and 94.5% in the lymphadenectomy group (hazard ratio [HR], 0.61; P = .12). However, the 3-year overall survival was significantly higher in biopsy-only group — 100% vs 97.8% in the lymphadenectomy group (HR, 0.21; P = .007). Overall, three patients (19%) in the biopsy-only group died from cervical cancer vs 14 (54%) in the lymphadenectomy group.

As for surgical complications, pelvic lymphadenectomy was associated with a higher incidence of pain (5.8% vs 1.7%), lymphocyst (22.1% vs 8.4%), and lymphedema (10.1% vs 2.4%), as well as longer operating time and more blood loss.

Offering perspective on PHENIX-I, discussant Premal Thaker, MD, noted that this is the first randomized trial to report on the use of sentinel lymph node biopsy alone vs biopsy plus pelvic lymphadenectomy after radical hysterectomy.

Key takeaways are the “equivalent” 3-year disease-free outcomes but “lower” overall survival in the pelvic lymphadenectomy group as well as more adverse events, said Thaker, gynecologic oncologist and surgeon, Siteman Cancer Center, Washington University, St Louis.

Although quality of life data was not presented in the trial, patients who skipped pelvic lymphadenectomy had fewer adverse events, “which is very important for our patients,” Thaker added.

This study had no commercial funding. Liu and Thaker had no relevant disclosures.

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

Results from the PHENIX-I trial support skipping pelvic lymphadenectomy in women with early cervical cancer who have a negative sentinel lymph node biopsy.

Omitting pelvic lymphadenectomy in these patients “did not compromise disease-free survival and potentially [led to] improved overall survival,” reported lead investigator Jihong Liu, MD, gynecologic oncologist, Sun Yat-sen University Cancer Center, Guangzhou, China.

Forgoing the additional procedure also decreased the incidence of retroperitoneal lymph node recurrence and adverse events and demonstrated superior surgical outcomes including shorter operative duration, reduced blood loss, and a lower morbidity.

Liu reported the PHENIX-I results at this year’s Society of Gynecologic Oncology Annual Meeting on Women’s Cancers (SGO) 2025.

Pelvic lymphadenectomy has been part of standard care for early-stage cervical cancer for over a century, even though the incidence of lymph node metastasis in early-stage cervical cancer is relatively low. Overtreatment and increased morbidity have been notable drawbacks of the procedure.

It may be possible to forgo pelvic lymphadenectomy in early-stage cervical cancer when sentinel lymph node biopsy findings are negative, but evidence from randomized controlled trials are lacking, Liu explained.

The PHENIX-I trial prospectively assessed survival outcomes among patients who received pelvic lymphadenectomy and those who did not. More specifically, all patients underwent sentinel lymph node biopsy and patients with negative lymph nodes were then intraoperatively randomized (1:1) to undergo pelvic lymphadenectomy (417 patients) or not (416 patients).

The multicenter, randomized controlled trial involved patients undergoing radical hysterectomy for stage IA1 (lymphovascular invasion), IA2, IB1, IB2 or IIA1 cervical cancer with tumor size not exceeding 3 cm.

“The only difference between the two groups was that patients in the experimental arm did not have pelvic lymphadenectomy,” Liu said.

Liu and colleagues reported that 23 patients (2.8%) had a positive lymph node on postoperative pathology examination. The rate of false-negative sentinel lymph node biopsy was < 1%. About half the patients in both groups received postoperative adjuvant therapy, and there was no significant between-group difference in the rates and time to initiate adjuvant therapy.

Overall, about 3.85% of patients (n = 16) in the biopsy-only group had a recurrence compared with 6.24% (n = 26) in the pelvic lymphadenectomy group at a median follow-up of 50 months.

But no patients in the biopsy-only group had a recurrence in the retroperitoneal lymph nodes compared with 9 patients in the pelvic lymphadenectomy group.

The 3-year disease-free survival (primary endpoint) rates were similar between the two groups — 96.8% in the biopsy-only group and 94.5% in the lymphadenectomy group (hazard ratio [HR], 0.61; P = .12). However, the 3-year overall survival was significantly higher in biopsy-only group — 100% vs 97.8% in the lymphadenectomy group (HR, 0.21; P = .007). Overall, three patients (19%) in the biopsy-only group died from cervical cancer vs 14 (54%) in the lymphadenectomy group.

As for surgical complications, pelvic lymphadenectomy was associated with a higher incidence of pain (5.8% vs 1.7%), lymphocyst (22.1% vs 8.4%), and lymphedema (10.1% vs 2.4%), as well as longer operating time and more blood loss.

Offering perspective on PHENIX-I, discussant Premal Thaker, MD, noted that this is the first randomized trial to report on the use of sentinel lymph node biopsy alone vs biopsy plus pelvic lymphadenectomy after radical hysterectomy.

Key takeaways are the “equivalent” 3-year disease-free outcomes but “lower” overall survival in the pelvic lymphadenectomy group as well as more adverse events, said Thaker, gynecologic oncologist and surgeon, Siteman Cancer Center, Washington University, St Louis.

Although quality of life data was not presented in the trial, patients who skipped pelvic lymphadenectomy had fewer adverse events, “which is very important for our patients,” Thaker added.

This study had no commercial funding. Liu and Thaker had no relevant disclosures.

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

ORLANDO, Fla. — A study of automated three-dimensional total-body photography (3D TBP) found that it improved “hit” rates of positive malignant biopsies and reduced unnecessary biopsies of skin lesions but left unanswered questions about the practicality of its widespread use and cost-effectiveness.

“We did observe improved biopsy practices and outcomes,” said Jordan Phillipps, MD, a dermatology resident at Mayo Clinic in Jacksonville, Florida, who reported the results of the study during a late-breaker session at the American Academy of Dermatology (AAD) 2025 Annual Meeting.

“We observed reduced unnecessary biopsies, which was driven by benign and premalignant, particularly actinic keratosis, lesions,” Phillipps said. “We observed improved malignancy detection, which was profoundly driven by nonmelanoma skin cancers.”

Study Design and Results

The retrospective study included 410 adult patients who had at least two sessions with the Vectra WB360 3D TBP imaging system at a dedicated 3D imaging clinic at Mayo Clinic in Rochester, Minnesota Patient eligibility for the 3D clinic requires a previous melanoma diagnosis. All study participants also underwent dermoscopy, Phillipps said. Their average age was 51.6 years, and 53% were women.

The study accounted for 5981 total patient encounters, including 1150 dedicated Vectra imaging sessions, Phillipps said. In this group, 3006 biopsies were performed, of which 56% were benign, 32% were malignant, and 12% were premalignant. The study also separately evaluated lesion type, focusing on keratinocytic and pigmented lesions.

Most of the keratinocytic lesions were nonmelanoma skin cancers, he said, whereas the pigmented lesions were mostly benign.

