Conference Coverage

MADRID — The role of vitamin D in the risk for overweight and obesity has been the subject of multiple studies. Though there’s still not enough evidence to reach a decisive conclusion, several ongoing debates are setting the stage for future research.

Irene Bretón, MD, PhD, discussed these debates in a presentation titled “Vitamin D Deficiency and Obesity: Cause or Consequence?” delivered at the 64th Congress of the Spanish Society of Endocrinology and Nutrition (SEEN). Dr. Bretón is president of the Foundation of the Spanish Society of Endocrinology and Nutrition.

“Vitamin D deficiency can arise from different causes. The percentage that can be attributed to solar radiation is extremely variable. Some studies put it at 80%, while others suggest lower figures. Many diseases have also been associated with vitamin D deficiency or with low vitamin D levels (which are not always at the level of deficiency). Nonetheless, we still have a lot to learn about these associations,” she said.

Dr. Bretón pointed out that many of these studies overlook parathyroid hormone testing. “I also think it’s more appropriate to discuss nutritional status of vitamin D as opposed to serum levels, because these data can be misleading. It would be interesting to focus more on vitamin D metabolism and not just plasma levels.”
 

Vitamin Deficiency 

To answer whether obesity and its complications could be related to low vitamin D levels, Dr. Bretón pointed to this vitamin’s profile in various regions of the world and called attention to the fact that none of the studies on this topic include populations with roughly adequate levels of this vitamin.

“This highlights the prevalence of vitamin D deficiency worldwide. It affects approximately 50% of the population, has been described in all age groups, and affects both men and women — particularly pregnant women and those in menopause — and older adults,” said Dr. Bretón.

She also cited the figures backing this fact: 88% have 25-hydroxyvitamin D levels < 30 ng/mL, 37% have levels < 20 ng/mL, and 7% have levels < 10 ng/mL.

“These percentages have brought us to consider their potential link to the current obesity epidemic. Studies in humans have observed a relationship between low plasma levels and markers for obesity and adiposity. Free 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D are known to be reduced in obesity, and treatments to correct vitamin D deficiency are less effective in people with the disease,” she noted.

Regarding the impact in “the opposite direction,” that is, whether obesity affects the nutritional status of vitamin D, Bretón explained that observational studies have generally found a relationship between overweight and obesity and lower plasma levels of vitamin D. “Data from these studies show that each kg/m² increase in [body mass index (BMI)] is associated with a 1.15% decrease in 25-hydroxyvitamin D. These studies also show that the prevalence of vitamin D deficiency is 35% higher in patients with obesity and 24% higher in those that are overweight compared with individuals of normal weight. A relationship has been observed between vitamin D deficiency and body fat percentage in men and women and in all age groups,” explained Dr. Bretón.

Dr. Bretón noted that the diseases most closely associated with obesity are type 2 diabetes, hypertension, ischemic heart disease, cancer (colon, breast, prostate, and ovarian), inflammatory liver disease, asthma, and inflammatory diseases.
 

Mechanisms Involved

Dr. Bretón reviewed the latest evidence on the mechanisms involved in the relationship between obesity and vitamin D deficiency. “People with obesity may experience less solar exposure (more of their body is covered, or they spend more time indoors), but reduced exposure to the sun is known to have less of an influence on vitamin D levels. Studies where people were given radiation to test how their plasma levels of vitamin D respond have found that there is a smaller effect in people with obesity, and that the effect is inversely correlated with BMI: the higher the BMI, the less vitamin D levels increase under exposure to solar radiation.”

Another mechanism is sequestration in adipose tissue, which is the largest reservoir of vitamin D in the body. Nevertheless, factors such as vitamin D concentration in this tissue, regulation of local metabolism, and vitamin uptake and release are less understood. It is therefore unclear whether this mechanism acts to regulate plasma levels.

“This is why severe vitamin D deficiencies (and deficiencies of other fat-soluble vitamins) that occur after bariatric surgery are often not seen in the first year after surgery but develop much later, when the vitamin that has accumulated in adipose tissue is released as weight is lost,” said Dr. Bretón.

“On the other hand, the volumetric dilution in blood that occurs in relation to total body fat content may explain the variability of plasma levels and the response to treatment. Predictive equations have been described,” she explained.
 

The Prenatal Stage

Dr. Bretón mentioned that the best setting for studying the impact of vitamin D and preventing future obesity is during the initial stages of life, when adipogenesis and fetal programming are occurring.

“Studies in animals have shown how maternal vitamin D deficiency (due to nongenetic or nonepigenetic mechanisms) leads to changes in adipogenesis and programming of adipose reserves. A fetal or perinatal environment with low vitamin D levels programs all these mechanisms differently, and not just adipogenesis and adipocyte differentiation in utero,” she added.

Various mechanisms involved in vitamin D deficiency as a cause of obesity are currently being studied in the prenatal setting. One such mechanism is the interaction between the vitamin D receptor and 1 alpha–hydroxylase, which are present in the adipose tissue and help modulate lipid metabolism.

