Liam Davenport

BUDAPEST, HUNGARY — Twice daily intranasal oxytocin has been associated with improved social functioning, quality of life, and overall symptoms in adults with autism spectrum disorder (ASD), results of a small randomized control trial showed.

“One of the challenges for adults with autism is experiencing poor social interactions and difficulties in making friends. Insufficient social support from peers, friends, and family members can contribute to loneliness in adolescents with ASD, which in turn leads to anxiety, sadness, and social isolation,” said study investigator Saba Faraji Niri, MD, assistant professor of psychiatry, Tehran University of Medical Sciences in Iran. 

Recent US data show it is relatively common. In addition, previous research suggests intranasal oxytocin significantly increases activity in brain regions that play a role in establishing social interactions.

To evaluate the therapeutic effects and safety of intranasal oxytocin the researchers randomly assigned 39 adult patients with ASD to receive intranasal oxytocin or placebo with 24 units administered every 12 hours for 8 weeks. 

Dr. Faraji Niri said study participants were required to stop all psychotropic medications for at least 8 weeks prior to study entry. 

Participants were assessed at baseline and weeks 4 and 8 using the Autism Quotient, Ritvo Autism Asperger Diagnostic Scale — Revised (RAADS-R), Social Responsiveness Scale (SRS), Clinical Global Impression (CGI) scale, and the World Health Organization Quality of Life-BREF (WHOQL-BREF) questionnaire. Adverse events were also evaluated.

Dr. Faraji Niri said that those receiving intranasal oxytocin showed clinical improvement on RAADS-R scores (P = .010), as well as on the social communication subscale of the SRS (P = .002), the CGI scale (P = .000), and the physical (P = .004), psychological (P = .006), and social relationships (P = .046) domains of the WHOQL-BREF. 

However, although the findings were positive, she said at this point it’s not possible to draw any definitive conclusions. She noted the study had several potential confounders. These included differences in baseline levels of endogenous oxytocin among study participants individuals, as well as difference in required treatment doses, which were adjusted by age and sex. The presence of comorbidities and interactions with other treatments could also affect the results.

Commenting on the findings for this news organization, session chair Szabolcs Kéri, PhD, Professor, Sztárai Institute, University of Tokaj, Sárospatak, Hungary, said the use of oxytocin for ASD is controversial. He said that, while the research contributes to the scientific debate, the clinical significance of the findings is unclear. 

The investigators and Dr Keri reported no relevant financial disclosures.

A version of this article appeared on Medscape.com .

BUDAPEST, HUNGARY — Twice daily intranasal oxytocin has been associated with improved social functioning, quality of life, and overall symptoms in adults with autism spectrum disorder (ASD), results of a small randomized control trial showed.

“One of the challenges for adults with autism is experiencing poor social interactions and difficulties in making friends. Insufficient social support from peers, friends, and family members can contribute to loneliness in adolescents with ASD, which in turn leads to anxiety, sadness, and social isolation,” said study investigator Saba Faraji Niri, MD, assistant professor of psychiatry, Tehran University of Medical Sciences in Iran. 

Recent US data show it is relatively common. In addition, previous research suggests intranasal oxytocin significantly increases activity in brain regions that play a role in establishing social interactions.

To evaluate the therapeutic effects and safety of intranasal oxytocin the researchers randomly assigned 39 adult patients with ASD to receive intranasal oxytocin or placebo with 24 units administered every 12 hours for 8 weeks. 

Dr. Faraji Niri said study participants were required to stop all psychotropic medications for at least 8 weeks prior to study entry. 

Participants were assessed at baseline and weeks 4 and 8 using the Autism Quotient, Ritvo Autism Asperger Diagnostic Scale — Revised (RAADS-R), Social Responsiveness Scale (SRS), Clinical Global Impression (CGI) scale, and the World Health Organization Quality of Life-BREF (WHOQL-BREF) questionnaire. Adverse events were also evaluated.

Dr. Faraji Niri said that those receiving intranasal oxytocin showed clinical improvement on RAADS-R scores (P = .010), as well as on the social communication subscale of the SRS (P = .002), the CGI scale (P = .000), and the physical (P = .004), psychological (P = .006), and social relationships (P = .046) domains of the WHOQL-BREF. 

However, although the findings were positive, she said at this point it’s not possible to draw any definitive conclusions. She noted the study had several potential confounders. These included differences in baseline levels of endogenous oxytocin among study participants individuals, as well as difference in required treatment doses, which were adjusted by age and sex. The presence of comorbidities and interactions with other treatments could also affect the results.

Commenting on the findings for this news organization, session chair Szabolcs Kéri, PhD, Professor, Sztárai Institute, University of Tokaj, Sárospatak, Hungary, said the use of oxytocin for ASD is controversial. He said that, while the research contributes to the scientific debate, the clinical significance of the findings is unclear. 

The investigators and Dr Keri reported no relevant financial disclosures.

A version of this article appeared on Medscape.com .

BUDAPEST, HUNGARY — Twice daily intranasal oxytocin has been associated with improved social functioning, quality of life, and overall symptoms in adults with autism spectrum disorder (ASD), results of a small randomized control trial showed.

“One of the challenges for adults with autism is experiencing poor social interactions and difficulties in making friends. Insufficient social support from peers, friends, and family members can contribute to loneliness in adolescents with ASD, which in turn leads to anxiety, sadness, and social isolation,” said study investigator Saba Faraji Niri, MD, assistant professor of psychiatry, Tehran University of Medical Sciences in Iran. 

Recent US data show it is relatively common. In addition, previous research suggests intranasal oxytocin significantly increases activity in brain regions that play a role in establishing social interactions.

To evaluate the therapeutic effects and safety of intranasal oxytocin the researchers randomly assigned 39 adult patients with ASD to receive intranasal oxytocin or placebo with 24 units administered every 12 hours for 8 weeks. 

Dr. Faraji Niri said study participants were required to stop all psychotropic medications for at least 8 weeks prior to study entry. 

Participants were assessed at baseline and weeks 4 and 8 using the Autism Quotient, Ritvo Autism Asperger Diagnostic Scale — Revised (RAADS-R), Social Responsiveness Scale (SRS), Clinical Global Impression (CGI) scale, and the World Health Organization Quality of Life-BREF (WHOQL-BREF) questionnaire. Adverse events were also evaluated.

Dr. Faraji Niri said that those receiving intranasal oxytocin showed clinical improvement on RAADS-R scores (P = .010), as well as on the social communication subscale of the SRS (P = .002), the CGI scale (P = .000), and the physical (P = .004), psychological (P = .006), and social relationships (P = .046) domains of the WHOQL-BREF. 

However, although the findings were positive, she said at this point it’s not possible to draw any definitive conclusions. She noted the study had several potential confounders. These included differences in baseline levels of endogenous oxytocin among study participants individuals, as well as difference in required treatment doses, which were adjusted by age and sex. The presence of comorbidities and interactions with other treatments could also affect the results.

Commenting on the findings for this news organization, session chair Szabolcs Kéri, PhD, Professor, Sztárai Institute, University of Tokaj, Sárospatak, Hungary, said the use of oxytocin for ASD is controversial. He said that, while the research contributes to the scientific debate, the clinical significance of the findings is unclear. 

The investigators and Dr Keri reported no relevant financial disclosures.

A version of this article appeared on Medscape.com .

BUDAPEST, Hungary — A single dose of intravenous esketamine during delivery or cesarean section appears to reduce the risk for postpartum depression (PPD) by more than 50% in the first 6 weeks, a new meta-analysis suggested. However, the long-term safety and efficacy of the drug are still unclear.

Study investigator Angelina Kozhokar, MD, Department of Medicine, Universitat Internacional de Catalunya, Barcelona, Sant Cugat del Valles, Spain, told this news organization she was “surprised” by the size of the PPD risk reduction associated with the drug.

However, she added, “it’s important to consider that preliminary studies on a lot of medications used for postpartum depression have also shown very big effect sizes.”

Dr. Kozhokar believes that as more studies examining esketamine for PPD are conducted, “we will see more definitive effect sizes, and the safety profile for this new treatment” will become clearer.

The findings were presented at the European Psychiatric Association (EPA) Congress.
 

Significant Reduction

As previously reported by this news organization, intranasal esketamine (Spravato, Janssen) was shown to be superior to extended-release quetiapine (Seroquel, AstraZeneca), an atypical antipsychotic, for treatment-resistant depression.

With up to 13% of women experiencing PPD in the perinatal period, the researchers sought to examine the impact of esketamine administered prophylactically during labor or cesarean section on the incidence of the disorder.

They searched the PubMed, Scopus, and Google Scholar databases for randomized controlled trials examining the efficacy of esketamine and screened for PPD using the Edinburgh Postpartum Depression Scale (EPDS).

While the intranasal spray is the only form of esketamine approved by the US Food and Drug Administration, an injectable solution is also available. The researchers identified seven eligible trials that included a total of 1287 women. Of these participants, 635 (49.3%) received esketamine. Esketamine was delivered as either patient-controlled intravenous analgesia or a single intravenous dose during delivery or cesarean section.

Across the seven trials, esketamine was associated with a significant reduction in PPD at 1 week after delivery at a risk ratio vs placebo of 0.459 (P < .05). At 6 weeks, the reduction in PPD incidence was maintained, at a risk ratio of 0.470 (P < .01).

However, Dr. Kozhokar pointed out that the EPDS is a subjective measure of PPD, and the studies used different cutoff scores for depression, ranging from 9 to 13 points.
 

Unanswered Questions

She also cautioned that the adverse effects of esketamine on maternal and neonatal health need to be assessed, as well as the long-term cost/benefit ratio of prophylactic treatment.

All seven studies included in the meta-analysis were conducted in China, which limits the generalizability of the findings.

“I suppose they were quicker to get to the topic than the rest of the world,” Dr. Kozhokar said, while also suggesting that, potentially, “we are more regulated here in Europe.”

She pointed out that there is “an important safety concern about the use of medications such as ketamine and esketamine” in terms of the potential for addiction and the effect on babies over the long term, which is currently unknown.

Session chair Linda Rubene, MD, a psychiatrist in the Department of Psychiatry and Narcology at Riga Stradinš University, Riga, Latvia, welcomed the study.

“If we had more options to treat postpartum depression and to treat depression during pregnancy, it would be a great improvement,” she said.

However, she noted, because there are no long-term outcome data for esketamine in PPD, more study is needed. It is possible, said Dr. Rubene, that esketamine may not work for all women.

The investigators and Dr. Rubene reported no relevant financial disclosures.

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

BUDAPEST, Hungary — A single dose of intravenous esketamine during delivery or cesarean section appears to reduce the risk for postpartum depression (PPD) by more than 50% in the first 6 weeks, a new meta-analysis suggested. However, the long-term safety and efficacy of the drug are still unclear.

Study investigator Angelina Kozhokar, MD, Department of Medicine, Universitat Internacional de Catalunya, Barcelona, Sant Cugat del Valles, Spain, told this news organization she was “surprised” by the size of the PPD risk reduction associated with the drug.

However, she added, “it’s important to consider that preliminary studies on a lot of medications used for postpartum depression have also shown very big effect sizes.”

Dr. Kozhokar believes that as more studies examining esketamine for PPD are conducted, “we will see more definitive effect sizes, and the safety profile for this new treatment” will become clearer.

The findings were presented at the European Psychiatric Association (EPA) Congress.
 

Significant Reduction

As previously reported by this news organization, intranasal esketamine (Spravato, Janssen) was shown to be superior to extended-release quetiapine (Seroquel, AstraZeneca), an atypical antipsychotic, for treatment-resistant depression.

With up to 13% of women experiencing PPD in the perinatal period, the researchers sought to examine the impact of esketamine administered prophylactically during labor or cesarean section on the incidence of the disorder.

They searched the PubMed, Scopus, and Google Scholar databases for randomized controlled trials examining the efficacy of esketamine and screened for PPD using the Edinburgh Postpartum Depression Scale (EPDS).

While the intranasal spray is the only form of esketamine approved by the US Food and Drug Administration, an injectable solution is also available. The researchers identified seven eligible trials that included a total of 1287 women. Of these participants, 635 (49.3%) received esketamine. Esketamine was delivered as either patient-controlled intravenous analgesia or a single intravenous dose during delivery or cesarean section.

Across the seven trials, esketamine was associated with a significant reduction in PPD at 1 week after delivery at a risk ratio vs placebo of 0.459 (P < .05). At 6 weeks, the reduction in PPD incidence was maintained, at a risk ratio of 0.470 (P < .01).

However, Dr. Kozhokar pointed out that the EPDS is a subjective measure of PPD, and the studies used different cutoff scores for depression, ranging from 9 to 13 points.
 

Unanswered Questions

She also cautioned that the adverse effects of esketamine on maternal and neonatal health need to be assessed, as well as the long-term cost/benefit ratio of prophylactic treatment.

All seven studies included in the meta-analysis were conducted in China, which limits the generalizability of the findings.

“I suppose they were quicker to get to the topic than the rest of the world,” Dr. Kozhokar said, while also suggesting that, potentially, “we are more regulated here in Europe.”

She pointed out that there is “an important safety concern about the use of medications such as ketamine and esketamine” in terms of the potential for addiction and the effect on babies over the long term, which is currently unknown.

Session chair Linda Rubene, MD, a psychiatrist in the Department of Psychiatry and Narcology at Riga Stradinš University, Riga, Latvia, welcomed the study.

“If we had more options to treat postpartum depression and to treat depression during pregnancy, it would be a great improvement,” she said.

However, she noted, because there are no long-term outcome data for esketamine in PPD, more study is needed. It is possible, said Dr. Rubene, that esketamine may not work for all women.

The investigators and Dr. Rubene reported no relevant financial disclosures.

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

BUDAPEST, Hungary — A single dose of intravenous esketamine during delivery or cesarean section appears to reduce the risk for postpartum depression (PPD) by more than 50% in the first 6 weeks, a new meta-analysis suggested. However, the long-term safety and efficacy of the drug are still unclear.

Study investigator Angelina Kozhokar, MD, Department of Medicine, Universitat Internacional de Catalunya, Barcelona, Sant Cugat del Valles, Spain, told this news organization she was “surprised” by the size of the PPD risk reduction associated with the drug.

However, she added, “it’s important to consider that preliminary studies on a lot of medications used for postpartum depression have also shown very big effect sizes.”

Dr. Kozhokar believes that as more studies examining esketamine for PPD are conducted, “we will see more definitive effect sizes, and the safety profile for this new treatment” will become clearer.

The findings were presented at the European Psychiatric Association (EPA) Congress.
 

Significant Reduction

As previously reported by this news organization, intranasal esketamine (Spravato, Janssen) was shown to be superior to extended-release quetiapine (Seroquel, AstraZeneca), an atypical antipsychotic, for treatment-resistant depression.

With up to 13% of women experiencing PPD in the perinatal period, the researchers sought to examine the impact of esketamine administered prophylactically during labor or cesarean section on the incidence of the disorder.

They searched the PubMed, Scopus, and Google Scholar databases for randomized controlled trials examining the efficacy of esketamine and screened for PPD using the Edinburgh Postpartum Depression Scale (EPDS).

While the intranasal spray is the only form of esketamine approved by the US Food and Drug Administration, an injectable solution is also available. The researchers identified seven eligible trials that included a total of 1287 women. Of these participants, 635 (49.3%) received esketamine. Esketamine was delivered as either patient-controlled intravenous analgesia or a single intravenous dose during delivery or cesarean section.

Across the seven trials, esketamine was associated with a significant reduction in PPD at 1 week after delivery at a risk ratio vs placebo of 0.459 (P < .05). At 6 weeks, the reduction in PPD incidence was maintained, at a risk ratio of 0.470 (P < .01).

However, Dr. Kozhokar pointed out that the EPDS is a subjective measure of PPD, and the studies used different cutoff scores for depression, ranging from 9 to 13 points.
 

Unanswered Questions

She also cautioned that the adverse effects of esketamine on maternal and neonatal health need to be assessed, as well as the long-term cost/benefit ratio of prophylactic treatment.

All seven studies included in the meta-analysis were conducted in China, which limits the generalizability of the findings.

“I suppose they were quicker to get to the topic than the rest of the world,” Dr. Kozhokar said, while also suggesting that, potentially, “we are more regulated here in Europe.”

She pointed out that there is “an important safety concern about the use of medications such as ketamine and esketamine” in terms of the potential for addiction and the effect on babies over the long term, which is currently unknown.

Session chair Linda Rubene, MD, a psychiatrist in the Department of Psychiatry and Narcology at Riga Stradinš University, Riga, Latvia, welcomed the study.

“If we had more options to treat postpartum depression and to treat depression during pregnancy, it would be a great improvement,” she said.