“The intervention did significantly reduce biopsies per encounter by 35%, and this was driven by benign lesions and premalignant lesions, particularly actinic keratosis lesions,” Phillipps said.

Previous studies of automated TBP have been hampered by small study populations, he said, and this is one of the largest studies of the Vectra WB360 device. “Nonmelanoma skin cancers are underreported,” Phillipps said, noting that most studies focus on melanoma and pigmented lesions. “Our aim was to assess the effect of Vectra implementation on biopsy practice and outcomes,” he explained.

For malignant lesions, the investigators observed an improvement in malignancy detection, a modest 1.6% increase in hit rates of positive malignant biopsies, and a modest 1.3% decrease in the number needed to biopsy, he said.

A subgroup analysis of pigmented and keratinocytic lesions demonstrated that improved malignancy detection is “profoundly driven by nonmelanoma skin cancers” of 71% per biopsy, Phillipps said, along with “sizable” increases in the hit rate (+17%) and a reduction in the number of biopsies (–14%).

Melanoma detection decreased by 62% per biopsy. Phillipps said the reduction was probably because of the study methodology, specifically the eligibility requirement of having had a previous melanoma diagnosis. “These patients typically develop only one primary melanoma,” Phillipps said. To test this, the investigators compared melanoma hit rates with a matched, unexposed cohort that did not have Vectra imaging. They found that the hit rates were similar. “So this was reassuring that we weren’t missing any melanomas,” Phillipps said.

The results also showed improved efficacy for detecting severely dysplastic nevi, for which the hit rate increased by 16% and the number needed to biopsy decreased by 13%. “Actinic keratoses lesions were biopsied less,” he said, noting a 50% decrease. Both benign keratinocytic lesions, predominantly seborrheic keratosis and benign lichenoid keratosis, and benign pigmented (benign nevi) lesions were biopsied less.

 

Limitations and Questions

The highly selective nature of the patient population was a limitation of the study, Phillipps noted, along with financial and logistical challenges that impede the generalizability of the findings. Overall, he said, the study emphasized that 3D TBP is effective in skin cancer screening and diagnosis, notably beyond pigmented lesions.

Kristina Callis Duffin, MD, MS, chair of dermatology at The University of Utah, Salt Lake City, Utah, called the findings “exciting” but noted that the study did not compare results to the gold standard of clinician-performed skin screenings. “That absolutely would be the important way to do it, through a randomized trial,” she said, “but that’s a hard study to do.”

The cost-effectiveness of total-body imaging also needs to be evaluated, Duffin said. “You really have to look at a number of factors in terms of protection compared to a human gold standard, the rates of biopsies,” she said. “There are a lot of things to unpack; that cost-effectiveness has to be balanced with a more accurate diagnosis and reduction of morbidity with multiple biopsies.” 

Phillipps reported no relevant financial relationships. Duffin disclosed financial relationships with AbbVie, Alumis, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, FIDE, Janssen Pharmaceuticals, Novartis, and Pfizer.

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

ORLANDO, Fla. — A study of automated three-dimensional total-body photography (3D TBP) found that it improved “hit” rates of positive malignant biopsies and reduced unnecessary biopsies of skin lesions but left unanswered questions about the practicality of its widespread use and cost-effectiveness.

“We did observe improved biopsy practices and outcomes,” said Jordan Phillipps, MD, a dermatology resident at Mayo Clinic in Jacksonville, Florida, who reported the results of the study during a late-breaker session at the American Academy of Dermatology (AAD) 2025 Annual Meeting.

“We observed reduced unnecessary biopsies, which was driven by benign and premalignant, particularly actinic keratosis, lesions,” Phillipps said. “We observed improved malignancy detection, which was profoundly driven by nonmelanoma skin cancers.”

Study Design and Results

The retrospective study included 410 adult patients who had at least two sessions with the Vectra WB360 3D TBP imaging system at a dedicated 3D imaging clinic at Mayo Clinic in Rochester, Minnesota Patient eligibility for the 3D clinic requires a previous melanoma diagnosis. All study participants also underwent dermoscopy, Phillipps said. Their average age was 51.6 years, and 53% were women.

The study accounted for 5981 total patient encounters, including 1150 dedicated Vectra imaging sessions, Phillipps said. In this group, 3006 biopsies were performed, of which 56% were benign, 32% were malignant, and 12% were premalignant. The study also separately evaluated lesion type, focusing on keratinocytic and pigmented lesions.

Most of the keratinocytic lesions were nonmelanoma skin cancers, he said, whereas the pigmented lesions were mostly benign.

“The intervention did significantly reduce biopsies per encounter by 35%, and this was driven by benign lesions and premalignant lesions, particularly actinic keratosis lesions,” Phillipps said.

Previous studies of automated TBP have been hampered by small study populations, he said, and this is one of the largest studies of the Vectra WB360 device. “Nonmelanoma skin cancers are underreported,” Phillipps said, noting that most studies focus on melanoma and pigmented lesions. “Our aim was to assess the effect of Vectra implementation on biopsy practice and outcomes,” he explained.

For malignant lesions, the investigators observed an improvement in malignancy detection, a modest 1.6% increase in hit rates of positive malignant biopsies, and a modest 1.3% decrease in the number needed to biopsy, he said.

A subgroup analysis of pigmented and keratinocytic lesions demonstrated that improved malignancy detection is “profoundly driven by nonmelanoma skin cancers” of 71% per biopsy, Phillipps said, along with “sizable” increases in the hit rate (+17%) and a reduction in the number of biopsies (–14%).

Melanoma detection decreased by 62% per biopsy. Phillipps said the reduction was probably because of the study methodology, specifically the eligibility requirement of having had a previous melanoma diagnosis. “These patients typically develop only one primary melanoma,” Phillipps said. To test this, the investigators compared melanoma hit rates with a matched, unexposed cohort that did not have Vectra imaging. They found that the hit rates were similar. “So this was reassuring that we weren’t missing any melanomas,” Phillipps said.

The results also showed improved efficacy for detecting severely dysplastic nevi, for which the hit rate increased by 16% and the number needed to biopsy decreased by 13%. “Actinic keratoses lesions were biopsied less,” he said, noting a 50% decrease. Both benign keratinocytic lesions, predominantly seborrheic keratosis and benign lichenoid keratosis, and benign pigmented (benign nevi) lesions were biopsied less.

 

Limitations and Questions

The highly selective nature of the patient population was a limitation of the study, Phillipps noted, along with financial and logistical challenges that impede the generalizability of the findings. Overall, he said, the study emphasized that 3D TBP is effective in skin cancer screening and diagnosis, notably beyond pigmented lesions.

Kristina Callis Duffin, MD, MS, chair of dermatology at The University of Utah, Salt Lake City, Utah, called the findings “exciting” but noted that the study did not compare results to the gold standard of clinician-performed skin screenings. “That absolutely would be the important way to do it, through a randomized trial,” she said, “but that’s a hard study to do.”