“The vitamin D receptor is particularly expressed in the early stages of adipocyte differentiation, but its expression drops off as the differentiation process continues. Vitamin D receptor knockout mice have a slender phenotype and are resistant to diet-induced obesity. They also accumulate less fat with age and a high-fat diet,” explained Dr. Bretón.

“However, vitamin D also influences the production of inflammatory adipokines in these early stages of life. It specifically plays a central role in modulating the inflammatory response in adipose tissue. These anti-inflammatory effects appear to be mediated by inhibition of [NF–kappa B] and MAPK signaling pathways. All of this suggests that vitamin D influences both adipogenesis and how the adipose tissue functions,” she added.
 

Weight Loss 

When considering the link between vitamin D and obesity in the context of weight loss, Dr. Bretón explained that studies in this area suggest that weight loss per se is not sufficient to increase serum 25-hydroxyvitamin D. Rather, increased synthesis by the skin or increased dietary intake are the most relevant factors for the nutritional status of this vitamin.

“A recent systematic review looking at the relationship between vitamin D levels and weight loss via caloric restriction and exercise showed a small but significant effect in the sense that weight loss increases vitamin D levels. However, other meta-analyses have not found significant results in this area,” she said.

“In my opinion, these results depend on how long the intervention is performed. If a lot of weight is lost in a short time frame, vitamin D is released into the adipose tissue, a process that doesn’t have any significant impact on the nutritional status of this vitamin. Generally, the effect of this relationship is small (1.5 ng/mL) and of little clinical relevance. Moreover, many systematic reviews have analyzed this relationship following bariatric surgery and have also come up with inconclusive results,” Dr. Bretón added.

What role do treatments play in correcting vitamin D deficiency? Dr. Bretón explained that studies that have examined how fortified foods affect obesity show that though these foods don’t cause significant weight changes, they do affect fat mass and waist circumference. This finding suggests that fortified foods have some impact, not necessarily on weight but perhaps on adiposity.

“To rightly value all this data, one has to pay special attention to the environment and the context where the research took place (children or adults, baseline vitamin D levels, and so on). If fortified foods are directly supplemented with cholecalciferol, the results are very inconsistent. We therefore cannot say that treatment with vitamin D can reduce body weight and adiposity,” she said.

When it comes to the complications from obesity, studies of vitamin D supplementation, cancer, and cardiovascular disease did not find any beneficial effect on preventing these pathologies.

For obesity’s impact on vitamin D supplementation, it is known that the levels achieved are lower in patients with obesity compared with patients of normal weight. “Compared with other interventions, however, these levels (15.27 ng/mL) are clinically relevant,” she noted.
 

Future Directions

Dr. Bretón explained that all this evidence has revealed many debates regarding the association of vitamin D levels with obesity. “For example, it appears that obesity could predict low vitamin D levels (not necessarily a deficiency). In turn, these low levels could cause obesity, especially during embryonic development, when programming of adipocyte physiology is taking place.”

Dr. Bretón sees many confounding factors that will need to be elucidated in the future. “One factor is that we aren’t sure whether the patient we’re seeing has vitamin D deficiency or if other factors are in play, like time since weight loss, laboratory technique used to measure vitamin D, nutritional status, geographic location, time of year when the test is performed, et cetera. You also have to assess other factors having to do with obesity, like how adiposity is being measured and whether BMI reflects that adiposity.”

Last, the expert reviewed the major research efforts underway that are based on evidence that vitamin D is associated with insulin resistance. Studies are being performed on pancreatic function, the role of vitamin D levels in ovarian physiology related to insulin resistance (specifically, the role of hyperandrogenism), adipose tissue (vitamin D receptor expression, volumetric dilution), and other components of metabolic syndrome to determine how this vitamin’s status influences the renin-angiotensin system, apoptosis, and cardiovascular risk.

“There is also plenty of research going on surrounding metabolic liver disease, which has a lot to do with the microbiota. So, they’re studying the relationship between vitamin D and dysbiosis, especially regarding local immunomodulation in the gut in relation to the microbiota,” she added.

Another area of research is cancer, focusing primarily on analyzing the nutritional status of vitamin D in relation to the microbiome and how this status may affect the therapeutic effect of chemotherapy and radiation therapy. “It would be interesting to find out whether the effect of immunotherapy varies depending on the patient’s vitamin D status,” concluded Dr. Bretón.

Dr. Bretón’s lecture at the 64th Congress of the SEEN was sponsored by the Foundation for Analysis and Social Studies (FAES).

This article was translated from the Medscape Spanish edition.  A version of this article appeared on Medscape.com.

MADRID — The role of vitamin D in the risk for overweight and obesity has been the subject of multiple studies. Though there’s still not enough evidence to reach a decisive conclusion, several ongoing debates are setting the stage for future research.

Irene Bretón, MD, PhD, discussed these debates in a presentation titled “Vitamin D Deficiency and Obesity: Cause or Consequence?” delivered at the 64th Congress of the Spanish Society of Endocrinology and Nutrition (SEEN). Dr. Bretón is president of the Foundation of the Spanish Society of Endocrinology and Nutrition.