However, she noted, because there are no long-term outcome data for esketamine in PPD, more study is needed. It is possible, said Dr. Rubene, that esketamine may not work for all women.

The investigators and Dr. Rubene reported no relevant financial disclosures.

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

The investigational bispecific T-cell engager tarlatamab achieved durable responses and clinically meaningful survival outcomes in patients with small-cell lung cancer (SCLC), particularly at lower doses, according to a follow-up analysis of the phase 1 DeLLphi-300 trial.

Most patients with central nervous system tumors also sustained tumor shrinkage long after receiving radiotherapy, providing “encouraging evidence” of the new agent’s intracranial activity, said study presenter Horst-Dieter Hummel, MD, Comprehensive Cancer Center Mainfranken, Würzburg, Germany.

The research was presented at the European Lung Cancer Congress 2024 on March 22.

Tarlatamab targets cancer cells that express the delta-like ligand 3 (DLL3), which occurs infrequently on normal cells but on most SCLC cells. 

Data from the phase 1 and phase 2 DeLLphi trials, published last year, showed the compound achieved “encouraging clinical activity” in pretreated patients, said Dr. Hummel.

The initial phase 1 DeLLphi study found that after a median follow-up of 8.7 months, the immunotherapy led to a disease control rate of 51.4%, a median progression-free survival of 3.7 months, and median overall survival of 13.2 months.

At the meeting, Dr. Hummel reported longer-term outcomes from the phase 1 study over a median of 12.1 months as well as intracranial activity in patients who received clinically relevant doses of tarlatamab, defined as ≥ 10 mg.

The 152 patients included in the analysis had a median of two prior lines of therapy; 76.3% had undergone radiotherapy, and 63.2% had received immunotherapy. Liver metastases were present in 42.1% of patients, and 25.0% had brain metastases.

Doses varied among participants, with 76 patients (50.0%) receiving 100 mg, 32 (21.0%) receiving 100 mg via extended intravenous infusion, 17 (11.2%) receiving 10 mg, and 8 (5.3%) receiving 30 mg.

The overall objective response rate was 25.0%, with a median duration of response of 11.2 months. Among patients given the 10-mg dose, the objective response rate was higher, at 35.3%, as was the median duration of response, at 14.9 months.

Tarlatamab was associated with a median overall survival of 17.5 months, with 57.9% of patients alive at 12 months. Patients receiving the 10 mg dose had a better median overall survival of 20.3 months.

Of the 16 patients with analyzable central nervous system tumors, 62.5% experienced tumor shrinkage by ≥ 30% and 87.5% experienced intracranial disease control, which lasted for a median of 7.4 months.

In this follow-up study, tarlatamab demonstrated “clinically meaningful survival outcomes in patients with previously treated SCLC, particularly with the 10 mg dose,” Dr. Hummel concluded in his presentation.

No new safety signals emerged, though almost all patients did experience tarlatamab-related adverse events (94.8% for doses > 10 mg and 100% of patients with 10 mg doses). Overall, 66.4% of the total cohort experienced cytokine release syndrome of any grade, and 11.8% developed immune effector cell-associated neurotoxicity syndrome. 

Discontinuation due to treatment-related adverse events occurred in 9 patients overall, and adverse events that led to dose interruption or reduction occurred in 32 patients overall. 

“After many efforts at DLL3 targeting, we finally have an agent that shows activity and efficacy, and with convincing data,” said Jessica Menis, MD, a medical oncologist at the oncology department of the University Hospital of Verona, Italy, who was not involved in the study. The intracranial activity of tarlatamab “needs to be further evaluated in untreated patients,” Dr. Menis noted, because the study included only patients with stable, treated brain metastases.

And given the high rates of adverse events, Dr. Menis cautioned that adverse event management “will be a challenge.”

On X (Twitter), Tom Newsom-Davis, MBBS, PhD, a consultant in medical oncology at Chelsea and Westminster Hospital, London, said that tarlatamab is “not a straightforward drug to use,” highlighting the occurrence of cytokine release syndrome.

“But in this significantly pretreated population and in this hard-to-treat tumor type,” the rate and duration of responses seen with the extended follow-up are ‘impressive’,” he added.

DeLLphi-300, 301, and 304 were funded by Amgen Inc. Dr. Hummel declared relationships with several companies, including Amgen, Bristol Myers Squibb, AstraZeneca, Celgene, Merck, Novartis, Daiichi Sankyo, and Roche. Dr. Menis declared relationships with AstraZeneca, BMS, MSD, Roche, and Novartis.
 

A version of this article appeared on Medscape.com.

The investigational bispecific T-cell engager tarlatamab achieved durable responses and clinically meaningful survival outcomes in patients with small-cell lung cancer (SCLC), particularly at lower doses, according to a follow-up analysis of the phase 1 DeLLphi-300 trial.

Most patients with central nervous system tumors also sustained tumor shrinkage long after receiving radiotherapy, providing “encouraging evidence” of the new agent’s intracranial activity, said study presenter Horst-Dieter Hummel, MD, Comprehensive Cancer Center Mainfranken, Würzburg, Germany.

The research was presented at the European Lung Cancer Congress 2024 on March 22.

Tarlatamab targets cancer cells that express the delta-like ligand 3 (DLL3), which occurs infrequently on normal cells but on most SCLC cells. 

Data from the phase 1 and phase 2 DeLLphi trials, published last year, showed the compound achieved “encouraging clinical activity” in pretreated patients, said Dr. Hummel.

The initial phase 1 DeLLphi study found that after a median follow-up of 8.7 months, the immunotherapy led to a disease control rate of 51.4%, a median progression-free survival of 3.7 months, and median overall survival of 13.2 months.

At the meeting, Dr. Hummel reported longer-term outcomes from the phase 1 study over a median of 12.1 months as well as intracranial activity in patients who received clinically relevant doses of tarlatamab, defined as ≥ 10 mg.

The 152 patients included in the analysis had a median of two prior lines of therapy; 76.3% had undergone radiotherapy, and 63.2% had received immunotherapy. Liver metastases were present in 42.1% of patients, and 25.0% had brain metastases.

Doses varied among participants, with 76 patients (50.0%) receiving 100 mg, 32 (21.0%) receiving 100 mg via extended intravenous infusion, 17 (11.2%) receiving 10 mg, and 8 (5.3%) receiving 30 mg.

The overall objective response rate was 25.0%, with a median duration of response of 11.2 months. Among patients given the 10-mg dose, the objective response rate was higher, at 35.3%, as was the median duration of response, at 14.9 months.

Tarlatamab was associated with a median overall survival of 17.5 months, with 57.9% of patients alive at 12 months. Patients receiving the 10 mg dose had a better median overall survival of 20.3 months.

Of the 16 patients with analyzable central nervous system tumors, 62.5% experienced tumor shrinkage by ≥ 30% and 87.5% experienced intracranial disease control, which lasted for a median of 7.4 months.

In this follow-up study, tarlatamab demonstrated “clinically meaningful survival outcomes in patients with previously treated SCLC, particularly with the 10 mg dose,” Dr. Hummel concluded in his presentation.

No new safety signals emerged, though almost all patients did experience tarlatamab-related adverse events (94.8% for doses > 10 mg and 100% of patients with 10 mg doses). Overall, 66.4% of the total cohort experienced cytokine release syndrome of any grade, and 11.8% developed immune effector cell-associated neurotoxicity syndrome. 

Discontinuation due to treatment-related adverse events occurred in 9 patients overall, and adverse events that led to dose interruption or reduction occurred in 32 patients overall. 

“After many efforts at DLL3 targeting, we finally have an agent that shows activity and efficacy, and with convincing data,” said Jessica Menis, MD, a medical oncologist at the oncology department of the University Hospital of Verona, Italy, who was not involved in the study. The intracranial activity of tarlatamab “needs to be further evaluated in untreated patients,” Dr. Menis noted, because the study included only patients with stable, treated brain metastases.

And given the high rates of adverse events, Dr. Menis cautioned that adverse event management “will be a challenge.”

On X (Twitter), Tom Newsom-Davis, MBBS, PhD, a consultant in medical oncology at Chelsea and Westminster Hospital, London, said that tarlatamab is “not a straightforward drug to use,” highlighting the occurrence of cytokine release syndrome.

“But in this significantly pretreated population and in this hard-to-treat tumor type,” the rate and duration of responses seen with the extended follow-up are ‘impressive’,” he added.

DeLLphi-300, 301, and 304 were funded by Amgen Inc. Dr. Hummel declared relationships with several companies, including Amgen, Bristol Myers Squibb, AstraZeneca, Celgene, Merck, Novartis, Daiichi Sankyo, and Roche. Dr. Menis declared relationships with AstraZeneca, BMS, MSD, Roche, and Novartis.
 

A version of this article appeared on Medscape.com.

The investigational bispecific T-cell engager tarlatamab achieved durable responses and clinically meaningful survival outcomes in patients with small-cell lung cancer (SCLC), particularly at lower doses, according to a follow-up analysis of the phase 1 DeLLphi-300 trial.

Most patients with central nervous system tumors also sustained tumor shrinkage long after receiving radiotherapy, providing “encouraging evidence” of the new agent’s intracranial activity, said study presenter Horst-Dieter Hummel, MD, Comprehensive Cancer Center Mainfranken, Würzburg, Germany.

The research was presented at the European Lung Cancer Congress 2024 on March 22.

Tarlatamab targets cancer cells that express the delta-like ligand 3 (DLL3), which occurs infrequently on normal cells but on most SCLC cells. 

Data from the phase 1 and phase 2 DeLLphi trials, published last year, showed the compound achieved “encouraging clinical activity” in pretreated patients, said Dr. Hummel.

The initial phase 1 DeLLphi study found that after a median follow-up of 8.7 months, the immunotherapy led to a disease control rate of 51.4%, a median progression-free survival of 3.7 months, and median overall survival of 13.2 months.

At the meeting, Dr. Hummel reported longer-term outcomes from the phase 1 study over a median of 12.1 months as well as intracranial activity in patients who received clinically relevant doses of tarlatamab, defined as ≥ 10 mg.

The 152 patients included in the analysis had a median of two prior lines of therapy; 76.3% had undergone radiotherapy, and 63.2% had received immunotherapy. Liver metastases were present in 42.1% of patients, and 25.0% had brain metastases.

Doses varied among participants, with 76 patients (50.0%) receiving 100 mg, 32 (21.0%) receiving 100 mg via extended intravenous infusion, 17 (11.2%) receiving 10 mg, and 8 (5.3%) receiving 30 mg.

The overall objective response rate was 25.0%, with a median duration of response of 11.2 months. Among patients given the 10-mg dose, the objective response rate was higher, at 35.3%, as was the median duration of response, at 14.9 months.

Tarlatamab was associated with a median overall survival of 17.5 months, with 57.9% of patients alive at 12 months. Patients receiving the 10 mg dose had a better median overall survival of 20.3 months.

Of the 16 patients with analyzable central nervous system tumors, 62.5% experienced tumor shrinkage by ≥ 30% and 87.5% experienced intracranial disease control, which lasted for a median of 7.4 months.

In this follow-up study, tarlatamab demonstrated “clinically meaningful survival outcomes in patients with previously treated SCLC, particularly with the 10 mg dose,” Dr. Hummel concluded in his presentation.

No new safety signals emerged, though almost all patients did experience tarlatamab-related adverse events (94.8% for doses > 10 mg and 100% of patients with 10 mg doses). Overall, 66.4% of the total cohort experienced cytokine release syndrome of any grade, and 11.8% developed immune effector cell-associated neurotoxicity syndrome. 

Discontinuation due to treatment-related adverse events occurred in 9 patients overall, and adverse events that led to dose interruption or reduction occurred in 32 patients overall. 

“After many efforts at DLL3 targeting, we finally have an agent that shows activity and efficacy, and with convincing data,” said Jessica Menis, MD, a medical oncologist at the oncology department of the University Hospital of Verona, Italy, who was not involved in the study. The intracranial activity of tarlatamab “needs to be further evaluated in untreated patients,” Dr. Menis noted, because the study included only patients with stable, treated brain metastases.

And given the high rates of adverse events, Dr. Menis cautioned that adverse event management “will be a challenge.”

On X (Twitter), Tom Newsom-Davis, MBBS, PhD, a consultant in medical oncology at Chelsea and Westminster Hospital, London, said that tarlatamab is “not a straightforward drug to use,” highlighting the occurrence of cytokine release syndrome.

“But in this significantly pretreated population and in this hard-to-treat tumor type,” the rate and duration of responses seen with the extended follow-up are ‘impressive’,” he added.

DeLLphi-300, 301, and 304 were funded by Amgen Inc. Dr. Hummel declared relationships with several companies, including Amgen, Bristol Myers Squibb, AstraZeneca, Celgene, Merck, Novartis, Daiichi Sankyo, and Roche. Dr. Menis declared relationships with AstraZeneca, BMS, MSD, Roche, and Novartis.
 

A version of this article appeared on Medscape.com.

While it is increasingly apparent that clonal hematopoiesis of indeterminate potential (CHIP) is associated with conditions that can dramatically affect an individual’s risk for both malignant and cardiovascular diseases, and even death, it has not been clear what to do about it.

Now, researchers at the cutting edge of both oncologic and cardiovascular research are not only defining the prognosis of CHIP with greater granularity but are also finding clues to mitigate the risks.

“It’s a very, very rapidly moving area,” said Christie M. Ballantyne, MD, Director, Center for Cardiometabolic Disease Prevention, Baylor College of Medicine, Houston, adding that, in many respects, “it’s a totally new area.”
 

CHIP Defined

CHIP was first recognized in the 1990s, when Martin F. Fey, MD, and colleagues from University and Inselspital, Bern, Switzerland, found X-linked inactivation in older women and suggested it was the result of acquired clonality later referred to as being of “indeterminate potential,” although that added syntax is currently a matter of debate.

Further work showed that, while somatic gene mutations occur spontaneously and are an unavoidable consequence of aging, their impact can vary widely.

The majority are “functionally silent,” while others may affect genes crucial to tissue self-renewal and differentiation, Lukasz Gondek, MD, PhD, assistant professor, Johns Hopkins Cellular and Molecular Medicine Program, Baltimore, and colleagues, noted in a recent review.

This results in the outgrowth of affected cells, known as clonal expansion, further dubbed clonal hematopoiesis when it occurs in hematopoietic tissue.

“Even though there’s clonal expansion, there’s no one CHIP,” Dr. Gondek said. “There are different flavors, and it depends on the genes that are mutated in the hematopoietic cells.”

He continued: “The older we get, the more mutations we acquire, and the probability that this mutation will hit the gene that’s responsible for expansion of the clone is higher.”

“That’s why CHIP is very uncommon in people under the age of 40, but it becomes more common in the fifth, sixth, and seventh decade of life and beyond.”

Indeed, it occurs in 10% to 15% of people aged 65 years or older, and in at least 30% of individuals by 80 years of age. In contrast, just 1% of those aged less than 50 years have the condition.

The most commonly affected genes, in around 80% of patients with CHIP, are the epigenetic regulators DNMT3A, TET2, and ASXL1; the DNA damage repair genes PPM1D and TP53; the regulatory tyrosine kinase JAK2; and the messenger RNA spliceosome components SF3B1 and SRSF2.

These mutations can have “two potential consequences,” explained Lachelle D. Weeks, MD, PhD, a hematologist at the Dana-Farber Cancer Institute, Boston.

“One is that there’s a risk of blood cancer development,” as several of the mutations are known drivers of leukemia or myelodysplastic syndromes (MDS).

Although the majority of individuals who acquire clonal hematopoiesis with age will never develop MDS, it nevertheless confers an 11- to 13-fold increased risk or an absolute risk of approximately 0.5%-1.0% per year.

Dr. Weeks continued that “the other side of it, though, is that those cells that have these mutations can also accelerate the risk of developing nonmalignant diseases like cardiovascular disease.”

This, Dr. Gondek explained, is because the mutations will be retained when the stem cells become monocytes or macrophages and, by either silencing or activating individual genes, they can make the cells more pro-inflammatory.

The result is that CHIP is associated with a marked increased risk for arteriosclerotic events such as stroke, myocardial infarction, decompensated heart failure, and cardiogenic shock, and worse outcomes after these events.

Researchers have shown that CHIP-related somatic mutations are associated with a twofold increased risk for coronary heart disease, a more than 2.5-fold increased risk for ischemic stroke, and a fourfold greater risk for myocardial infarction. A study from earlier this year found that CHIP also increases the risk for heart failure with preserved ejection fraction more than twofold.

There is even evidence to suggest that CHIP is associated with more severe acute kidney injury (AKI) and greater post-AKI kidney fibrosis.

The consequence is that individuals with CHIP face a 40% increased risk for all-cause mortality over 8 years.
 

No CHIP Test Yet

All of which has led for some to call for CHIP testing.