The cost-effectiveness of total-body imaging also needs to be evaluated, Duffin said. “You really have to look at a number of factors in terms of protection compared to a human gold standard, the rates of biopsies,” she said. “There are a lot of things to unpack; that cost-effectiveness has to be balanced with a more accurate diagnosis and reduction of morbidity with multiple biopsies.” 

Phillipps reported no relevant financial relationships. Duffin disclosed financial relationships with AbbVie, Alumis, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, FIDE, Janssen Pharmaceuticals, Novartis, and Pfizer.

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

ORLANDO, Fla. — A study of automated three-dimensional total-body photography (3D TBP) found that it improved “hit” rates of positive malignant biopsies and reduced unnecessary biopsies of skin lesions but left unanswered questions about the practicality of its widespread use and cost-effectiveness.

“We did observe improved biopsy practices and outcomes,” said Jordan Phillipps, MD, a dermatology resident at Mayo Clinic in Jacksonville, Florida, who reported the results of the study during a late-breaker session at the American Academy of Dermatology (AAD) 2025 Annual Meeting.

“We observed reduced unnecessary biopsies, which was driven by benign and premalignant, particularly actinic keratosis, lesions,” Phillipps said. “We observed improved malignancy detection, which was profoundly driven by nonmelanoma skin cancers.”

Study Design and Results

The retrospective study included 410 adult patients who had at least two sessions with the Vectra WB360 3D TBP imaging system at a dedicated 3D imaging clinic at Mayo Clinic in Rochester, Minnesota Patient eligibility for the 3D clinic requires a previous melanoma diagnosis. All study participants also underwent dermoscopy, Phillipps said. Their average age was 51.6 years, and 53% were women.

The study accounted for 5981 total patient encounters, including 1150 dedicated Vectra imaging sessions, Phillipps said. In this group, 3006 biopsies were performed, of which 56% were benign, 32% were malignant, and 12% were premalignant. The study also separately evaluated lesion type, focusing on keratinocytic and pigmented lesions.

Most of the keratinocytic lesions were nonmelanoma skin cancers, he said, whereas the pigmented lesions were mostly benign.

“The intervention did significantly reduce biopsies per encounter by 35%, and this was driven by benign lesions and premalignant lesions, particularly actinic keratosis lesions,” Phillipps said.

Previous studies of automated TBP have been hampered by small study populations, he said, and this is one of the largest studies of the Vectra WB360 device. “Nonmelanoma skin cancers are underreported,” Phillipps said, noting that most studies focus on melanoma and pigmented lesions. “Our aim was to assess the effect of Vectra implementation on biopsy practice and outcomes,” he explained.

For malignant lesions, the investigators observed an improvement in malignancy detection, a modest 1.6% increase in hit rates of positive malignant biopsies, and a modest 1.3% decrease in the number needed to biopsy, he said.

A subgroup analysis of pigmented and keratinocytic lesions demonstrated that improved malignancy detection is “profoundly driven by nonmelanoma skin cancers” of 71% per biopsy, Phillipps said, along with “sizable” increases in the hit rate (+17%) and a reduction in the number of biopsies (–14%).

Melanoma detection decreased by 62% per biopsy. Phillipps said the reduction was probably because of the study methodology, specifically the eligibility requirement of having had a previous melanoma diagnosis. “These patients typically develop only one primary melanoma,” Phillipps said. To test this, the investigators compared melanoma hit rates with a matched, unexposed cohort that did not have Vectra imaging. They found that the hit rates were similar. “So this was reassuring that we weren’t missing any melanomas,” Phillipps said.

The results also showed improved efficacy for detecting severely dysplastic nevi, for which the hit rate increased by 16% and the number needed to biopsy decreased by 13%. “Actinic keratoses lesions were biopsied less,” he said, noting a 50% decrease. Both benign keratinocytic lesions, predominantly seborrheic keratosis and benign lichenoid keratosis, and benign pigmented (benign nevi) lesions were biopsied less.

 

Limitations and Questions

The highly selective nature of the patient population was a limitation of the study, Phillipps noted, along with financial and logistical challenges that impede the generalizability of the findings. Overall, he said, the study emphasized that 3D TBP is effective in skin cancer screening and diagnosis, notably beyond pigmented lesions.

Kristina Callis Duffin, MD, MS, chair of dermatology at The University of Utah, Salt Lake City, Utah, called the findings “exciting” but noted that the study did not compare results to the gold standard of clinician-performed skin screenings. “That absolutely would be the important way to do it, through a randomized trial,” she said, “but that’s a hard study to do.”

The cost-effectiveness of total-body imaging also needs to be evaluated, Duffin said. “You really have to look at a number of factors in terms of protection compared to a human gold standard, the rates of biopsies,” she said. “There are a lot of things to unpack; that cost-effectiveness has to be balanced with a more accurate diagnosis and reduction of morbidity with multiple biopsies.” 

Phillipps reported no relevant financial relationships. Duffin disclosed financial relationships with AbbVie, Alumis, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, FIDE, Janssen Pharmaceuticals, Novartis, and Pfizer.

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

The American College of Gastroenterology (ACG) has issued its first clinical practice guideline on the diagnosis and management of gastric premalignant conditions (GPMCs) including atrophic gastritis, gastric intestinal metaplasia, dysplasia, and certain gastric epithelial polyps, all of which have an increased risk of progressing to gastric cancer.

The guideline was published online in The American Journal of Gastroenterology.

GPMCs are “common in gastroenterology practices, but in the US, at least, we’ve not had concrete guidance,” first author Douglas Morgan, MD, MPH, AGAF, Division of Gastroenterology, The University of Alabama at Birmingham, noted in an interview.

With these guidelines, we hope there “will be a paradigm shift to finally establish surveillance in the stomach, much like we’ve been doing for decades in the colon and the esophagus,” Morgan said.

Gastric cancer is a common cancer in the United States with disproportionately higher incidence rates in immigrants from countries with a high incidence of gastric cancer and certain non-White populations.

In addition, the 5-year survival rate in the United States for gastric cancer is 36%, which falls short of global standards and is driven by the fact that only a small percentage of these cancers are diagnosed in the early, curable stage.

These guidelines will help address this marked disparity and the burden on minority and marginalized populations, the guideline authors wrote. “The overarching goals are to reduce [gastric cancer] incidence in the United States, increase the detection of early-stage disease (early gastric cancer), and to significantly increase the 5-year survival rates in the near term.”

 

Key Recommendations

The guideline includes recommendations on endoscopic surveillance for high-risk patients, the performance of high-quality endoscopy and image-enhanced endoscopy (IEE) for diagnosis and surveillance, GPMC histology criteria and reporting, endoscopic treatment of dysplasia, the role of Helicobacter pylori eradication, general risk reduction measures, and the management of autoimmune gastritis and gastric epithelial polyps.

In terms of screening, the guidelines recommend against routine upper endoscopy screening for gastric cancer and GPMC in the general US population (low quality of evidence; conditional recommendation).

They also noted that there is “insufficient” direct US evidence to make a recommendation on opportunistic endoscopy screening for gastric cancer and GPMC in patients deemed at high risk based on race/ethnicity and family history. In addition, they recommend against the use of noninvasive biomarkers for screening or surveillance of GPMC or gastric cancer.

In terms of endoscopic and histologic diagnosis of GPMC, high-quality endoscopic evaluation is crucial to detect premalignant conditions or gastric cancer, the authors said. This includes adequate mucosal cleansing and insufflation, and photodocumentation of anatomic landmarks, as well as use of high-definition white light endoscopy (HDWLE) and IEE.

Systematic gastric biopsies should follow the updated Sydney protocol, with at least two separate containers for antrum/incisura and corpus biopsies. Histology should document the subtype of gastric intestinal metaplasia — incomplete, complete, or mixed — and severity and extent of atrophic gastritis and metaplasia.

Morgan emphasized the importance of coordination between the gastroenterologist and pathologist. “Several of these measures are not routinely reported, so we need to be in conversations with our collaborating pathologists,” he told this news organization.

In terms of GPMC surveillance, the authors suggest surveillance endoscopy every 3 years in high-risk patients with gastric intestinal metaplasia who meet one of the following criteria: High-risk histology (incomplete vs complete subtype, extending into the corpus); family history of gastric cancer in a first-degree relative; foreign-born individuals from high-gastric cancer incidence nations; or high-risk race/ethnicity (East Asian, Latino/a, Black, American Indian, or Alaska Native).

Individuals with multiple risk factors for gastric cancer may be considered for shorter than 3-year intervals.

Low-risk gastric intestinal metaplasia (limited to antrum, mild atrophy, and complete gastric intestinal metaplasia subtype) does not require routine endoscopic surveillance.

In terms of endoscopic management of dysplastic GPMC, endoscopic resection is suggested for dysplasia with visible margins. If dysplasia is not visible, repeat endoscopy with HDWLE and IEE by an experienced endoscopist is advised.

In patients appropriate for endoscopic resection of dysplasia, particularly endoscopic submucosal dissection, referral to a high-volume center with appropriate expertise in the diagnosis and therapeutic resection of gastric neoplasia is strongly recommended.

In patients with confirmed complete resection of dysplasia, endoscopic surveillance is also strongly recommended. Surveillance examinations should be performed by an experienced endoscopist using HDWLE and IEE, with biopsies according to the systematic biopsy protocol in addition to targeted biopsies.

In terms of nonendoscopic GPMC management, testing for H pylori (and eradication treatment if possible) is strongly recommended for patients with GPMC and those with a history of resected early gastric cancer.

Aspirin, nonsteroidal anti-inflammatory drugs, cyclooxygenase 2 inhibitors, or antioxidants are not recommended for patients with GPMC for the purpose of preventing gastric cancer.

In patients with autoimmune gastritis, testing for H pylori with a nonserological test, eradication treatment if positive, and posttreatment testing to confirm eradication is advised.

There is not enough evidence to make a formal recommendation on endoscopic surveillance in those with autoimmune gastritis; surveillance should be individualized, considering the risk for neuroendocrine tumors and possibly gastric cancer.

In terms of gastric epithelial polyps, endoscopic resection of all gastric adenomas is recommended, regardless of size, to exclude or prevent dysplasia and early gastric cancer. Adenomas that are not amenable to endoscopic resection should be referred for surgical resection, if clinically appropriate.

Morgan noted that the ACG GPMC guideline aligns with the updated ACG/American Society for Gastrointestinal Endoscopy upper endoscopy quality indicators released earlier this year.

Implementation of the ACG GPMC guideline and “change in clinical practice will require concrete targets and include training and quality initiatives,” the authors said.

This research received no commercial support. Morgan disclosed research support from Panbela Therapeutics, Thorne, and American Molecular Laboratories.

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

The American College of Gastroenterology (ACG) has issued its first clinical practice guideline on the diagnosis and management of gastric premalignant conditions (GPMCs) including atrophic gastritis, gastric intestinal metaplasia, dysplasia, and certain gastric epithelial polyps, all of which have an increased risk of progressing to gastric cancer.

The guideline was published online in The American Journal of Gastroenterology.

GPMCs are “common in gastroenterology practices, but in the US, at least, we’ve not had concrete guidance,” first author Douglas Morgan, MD, MPH, AGAF, Division of Gastroenterology, The University of Alabama at Birmingham, noted in an interview.

With these guidelines, we hope there “will be a paradigm shift to finally establish surveillance in the stomach, much like we’ve been doing for decades in the colon and the esophagus,” Morgan said.

Gastric cancer is a common cancer in the United States with disproportionately higher incidence rates in immigrants from countries with a high incidence of gastric cancer and certain non-White populations.

In addition, the 5-year survival rate in the United States for gastric cancer is 36%, which falls short of global standards and is driven by the fact that only a small percentage of these cancers are diagnosed in the early, curable stage.

These guidelines will help address this marked disparity and the burden on minority and marginalized populations, the guideline authors wrote. “The overarching goals are to reduce [gastric cancer] incidence in the United States, increase the detection of early-stage disease (early gastric cancer), and to significantly increase the 5-year survival rates in the near term.”

 

Key Recommendations

The guideline includes recommendations on endoscopic surveillance for high-risk patients, the performance of high-quality endoscopy and image-enhanced endoscopy (IEE) for diagnosis and surveillance, GPMC histology criteria and reporting, endoscopic treatment of dysplasia, the role of Helicobacter pylori eradication, general risk reduction measures, and the management of autoimmune gastritis and gastric epithelial polyps.

In terms of screening, the guidelines recommend against routine upper endoscopy screening for gastric cancer and GPMC in the general US population (low quality of evidence; conditional recommendation).

They also noted that there is “insufficient” direct US evidence to make a recommendation on opportunistic endoscopy screening for gastric cancer and GPMC in patients deemed at high risk based on race/ethnicity and family history. In addition, they recommend against the use of noninvasive biomarkers for screening or surveillance of GPMC or gastric cancer.

In terms of endoscopic and histologic diagnosis of GPMC, high-quality endoscopic evaluation is crucial to detect premalignant conditions or gastric cancer, the authors said. This includes adequate mucosal cleansing and insufflation, and photodocumentation of anatomic landmarks, as well as use of high-definition white light endoscopy (HDWLE) and IEE.

Systematic gastric biopsies should follow the updated Sydney protocol, with at least two separate containers for antrum/incisura and corpus biopsies. Histology should document the subtype of gastric intestinal metaplasia — incomplete, complete, or mixed — and severity and extent of atrophic gastritis and metaplasia.