However, there are currently no screening programs for CHIP and no plans to introduce any. “So most CHIP is actually being diagnosed incidentally, when patients get genetic testing for some other indication,” said Dr. Weeks.

“The patients that we see in our CHIP clinic at Dana-Farber have genetic testing because they have low blood counts,” she continued, “and somebody’s trying to figure out: Do you have MDS?”

Other patients have genetic testing due to a family history of other cancers, “and so they’re getting hereditary cancer panels to determine if they have Lynch syndrome, or other hereditary syndromes,” which are picking up gene mutations associated with CHIP.

In other cases, study protocols are identifying CHIP “in various research contexts, and then as a follow-up, some of those patients end up with our clinic,” added Dr. Weeks.

Due to the associated risks for CHIP, “obviously everyone wants to know whether they are at risk for hematologic malignancy, or not,” said Dr. Gondek. To those ends, Dr. Weeks and colleagues developed the clonal hematopoiesis risk score (CHRS).

Published by NEJM Evidence in 2023, the score takes a range of predictive variables, such as age, number of mutations and their degree of associated risk, the variant allele fraction, and a series of blood indices to define patients as low-, intermediate-, or high-risk.

“A little over half” of high-risk individuals “will develop a blood cancer” such as MDS or acute myeloid leukemia (AML)” over the next 10 years, Weeks explained, while “for your intermediate risk folks, in that same time period, 7%-8% of them will develop a blood cancer.”

In low-risk individuals, the 10-year risk for MDS or AML is just 1%.

Dr. Weeks noted the “caveat that there are environmental factors or patient-specific issues that might increase your risk that are not considered in the calculator,” such the presence of hereditary cancer syndromes, “or if you’re getting chemotherapy for other cancers.”

From a cardiology point of view, Dr. Ballantyne said that, above all, “cardiologists need to be aware that some of these people are at increased risk for cardiovascular events.” This prompted a team including Dr. Weeks and Dr. Ballantyne to study whether the CHRS can also predict cardiovascular risk.

They found that people designated low-risk on the score faced an 8% increased risk for all-cause mortality vs individuals without CHIP during a median follow-up of 7 years. This rose to a 12% increase in intermediate-risk individuals.

And those deemed high-risk had a 2.5-fold increased risk for early mortality and a threefold higher risk for cardiovascular death.

Dr. Weeks noted: “We have not done a dedicated study to define a cardiovascular disease-specific calculator for CHIP,” but in the meantime, the CHRS is a “very reasonable way to estimate what someone’s risk of progression or adverse events is for cardiovascular disease.”

For clinicians, however, the key question becomes: What can be done to mitigate the risks, particularly in high-risk individuals?

For malignant conditions, the approach is to monitor patients, although “we and other centers are in the process of developing various interventional clinical trials to test various agents on their ability to improve blood counts, as well as to mitigate the risk of progression to overt blood cancer,” said Dr. Weeks.
 

Treat CHIP Like Lipoprotein(a)?

As for cardiovascular risk, Dr. Ballantyne believes that, because CHIP is an unmodifiable risk factor, an example to follow could be lipoprotein(a) (LP[a]).

“We don’t have a therapy specifically to target LP(a) yet, but we do know that the things that benefit in general,” he said, such as “taking a statin, lowering blood pressure into the optimal zone, diet ,and exercise.”

“What we do in our clinic, and what others have been doing,” Dr. Weeks added, “is for every patient who comes in and is diagnosed with CHIP, we are referring them to preventative cardiology for very aggressive preventative management.”

Finally, both Dr. Ballantyne and Dr. Weeks agree that there are many potential innovations on the horizon.

“It’s pretty exciting in terms of beginning to understand some of the links between aging, cardiovascular disease, and cancer that we had not been thinking about,” Dr. Ballantyne said.

On the malignant side, Dr. Weeks is already working on a prospective study to determine how the risks associated with CHIP evolve when patients undergo chemotherapy and radiation for other cancers.

“That will be really exciting and will help us to develop a specific calculator in that context,” she said, adding that a cardiovascular-specific calculator “is also coming down the line.”

Dr. Weeks declared relationships with Abbvie, Vertex, and Sobi. Dr. Ballantyne declared a relationship with Ten Sixteen Bio, and funding from the National Heart, Lung, and Blood Institute. No other relevant financial relationships were declared.
 

A version of this article appeared on Medscape.com.

While it is increasingly apparent that clonal hematopoiesis of indeterminate potential (CHIP) is associated with conditions that can dramatically affect an individual’s risk for both malignant and cardiovascular diseases, and even death, it has not been clear what to do about it.

Now, researchers at the cutting edge of both oncologic and cardiovascular research are not only defining the prognosis of CHIP with greater granularity but are also finding clues to mitigate the risks.

“It’s a very, very rapidly moving area,” said Christie M. Ballantyne, MD, Director, Center for Cardiometabolic Disease Prevention, Baylor College of Medicine, Houston, adding that, in many respects, “it’s a totally new area.”
 

CHIP Defined

CHIP was first recognized in the 1990s, when Martin F. Fey, MD, and colleagues from University and Inselspital, Bern, Switzerland, found X-linked inactivation in older women and suggested it was the result of acquired clonality later referred to as being of “indeterminate potential,” although that added syntax is currently a matter of debate.

Further work showed that, while somatic gene mutations occur spontaneously and are an unavoidable consequence of aging, their impact can vary widely.

The majority are “functionally silent,” while others may affect genes crucial to tissue self-renewal and differentiation, Lukasz Gondek, MD, PhD, assistant professor, Johns Hopkins Cellular and Molecular Medicine Program, Baltimore, and colleagues, noted in a recent review.

This results in the outgrowth of affected cells, known as clonal expansion, further dubbed clonal hematopoiesis when it occurs in hematopoietic tissue.

“Even though there’s clonal expansion, there’s no one CHIP,” Dr. Gondek said. “There are different flavors, and it depends on the genes that are mutated in the hematopoietic cells.”

He continued: “The older we get, the more mutations we acquire, and the probability that this mutation will hit the gene that’s responsible for expansion of the clone is higher.”

“That’s why CHIP is very uncommon in people under the age of 40, but it becomes more common in the fifth, sixth, and seventh decade of life and beyond.”

Indeed, it occurs in 10% to 15% of people aged 65 years or older, and in at least 30% of individuals by 80 years of age. In contrast, just 1% of those aged less than 50 years have the condition.

The most commonly affected genes, in around 80% of patients with CHIP, are the epigenetic regulators DNMT3A, TET2, and ASXL1; the DNA damage repair genes PPM1D and TP53; the regulatory tyrosine kinase JAK2; and the messenger RNA spliceosome components SF3B1 and SRSF2.

These mutations can have “two potential consequences,” explained Lachelle D. Weeks, MD, PhD, a hematologist at the Dana-Farber Cancer Institute, Boston.

“One is that there’s a risk of blood cancer development,” as several of the mutations are known drivers of leukemia or myelodysplastic syndromes (MDS).

Although the majority of individuals who acquire clonal hematopoiesis with age will never develop MDS, it nevertheless confers an 11- to 13-fold increased risk or an absolute risk of approximately 0.5%-1.0% per year.

Dr. Weeks continued that “the other side of it, though, is that those cells that have these mutations can also accelerate the risk of developing nonmalignant diseases like cardiovascular disease.”

This, Dr. Gondek explained, is because the mutations will be retained when the stem cells become monocytes or macrophages and, by either silencing or activating individual genes, they can make the cells more pro-inflammatory.

The result is that CHIP is associated with a marked increased risk for arteriosclerotic events such as stroke, myocardial infarction, decompensated heart failure, and cardiogenic shock, and worse outcomes after these events.

Researchers have shown that CHIP-related somatic mutations are associated with a twofold increased risk for coronary heart disease, a more than 2.5-fold increased risk for ischemic stroke, and a fourfold greater risk for myocardial infarction. A study from earlier this year found that CHIP also increases the risk for heart failure with preserved ejection fraction more than twofold.

There is even evidence to suggest that CHIP is associated with more severe acute kidney injury (AKI) and greater post-AKI kidney fibrosis.

The consequence is that individuals with CHIP face a 40% increased risk for all-cause mortality over 8 years.
 

No CHIP Test Yet

All of which has led for some to call for CHIP testing.

However, there are currently no screening programs for CHIP and no plans to introduce any. “So most CHIP is actually being diagnosed incidentally, when patients get genetic testing for some other indication,” said Dr. Weeks.

“The patients that we see in our CHIP clinic at Dana-Farber have genetic testing because they have low blood counts,” she continued, “and somebody’s trying to figure out: Do you have MDS?”

Other patients have genetic testing due to a family history of other cancers, “and so they’re getting hereditary cancer panels to determine if they have Lynch syndrome, or other hereditary syndromes,” which are picking up gene mutations associated with CHIP.

In other cases, study protocols are identifying CHIP “in various research contexts, and then as a follow-up, some of those patients end up with our clinic,” added Dr. Weeks.

Due to the associated risks for CHIP, “obviously everyone wants to know whether they are at risk for hematologic malignancy, or not,” said Dr. Gondek. To those ends, Dr. Weeks and colleagues developed the clonal hematopoiesis risk score (CHRS).

Published by NEJM Evidence in 2023, the score takes a range of predictive variables, such as age, number of mutations and their degree of associated risk, the variant allele fraction, and a series of blood indices to define patients as low-, intermediate-, or high-risk.

“A little over half” of high-risk individuals “will develop a blood cancer” such as MDS or acute myeloid leukemia (AML)” over the next 10 years, Weeks explained, while “for your intermediate risk folks, in that same time period, 7%-8% of them will develop a blood cancer.”

In low-risk individuals, the 10-year risk for MDS or AML is just 1%.

Dr. Weeks noted the “caveat that there are environmental factors or patient-specific issues that might increase your risk that are not considered in the calculator,” such the presence of hereditary cancer syndromes, “or if you’re getting chemotherapy for other cancers.”

From a cardiology point of view, Dr. Ballantyne said that, above all, “cardiologists need to be aware that some of these people are at increased risk for cardiovascular events.” This prompted a team including Dr. Weeks and Dr. Ballantyne to study whether the CHRS can also predict cardiovascular risk.

They found that people designated low-risk on the score faced an 8% increased risk for all-cause mortality vs individuals without CHIP during a median follow-up of 7 years. This rose to a 12% increase in intermediate-risk individuals.

And those deemed high-risk had a 2.5-fold increased risk for early mortality and a threefold higher risk for cardiovascular death.

Dr. Weeks noted: “We have not done a dedicated study to define a cardiovascular disease-specific calculator for CHIP,” but in the meantime, the CHRS is a “very reasonable way to estimate what someone’s risk of progression or adverse events is for cardiovascular disease.”

For clinicians, however, the key question becomes: What can be done to mitigate the risks, particularly in high-risk individuals?

For malignant conditions, the approach is to monitor patients, although “we and other centers are in the process of developing various interventional clinical trials to test various agents on their ability to improve blood counts, as well as to mitigate the risk of progression to overt blood cancer,” said Dr. Weeks.
 

Treat CHIP Like Lipoprotein(a)?

As for cardiovascular risk, Dr. Ballantyne believes that, because CHIP is an unmodifiable risk factor, an example to follow could be lipoprotein(a) (LP[a]).

“We don’t have a therapy specifically to target LP(a) yet, but we do know that the things that benefit in general,” he said, such as “taking a statin, lowering blood pressure into the optimal zone, diet ,and exercise.”

“What we do in our clinic, and what others have been doing,” Dr. Weeks added, “is for every patient who comes in and is diagnosed with CHIP, we are referring them to preventative cardiology for very aggressive preventative management.”

Finally, both Dr. Ballantyne and Dr. Weeks agree that there are many potential innovations on the horizon.

“It’s pretty exciting in terms of beginning to understand some of the links between aging, cardiovascular disease, and cancer that we had not been thinking about,” Dr. Ballantyne said.

On the malignant side, Dr. Weeks is already working on a prospective study to determine how the risks associated with CHIP evolve when patients undergo chemotherapy and radiation for other cancers.

“That will be really exciting and will help us to develop a specific calculator in that context,” she said, adding that a cardiovascular-specific calculator “is also coming down the line.”

Dr. Weeks declared relationships with Abbvie, Vertex, and Sobi. Dr. Ballantyne declared a relationship with Ten Sixteen Bio, and funding from the National Heart, Lung, and Blood Institute. No other relevant financial relationships were declared.
 

A version of this article appeared on Medscape.com.

While it is increasingly apparent that clonal hematopoiesis of indeterminate potential (CHIP) is associated with conditions that can dramatically affect an individual’s risk for both malignant and cardiovascular diseases, and even death, it has not been clear what to do about it.

Now, researchers at the cutting edge of both oncologic and cardiovascular research are not only defining the prognosis of CHIP with greater granularity but are also finding clues to mitigate the risks.

“It’s a very, very rapidly moving area,” said Christie M. Ballantyne, MD, Director, Center for Cardiometabolic Disease Prevention, Baylor College of Medicine, Houston, adding that, in many respects, “it’s a totally new area.”
 

CHIP Defined

CHIP was first recognized in the 1990s, when Martin F. Fey, MD, and colleagues from University and Inselspital, Bern, Switzerland, found X-linked inactivation in older women and suggested it was the result of acquired clonality later referred to as being of “indeterminate potential,” although that added syntax is currently a matter of debate.

Further work showed that, while somatic gene mutations occur spontaneously and are an unavoidable consequence of aging, their impact can vary widely.

The majority are “functionally silent,” while others may affect genes crucial to tissue self-renewal and differentiation, Lukasz Gondek, MD, PhD, assistant professor, Johns Hopkins Cellular and Molecular Medicine Program, Baltimore, and colleagues, noted in a recent review.

This results in the outgrowth of affected cells, known as clonal expansion, further dubbed clonal hematopoiesis when it occurs in hematopoietic tissue.

“Even though there’s clonal expansion, there’s no one CHIP,” Dr. Gondek said. “There are different flavors, and it depends on the genes that are mutated in the hematopoietic cells.”

He continued: “The older we get, the more mutations we acquire, and the probability that this mutation will hit the gene that’s responsible for expansion of the clone is higher.”

“That’s why CHIP is very uncommon in people under the age of 40, but it becomes more common in the fifth, sixth, and seventh decade of life and beyond.”

Indeed, it occurs in 10% to 15% of people aged 65 years or older, and in at least 30% of individuals by 80 years of age. In contrast, just 1% of those aged less than 50 years have the condition.

The most commonly affected genes, in around 80% of patients with CHIP, are the epigenetic regulators DNMT3A, TET2, and ASXL1; the DNA damage repair genes PPM1D and TP53; the regulatory tyrosine kinase JAK2; and the messenger RNA spliceosome components SF3B1 and SRSF2.

These mutations can have “two potential consequences,” explained Lachelle D. Weeks, MD, PhD, a hematologist at the Dana-Farber Cancer Institute, Boston.

“One is that there’s a risk of blood cancer development,” as several of the mutations are known drivers of leukemia or myelodysplastic syndromes (MDS).

Although the majority of individuals who acquire clonal hematopoiesis with age will never develop MDS, it nevertheless confers an 11- to 13-fold increased risk or an absolute risk of approximately 0.5%-1.0% per year.

Dr. Weeks continued that “the other side of it, though, is that those cells that have these mutations can also accelerate the risk of developing nonmalignant diseases like cardiovascular disease.”

This, Dr. Gondek explained, is because the mutations will be retained when the stem cells become monocytes or macrophages and, by either silencing or activating individual genes, they can make the cells more pro-inflammatory.

The result is that CHIP is associated with a marked increased risk for arteriosclerotic events such as stroke, myocardial infarction, decompensated heart failure, and cardiogenic shock, and worse outcomes after these events.

Researchers have shown that CHIP-related somatic mutations are associated with a twofold increased risk for coronary heart disease, a more than 2.5-fold increased risk for ischemic stroke, and a fourfold greater risk for myocardial infarction. A study from earlier this year found that CHIP also increases the risk for heart failure with preserved ejection fraction more than twofold.

There is even evidence to suggest that CHIP is associated with more severe acute kidney injury (AKI) and greater post-AKI kidney fibrosis.

The consequence is that individuals with CHIP face a 40% increased risk for all-cause mortality over 8 years.
 

No CHIP Test Yet

All of which has led for some to call for CHIP testing.

However, there are currently no screening programs for CHIP and no plans to introduce any. “So most CHIP is actually being diagnosed incidentally, when patients get genetic testing for some other indication,” said Dr. Weeks.

“The patients that we see in our CHIP clinic at Dana-Farber have genetic testing because they have low blood counts,” she continued, “and somebody’s trying to figure out: Do you have MDS?”