Morgan emphasized the importance of coordination between the gastroenterologist and pathologist. “Several of these measures are not routinely reported, so we need to be in conversations with our collaborating pathologists,” he told this news organization.

In terms of GPMC surveillance, the authors suggest surveillance endoscopy every 3 years in high-risk patients with gastric intestinal metaplasia who meet one of the following criteria: High-risk histology (incomplete vs complete subtype, extending into the corpus); family history of gastric cancer in a first-degree relative; foreign-born individuals from high-gastric cancer incidence nations; or high-risk race/ethnicity (East Asian, Latino/a, Black, American Indian, or Alaska Native).

Individuals with multiple risk factors for gastric cancer may be considered for shorter than 3-year intervals.

Low-risk gastric intestinal metaplasia (limited to antrum, mild atrophy, and complete gastric intestinal metaplasia subtype) does not require routine endoscopic surveillance.

In terms of endoscopic management of dysplastic GPMC, endoscopic resection is suggested for dysplasia with visible margins. If dysplasia is not visible, repeat endoscopy with HDWLE and IEE by an experienced endoscopist is advised.

In patients appropriate for endoscopic resection of dysplasia, particularly endoscopic submucosal dissection, referral to a high-volume center with appropriate expertise in the diagnosis and therapeutic resection of gastric neoplasia is strongly recommended.

In patients with confirmed complete resection of dysplasia, endoscopic surveillance is also strongly recommended. Surveillance examinations should be performed by an experienced endoscopist using HDWLE and IEE, with biopsies according to the systematic biopsy protocol in addition to targeted biopsies.

In terms of nonendoscopic GPMC management, testing for H pylori (and eradication treatment if possible) is strongly recommended for patients with GPMC and those with a history of resected early gastric cancer.

Aspirin, nonsteroidal anti-inflammatory drugs, cyclooxygenase 2 inhibitors, or antioxidants are not recommended for patients with GPMC for the purpose of preventing gastric cancer.

In patients with autoimmune gastritis, testing for H pylori with a nonserological test, eradication treatment if positive, and posttreatment testing to confirm eradication is advised.

There is not enough evidence to make a formal recommendation on endoscopic surveillance in those with autoimmune gastritis; surveillance should be individualized, considering the risk for neuroendocrine tumors and possibly gastric cancer.

In terms of gastric epithelial polyps, endoscopic resection of all gastric adenomas is recommended, regardless of size, to exclude or prevent dysplasia and early gastric cancer. Adenomas that are not amenable to endoscopic resection should be referred for surgical resection, if clinically appropriate.

Morgan noted that the ACG GPMC guideline aligns with the updated ACG/American Society for Gastrointestinal Endoscopy upper endoscopy quality indicators released earlier this year.

Implementation of the ACG GPMC guideline and “change in clinical practice will require concrete targets and include training and quality initiatives,” the authors said.

This research received no commercial support. Morgan disclosed research support from Panbela Therapeutics, Thorne, and American Molecular Laboratories.

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

The American College of Gastroenterology (ACG) has issued its first clinical practice guideline on the diagnosis and management of gastric premalignant conditions (GPMCs) including atrophic gastritis, gastric intestinal metaplasia, dysplasia, and certain gastric epithelial polyps, all of which have an increased risk of progressing to gastric cancer.

The guideline was published online in The American Journal of Gastroenterology.

GPMCs are “common in gastroenterology practices, but in the US, at least, we’ve not had concrete guidance,” first author Douglas Morgan, MD, MPH, AGAF, Division of Gastroenterology, The University of Alabama at Birmingham, noted in an interview.

With these guidelines, we hope there “will be a paradigm shift to finally establish surveillance in the stomach, much like we’ve been doing for decades in the colon and the esophagus,” Morgan said.

Gastric cancer is a common cancer in the United States with disproportionately higher incidence rates in immigrants from countries with a high incidence of gastric cancer and certain non-White populations.

In addition, the 5-year survival rate in the United States for gastric cancer is 36%, which falls short of global standards and is driven by the fact that only a small percentage of these cancers are diagnosed in the early, curable stage.

These guidelines will help address this marked disparity and the burden on minority and marginalized populations, the guideline authors wrote. “The overarching goals are to reduce [gastric cancer] incidence in the United States, increase the detection of early-stage disease (early gastric cancer), and to significantly increase the 5-year survival rates in the near term.”

 

Key Recommendations

The guideline includes recommendations on endoscopic surveillance for high-risk patients, the performance of high-quality endoscopy and image-enhanced endoscopy (IEE) for diagnosis and surveillance, GPMC histology criteria and reporting, endoscopic treatment of dysplasia, the role of Helicobacter pylori eradication, general risk reduction measures, and the management of autoimmune gastritis and gastric epithelial polyps.

In terms of screening, the guidelines recommend against routine upper endoscopy screening for gastric cancer and GPMC in the general US population (low quality of evidence; conditional recommendation).

They also noted that there is “insufficient” direct US evidence to make a recommendation on opportunistic endoscopy screening for gastric cancer and GPMC in patients deemed at high risk based on race/ethnicity and family history. In addition, they recommend against the use of noninvasive biomarkers for screening or surveillance of GPMC or gastric cancer.

In terms of endoscopic and histologic diagnosis of GPMC, high-quality endoscopic evaluation is crucial to detect premalignant conditions or gastric cancer, the authors said. This includes adequate mucosal cleansing and insufflation, and photodocumentation of anatomic landmarks, as well as use of high-definition white light endoscopy (HDWLE) and IEE.

Systematic gastric biopsies should follow the updated Sydney protocol, with at least two separate containers for antrum/incisura and corpus biopsies. Histology should document the subtype of gastric intestinal metaplasia — incomplete, complete, or mixed — and severity and extent of atrophic gastritis and metaplasia.

Morgan emphasized the importance of coordination between the gastroenterologist and pathologist. “Several of these measures are not routinely reported, so we need to be in conversations with our collaborating pathologists,” he told this news organization.

In terms of GPMC surveillance, the authors suggest surveillance endoscopy every 3 years in high-risk patients with gastric intestinal metaplasia who meet one of the following criteria: High-risk histology (incomplete vs complete subtype, extending into the corpus); family history of gastric cancer in a first-degree relative; foreign-born individuals from high-gastric cancer incidence nations; or high-risk race/ethnicity (East Asian, Latino/a, Black, American Indian, or Alaska Native).

Individuals with multiple risk factors for gastric cancer may be considered for shorter than 3-year intervals.

Low-risk gastric intestinal metaplasia (limited to antrum, mild atrophy, and complete gastric intestinal metaplasia subtype) does not require routine endoscopic surveillance.

In terms of endoscopic management of dysplastic GPMC, endoscopic resection is suggested for dysplasia with visible margins. If dysplasia is not visible, repeat endoscopy with HDWLE and IEE by an experienced endoscopist is advised.

In patients appropriate for endoscopic resection of dysplasia, particularly endoscopic submucosal dissection, referral to a high-volume center with appropriate expertise in the diagnosis and therapeutic resection of gastric neoplasia is strongly recommended.

In patients with confirmed complete resection of dysplasia, endoscopic surveillance is also strongly recommended. Surveillance examinations should be performed by an experienced endoscopist using HDWLE and IEE, with biopsies according to the systematic biopsy protocol in addition to targeted biopsies.

In terms of nonendoscopic GPMC management, testing for H pylori (and eradication treatment if possible) is strongly recommended for patients with GPMC and those with a history of resected early gastric cancer.

Aspirin, nonsteroidal anti-inflammatory drugs, cyclooxygenase 2 inhibitors, or antioxidants are not recommended for patients with GPMC for the purpose of preventing gastric cancer.

In patients with autoimmune gastritis, testing for H pylori with a nonserological test, eradication treatment if positive, and posttreatment testing to confirm eradication is advised.

There is not enough evidence to make a formal recommendation on endoscopic surveillance in those with autoimmune gastritis; surveillance should be individualized, considering the risk for neuroendocrine tumors and possibly gastric cancer.

In terms of gastric epithelial polyps, endoscopic resection of all gastric adenomas is recommended, regardless of size, to exclude or prevent dysplasia and early gastric cancer. Adenomas that are not amenable to endoscopic resection should be referred for surgical resection, if clinically appropriate.

Morgan noted that the ACG GPMC guideline aligns with the updated ACG/American Society for Gastrointestinal Endoscopy upper endoscopy quality indicators released earlier this year.

Implementation of the ACG GPMC guideline and “change in clinical practice will require concrete targets and include training and quality initiatives,” the authors said.

This research received no commercial support. Morgan disclosed research support from Panbela Therapeutics, Thorne, and American Molecular Laboratories.

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

New research highlights the promise of artificial intelligence (AI) for opportunistic screening of chronic liver disease (CLD) through routine echocardiography. 

An AI algorithm called EchoNet-Liver demonstrated strong performance for detecting cirrhosis and steatotic liver disease (SLD) from routinely acquired transthoracic echocardiography studies containing subcostal images of the liver, the developers reported in NEJM AI.

“We hope that this algorithm enables physicians to opportunistically screen for chronic liver disease to identify asymptomatic and undiagnosed patients, thus enabling us to treat comorbidities relevant to the patient’s cardiovascular and noncardiovascular health,” Alan C. Kwan, MD, assistant professor, Department of Cardiology, Smidt Heart Institute at Cedars-Sinai, Los Angeles, California, told this news organization.

 

Harnessing Echo to Reveal Liver Trouble 

CLD affects over 1.5 billion people globally, with many cases remaining undiagnosed due to the asymptomatic nature of early disease and a lack of routine screening. Traditional diagnostic methods such as liver function tests, ultrasonography, and MRI are often limited by cost, availability, and patient access.

Echocardiography is a commonly performed imaging study that incidentally captures images of the liver but is not utilized for liver disease assessment.

EchoNet-Liver is an AI algorithm that can identify high-quality subcostal images from full echocardiography studies and detect the presence of cirrhosis and SLD. 

Kwan and colleagues trained it using nearly 1.6 million echocardiogram videos from 66,922 studies and 24,276 adult patients at Cedars-Sinai Medical Center (CSMC). The model predictions were compared with diagnoses from clinical evaluations of paired abdominal ultrasound or MRI studies. External validation studies were conducted using similar data from Stanford Health Care. 

In the “held-out” CSMC ultrasound dataset, EchoNet-Liver detected cirrhosis with an area under the receiver operating characteristic curve (AUROC) of 0.837 (95% CI, 0.828-0.848) and SLD with an AUROC of 0.799 (95% CI, 0.788-0.811).

The algorithm showed a sensitivity of 69.6% and a specificity of 84.6% for detecting cirrhosis, and a sensitivity of 74.1% and a specificity of 72.0% for detecting SLD. 

In the Stanford Health Care external-validation test ultrasound cohort, the model detected cirrhosis with an AUROC of 0.830 (95% CI, 0.799-0.859) and SLD with an AUROC of 0.769 (95% CI, 0.733-0.813), with sensitivity and specificity of 80.0% and 70.9%, respectively, for cirrhosis and 66.7% and 78.0%, respectively, for SLD. 

In the CSMC MRI-paired cohort, EchoNet-Liver detected cirrhosis with an AUROC of 0.704 (95% CI, 0.699-0.708) and SLD with an AUROC of 0.725 (95% CI, 0.707-0.762).

 

Identifying Subclinical Liver Disease to Improve Outcomes

“Across diverse populations and disease definitions, deep-learning-enhanced echocardiography enabled high-throughput, automated detection of CLD, which could enable opportunistic screening for asymptomatic liver disease,” the authors wrote. 

“By improving the diagnosis of subclinical CLD, we may be able to limit or reverse disease progression and improve care by triaging patients toward appropriate clinical and diagnostic management,” they said. 

By way of limitations, the researchers noted that the tool was developed using a cohort of patients who had both abdominal ultrasound and echocardiography within 30 days, and thus probably had a higher prevalence of liver disease compared with the general population receiving echocardiography. The true clinical utility of EchoNet-Liver will depend on whether its application to a general echocardiography population can efficiently detect undiagnosed CLD, they cautioned. 

“While we developed this algorithm based on clinical data, the application within the clinic would typically require FDA approval, which we have not yet applied for,” Kwan told this news organization.

“We plan to prospectively validate this algorithm at multiple sites to ensure that application of this algorithm improves patient care without causing excess diagnostic testing, thus providing value to patients and the healthcare system as a whole,” Kwan said.

Funding was provided in part by KAKENHI (Japan Society for the Promotion of Science). Kwan reported receiving consulting fees from InVision.

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

New research highlights the promise of artificial intelligence (AI) for opportunistic screening of chronic liver disease (CLD) through routine echocardiography. 

An AI algorithm called EchoNet-Liver demonstrated strong performance for detecting cirrhosis and steatotic liver disease (SLD) from routinely acquired transthoracic echocardiography studies containing subcostal images of the liver, the developers reported in NEJM AI.

“We hope that this algorithm enables physicians to opportunistically screen for chronic liver disease to identify asymptomatic and undiagnosed patients, thus enabling us to treat comorbidities relevant to the patient’s cardiovascular and noncardiovascular health,” Alan C. Kwan, MD, assistant professor, Department of Cardiology, Smidt Heart Institute at Cedars-Sinai, Los Angeles, California, told this news organization.