Other patients have genetic testing due to a family history of other cancers, “and so they’re getting hereditary cancer panels to determine if they have Lynch syndrome, or other hereditary syndromes,” which are picking up gene mutations associated with CHIP.

In other cases, study protocols are identifying CHIP “in various research contexts, and then as a follow-up, some of those patients end up with our clinic,” added Dr. Weeks.

Due to the associated risks for CHIP, “obviously everyone wants to know whether they are at risk for hematologic malignancy, or not,” said Dr. Gondek. To those ends, Dr. Weeks and colleagues developed the clonal hematopoiesis risk score (CHRS).

Published by NEJM Evidence in 2023, the score takes a range of predictive variables, such as age, number of mutations and their degree of associated risk, the variant allele fraction, and a series of blood indices to define patients as low-, intermediate-, or high-risk.

“A little over half” of high-risk individuals “will develop a blood cancer” such as MDS or acute myeloid leukemia (AML)” over the next 10 years, Weeks explained, while “for your intermediate risk folks, in that same time period, 7%-8% of them will develop a blood cancer.”

In low-risk individuals, the 10-year risk for MDS or AML is just 1%.

Dr. Weeks noted the “caveat that there are environmental factors or patient-specific issues that might increase your risk that are not considered in the calculator,” such the presence of hereditary cancer syndromes, “or if you’re getting chemotherapy for other cancers.”

From a cardiology point of view, Dr. Ballantyne said that, above all, “cardiologists need to be aware that some of these people are at increased risk for cardiovascular events.” This prompted a team including Dr. Weeks and Dr. Ballantyne to study whether the CHRS can also predict cardiovascular risk.

They found that people designated low-risk on the score faced an 8% increased risk for all-cause mortality vs individuals without CHIP during a median follow-up of 7 years. This rose to a 12% increase in intermediate-risk individuals.

And those deemed high-risk had a 2.5-fold increased risk for early mortality and a threefold higher risk for cardiovascular death.

Dr. Weeks noted: “We have not done a dedicated study to define a cardiovascular disease-specific calculator for CHIP,” but in the meantime, the CHRS is a “very reasonable way to estimate what someone’s risk of progression or adverse events is for cardiovascular disease.”

For clinicians, however, the key question becomes: What can be done to mitigate the risks, particularly in high-risk individuals?

For malignant conditions, the approach is to monitor patients, although “we and other centers are in the process of developing various interventional clinical trials to test various agents on their ability to improve blood counts, as well as to mitigate the risk of progression to overt blood cancer,” said Dr. Weeks.
 

Treat CHIP Like Lipoprotein(a)?

As for cardiovascular risk, Dr. Ballantyne believes that, because CHIP is an unmodifiable risk factor, an example to follow could be lipoprotein(a) (LP[a]).

“We don’t have a therapy specifically to target LP(a) yet, but we do know that the things that benefit in general,” he said, such as “taking a statin, lowering blood pressure into the optimal zone, diet ,and exercise.”

“What we do in our clinic, and what others have been doing,” Dr. Weeks added, “is for every patient who comes in and is diagnosed with CHIP, we are referring them to preventative cardiology for very aggressive preventative management.”

Finally, both Dr. Ballantyne and Dr. Weeks agree that there are many potential innovations on the horizon.

“It’s pretty exciting in terms of beginning to understand some of the links between aging, cardiovascular disease, and cancer that we had not been thinking about,” Dr. Ballantyne said.

On the malignant side, Dr. Weeks is already working on a prospective study to determine how the risks associated with CHIP evolve when patients undergo chemotherapy and radiation for other cancers.

“That will be really exciting and will help us to develop a specific calculator in that context,” she said, adding that a cardiovascular-specific calculator “is also coming down the line.”

Dr. Weeks declared relationships with Abbvie, Vertex, and Sobi. Dr. Ballantyne declared a relationship with Ten Sixteen Bio, and funding from the National Heart, Lung, and Blood Institute. No other relevant financial relationships were declared.
 

A version of this article appeared on Medscape.com.

A novel vibrating capsule that signals a postprandial feeling of fullness reduced both food and energy intake and lowered weight gain in animal studies, said researchers who are developing it as a more affordable treatment for obesity.

The capsule, called the Vibrating Ingestible BioElectronic Stimulator (VIBES), is the size of a large adult multivitamin pill and is meant to be swallowed before a meal. The VIBES capsule works by stimulating gastric stretch receptors that signal the brain through the vagal nerve and stimulate a sense of satiety.

“Application of mechanoreceptor biology could transform our capacity to help patients suffering from nutritional disorders,” wrote Shriya S. Srinivasan, PhD, at Harvard University, Boston, and her coauthors. Srinivasan, founder and director of the Biohybrid Organs and Neuroprosthetics (BIONIC) Lab, led the team that designed and prototyped the VIBES capsule.

In a pig model, the VIBES activated mechanoreceptors and triggered gastric mucosal receptors, the researchers reported. Across 108 meals, swine treated with VIBES had nearly 40% reduced food intake compared to controls given a sham pill, with no apparent neural adaptation observed.

The research was published online in Science Advances.
 

Satiety Signaling in Obesity Treatment

Caroline M. Apovian, MD, codirector, Center for Weight Management and Wellness, Brigham and Women’s Hospital, Boston, who was not involved in the study, said the concept of creating the illusion of satiety is not a new one.

She was part of team that showed medically meaningful weight loss at 2 years with a surgically implanted device that intermittently blocked the vagus nerves near the junction of the stomach and esophagus. “So we’ve been aware of the potential of things like this to produce a sense of satiety and weight loss,” she said.

However, Dr. Apovian believed that a capsule such as VIBES faces a number of hurdles before it is widely used in the clinic, even if it is successfully tested on humans.

She pointed to a superabsorbent hydrogel device, Plenity (Gelesis), delivered as three oral capsules that expand with water in the stomach to create a feeling of satiety. While approved by the US Food and Drug Administration (FDA), it is not widely used, she said, as there are “hurdles” for patients to overcome, particularly in obtaining it from the pharmacy.

The VIBES capsule would in theory be acceptable to patients, Apovian said, but they are “overwhelmed by the media attention” on medications such as glucagon-like peptide 1 (GLP-1) receptor agonists, which promise dramatic weight loss, far higher than the sorts of figures VIBES could achieve.

Nevertheless, the capsule could form a part of the obesity treatment armamentarium, with the idea that it could be combined with “an agent that would act more centrally to change the body weight setpoint,” she said.

Allan Geliebter, PhD, professor, department of psychiatry, Icahn School of Medicine at Mount Sinai, New York City, said that the thinking behind the capsule is a “clever, original approach,” but he is personally skeptical that people will take them.

“It’s the largest possible capsule that’s on the market today that is approved by the FDA for swallowing,” he said, and people “have to assume it’s going to come out the other end.”

“I think it will,” Dr. Geliebter added, “but if you’re taking at least two of these a day, what’s the guarantee one won’t get stuck along the ride?”

And when it does come out, “maybe it will be visible, maybe not,” but either way, “I can see people being anxious.”

He agreed with Dr. Apovian that the arrival of GLP-1 agonists has made obesity “a tough market to compete in right now,” although he noted that the drugs “do have side effects, and not everybody tolerates them.”

The VIBES Approach

The authors noted that another approved satiety device, intragastic balloons, also were designed to induce early satiety through distension of the stomach, but they do not lead to sustained changes in hunger or eating behavior due to neural adaptation to the continuing distension.

Moreover, some balloons have been withdrawn due to safety concerns, including several deaths.

The team reasoned a mechanism or device “capable of selective mechanoreceptor activation would pose great clinical value.”

Dr. Srinivasan explained: “While vibration has been known to create proprioceptive illusions in muscles, to our knowledge, no one has tried this in the stomach.”

“Given my penchant for mechanoreceptor physiology, I was curious to see if stretch receptors in the smooth muscle could be manipulated by mechanostimulation.”

The team designed an orally ingestible 3D-printed capsule in three sections, one of which allows entry of gastric fluid to dissolve a glucose layer. This causes the release of a spring-loaded pogo pin that completes a circuit to activate the vibrating motor.

Initial testing demonstrated that the capsule, which is the size of a triple zero pill, vibrated for an average of 38.3 minutes, which was deemed acceptable as “meals are generally consumed in a 20- to 30-min window and gastric contents undergo primary mixing in approximately an hour,” the authors wrote.

Immersing the capsule in simulated gastric fluid for 24 hours and simulated intestinal fluid for 10 days at 37 °C didn’t lead to changes in the capsule; thus, it “would not damage the gastrointestinal tract even if it were to reside in the stomach for a full day or in the intestines for over a week,” the authors wrote.

Testing VIBES Satiety in Swine

To test the capsule’s performance as a potential obesity treatment, the researchers turned to a model of Yorkshire pigs ages 4-6 months. Their “gastric anatomy is similar to that of humans,” the authors wrote, and they have been widely used to evaluate biomedical devices.

The researchers found that the vibration from the capsule not only induced the afferent neural activation of gastric mechanoreceptors sensitive to stomach distention but also triggered gastric secretory activity via by what the authors call “stroking” of the gastric mucosa.

To examine the impact of the capsule on hunger and feeding behavior, they monitored the food intake of four pigs in each of three conditions:

• No treatment (control)
• Treated with a sham capsule tethered via a percutaneous endoscopic gastrostomy (PEG) tube (PEG-control)
• Treated with a VIBES capsule tethered via a PEG tube

After 2 weeks, VIBES-treated pigs consumed an average of 58.1% of their meals (n = 108 meals), PEG-control pigs consumed 84.1% (n = 100 meals), and the control group consumed 78.4% (n = 96) meals among PEG-only swine.

Per animal on average, the capsule reduced intake by 31% (P < .001), and the energy consumed per meal for each treated animal was significantly lower than that in the control period (P < .001), with no significant difference between the control and PEG-only groups (P < .1).

In a cross-over experiment, treating the swine for three meals, leaving them untreated for three meals, then treating them for another three revealed that intake increased by 38% during the untreated window.

The crossover results suggest the capsule “functions through temporal vagal activation, with little neural adaptation or long-term effect,” the team wrote.

Weight gain in VIBES-treated pigs was also significantly lower than that in the control and in the PEG-control groups (P < .05).

“Together, these data suggest that the VIBES pill significantly decreases food intake and slows the rate of weight gain in a large animal model,” the team wrote.

The VIBES capsule passed out of the treated pigs after an average of 4.4 days vs 8.3 days for a sham pill. As the “pigs generally take 7-9 days to excrete a given meal,” Dr. Srinivasan noted, “4 days is actually quite fast.”

“In humans, we expect this to pass on the same timescale as a regular meal,” she said, or approximately 24 hours. With no safety concerns identified in the study, Dr. Srinivasan did not expect there to be any significant concern over having multiple devices in the intestines from ingesting one with every meal.

The study was supported in part by grants from the National Institutes of Health, Novo Nordisk, and MIT Department of Mechanical Engineering, alongside support to individual authors via a Schmidt Science Fellowship and a National Science Foundation grant to the Computing Research Association for the CIFellows Project.

Dr. Srinivasan and two coauthors were coinventors on a patent application (application filed by the Massachusetts Institute of Technology describing the developments discussed here). Another author declared a consulting relationship with Novo Nordisk.

No other relevant financial relationships were declared.

A version of this article appeared on Medscape.com.

A novel vibrating capsule that signals a postprandial feeling of fullness reduced both food and energy intake and lowered weight gain in animal studies, said researchers who are developing it as a more affordable treatment for obesity.

The capsule, called the Vibrating Ingestible BioElectronic Stimulator (VIBES), is the size of a large adult multivitamin pill and is meant to be swallowed before a meal. The VIBES capsule works by stimulating gastric stretch receptors that signal the brain through the vagal nerve and stimulate a sense of satiety.

“Application of mechanoreceptor biology could transform our capacity to help patients suffering from nutritional disorders,” wrote Shriya S. Srinivasan, PhD, at Harvard University, Boston, and her coauthors. Srinivasan, founder and director of the Biohybrid Organs and Neuroprosthetics (BIONIC) Lab, led the team that designed and prototyped the VIBES capsule.

In a pig model, the VIBES activated mechanoreceptors and triggered gastric mucosal receptors, the researchers reported. Across 108 meals, swine treated with VIBES had nearly 40% reduced food intake compared to controls given a sham pill, with no apparent neural adaptation observed.

The research was published online in Science Advances.
 

Satiety Signaling in Obesity Treatment

Caroline M. Apovian, MD, codirector, Center for Weight Management and Wellness, Brigham and Women’s Hospital, Boston, who was not involved in the study, said the concept of creating the illusion of satiety is not a new one.

She was part of team that showed medically meaningful weight loss at 2 years with a surgically implanted device that intermittently blocked the vagus nerves near the junction of the stomach and esophagus. “So we’ve been aware of the potential of things like this to produce a sense of satiety and weight loss,” she said.

However, Dr. Apovian believed that a capsule such as VIBES faces a number of hurdles before it is widely used in the clinic, even if it is successfully tested on humans.

She pointed to a superabsorbent hydrogel device, Plenity (Gelesis), delivered as three oral capsules that expand with water in the stomach to create a feeling of satiety. While approved by the US Food and Drug Administration (FDA), it is not widely used, she said, as there are “hurdles” for patients to overcome, particularly in obtaining it from the pharmacy.

The VIBES capsule would in theory be acceptable to patients, Apovian said, but they are “overwhelmed by the media attention” on medications such as glucagon-like peptide 1 (GLP-1) receptor agonists, which promise dramatic weight loss, far higher than the sorts of figures VIBES could achieve.

Nevertheless, the capsule could form a part of the obesity treatment armamentarium, with the idea that it could be combined with “an agent that would act more centrally to change the body weight setpoint,” she said.

Allan Geliebter, PhD, professor, department of psychiatry, Icahn School of Medicine at Mount Sinai, New York City, said that the thinking behind the capsule is a “clever, original approach,” but he is personally skeptical that people will take them.

“It’s the largest possible capsule that’s on the market today that is approved by the FDA for swallowing,” he said, and people “have to assume it’s going to come out the other end.”

“I think it will,” Dr. Geliebter added, “but if you’re taking at least two of these a day, what’s the guarantee one won’t get stuck along the ride?”

And when it does come out, “maybe it will be visible, maybe not,” but either way, “I can see people being anxious.”

He agreed with Dr. Apovian that the arrival of GLP-1 agonists has made obesity “a tough market to compete in right now,” although he noted that the drugs “do have side effects, and not everybody tolerates them.”

The VIBES Approach

The authors noted that another approved satiety device, intragastic balloons, also were designed to induce early satiety through distension of the stomach, but they do not lead to sustained changes in hunger or eating behavior due to neural adaptation to the continuing distension.

Moreover, some balloons have been withdrawn due to safety concerns, including several deaths.

The team reasoned a mechanism or device “capable of selective mechanoreceptor activation would pose great clinical value.”

Dr. Srinivasan explained: “While vibration has been known to create proprioceptive illusions in muscles, to our knowledge, no one has tried this in the stomach.”

“Given my penchant for mechanoreceptor physiology, I was curious to see if stretch receptors in the smooth muscle could be manipulated by mechanostimulation.”

The team designed an orally ingestible 3D-printed capsule in three sections, one of which allows entry of gastric fluid to dissolve a glucose layer. This causes the release of a spring-loaded pogo pin that completes a circuit to activate the vibrating motor.

Initial testing demonstrated that the capsule, which is the size of a triple zero pill, vibrated for an average of 38.3 minutes, which was deemed acceptable as “meals are generally consumed in a 20- to 30-min window and gastric contents undergo primary mixing in approximately an hour,” the authors wrote.

Immersing the capsule in simulated gastric fluid for 24 hours and simulated intestinal fluid for 10 days at 37 °C didn’t lead to changes in the capsule; thus, it “would not damage the gastrointestinal tract even if it were to reside in the stomach for a full day or in the intestines for over a week,” the authors wrote.

Testing VIBES Satiety in Swine

To test the capsule’s performance as a potential obesity treatment, the researchers turned to a model of Yorkshire pigs ages 4-6 months. Their “gastric anatomy is similar to that of humans,” the authors wrote, and they have been widely used to evaluate biomedical devices.

The researchers found that the vibration from the capsule not only induced the afferent neural activation of gastric mechanoreceptors sensitive to stomach distention but also triggered gastric secretory activity via by what the authors call “stroking” of the gastric mucosa.

To examine the impact of the capsule on hunger and feeding behavior, they monitored the food intake of four pigs in each of three conditions:

• No treatment (control)
• Treated with a sham capsule tethered via a percutaneous endoscopic gastrostomy (PEG) tube (PEG-control)
• Treated with a VIBES capsule tethered via a PEG tube

After 2 weeks, VIBES-treated pigs consumed an average of 58.1% of their meals (n = 108 meals), PEG-control pigs consumed 84.1% (n = 100 meals), and the control group consumed 78.4% (n = 96) meals among PEG-only swine.