 

Harnessing Echo to Reveal Liver Trouble 

CLD affects over 1.5 billion people globally, with many cases remaining undiagnosed due to the asymptomatic nature of early disease and a lack of routine screening. Traditional diagnostic methods such as liver function tests, ultrasonography, and MRI are often limited by cost, availability, and patient access.

Echocardiography is a commonly performed imaging study that incidentally captures images of the liver but is not utilized for liver disease assessment.

EchoNet-Liver is an AI algorithm that can identify high-quality subcostal images from full echocardiography studies and detect the presence of cirrhosis and SLD. 

Kwan and colleagues trained it using nearly 1.6 million echocardiogram videos from 66,922 studies and 24,276 adult patients at Cedars-Sinai Medical Center (CSMC). The model predictions were compared with diagnoses from clinical evaluations of paired abdominal ultrasound or MRI studies. External validation studies were conducted using similar data from Stanford Health Care. 

In the “held-out” CSMC ultrasound dataset, EchoNet-Liver detected cirrhosis with an area under the receiver operating characteristic curve (AUROC) of 0.837 (95% CI, 0.828-0.848) and SLD with an AUROC of 0.799 (95% CI, 0.788-0.811).

The algorithm showed a sensitivity of 69.6% and a specificity of 84.6% for detecting cirrhosis, and a sensitivity of 74.1% and a specificity of 72.0% for detecting SLD. 

In the Stanford Health Care external-validation test ultrasound cohort, the model detected cirrhosis with an AUROC of 0.830 (95% CI, 0.799-0.859) and SLD with an AUROC of 0.769 (95% CI, 0.733-0.813), with sensitivity and specificity of 80.0% and 70.9%, respectively, for cirrhosis and 66.7% and 78.0%, respectively, for SLD. 

In the CSMC MRI-paired cohort, EchoNet-Liver detected cirrhosis with an AUROC of 0.704 (95% CI, 0.699-0.708) and SLD with an AUROC of 0.725 (95% CI, 0.707-0.762).

 

Identifying Subclinical Liver Disease to Improve Outcomes

“Across diverse populations and disease definitions, deep-learning-enhanced echocardiography enabled high-throughput, automated detection of CLD, which could enable opportunistic screening for asymptomatic liver disease,” the authors wrote. 

“By improving the diagnosis of subclinical CLD, we may be able to limit or reverse disease progression and improve care by triaging patients toward appropriate clinical and diagnostic management,” they said. 

By way of limitations, the researchers noted that the tool was developed using a cohort of patients who had both abdominal ultrasound and echocardiography within 30 days, and thus probably had a higher prevalence of liver disease compared with the general population receiving echocardiography. The true clinical utility of EchoNet-Liver will depend on whether its application to a general echocardiography population can efficiently detect undiagnosed CLD, they cautioned. 

“While we developed this algorithm based on clinical data, the application within the clinic would typically require FDA approval, which we have not yet applied for,” Kwan told this news organization.

“We plan to prospectively validate this algorithm at multiple sites to ensure that application of this algorithm improves patient care without causing excess diagnostic testing, thus providing value to patients and the healthcare system as a whole,” Kwan said.

Funding was provided in part by KAKENHI (Japan Society for the Promotion of Science). Kwan reported receiving consulting fees from InVision.

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

New research highlights the promise of artificial intelligence (AI) for opportunistic screening of chronic liver disease (CLD) through routine echocardiography. 

An AI algorithm called EchoNet-Liver demonstrated strong performance for detecting cirrhosis and steatotic liver disease (SLD) from routinely acquired transthoracic echocardiography studies containing subcostal images of the liver, the developers reported in NEJM AI.

“We hope that this algorithm enables physicians to opportunistically screen for chronic liver disease to identify asymptomatic and undiagnosed patients, thus enabling us to treat comorbidities relevant to the patient’s cardiovascular and noncardiovascular health,” Alan C. Kwan, MD, assistant professor, Department of Cardiology, Smidt Heart Institute at Cedars-Sinai, Los Angeles, California, told this news organization.

 

Harnessing Echo to Reveal Liver Trouble 

CLD affects over 1.5 billion people globally, with many cases remaining undiagnosed due to the asymptomatic nature of early disease and a lack of routine screening. Traditional diagnostic methods such as liver function tests, ultrasonography, and MRI are often limited by cost, availability, and patient access.

Echocardiography is a commonly performed imaging study that incidentally captures images of the liver but is not utilized for liver disease assessment.

EchoNet-Liver is an AI algorithm that can identify high-quality subcostal images from full echocardiography studies and detect the presence of cirrhosis and SLD. 

Kwan and colleagues trained it using nearly 1.6 million echocardiogram videos from 66,922 studies and 24,276 adult patients at Cedars-Sinai Medical Center (CSMC). The model predictions were compared with diagnoses from clinical evaluations of paired abdominal ultrasound or MRI studies. External validation studies were conducted using similar data from Stanford Health Care. 

In the “held-out” CSMC ultrasound dataset, EchoNet-Liver detected cirrhosis with an area under the receiver operating characteristic curve (AUROC) of 0.837 (95% CI, 0.828-0.848) and SLD with an AUROC of 0.799 (95% CI, 0.788-0.811).

The algorithm showed a sensitivity of 69.6% and a specificity of 84.6% for detecting cirrhosis, and a sensitivity of 74.1% and a specificity of 72.0% for detecting SLD. 

In the Stanford Health Care external-validation test ultrasound cohort, the model detected cirrhosis with an AUROC of 0.830 (95% CI, 0.799-0.859) and SLD with an AUROC of 0.769 (95% CI, 0.733-0.813), with sensitivity and specificity of 80.0% and 70.9%, respectively, for cirrhosis and 66.7% and 78.0%, respectively, for SLD. 

In the CSMC MRI-paired cohort, EchoNet-Liver detected cirrhosis with an AUROC of 0.704 (95% CI, 0.699-0.708) and SLD with an AUROC of 0.725 (95% CI, 0.707-0.762).

 

Identifying Subclinical Liver Disease to Improve Outcomes

“Across diverse populations and disease definitions, deep-learning-enhanced echocardiography enabled high-throughput, automated detection of CLD, which could enable opportunistic screening for asymptomatic liver disease,” the authors wrote. 

“By improving the diagnosis of subclinical CLD, we may be able to limit or reverse disease progression and improve care by triaging patients toward appropriate clinical and diagnostic management,” they said. 

By way of limitations, the researchers noted that the tool was developed using a cohort of patients who had both abdominal ultrasound and echocardiography within 30 days, and thus probably had a higher prevalence of liver disease compared with the general population receiving echocardiography. The true clinical utility of EchoNet-Liver will depend on whether its application to a general echocardiography population can efficiently detect undiagnosed CLD, they cautioned. 

“While we developed this algorithm based on clinical data, the application within the clinic would typically require FDA approval, which we have not yet applied for,” Kwan told this news organization.