Per animal on average, the capsule reduced intake by 31% (P < .001), and the energy consumed per meal for each treated animal was significantly lower than that in the control period (P < .001), with no significant difference between the control and PEG-only groups (P < .1).

In a cross-over experiment, treating the swine for three meals, leaving them untreated for three meals, then treating them for another three revealed that intake increased by 38% during the untreated window.

The crossover results suggest the capsule “functions through temporal vagal activation, with little neural adaptation or long-term effect,” the team wrote.

Weight gain in VIBES-treated pigs was also significantly lower than that in the control and in the PEG-control groups (P < .05).

“Together, these data suggest that the VIBES pill significantly decreases food intake and slows the rate of weight gain in a large animal model,” the team wrote.

The VIBES capsule passed out of the treated pigs after an average of 4.4 days vs 8.3 days for a sham pill. As the “pigs generally take 7-9 days to excrete a given meal,” Dr. Srinivasan noted, “4 days is actually quite fast.”

“In humans, we expect this to pass on the same timescale as a regular meal,” she said, or approximately 24 hours. With no safety concerns identified in the study, Dr. Srinivasan did not expect there to be any significant concern over having multiple devices in the intestines from ingesting one with every meal.

The study was supported in part by grants from the National Institutes of Health, Novo Nordisk, and MIT Department of Mechanical Engineering, alongside support to individual authors via a Schmidt Science Fellowship and a National Science Foundation grant to the Computing Research Association for the CIFellows Project.

Dr. Srinivasan and two coauthors were coinventors on a patent application (application filed by the Massachusetts Institute of Technology describing the developments discussed here). Another author declared a consulting relationship with Novo Nordisk.

No other relevant financial relationships were declared.

A version of this article appeared on Medscape.com.

A novel vibrating capsule that signals a postprandial feeling of fullness reduced both food and energy intake and lowered weight gain in animal studies, said researchers who are developing it as a more affordable treatment for obesity.

The capsule, called the Vibrating Ingestible BioElectronic Stimulator (VIBES), is the size of a large adult multivitamin pill and is meant to be swallowed before a meal. The VIBES capsule works by stimulating gastric stretch receptors that signal the brain through the vagal nerve and stimulate a sense of satiety.

“Application of mechanoreceptor biology could transform our capacity to help patients suffering from nutritional disorders,” wrote Shriya S. Srinivasan, PhD, at Harvard University, Boston, and her coauthors. Srinivasan, founder and director of the Biohybrid Organs and Neuroprosthetics (BIONIC) Lab, led the team that designed and prototyped the VIBES capsule.

In a pig model, the VIBES activated mechanoreceptors and triggered gastric mucosal receptors, the researchers reported. Across 108 meals, swine treated with VIBES had nearly 40% reduced food intake compared to controls given a sham pill, with no apparent neural adaptation observed.

The research was published online in Science Advances.
 

Satiety Signaling in Obesity Treatment

Caroline M. Apovian, MD, codirector, Center for Weight Management and Wellness, Brigham and Women’s Hospital, Boston, who was not involved in the study, said the concept of creating the illusion of satiety is not a new one.

She was part of team that showed medically meaningful weight loss at 2 years with a surgically implanted device that intermittently blocked the vagus nerves near the junction of the stomach and esophagus. “So we’ve been aware of the potential of things like this to produce a sense of satiety and weight loss,” she said.

However, Dr. Apovian believed that a capsule such as VIBES faces a number of hurdles before it is widely used in the clinic, even if it is successfully tested on humans.

She pointed to a superabsorbent hydrogel device, Plenity (Gelesis), delivered as three oral capsules that expand with water in the stomach to create a feeling of satiety. While approved by the US Food and Drug Administration (FDA), it is not widely used, she said, as there are “hurdles” for patients to overcome, particularly in obtaining it from the pharmacy.

The VIBES capsule would in theory be acceptable to patients, Apovian said, but they are “overwhelmed by the media attention” on medications such as glucagon-like peptide 1 (GLP-1) receptor agonists, which promise dramatic weight loss, far higher than the sorts of figures VIBES could achieve.

Nevertheless, the capsule could form a part of the obesity treatment armamentarium, with the idea that it could be combined with “an agent that would act more centrally to change the body weight setpoint,” she said.

Allan Geliebter, PhD, professor, department of psychiatry, Icahn School of Medicine at Mount Sinai, New York City, said that the thinking behind the capsule is a “clever, original approach,” but he is personally skeptical that people will take them.

“It’s the largest possible capsule that’s on the market today that is approved by the FDA for swallowing,” he said, and people “have to assume it’s going to come out the other end.”

“I think it will,” Dr. Geliebter added, “but if you’re taking at least two of these a day, what’s the guarantee one won’t get stuck along the ride?”

And when it does come out, “maybe it will be visible, maybe not,” but either way, “I can see people being anxious.”

He agreed with Dr. Apovian that the arrival of GLP-1 agonists has made obesity “a tough market to compete in right now,” although he noted that the drugs “do have side effects, and not everybody tolerates them.”

The VIBES Approach

The authors noted that another approved satiety device, intragastic balloons, also were designed to induce early satiety through distension of the stomach, but they do not lead to sustained changes in hunger or eating behavior due to neural adaptation to the continuing distension.

Moreover, some balloons have been withdrawn due to safety concerns, including several deaths.

The team reasoned a mechanism or device “capable of selective mechanoreceptor activation would pose great clinical value.”

Dr. Srinivasan explained: “While vibration has been known to create proprioceptive illusions in muscles, to our knowledge, no one has tried this in the stomach.”

“Given my penchant for mechanoreceptor physiology, I was curious to see if stretch receptors in the smooth muscle could be manipulated by mechanostimulation.”

The team designed an orally ingestible 3D-printed capsule in three sections, one of which allows entry of gastric fluid to dissolve a glucose layer. This causes the release of a spring-loaded pogo pin that completes a circuit to activate the vibrating motor.

Initial testing demonstrated that the capsule, which is the size of a triple zero pill, vibrated for an average of 38.3 minutes, which was deemed acceptable as “meals are generally consumed in a 20- to 30-min window and gastric contents undergo primary mixing in approximately an hour,” the authors wrote.

Immersing the capsule in simulated gastric fluid for 24 hours and simulated intestinal fluid for 10 days at 37 °C didn’t lead to changes in the capsule; thus, it “would not damage the gastrointestinal tract even if it were to reside in the stomach for a full day or in the intestines for over a week,” the authors wrote.

Testing VIBES Satiety in Swine

To test the capsule’s performance as a potential obesity treatment, the researchers turned to a model of Yorkshire pigs ages 4-6 months. Their “gastric anatomy is similar to that of humans,” the authors wrote, and they have been widely used to evaluate biomedical devices.

The researchers found that the vibration from the capsule not only induced the afferent neural activation of gastric mechanoreceptors sensitive to stomach distention but also triggered gastric secretory activity via by what the authors call “stroking” of the gastric mucosa.

To examine the impact of the capsule on hunger and feeding behavior, they monitored the food intake of four pigs in each of three conditions:

• No treatment (control)
• Treated with a sham capsule tethered via a percutaneous endoscopic gastrostomy (PEG) tube (PEG-control)
• Treated with a VIBES capsule tethered via a PEG tube

After 2 weeks, VIBES-treated pigs consumed an average of 58.1% of their meals (n = 108 meals), PEG-control pigs consumed 84.1% (n = 100 meals), and the control group consumed 78.4% (n = 96) meals among PEG-only swine.

Per animal on average, the capsule reduced intake by 31% (P < .001), and the energy consumed per meal for each treated animal was significantly lower than that in the control period (P < .001), with no significant difference between the control and PEG-only groups (P < .1).

In a cross-over experiment, treating the swine for three meals, leaving them untreated for three meals, then treating them for another three revealed that intake increased by 38% during the untreated window.

The crossover results suggest the capsule “functions through temporal vagal activation, with little neural adaptation or long-term effect,” the team wrote.

Weight gain in VIBES-treated pigs was also significantly lower than that in the control and in the PEG-control groups (P < .05).

“Together, these data suggest that the VIBES pill significantly decreases food intake and slows the rate of weight gain in a large animal model,” the team wrote.

The VIBES capsule passed out of the treated pigs after an average of 4.4 days vs 8.3 days for a sham pill. As the “pigs generally take 7-9 days to excrete a given meal,” Dr. Srinivasan noted, “4 days is actually quite fast.”

“In humans, we expect this to pass on the same timescale as a regular meal,” she said, or approximately 24 hours. With no safety concerns identified in the study, Dr. Srinivasan did not expect there to be any significant concern over having multiple devices in the intestines from ingesting one with every meal.

The study was supported in part by grants from the National Institutes of Health, Novo Nordisk, and MIT Department of Mechanical Engineering, alongside support to individual authors via a Schmidt Science Fellowship and a National Science Foundation grant to the Computing Research Association for the CIFellows Project.

Dr. Srinivasan and two coauthors were coinventors on a patent application (application filed by the Massachusetts Institute of Technology describing the developments discussed here). Another author declared a consulting relationship with Novo Nordisk.

No other relevant financial relationships were declared.

A version of this article appeared on Medscape.com.

TOPLINE:

Low-dose aspirin use is associated with a reduced risk for colorectal cancer (CRC), confirms a large-scale cohort study, which also suggests that the risk reduction is greatest for metastatic disease and in individuals who take the drug for at least 5 years.

METHODOLOGY:

• Researchers used several population-based registries to identify individuals aged ≥ 50 years living in Norway between 2014 and 2018, excluding those with a prior history of invasive cancer or who had lived in Norway for less than 6 months before study commencement.
• Sociodemographic information was obtained, as well as low-dose aspirin prescription data to determine the prescription date, number of dispensed packages, and defined daily dose.
• Follow-up began 6 months after entering the cohort and continued until CRC diagnosis, another cancer diagnosis, death, emigration, or the end of follow-up on December 31, 2018.
• CRC cases were categorized by site as well as by clinical stage.

TAKEAWAY:

• Of 2,186,390 individuals included, 38,577 (1.8%) were diagnosed with CRC after a median follow-up of 10.9 years. Low-dose aspirin was used at least once by 579,196 (26.5%) individuals.
• Low-dose aspirin use was more common among males, older individuals, those with a lower education or lower income, those of Norwegian origin, and individuals using other medications, including those targeting cardiovascular conditions.
• Compared with never-use, current aspirin use was associated with a lower CRC risk (hazard ratio [HR], 0.87), an association that was more pronounced for metastatic CRC (HR, 0.79) than for regionally advanced (HR, 0.89) and localized disease (HR, 0.93).
• Duration of current aspirin use was also associated with the degree of CRC risk, at HRs of 0.91 for < 3 years, 0.85 for ≥ 3 and < 5 years, and 0.84 for ≥ 5 years.
• It was estimated that aspirin use averted 1073 cases of CRC over the study period.

IN PRACTICE:

“We believe that new randomized controlled trials are urgently needed to confirm the potential protective effect of aspirin against CRC and to identify subgroups in the population who might benefit the most from the use of aspirin,” the authors wrote.

SOURCE:

The research, led by Edoardo Botteri, PhD, Department of Research, Cancer Registry of Norway, National Institute of Public Health, Oslo, Norway, was published online in The American Journal of Gastroenterology.

LIMITATIONS:

This study is limited by its observational nature. Users and nonusers are also “incomparable,” as aspirin is used for the primary prevention of cardiovascular events. Moreover, information was lacking in the registries about “several known risk factors for CRC,” and so the link between aspirin and CRC risk could have been over- or underestimated. Finally, the defined daily dose may not necessarily reflect the dose actually taken by the individual or how often it was taken.

DISCLOSURES:

No relevant financial relationships were declared. The study was funded by the Norwegian Research Council.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Low-dose aspirin use is associated with a reduced risk for colorectal cancer (CRC), confirms a large-scale cohort study, which also suggests that the risk reduction is greatest for metastatic disease and in individuals who take the drug for at least 5 years.

METHODOLOGY:

• Researchers used several population-based registries to identify individuals aged ≥ 50 years living in Norway between 2014 and 2018, excluding those with a prior history of invasive cancer or who had lived in Norway for less than 6 months before study commencement.
• Sociodemographic information was obtained, as well as low-dose aspirin prescription data to determine the prescription date, number of dispensed packages, and defined daily dose.
• Follow-up began 6 months after entering the cohort and continued until CRC diagnosis, another cancer diagnosis, death, emigration, or the end of follow-up on December 31, 2018.
• CRC cases were categorized by site as well as by clinical stage.

TAKEAWAY:

• Of 2,186,390 individuals included, 38,577 (1.8%) were diagnosed with CRC after a median follow-up of 10.9 years. Low-dose aspirin was used at least once by 579,196 (26.5%) individuals.
• Low-dose aspirin use was more common among males, older individuals, those with a lower education or lower income, those of Norwegian origin, and individuals using other medications, including those targeting cardiovascular conditions.
• Compared with never-use, current aspirin use was associated with a lower CRC risk (hazard ratio [HR], 0.87), an association that was more pronounced for metastatic CRC (HR, 0.79) than for regionally advanced (HR, 0.89) and localized disease (HR, 0.93).
• Duration of current aspirin use was also associated with the degree of CRC risk, at HRs of 0.91 for < 3 years, 0.85 for ≥ 3 and < 5 years, and 0.84 for ≥ 5 years.
• It was estimated that aspirin use averted 1073 cases of CRC over the study period.

IN PRACTICE:

“We believe that new randomized controlled trials are urgently needed to confirm the potential protective effect of aspirin against CRC and to identify subgroups in the population who might benefit the most from the use of aspirin,” the authors wrote.

SOURCE:

The research, led by Edoardo Botteri, PhD, Department of Research, Cancer Registry of Norway, National Institute of Public Health, Oslo, Norway, was published online in The American Journal of Gastroenterology.

LIMITATIONS:

This study is limited by its observational nature. Users and nonusers are also “incomparable,” as aspirin is used for the primary prevention of cardiovascular events. Moreover, information was lacking in the registries about “several known risk factors for CRC,” and so the link between aspirin and CRC risk could have been over- or underestimated. Finally, the defined daily dose may not necessarily reflect the dose actually taken by the individual or how often it was taken.

DISCLOSURES:

No relevant financial relationships were declared. The study was funded by the Norwegian Research Council.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Low-dose aspirin use is associated with a reduced risk for colorectal cancer (CRC), confirms a large-scale cohort study, which also suggests that the risk reduction is greatest for metastatic disease and in individuals who take the drug for at least 5 years.

METHODOLOGY:

• Researchers used several population-based registries to identify individuals aged ≥ 50 years living in Norway between 2014 and 2018, excluding those with a prior history of invasive cancer or who had lived in Norway for less than 6 months before study commencement.
• Sociodemographic information was obtained, as well as low-dose aspirin prescription data to determine the prescription date, number of dispensed packages, and defined daily dose.
• Follow-up began 6 months after entering the cohort and continued until CRC diagnosis, another cancer diagnosis, death, emigration, or the end of follow-up on December 31, 2018.
• CRC cases were categorized by site as well as by clinical stage.

TAKEAWAY:

• Of 2,186,390 individuals included, 38,577 (1.8%) were diagnosed with CRC after a median follow-up of 10.9 years. Low-dose aspirin was used at least once by 579,196 (26.5%) individuals.
• Low-dose aspirin use was more common among males, older individuals, those with a lower education or lower income, those of Norwegian origin, and individuals using other medications, including those targeting cardiovascular conditions.
• Compared with never-use, current aspirin use was associated with a lower CRC risk (hazard ratio [HR], 0.87), an association that was more pronounced for metastatic CRC (HR, 0.79) than for regionally advanced (HR, 0.89) and localized disease (HR, 0.93).
• Duration of current aspirin use was also associated with the degree of CRC risk, at HRs of 0.91 for < 3 years, 0.85 for ≥ 3 and < 5 years, and 0.84 for ≥ 5 years.
• It was estimated that aspirin use averted 1073 cases of CRC over the study period.

IN PRACTICE:

“We believe that new randomized controlled trials are urgently needed to confirm the potential protective effect of aspirin against CRC and to identify subgroups in the population who might benefit the most from the use of aspirin,” the authors wrote.

SOURCE:

The research, led by Edoardo Botteri, PhD, Department of Research, Cancer Registry of Norway, National Institute of Public Health, Oslo, Norway, was published online in The American Journal of Gastroenterology.

LIMITATIONS:

This study is limited by its observational nature. Users and nonusers are also “incomparable,” as aspirin is used for the primary prevention of cardiovascular events. Moreover, information was lacking in the registries about “several known risk factors for CRC,” and so the link between aspirin and CRC risk could have been over- or underestimated. Finally, the defined daily dose may not necessarily reflect the dose actually taken by the individual or how often it was taken.