“We plan to prospectively validate this algorithm at multiple sites to ensure that application of this algorithm improves patient care without causing excess diagnostic testing, thus providing value to patients and the healthcare system as a whole,” Kwan said.

Funding was provided in part by KAKENHI (Japan Society for the Promotion of Science). Kwan reported receiving consulting fees from InVision.

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

Diets in wealthier countries often include processed foods that contain additives, particularly emulsifiers. These additives are increasingly associated with the development of various diseases, including inflammatory bowel disease (IBD).

A research team led by Benoit Chassaing, PhD, research director at the French National Institute of Health and Medical Research (Inserm), focused on one such emulsifier — carboxymethylcellulose (CMC) — which is commonly found in processed baked goods, such as brioche and sandwich bread, and ice cream.

The study, published in the journal Gut, describes how the team developed a new method that uses a simple stool sample to predict an individual’s sensitivity to CMC.

 

Sensitivity Detection

In a previous clinical trial conducted on healthy volunteers, Chassaing and colleagues found that CMC consumption altered the gut microbiota and fecal metabolome in some healthy individuals. In mice, transplanting fecal microbiota from CMC-sensitive animals made other animals susceptible. This has led researchers to investigate the characteristics of sensitive microbiota.

To explore this, the researchers developed an in vitro microbiota model capable of replicating multiple healthy human microbiota. CMC sensitivity was tested using this model, and the findings were validated in vivo by transplanting microbiota classified as sensitive or resistant to mice. Only mice that received microbiota predicted to be CMC-sensitive developed severe colitis after consuming CMC.

 

Predictive Signature

Next, the team analyzed the stool metagenomes of individuals with microbiotas classified as sensitive or resistant to CMC. They identified a specific microbial signature that could predict whether a given microbiota would react negatively to emulsifiers. Using molecular analyses, this signature allows researchers to predict whether an individual’s microbiota is susceptible or resistant to CMC exposure.

For the research team, these findings open the possibility of determining whether an individual is sensitive to a particular emulsifier, allowing for personalized dietary recommendations. This is particularly relevant for patients with chronic IBD and may also help prevent these conditions in those not previously affected.

These findings could pave the way for personalized dietary recommendations, particularly for patients with chronic IBD. By identifying individuals sensitive to specific emulsifiers, clinicians can tailor diets to reduce inflammation and potentially prevent disease onset in those at risk.

To further validate these insights, the team is launching a cohort study in patients with Crohn’s to explore why some individuals are more susceptible to food additives than others.

This story was translated from Univadis France using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

Diets in wealthier countries often include processed foods that contain additives, particularly emulsifiers. These additives are increasingly associated with the development of various diseases, including inflammatory bowel disease (IBD).

A research team led by Benoit Chassaing, PhD, research director at the French National Institute of Health and Medical Research (Inserm), focused on one such emulsifier — carboxymethylcellulose (CMC) — which is commonly found in processed baked goods, such as brioche and sandwich bread, and ice cream.

The study, published in the journal Gut, describes how the team developed a new method that uses a simple stool sample to predict an individual’s sensitivity to CMC.

 

Sensitivity Detection

In a previous clinical trial conducted on healthy volunteers, Chassaing and colleagues found that CMC consumption altered the gut microbiota and fecal metabolome in some healthy individuals. In mice, transplanting fecal microbiota from CMC-sensitive animals made other animals susceptible. This has led researchers to investigate the characteristics of sensitive microbiota.

To explore this, the researchers developed an in vitro microbiota model capable of replicating multiple healthy human microbiota. CMC sensitivity was tested using this model, and the findings were validated in vivo by transplanting microbiota classified as sensitive or resistant to mice. Only mice that received microbiota predicted to be CMC-sensitive developed severe colitis after consuming CMC.

 

Predictive Signature

Next, the team analyzed the stool metagenomes of individuals with microbiotas classified as sensitive or resistant to CMC. They identified a specific microbial signature that could predict whether a given microbiota would react negatively to emulsifiers. Using molecular analyses, this signature allows researchers to predict whether an individual’s microbiota is susceptible or resistant to CMC exposure.

For the research team, these findings open the possibility of determining whether an individual is sensitive to a particular emulsifier, allowing for personalized dietary recommendations. This is particularly relevant for patients with chronic IBD and may also help prevent these conditions in those not previously affected.

These findings could pave the way for personalized dietary recommendations, particularly for patients with chronic IBD. By identifying individuals sensitive to specific emulsifiers, clinicians can tailor diets to reduce inflammation and potentially prevent disease onset in those at risk.

To further validate these insights, the team is launching a cohort study in patients with Crohn’s to explore why some individuals are more susceptible to food additives than others.

This story was translated from Univadis France using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

Diets in wealthier countries often include processed foods that contain additives, particularly emulsifiers. These additives are increasingly associated with the development of various diseases, including inflammatory bowel disease (IBD).

A research team led by Benoit Chassaing, PhD, research director at the French National Institute of Health and Medical Research (Inserm), focused on one such emulsifier — carboxymethylcellulose (CMC) — which is commonly found in processed baked goods, such as brioche and sandwich bread, and ice cream.

The study, published in the journal Gut, describes how the team developed a new method that uses a simple stool sample to predict an individual’s sensitivity to CMC.

 

Sensitivity Detection

In a previous clinical trial conducted on healthy volunteers, Chassaing and colleagues found that CMC consumption altered the gut microbiota and fecal metabolome in some healthy individuals. In mice, transplanting fecal microbiota from CMC-sensitive animals made other animals susceptible. This has led researchers to investigate the characteristics of sensitive microbiota.

To explore this, the researchers developed an in vitro microbiota model capable of replicating multiple healthy human microbiota. CMC sensitivity was tested using this model, and the findings were validated in vivo by transplanting microbiota classified as sensitive or resistant to mice. Only mice that received microbiota predicted to be CMC-sensitive developed severe colitis after consuming CMC.

 

Predictive Signature

Next, the team analyzed the stool metagenomes of individuals with microbiotas classified as sensitive or resistant to CMC. They identified a specific microbial signature that could predict whether a given microbiota would react negatively to emulsifiers. Using molecular analyses, this signature allows researchers to predict whether an individual’s microbiota is susceptible or resistant to CMC exposure.

For the research team, these findings open the possibility of determining whether an individual is sensitive to a particular emulsifier, allowing for personalized dietary recommendations. This is particularly relevant for patients with chronic IBD and may also help prevent these conditions in those not previously affected.

These findings could pave the way for personalized dietary recommendations, particularly for patients with chronic IBD. By identifying individuals sensitive to specific emulsifiers, clinicians can tailor diets to reduce inflammation and potentially prevent disease onset in those at risk.

To further validate these insights, the team is launching a cohort study in patients with Crohn’s to explore why some individuals are more susceptible to food additives than others.

This story was translated from Univadis France using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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