DISCLOSURES:

No relevant financial relationships were declared. The study was funded by the Norwegian Research Council.
 

A version of this article appeared on Medscape.com.

TOPLINE:

The sequence of systematic therapies for unresectable or metastatic pancreatic ductal adenocarcinoma may have an impact on patient survival, a new retrospective analysis suggests.

METHODOLOGY:

• Despite therapeutic advances, survival among patients with unresectable and/or metastatic pancreatic ductal adenocarcinoma has not markedly improved in recent years.
• In the current analysis, researchers evaluated whether treatment sequence could affect survival outcomes in this patient population.
• To this end , researchers conducted a single institution, retrospective analysis of patients who received different lines of treatment between January 2015 and December 2021.
• The most common first-line therapy was nab-paclitaxel plus S-1 (58%), followed by FOLFIRINOX (10%), nab-paclitaxel plus gemcitabine (8%), gemcitabine alone (7%), gemcitabine plus oxaliplatin (6%); second-line therapies, in order of frequency, included gemcitabine combination therapy (48%), nab-paclitaxel combination therapy (19%), FOLFIRINOX (10%), and gemcitabine alone (7%); third-line treatments consisted of FOLFIRINOX (31%), irinotecan or oxaliplatin combination therapy (23%), immunotherapy (19%), and gemcitabine combination therapy (10%).

TAKEAWAY:

• Overall, progression occurred in 90% of patients, and the median overall survival was 12.0 months, with only 48% of patients able to start a third-line therapy.
• The researchers focused on three common therapy sequences: nab-paclitaxel plus gemcitabine or nab-paclitaxel combination therapy as first-line and FOLFIRINOX as second-line (line A); nab-paclitaxel combination therapy to gemcitabine combination therapy to FOLFIRINOX (line B); and nab-paclitaxel combination therapy, to gemcitabine combination therapy, to oxaliplatin or irinotecan combination therapy (line C).
• Overall, the researchers observed a median overall survival of 14 months among patients receiving line A and C sequences and 18 months with line B.
• Patients receiving line B therapy demonstrated a 52% lower risk for death compared with those receiving line A treatment (hazard ratio [HR], 0.48; P = .018) and a 75% reduced risk for death compared with those on the line C sequence (HR, 0.25; P = .040).

IN PRACTICE:

“Our study provides real-world evidence for the effectiveness of different treatment sequences and underscores the [impact of] treatment sequences on survival outcome when considering the entire management in advanced pancreatic ductal adenocarcinoma,” the authors concluded.

SOURCE:

The study, led by Guanghai Dai, MD, from the Chinese People’s Liberation Army General Hospital, Beijing, was published in BMC Cancer on January 12, 2024.

LIMITATIONS:

The study was a single-center, retrospective analysis. 

DISCLOSURES:

The paper was funded by Beijing natural science foundation. The authors did not declare any relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

The sequence of systematic therapies for unresectable or metastatic pancreatic ductal adenocarcinoma may have an impact on patient survival, a new retrospective analysis suggests.

METHODOLOGY:

• Despite therapeutic advances, survival among patients with unresectable and/or metastatic pancreatic ductal adenocarcinoma has not markedly improved in recent years.
• In the current analysis, researchers evaluated whether treatment sequence could affect survival outcomes in this patient population.
• To this end , researchers conducted a single institution, retrospective analysis of patients who received different lines of treatment between January 2015 and December 2021.
• The most common first-line therapy was nab-paclitaxel plus S-1 (58%), followed by FOLFIRINOX (10%), nab-paclitaxel plus gemcitabine (8%), gemcitabine alone (7%), gemcitabine plus oxaliplatin (6%); second-line therapies, in order of frequency, included gemcitabine combination therapy (48%), nab-paclitaxel combination therapy (19%), FOLFIRINOX (10%), and gemcitabine alone (7%); third-line treatments consisted of FOLFIRINOX (31%), irinotecan or oxaliplatin combination therapy (23%), immunotherapy (19%), and gemcitabine combination therapy (10%).

TAKEAWAY:

• Overall, progression occurred in 90% of patients, and the median overall survival was 12.0 months, with only 48% of patients able to start a third-line therapy.
• The researchers focused on three common therapy sequences: nab-paclitaxel plus gemcitabine or nab-paclitaxel combination therapy as first-line and FOLFIRINOX as second-line (line A); nab-paclitaxel combination therapy to gemcitabine combination therapy to FOLFIRINOX (line B); and nab-paclitaxel combination therapy, to gemcitabine combination therapy, to oxaliplatin or irinotecan combination therapy (line C).
• Overall, the researchers observed a median overall survival of 14 months among patients receiving line A and C sequences and 18 months with line B.
• Patients receiving line B therapy demonstrated a 52% lower risk for death compared with those receiving line A treatment (hazard ratio [HR], 0.48; P = .018) and a 75% reduced risk for death compared with those on the line C sequence (HR, 0.25; P = .040).

IN PRACTICE:

“Our study provides real-world evidence for the effectiveness of different treatment sequences and underscores the [impact of] treatment sequences on survival outcome when considering the entire management in advanced pancreatic ductal adenocarcinoma,” the authors concluded.

SOURCE:

The study, led by Guanghai Dai, MD, from the Chinese People’s Liberation Army General Hospital, Beijing, was published in BMC Cancer on January 12, 2024.

LIMITATIONS:

The study was a single-center, retrospective analysis. 

DISCLOSURES:

The paper was funded by Beijing natural science foundation. The authors did not declare any relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

The sequence of systematic therapies for unresectable or metastatic pancreatic ductal adenocarcinoma may have an impact on patient survival, a new retrospective analysis suggests.

METHODOLOGY:

• Despite therapeutic advances, survival among patients with unresectable and/or metastatic pancreatic ductal adenocarcinoma has not markedly improved in recent years.
• In the current analysis, researchers evaluated whether treatment sequence could affect survival outcomes in this patient population.
• To this end , researchers conducted a single institution, retrospective analysis of patients who received different lines of treatment between January 2015 and December 2021.
• The most common first-line therapy was nab-paclitaxel plus S-1 (58%), followed by FOLFIRINOX (10%), nab-paclitaxel plus gemcitabine (8%), gemcitabine alone (7%), gemcitabine plus oxaliplatin (6%); second-line therapies, in order of frequency, included gemcitabine combination therapy (48%), nab-paclitaxel combination therapy (19%), FOLFIRINOX (10%), and gemcitabine alone (7%); third-line treatments consisted of FOLFIRINOX (31%), irinotecan or oxaliplatin combination therapy (23%), immunotherapy (19%), and gemcitabine combination therapy (10%).

TAKEAWAY:

• Overall, progression occurred in 90% of patients, and the median overall survival was 12.0 months, with only 48% of patients able to start a third-line therapy.
• The researchers focused on three common therapy sequences: nab-paclitaxel plus gemcitabine or nab-paclitaxel combination therapy as first-line and FOLFIRINOX as second-line (line A); nab-paclitaxel combination therapy to gemcitabine combination therapy to FOLFIRINOX (line B); and nab-paclitaxel combination therapy, to gemcitabine combination therapy, to oxaliplatin or irinotecan combination therapy (line C).
• Overall, the researchers observed a median overall survival of 14 months among patients receiving line A and C sequences and 18 months with line B.
• Patients receiving line B therapy demonstrated a 52% lower risk for death compared with those receiving line A treatment (hazard ratio [HR], 0.48; P = .018) and a 75% reduced risk for death compared with those on the line C sequence (HR, 0.25; P = .040).

IN PRACTICE:

“Our study provides real-world evidence for the effectiveness of different treatment sequences and underscores the [impact of] treatment sequences on survival outcome when considering the entire management in advanced pancreatic ductal adenocarcinoma,” the authors concluded.

SOURCE:

The study, led by Guanghai Dai, MD, from the Chinese People’s Liberation Army General Hospital, Beijing, was published in BMC Cancer on January 12, 2024.

LIMITATIONS:

The study was a single-center, retrospective analysis. 

DISCLOSURES:

The paper was funded by Beijing natural science foundation. The authors did not declare any relevant financial relationships.

A version of this article appeared on Medscape.com.

When the American Cancer Society recently unveiled changes to its lung cancer screening guidance, the aim was to remove barriers to screening and catch more cancers in high-risk people earlier.

Although the lung cancer death rate has declined significantly over the past few decades, lung cancer remains the leading cause of cancer deaths worldwide.

Detecting lung cancer early is key to improving survival. Still, lung cancer screening rates are poor. In 2021, the American Lung Association estimated that 14 million US adults qualified for lung cancer screening, but only 5.8% received it.

Smokers or former smokers without symptoms may forgo regular screening and only receive their screening scan after symptoms emerge, explained Janani S. Reisenauer, MD, Division Chair of Thoracic Surgery at Mayo Clinic, Rochester, Minnesota. But by the time symptoms develop, the cancer is typically more advanced, and treatment options become more limited.

The goal of the new American Cancer Society guidelines, published in early November 2023 in CA: A Cancer Journal for Physicians, is to identify lung cancers at earlier stages when they are easier to treat.

The new guidelines, which update a 2013 version, expand the eligibility age for screening and the pool of current and former smokers who qualify for annual screening with low-dose CT. Almost 5 million more high-risk people will now qualify for regular lung cancer screening, the guideline authors estimated.

But will expanding screening help reduce deaths from lung cancer? And perhaps just as important, will the guidelines move the needle on the “disappointingly low” lung cancer screening rates up to this point?

“I definitely think it’s a step in the right direction,” said Lecia V. Sequist, MD, MPH, clinical researcher and lung cancer medical oncologist, Massachusetts General Hospital Cancer Center, Boston, Massachusetts.

The new guidelines lowered the age for annual lung cancer screening among asymptomatic former or current smokers from 55-74 years to 50-80 years. The update also now considers a high-risk person anyone with a 20-pack-year history, down from a 30-pack-year history, and removes the requirement that former smokers must have quit within 15 years to be eligible for screening.

As people age, their risk for lung cancer increases, so it makes sense to screen all former smokers regardless of when they quit, explained Kim Lori Sandler, MD, from Vanderbilt University Medical Center, Nashville, Tennessee, and cochair of the American College of Radiology’s Lung Cancer Screening Steering Committee.

“There’s really nothing magical or drastic that happens at the 15-year mark,” Dr. Sequist agreed. For “someone who quit 14 years ago versus 16 years ago, it is essentially the same risk, and so scientifically it doesn’t really make sense to impose an artificial cut-off where no change in risk exists.”

The latest evidence reviewed in the new guidelines shows that expanding the guidelines would identify more early-stage cancers and potentially save lives. The authors modeled the benefits and harms of lung cancer screening using several scenarios.

Moving the start age from 55 to 50 years would lead to a 15% reduction in lung cancer mortality in men aged 50-54 years, the model suggested.

Removing the 15-year timeline for quitting smoking also would also improve outcomes. Compared with scenarios that included the 15-year quit timeline for former smokers, those that removed the limit would result in a 37.3% increase in screening exams, a 21% increase in would avert lung cancer deaths, and offer a 19% increase in life-years gained per 100,000 population.

Overall, the evidence indicates that, “if fully implemented, these recommendations have a high likelihood of significantly reducing death and suffering from lung cancer in the United States,” the guideline authors wrote.

But screening more people also comes with risks, such as more false-positive findings, which could lead to extra scans, invasive tests for tissue sampling, or even procedures for benign disease, Dr. Sandler explained. The latter “is what we really need to avoid.”

Even so, Dr. Sandler believes the current guidelines show that the benefit of screening “is great enough that it’s worth including these additional individuals.”
 

Guidelines Are Not Enough

But will expanding the screening criteria prompt more eligible individuals to receive their CT scans?

Simply expanding the eligibility criteria, by itself, likely won’t measurably improve screening uptake, said Paolo Boffetta, MD, MPH, of Stony Brook Cancer Center, Stony Brook, New York.

Healthcare and insurance access along with patient demand may present the most significant barriers to improving screening uptake.

The “issue is not the guideline as much as it’s the healthcare system,” said Otis W. Brawley, MD, professor of oncology at the Johns Hopkins University School of Medicine, Baltimore, Maryland.

Access to screening at hospitals with limited CT scanners and staff could present one major issue.

When Dr. Brawley worked at a large inner-city safety net hospital in Atlanta, patients with lung cancer frequently had to wait over a week to use one of the four CT scanners, he recalled. Adding to these delays, we didn’t have enough people to read the screens or enough people to do the diagnostics for those who had abnormalities, said Dr. Brawley.

To increase lung cancer screening in this context would increase the wait time for patients who do have cancer, he said.

Insurance coverage could present a roadblock for some as well. While the 2021 US Preventive Services Task Force (USPSTF) recommendations largely align with the new ones from the American Cancer Society, there’s one key difference: The USPSTF still requires former smokers to have quit within 15 years to be eligible for annual screening.

Because the USPSTF recommendations dictate insurance coverage, some former smokers — those who quit more than 15 years ago — may not qualify for coverage and would have to pay out-of-pocket for screening.

Dr. Sequist, however, had a more optimistic outlook about screening uptake.

The American Cancer Society guidelines should remove some of the stigma surrounding lung cancer screening. Most people, when asked a lot of questions about their tobacco use and history, tend to downplay it because there’s shame associated with smoking, Dr. Sequist said. The new guidelines limit the information needed to determine eligibility.

Dr. Sequist also noted that the updated American Cancer Society guideline would improve screening rates because it simplifies the eligibility criteria and makes it easier for physicians to determine who qualifies.

The issue, however, is that some of these individuals — those who quit over 15 years ago — may not have their scan covered by insurance, which could preclude lower-income individuals from getting screened.

The American Cancer Society guidelines” do not necessarily translate into a change in policy,” which is “dictated by the USPSTF and payors such as Medicare,” explained Peter Mazzone, MD, MPH, director of the Lung Cancer Program and Lung Cancer Screening Program for the Respiratory Institute, Cleveland Clinic, Cleveland, Ohio.

On the patient side, Dr. Brawley noted, “we don’t yet have a large demand” for screening.

Many current and former smokers may put off lung cancer screening or not seek it out. Some may be unaware of their eligibility, while others may fear the outcome of a scan. Even among eligible individuals who do receive an initial scan, most — more than 75% — do not return for their next scan a year later, research showed.

Enhancing patient education and launching strong marketing campaigns would be a key element to encourage more people to get their annual screening and reduce the stigma associated with lung cancer as a smoker’s disease.

“Primary care physicians are integral in ensuring all eligible patients receive appropriate screening for lung cancer,” said Steven P. Furr, MD, president of the American Academy of Family Physicians and a family physician in Jackson, Alabama. “It is imperative that family physicians encourage screening in at-risk patients and counsel them on the importance of continued screening, as well as smoking cessation, if needed.”

Two authors of the new guidelines reported financial relationships with Seno Medical Instruments, the Genentech Foundation, Crispr Therapeutics, BEAM Therapeutics, Intellia Therapeutics, Editas Medicine, Freenome, and Guardant Health.

A version of this article appeared on Medscape.com.

When the American Cancer Society recently unveiled changes to its lung cancer screening guidance, the aim was to remove barriers to screening and catch more cancers in high-risk people earlier.

Although the lung cancer death rate has declined significantly over the past few decades, lung cancer remains the leading cause of cancer deaths worldwide.

Detecting lung cancer early is key to improving survival. Still, lung cancer screening rates are poor. In 2021, the American Lung Association estimated that 14 million US adults qualified for lung cancer screening, but only 5.8% received it.

Smokers or former smokers without symptoms may forgo regular screening and only receive their screening scan after symptoms emerge, explained Janani S. Reisenauer, MD, Division Chair of Thoracic Surgery at Mayo Clinic, Rochester, Minnesota. But by the time symptoms develop, the cancer is typically more advanced, and treatment options become more limited.

The goal of the new American Cancer Society guidelines, published in early November 2023 in CA: A Cancer Journal for Physicians, is to identify lung cancers at earlier stages when they are easier to treat.

The new guidelines, which update a 2013 version, expand the eligibility age for screening and the pool of current and former smokers who qualify for annual screening with low-dose CT. Almost 5 million more high-risk people will now qualify for regular lung cancer screening, the guideline authors estimated.

But will expanding screening help reduce deaths from lung cancer? And perhaps just as important, will the guidelines move the needle on the “disappointingly low” lung cancer screening rates up to this point?

“I definitely think it’s a step in the right direction,” said Lecia V. Sequist, MD, MPH, clinical researcher and lung cancer medical oncologist, Massachusetts General Hospital Cancer Center, Boston, Massachusetts.

The new guidelines lowered the age for annual lung cancer screening among asymptomatic former or current smokers from 55-74 years to 50-80 years. The update also now considers a high-risk person anyone with a 20-pack-year history, down from a 30-pack-year history, and removes the requirement that former smokers must have quit within 15 years to be eligible for screening.

As people age, their risk for lung cancer increases, so it makes sense to screen all former smokers regardless of when they quit, explained Kim Lori Sandler, MD, from Vanderbilt University Medical Center, Nashville, Tennessee, and cochair of the American College of Radiology’s Lung Cancer Screening Steering Committee.

“There’s really nothing magical or drastic that happens at the 15-year mark,” Dr. Sequist agreed. For “someone who quit 14 years ago versus 16 years ago, it is essentially the same risk, and so scientifically it doesn’t really make sense to impose an artificial cut-off where no change in risk exists.”

The latest evidence reviewed in the new guidelines shows that expanding the guidelines would identify more early-stage cancers and potentially save lives. The authors modeled the benefits and harms of lung cancer screening using several scenarios.

Moving the start age from 55 to 50 years would lead to a 15% reduction in lung cancer mortality in men aged 50-54 years, the model suggested.

Removing the 15-year timeline for quitting smoking also would also improve outcomes. Compared with scenarios that included the 15-year quit timeline for former smokers, those that removed the limit would result in a 37.3% increase in screening exams, a 21% increase in would avert lung cancer deaths, and offer a 19% increase in life-years gained per 100,000 population.

Overall, the evidence indicates that, “if fully implemented, these recommendations have a high likelihood of significantly reducing death and suffering from lung cancer in the United States,” the guideline authors wrote.

But screening more people also comes with risks, such as more false-positive findings, which could lead to extra scans, invasive tests for tissue sampling, or even procedures for benign disease, Dr. Sandler explained. The latter “is what we really need to avoid.”

Even so, Dr. Sandler believes the current guidelines show that the benefit of screening “is great enough that it’s worth including these additional individuals.”
 

Guidelines Are Not Enough

But will expanding the screening criteria prompt more eligible individuals to receive their CT scans?

Simply expanding the eligibility criteria, by itself, likely won’t measurably improve screening uptake, said Paolo Boffetta, MD, MPH, of Stony Brook Cancer Center, Stony Brook, New York.

Healthcare and insurance access along with patient demand may present the most significant barriers to improving screening uptake.

The “issue is not the guideline as much as it’s the healthcare system,” said Otis W. Brawley, MD, professor of oncology at the Johns Hopkins University School of Medicine, Baltimore, Maryland.

Access to screening at hospitals with limited CT scanners and staff could present one major issue.

When Dr. Brawley worked at a large inner-city safety net hospital in Atlanta, patients with lung cancer frequently had to wait over a week to use one of the four CT scanners, he recalled. Adding to these delays, we didn’t have enough people to read the screens or enough people to do the diagnostics for those who had abnormalities, said Dr. Brawley.

To increase lung cancer screening in this context would increase the wait time for patients who do have cancer, he said.

Insurance coverage could present a roadblock for some as well. While the 2021 US Preventive Services Task Force (USPSTF) recommendations largely align with the new ones from the American Cancer Society, there’s one key difference: The USPSTF still requires former smokers to have quit within 15 years to be eligible for annual screening.

Because the USPSTF recommendations dictate insurance coverage, some former smokers — those who quit more than 15 years ago — may not qualify for coverage and would have to pay out-of-pocket for screening.

Dr. Sequist, however, had a more optimistic outlook about screening uptake.

The American Cancer Society guidelines should remove some of the stigma surrounding lung cancer screening. Most people, when asked a lot of questions about their tobacco use and history, tend to downplay it because there’s shame associated with smoking, Dr. Sequist said. The new guidelines limit the information needed to determine eligibility.

Dr. Sequist also noted that the updated American Cancer Society guideline would improve screening rates because it simplifies the eligibility criteria and makes it easier for physicians to determine who qualifies.

The issue, however, is that some of these individuals — those who quit over 15 years ago — may not have their scan covered by insurance, which could preclude lower-income individuals from getting screened.

The American Cancer Society guidelines” do not necessarily translate into a change in policy,” which is “dictated by the USPSTF and payors such as Medicare,” explained Peter Mazzone, MD, MPH, director of the Lung Cancer Program and Lung Cancer Screening Program for the Respiratory Institute, Cleveland Clinic, Cleveland, Ohio.

On the patient side, Dr. Brawley noted, “we don’t yet have a large demand” for screening.

Many current and former smokers may put off lung cancer screening or not seek it out. Some may be unaware of their eligibility, while others may fear the outcome of a scan. Even among eligible individuals who do receive an initial scan, most — more than 75% — do not return for their next scan a year later, research showed.

Enhancing patient education and launching strong marketing campaigns would be a key element to encourage more people to get their annual screening and reduce the stigma associated with lung cancer as a smoker’s disease.

“Primary care physicians are integral in ensuring all eligible patients receive appropriate screening for lung cancer,” said Steven P. Furr, MD, president of the American Academy of Family Physicians and a family physician in Jackson, Alabama. “It is imperative that family physicians encourage screening in at-risk patients and counsel them on the importance of continued screening, as well as smoking cessation, if needed.”

Two authors of the new guidelines reported financial relationships with Seno Medical Instruments, the Genentech Foundation, Crispr Therapeutics, BEAM Therapeutics, Intellia Therapeutics, Editas Medicine, Freenome, and Guardant Health.

A version of this article appeared on Medscape.com.

When the American Cancer Society recently unveiled changes to its lung cancer screening guidance, the aim was to remove barriers to screening and catch more cancers in high-risk people earlier.

Although the lung cancer death rate has declined significantly over the past few decades, lung cancer remains the leading cause of cancer deaths worldwide.

Detecting lung cancer early is key to improving survival. Still, lung cancer screening rates are poor. In 2021, the American Lung Association estimated that 14 million US adults qualified for lung cancer screening, but only 5.8% received it.

Smokers or former smokers without symptoms may forgo regular screening and only receive their screening scan after symptoms emerge, explained Janani S. Reisenauer, MD, Division Chair of Thoracic Surgery at Mayo Clinic, Rochester, Minnesota. But by the time symptoms develop, the cancer is typically more advanced, and treatment options become more limited.

The goal of the new American Cancer Society guidelines, published in early November 2023 in CA: A Cancer Journal for Physicians, is to identify lung cancers at earlier stages when they are easier to treat.

The new guidelines, which update a 2013 version, expand the eligibility age for screening and the pool of current and former smokers who qualify for annual screening with low-dose CT. Almost 5 million more high-risk people will now qualify for regular lung cancer screening, the guideline authors estimated.

But will expanding screening help reduce deaths from lung cancer? And perhaps just as important, will the guidelines move the needle on the “disappointingly low” lung cancer screening rates up to this point?

“I definitely think it’s a step in the right direction,” said Lecia V. Sequist, MD, MPH, clinical researcher and lung cancer medical oncologist, Massachusetts General Hospital Cancer Center, Boston, Massachusetts.

The new guidelines lowered the age for annual lung cancer screening among asymptomatic former or current smokers from 55-74 years to 50-80 years. The update also now considers a high-risk person anyone with a 20-pack-year history, down from a 30-pack-year history, and removes the requirement that former smokers must have quit within 15 years to be eligible for screening.

As people age, their risk for lung cancer increases, so it makes sense to screen all former smokers regardless of when they quit, explained Kim Lori Sandler, MD, from Vanderbilt University Medical Center, Nashville, Tennessee, and cochair of the American College of Radiology’s Lung Cancer Screening Steering Committee.

“There’s really nothing magical or drastic that happens at the 15-year mark,” Dr. Sequist agreed. For “someone who quit 14 years ago versus 16 years ago, it is essentially the same risk, and so scientifically it doesn’t really make sense to impose an artificial cut-off where no change in risk exists.”

The latest evidence reviewed in the new guidelines shows that expanding the guidelines would identify more early-stage cancers and potentially save lives. The authors modeled the benefits and harms of lung cancer screening using several scenarios.

Moving the start age from 55 to 50 years would lead to a 15% reduction in lung cancer mortality in men aged 50-54 years, the model suggested.

Removing the 15-year timeline for quitting smoking also would also improve outcomes. Compared with scenarios that included the 15-year quit timeline for former smokers, those that removed the limit would result in a 37.3% increase in screening exams, a 21% increase in would avert lung cancer deaths, and offer a 19% increase in life-years gained per 100,000 population.

Overall, the evidence indicates that, “if fully implemented, these recommendations have a high likelihood of significantly reducing death and suffering from lung cancer in the United States,” the guideline authors wrote.

But screening more people also comes with risks, such as more false-positive findings, which could lead to extra scans, invasive tests for tissue sampling, or even procedures for benign disease, Dr. Sandler explained. The latter “is what we really need to avoid.”

Even so, Dr. Sandler believes the current guidelines show that the benefit of screening “is great enough that it’s worth including these additional individuals.”
 

Guidelines Are Not Enough

But will expanding the screening criteria prompt more eligible individuals to receive their CT scans?

Simply expanding the eligibility criteria, by itself, likely won’t measurably improve screening uptake, said Paolo Boffetta, MD, MPH, of Stony Brook Cancer Center, Stony Brook, New York.

Healthcare and insurance access along with patient demand may present the most significant barriers to improving screening uptake.

The “issue is not the guideline as much as it’s the healthcare system,” said Otis W. Brawley, MD, professor of oncology at the Johns Hopkins University School of Medicine, Baltimore, Maryland.

Access to screening at hospitals with limited CT scanners and staff could present one major issue.

When Dr. Brawley worked at a large inner-city safety net hospital in Atlanta, patients with lung cancer frequently had to wait over a week to use one of the four CT scanners, he recalled. Adding to these delays, we didn’t have enough people to read the screens or enough people to do the diagnostics for those who had abnormalities, said Dr. Brawley.

To increase lung cancer screening in this context would increase the wait time for patients who do have cancer, he said.

Insurance coverage could present a roadblock for some as well. While the 2021 US Preventive Services Task Force (USPSTF) recommendations largely align with the new ones from the American Cancer Society, there’s one key difference: The USPSTF still requires former smokers to have quit within 15 years to be eligible for annual screening.

Because the USPSTF recommendations dictate insurance coverage, some former smokers — those who quit more than 15 years ago — may not qualify for coverage and would have to pay out-of-pocket for screening.

Dr. Sequist, however, had a more optimistic outlook about screening uptake.

The American Cancer Society guidelines should remove some of the stigma surrounding lung cancer screening. Most people, when asked a lot of questions about their tobacco use and history, tend to downplay it because there’s shame associated with smoking, Dr. Sequist said. The new guidelines limit the information needed to determine eligibility.

Dr. Sequist also noted that the updated American Cancer Society guideline would improve screening rates because it simplifies the eligibility criteria and makes it easier for physicians to determine who qualifies.

The issue, however, is that some of these individuals — those who quit over 15 years ago — may not have their scan covered by insurance, which could preclude lower-income individuals from getting screened.

The American Cancer Society guidelines” do not necessarily translate into a change in policy,” which is “dictated by the USPSTF and payors such as Medicare,” explained Peter Mazzone, MD, MPH, director of the Lung Cancer Program and Lung Cancer Screening Program for the Respiratory Institute, Cleveland Clinic, Cleveland, Ohio.

On the patient side, Dr. Brawley noted, “we don’t yet have a large demand” for screening.

Many current and former smokers may put off lung cancer screening or not seek it out. Some may be unaware of their eligibility, while others may fear the outcome of a scan. Even among eligible individuals who do receive an initial scan, most — more than 75% — do not return for their next scan a year later, research showed.

Enhancing patient education and launching strong marketing campaigns would be a key element to encourage more people to get their annual screening and reduce the stigma associated with lung cancer as a smoker’s disease.

“Primary care physicians are integral in ensuring all eligible patients receive appropriate screening for lung cancer,” said Steven P. Furr, MD, president of the American Academy of Family Physicians and a family physician in Jackson, Alabama. “It is imperative that family physicians encourage screening in at-risk patients and counsel them on the importance of continued screening, as well as smoking cessation, if needed.”

Two authors of the new guidelines reported financial relationships with Seno Medical Instruments, the Genentech Foundation, Crispr Therapeutics, BEAM Therapeutics, Intellia Therapeutics, Editas Medicine, Freenome, and Guardant Health.

A version of this article appeared on Medscape.com.

Exposure to endocrine-disrupting chemicals (EDCs) via daily use of plastics is a major contributor to the overall disease burden in the United States and the associated costs to society amount to more than 1% of the gross domestic product, revealed a large-scale analysis.

The research, published in the Journal of the Endocrine Society, indicated that taken together, the disease burden attributable to EDCs used in the manufacture of plastics added up to almost $250 billion in 2018 alone.

“The diseases due to plastics run the entire life course from preterm birth to obesity, heart disease, and cancers,” commented lead author Leonardo Trasande, MD, MPP, Jim G. Hendrick, MD Professor of Pediatrics, Department of Pediatrics, NYU Langone Medical Center, New York, in a release.

“Our study drives home the need to address chemicals used in plastic materials” through global treaties and other policy initiatives, he said, so as to “reduce these costs” in line with reductions in exposure to the chemicals.

Co-author Michael Belliveau, Executive Director at Defend Our Health in Portland, ME, agreed, saying: “We can reduce these health costs and the prevalence of chronic endocrine diseases such as diabetes and obesity if governments and companies enact policies that minimize exposure to EDCs to protect public health and the environment.”

Plastics may contain any one of a number of EDCs, such as polybrominated diphenylethers in flame retardant additives, phthalates in food packaging, bisphenols in can linings, and perfluoroalkyl and polyfluoroalkyl substances (PFAS) in nonstick cooking utensils.

These chemicals have been shown to leach and disturb the body’s hormone systems, increasing the risk for cancer, diabetes, reproductive disorders, neurological impairments in developing fetuses and children, and even death.

In March 2022, the United Nations Environment Assembly committed to a global plastics treaty to “end plastic pollution and forge an international legally binding agreement by 2024” that “addresses the full life cycle of plastic, including its production, design and disposal.”

Minimizing EDC Exposure

But what can doctors tell their patients today to help them reduce their exposure to EDCs?

“There are safe and simple steps that people can take to limit their exposure to the chemicals of greatest concern,” Dr. Trasande told this news organization.

This can be partly achieved by reducing plastic use down to its essentials. “To use an example, when you are flying, fill up a stainless steel container after clearing security. At home, use glass or stainless steel” rather than plastic bottles or containers.

In particular, “avoiding microwaving plastic is important,” Dr. Trasande said, “even if a container says it’s microwave-safe.”

He warned that “many chemicals used in plastic are not covalently bound, and heat facilitates leaching into food. Microscopic contaminants can also get into food when you microwave plastic.”

Dr. Trasande also suggests limiting canned food consumption and avoiding cleaning plastic food containers in machine dishwashers.

Calculating the Disease Burden

To accurately assess the “the tradeoffs involved in the ongoing reliance on plastic production as a source of economic productivity,” the current researchers calculated the attributable disease burden and cost related to EDCs used in plastic materials in the United States in 2018.

Building on previously published analyses, they used industry reports, publications by national and international governing bodies, and peer-reviewed publications to determine the usage of each type of EDC and its attributable disease and disability burden.

This plastic-related fraction (PRF) of disease burden was then used to calculate an updated cost estimate for each EDC, based on the assumption that the disease burden is directly proportional to its exposure.

They found that for bisphenol A, 97.5% of its use, and therefore its estimated PRF of disease burden, was related to the manufacture of plastics, while this figure was 98%-100% for phthalates. For PDBE, 98% of its use was in plastics vs 93% for PFAS.

The researchers then estimated that the total plastic-attributable disease burden in the United States in 2018 cost the nation $249 billion, or 1.22% of the gross domestic product. Of this, $159 billion was linked to PDBE exposure, which is associated with diseases such as cancer.

Moreover, $1.02 billion plastic-attributable disease burden was associated with bisphenol A exposure, which can have potentially harmful health effects on the immune system; followed by $66.7 billion due to phthalates, which are linked to preterm birth, reduced sperm count, and childhood obesity; and $22.4 billion due to PFAS, which are associated with kidney failure and gestational diabetes.

The study was supported by the National Institutes of Health and the Passport Foundation.

Dr. Trasande declared relationships with Audible, Houghton Mifflin, Paidos, and Kobunsha, none of which relate to the present manuscript.

No other financial relationships were declared.

A version of this article appeared on Medscape.com.

Exposure to endocrine-disrupting chemicals (EDCs) via daily use of plastics is a major contributor to the overall disease burden in the United States and the associated costs to society amount to more than 1% of the gross domestic product, revealed a large-scale analysis.

The research, published in the Journal of the Endocrine Society, indicated that taken together, the disease burden attributable to EDCs used in the manufacture of plastics added up to almost $250 billion in 2018 alone.

“The diseases due to plastics run the entire life course from preterm birth to obesity, heart disease, and cancers,” commented lead author Leonardo Trasande, MD, MPP, Jim G. Hendrick, MD Professor of Pediatrics, Department of Pediatrics, NYU Langone Medical Center, New York, in a release.

“Our study drives home the need to address chemicals used in plastic materials” through global treaties and other policy initiatives, he said, so as to “reduce these costs” in line with reductions in exposure to the chemicals.

Co-author Michael Belliveau, Executive Director at Defend Our Health in Portland, ME, agreed, saying: “We can reduce these health costs and the prevalence of chronic endocrine diseases such as diabetes and obesity if governments and companies enact policies that minimize exposure to EDCs to protect public health and the environment.”

Plastics may contain any one of a number of EDCs, such as polybrominated diphenylethers in flame retardant additives, phthalates in food packaging, bisphenols in can linings, and perfluoroalkyl and polyfluoroalkyl substances (PFAS) in nonstick cooking utensils.

These chemicals have been shown to leach and disturb the body’s hormone systems, increasing the risk for cancer, diabetes, reproductive disorders, neurological impairments in developing fetuses and children, and even death.

In March 2022, the United Nations Environment Assembly committed to a global plastics treaty to “end plastic pollution and forge an international legally binding agreement by 2024” that “addresses the full life cycle of plastic, including its production, design and disposal.”

Minimizing EDC Exposure

But what can doctors tell their patients today to help them reduce their exposure to EDCs?

“There are safe and simple steps that people can take to limit their exposure to the chemicals of greatest concern,” Dr. Trasande told this news organization.

This can be partly achieved by reducing plastic use down to its essentials. “To use an example, when you are flying, fill up a stainless steel container after clearing security. At home, use glass or stainless steel” rather than plastic bottles or containers.

In particular, “avoiding microwaving plastic is important,” Dr. Trasande said, “even if a container says it’s microwave-safe.”

He warned that “many chemicals used in plastic are not covalently bound, and heat facilitates leaching into food. Microscopic contaminants can also get into food when you microwave plastic.”

Dr. Trasande also suggests limiting canned food consumption and avoiding cleaning plastic food containers in machine dishwashers.

Calculating the Disease Burden

To accurately assess the “the tradeoffs involved in the ongoing reliance on plastic production as a source of economic productivity,” the current researchers calculated the attributable disease burden and cost related to EDCs used in plastic materials in the United States in 2018.

Building on previously published analyses, they used industry reports, publications by national and international governing bodies, and peer-reviewed publications to determine the usage of each type of EDC and its attributable disease and disability burden.

This plastic-related fraction (PRF) of disease burden was then used to calculate an updated cost estimate for each EDC, based on the assumption that the disease burden is directly proportional to its exposure.

They found that for bisphenol A, 97.5% of its use, and therefore its estimated PRF of disease burden, was related to the manufacture of plastics, while this figure was 98%-100% for phthalates. For PDBE, 98% of its use was in plastics vs 93% for PFAS.

The researchers then estimated that the total plastic-attributable disease burden in the United States in 2018 cost the nation $249 billion, or 1.22% of the gross domestic product. Of this, $159 billion was linked to PDBE exposure, which is associated with diseases such as cancer.

Moreover, $1.02 billion plastic-attributable disease burden was associated with bisphenol A exposure, which can have potentially harmful health effects on the immune system; followed by $66.7 billion due to phthalates, which are linked to preterm birth, reduced sperm count, and childhood obesity; and $22.4 billion due to PFAS, which are associated with kidney failure and gestational diabetes.

The study was supported by the National Institutes of Health and the Passport Foundation.

Dr. Trasande declared relationships with Audible, Houghton Mifflin, Paidos, and Kobunsha, none of which relate to the present manuscript.

No other financial relationships were declared.

A version of this article appeared on Medscape.com.

Exposure to endocrine-disrupting chemicals (EDCs) via daily use of plastics is a major contributor to the overall disease burden in the United States and the associated costs to society amount to more than 1% of the gross domestic product, revealed a large-scale analysis.

The research, published in the Journal of the Endocrine Society, indicated that taken together, the disease burden attributable to EDCs used in the manufacture of plastics added up to almost $250 billion in 2018 alone.

“The diseases due to plastics run the entire life course from preterm birth to obesity, heart disease, and cancers,” commented lead author Leonardo Trasande, MD, MPP, Jim G. Hendrick, MD Professor of Pediatrics, Department of Pediatrics, NYU Langone Medical Center, New York, in a release.

“Our study drives home the need to address chemicals used in plastic materials” through global treaties and other policy initiatives, he said, so as to “reduce these costs” in line with reductions in exposure to the chemicals.

Co-author Michael Belliveau, Executive Director at Defend Our Health in Portland, ME, agreed, saying: “We can reduce these health costs and the prevalence of chronic endocrine diseases such as diabetes and obesity if governments and companies enact policies that minimize exposure to EDCs to protect public health and the environment.”

Plastics may contain any one of a number of EDCs, such as polybrominated diphenylethers in flame retardant additives, phthalates in food packaging, bisphenols in can linings, and perfluoroalkyl and polyfluoroalkyl substances (PFAS) in nonstick cooking utensils.

These chemicals have been shown to leach and disturb the body’s hormone systems, increasing the risk for cancer, diabetes, reproductive disorders, neurological impairments in developing fetuses and children, and even death.

In March 2022, the United Nations Environment Assembly committed to a global plastics treaty to “end plastic pollution and forge an international legally binding agreement by 2024” that “addresses the full life cycle of plastic, including its production, design and disposal.”

Minimizing EDC Exposure

But what can doctors tell their patients today to help them reduce their exposure to EDCs?

“There are safe and simple steps that people can take to limit their exposure to the chemicals of greatest concern,” Dr. Trasande told this news organization.

This can be partly achieved by reducing plastic use down to its essentials. “To use an example, when you are flying, fill up a stainless steel container after clearing security. At home, use glass or stainless steel” rather than plastic bottles or containers.

In particular, “avoiding microwaving plastic is important,” Dr. Trasande said, “even if a container says it’s microwave-safe.”

He warned that “many chemicals used in plastic are not covalently bound, and heat facilitates leaching into food. Microscopic contaminants can also get into food when you microwave plastic.”

Dr. Trasande also suggests limiting canned food consumption and avoiding cleaning plastic food containers in machine dishwashers.

Calculating the Disease Burden

To accurately assess the “the tradeoffs involved in the ongoing reliance on plastic production as a source of economic productivity,” the current researchers calculated the attributable disease burden and cost related to EDCs used in plastic materials in the United States in 2018.

Building on previously published analyses, they used industry reports, publications by national and international governing bodies, and peer-reviewed publications to determine the usage of each type of EDC and its attributable disease and disability burden.

This plastic-related fraction (PRF) of disease burden was then used to calculate an updated cost estimate for each EDC, based on the assumption that the disease burden is directly proportional to its exposure.

They found that for bisphenol A, 97.5% of its use, and therefore its estimated PRF of disease burden, was related to the manufacture of plastics, while this figure was 98%-100% for phthalates. For PDBE, 98% of its use was in plastics vs 93% for PFAS.

The researchers then estimated that the total plastic-attributable disease burden in the United States in 2018 cost the nation $249 billion, or 1.22% of the gross domestic product. Of this, $159 billion was linked to PDBE exposure, which is associated with diseases such as cancer.

Moreover, $1.02 billion plastic-attributable disease burden was associated with bisphenol A exposure, which can have potentially harmful health effects on the immune system; followed by $66.7 billion due to phthalates, which are linked to preterm birth, reduced sperm count, and childhood obesity; and $22.4 billion due to PFAS, which are associated with kidney failure and gestational diabetes.

The study was supported by the National Institutes of Health and the Passport Foundation.

Dr. Trasande declared relationships with Audible, Houghton Mifflin, Paidos, and Kobunsha, none of which relate to the present manuscript.

No other financial relationships were declared.

A version of this article appeared on Medscape.com.

TOPLINE:

Overall survival among US patients with resected stage II or III gastric cancer differs by race and ethnicity, with Asian and Hispanic patients demonstrating better overall survival than White and Black patients.

METHODOLOGY:

• Studies have revealed disparities in gastric cancer outcomes among different racial and ethnic groups in the United States, but the reasons are unclear.
• To better understand the disparities, researchers analyzed survival outcomes by race and ethnicity, treatment type, and a range of other factors.
• The retrospective analysis included 6938 patients with clinical stages IIA-IIIC gastric adenocarcinoma who underwent partial or total gastrectomy between 2006 and 2019, excluding those with a history of cancer. Patient data came from the National Cancer Database, which covers about 70% of all new cancer diagnoses.
• The researchers compared factors, including race and ethnicity, surgical margins, and lymph nodes, as well as treatment modality (neoadjuvant or adjuvant chemotherapy only, neoadjuvant or adjuvant chemoradiation only, or perioperative chemotherapy with radiation or surgical care only).
• Just over half of the patients (53.6%) were White, 24.3% were Black, 17.8% were Hispanic, 15.8% were Asian, and 2.6% were other race or ethnicity (information was missing for 4.8%). White patients were more likely to be older and insured; Black and White patients had more comorbidities than Asian and Hispanic patients.

TAKEAWAY:

• Perioperative chemotherapy was associated with improved overall survival (hazard ratio [HR], 0.79), while surgical resection alone (HR, 1.79), more positive lymph nodes (HR, 2.95 for 10 or more), and positive surgical margins were associated with the biggest decreases in overall survival.
• Asian and Hispanic patients had significantly better overall survival (HR, 0.64 and 0.77, respectively) than White patients.
• In general, Black and White patients had similar overall survival (HR, 0.96), except among Black patients who received neoadjuvant therapy — these patients had better overall survival than White patients (HR, 0.78).
• Black and Asian patients were more likely to be downstaged or achieve a pathologic complete response after neoadjuvant therapy (34.4% and 35.3%, respectively) than White (28.4%) and Hispanic patients (30.8%).

IN PRACTICE:

The authors found that “Asian and Hispanic race and ethnicity were independently associated with improved [overall survival] compared with Black and White race,” even after adjusting for variables including multimodality treatment regimen and response to neoadjuvant therapy.

The authors explained that overall Asian and Black patients responded more favorably to neoadjuvant therapy, demonstrating significantly higher rates of downstaging or pathologic complete response, which may help explain why Black patients demonstrated better overall survival than White patients who received neoadjuvant therapy.

SOURCE:

The research, led by Steve Kwon, MD, MPH, of Roger Williams Medical Center and Boston University, Providence, Rhode Island, was published online on December 21 in JAMA Network Open.

LIMITATIONS:

The analysis is constrained by the database, which may limit the generalizability of the findings. The authors determined the response to neoadjuvant therapy by comparing clinical stage with postoperative pathologic stage.

DISCLOSURES:

No funding was declared. No relevant financial relationships were declared.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Overall survival among US patients with resected stage II or III gastric cancer differs by race and ethnicity, with Asian and Hispanic patients demonstrating better overall survival than White and Black patients.

METHODOLOGY:

• Studies have revealed disparities in gastric cancer outcomes among different racial and ethnic groups in the United States, but the reasons are unclear.
• To better understand the disparities, researchers analyzed survival outcomes by race and ethnicity, treatment type, and a range of other factors.
• The retrospective analysis included 6938 patients with clinical stages IIA-IIIC gastric adenocarcinoma who underwent partial or total gastrectomy between 2006 and 2019, excluding those with a history of cancer. Patient data came from the National Cancer Database, which covers about 70% of all new cancer diagnoses.
• The researchers compared factors, including race and ethnicity, surgical margins, and lymph nodes, as well as treatment modality (neoadjuvant or adjuvant chemotherapy only, neoadjuvant or adjuvant chemoradiation only, or perioperative chemotherapy with radiation or surgical care only).
• Just over half of the patients (53.6%) were White, 24.3% were Black, 17.8% were Hispanic, 15.8% were Asian, and 2.6% were other race or ethnicity (information was missing for 4.8%). White patients were more likely to be older and insured; Black and White patients had more comorbidities than Asian and Hispanic patients.

TAKEAWAY:

• Perioperative chemotherapy was associated with improved overall survival (hazard ratio [HR], 0.79), while surgical resection alone (HR, 1.79), more positive lymph nodes (HR, 2.95 for 10 or more), and positive surgical margins were associated with the biggest decreases in overall survival.
• Asian and Hispanic patients had significantly better overall survival (HR, 0.64 and 0.77, respectively) than White patients.
• In general, Black and White patients had similar overall survival (HR, 0.96), except among Black patients who received neoadjuvant therapy — these patients had better overall survival than White patients (HR, 0.78).
• Black and Asian patients were more likely to be downstaged or achieve a pathologic complete response after neoadjuvant therapy (34.4% and 35.3%, respectively) than White (28.4%) and Hispanic patients (30.8%).

IN PRACTICE:

The authors found that “Asian and Hispanic race and ethnicity were independently associated with improved [overall survival] compared with Black and White race,” even after adjusting for variables including multimodality treatment regimen and response to neoadjuvant therapy.

The authors explained that overall Asian and Black patients responded more favorably to neoadjuvant therapy, demonstrating significantly higher rates of downstaging or pathologic complete response, which may help explain why Black patients demonstrated better overall survival than White patients who received neoadjuvant therapy.

SOURCE:

The research, led by Steve Kwon, MD, MPH, of Roger Williams Medical Center and Boston University, Providence, Rhode Island, was published online on December 21 in JAMA Network Open.

LIMITATIONS:

The analysis is constrained by the database, which may limit the generalizability of the findings. The authors determined the response to neoadjuvant therapy by comparing clinical stage with postoperative pathologic stage.

DISCLOSURES:

No funding was declared. No relevant financial relationships were declared.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Overall survival among US patients with resected stage II or III gastric cancer differs by race and ethnicity, with Asian and Hispanic patients demonstrating better overall survival than White and Black patients.

METHODOLOGY:

• Studies have revealed disparities in gastric cancer outcomes among different racial and ethnic groups in the United States, but the reasons are unclear.
• To better understand the disparities, researchers analyzed survival outcomes by race and ethnicity, treatment type, and a range of other factors.
• The retrospective analysis included 6938 patients with clinical stages IIA-IIIC gastric adenocarcinoma who underwent partial or total gastrectomy between 2006 and 2019, excluding those with a history of cancer. Patient data came from the National Cancer Database, which covers about 70% of all new cancer diagnoses.
• The researchers compared factors, including race and ethnicity, surgical margins, and lymph nodes, as well as treatment modality (neoadjuvant or adjuvant chemotherapy only, neoadjuvant or adjuvant chemoradiation only, or perioperative chemotherapy with radiation or surgical care only).
• Just over half of the patients (53.6%) were White, 24.3% were Black, 17.8% were Hispanic, 15.8% were Asian, and 2.6% were other race or ethnicity (information was missing for 4.8%). White patients were more likely to be older and insured; Black and White patients had more comorbidities than Asian and Hispanic patients.

TAKEAWAY:

• Perioperative chemotherapy was associated with improved overall survival (hazard ratio [HR], 0.79), while surgical resection alone (HR, 1.79), more positive lymph nodes (HR, 2.95 for 10 or more), and positive surgical margins were associated with the biggest decreases in overall survival.
• Asian and Hispanic patients had significantly better overall survival (HR, 0.64 and 0.77, respectively) than White patients.
• In general, Black and White patients had similar overall survival (HR, 0.96), except among Black patients who received neoadjuvant therapy — these patients had better overall survival than White patients (HR, 0.78).
• Black and Asian patients were more likely to be downstaged or achieve a pathologic complete response after neoadjuvant therapy (34.4% and 35.3%, respectively) than White (28.4%) and Hispanic patients (30.8%).

IN PRACTICE:

The authors found that “Asian and Hispanic race and ethnicity were independently associated with improved [overall survival] compared with Black and White race,” even after adjusting for variables including multimodality treatment regimen and response to neoadjuvant therapy.

The authors explained that overall Asian and Black patients responded more favorably to neoadjuvant therapy, demonstrating significantly higher rates of downstaging or pathologic complete response, which may help explain why Black patients demonstrated better overall survival than White patients who received neoadjuvant therapy.

SOURCE:

The research, led by Steve Kwon, MD, MPH, of Roger Williams Medical Center and Boston University, Providence, Rhode Island, was published online on December 21 in JAMA Network Open.

LIMITATIONS:

The analysis is constrained by the database, which may limit the generalizability of the findings. The authors determined the response to neoadjuvant therapy by comparing clinical stage with postoperative pathologic stage.

DISCLOSURES:

No funding was declared. No relevant financial relationships were declared.
 

A version of this article appeared on Medscape.com.