“Vitamin D deficiency can arise from different causes. The percentage that can be attributed to solar radiation is extremely variable. Some studies put it at 80%, while others suggest lower figures. Many diseases have also been associated with vitamin D deficiency or with low vitamin D levels (which are not always at the level of deficiency). Nonetheless, we still have a lot to learn about these associations,” she said.

Dr. Bretón pointed out that many of these studies overlook parathyroid hormone testing. “I also think it’s more appropriate to discuss nutritional status of vitamin D as opposed to serum levels, because these data can be misleading. It would be interesting to focus more on vitamin D metabolism and not just plasma levels.”
 

Vitamin Deficiency 

To answer whether obesity and its complications could be related to low vitamin D levels, Dr. Bretón pointed to this vitamin’s profile in various regions of the world and called attention to the fact that none of the studies on this topic include populations with roughly adequate levels of this vitamin.

“This highlights the prevalence of vitamin D deficiency worldwide. It affects approximately 50% of the population, has been described in all age groups, and affects both men and women — particularly pregnant women and those in menopause — and older adults,” said Dr. Bretón.

She also cited the figures backing this fact: 88% have 25-hydroxyvitamin D levels < 30 ng/mL, 37% have levels < 20 ng/mL, and 7% have levels < 10 ng/mL.

“These percentages have brought us to consider their potential link to the current obesity epidemic. Studies in humans have observed a relationship between low plasma levels and markers for obesity and adiposity. Free 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D are known to be reduced in obesity, and treatments to correct vitamin D deficiency are less effective in people with the disease,” she noted.

Regarding the impact in “the opposite direction,” that is, whether obesity affects the nutritional status of vitamin D, Bretón explained that observational studies have generally found a relationship between overweight and obesity and lower plasma levels of vitamin D. “Data from these studies show that each kg/m² increase in [body mass index (BMI)] is associated with a 1.15% decrease in 25-hydroxyvitamin D. These studies also show that the prevalence of vitamin D deficiency is 35% higher in patients with obesity and 24% higher in those that are overweight compared with individuals of normal weight. A relationship has been observed between vitamin D deficiency and body fat percentage in men and women and in all age groups,” explained Dr. Bretón.

Dr. Bretón noted that the diseases most closely associated with obesity are type 2 diabetes, hypertension, ischemic heart disease, cancer (colon, breast, prostate, and ovarian), inflammatory liver disease, asthma, and inflammatory diseases.
 

Mechanisms Involved

Dr. Bretón reviewed the latest evidence on the mechanisms involved in the relationship between obesity and vitamin D deficiency. “People with obesity may experience less solar exposure (more of their body is covered, or they spend more time indoors), but reduced exposure to the sun is known to have less of an influence on vitamin D levels. Studies where people were given radiation to test how their plasma levels of vitamin D respond have found that there is a smaller effect in people with obesity, and that the effect is inversely correlated with BMI: the higher the BMI, the less vitamin D levels increase under exposure to solar radiation.”

Another mechanism is sequestration in adipose tissue, which is the largest reservoir of vitamin D in the body. Nevertheless, factors such as vitamin D concentration in this tissue, regulation of local metabolism, and vitamin uptake and release are less understood. It is therefore unclear whether this mechanism acts to regulate plasma levels.

“This is why severe vitamin D deficiencies (and deficiencies of other fat-soluble vitamins) that occur after bariatric surgery are often not seen in the first year after surgery but develop much later, when the vitamin that has accumulated in adipose tissue is released as weight is lost,” said Dr. Bretón.

“On the other hand, the volumetric dilution in blood that occurs in relation to total body fat content may explain the variability of plasma levels and the response to treatment. Predictive equations have been described,” she explained.
 

The Prenatal Stage

Dr. Bretón mentioned that the best setting for studying the impact of vitamin D and preventing future obesity is during the initial stages of life, when adipogenesis and fetal programming are occurring.

“Studies in animals have shown how maternal vitamin D deficiency (due to nongenetic or nonepigenetic mechanisms) leads to changes in adipogenesis and programming of adipose reserves. A fetal or perinatal environment with low vitamin D levels programs all these mechanisms differently, and not just adipogenesis and adipocyte differentiation in utero,” she added.

Various mechanisms involved in vitamin D deficiency as a cause of obesity are currently being studied in the prenatal setting. One such mechanism is the interaction between the vitamin D receptor and 1 alpha–hydroxylase, which are present in the adipose tissue and help modulate lipid metabolism.

“The vitamin D receptor is particularly expressed in the early stages of adipocyte differentiation, but its expression drops off as the differentiation process continues. Vitamin D receptor knockout mice have a slender phenotype and are resistant to diet-induced obesity. They also accumulate less fat with age and a high-fat diet,” explained Dr. Bretón.

“However, vitamin D also influences the production of inflammatory adipokines in these early stages of life. It specifically plays a central role in modulating the inflammatory response in adipose tissue. These anti-inflammatory effects appear to be mediated by inhibition of [NF–kappa B] and MAPK signaling pathways. All of this suggests that vitamin D influences both adipogenesis and how the adipose tissue functions,” she added.
 

Weight Loss 

When considering the link between vitamin D and obesity in the context of weight loss, Dr. Bretón explained that studies in this area suggest that weight loss per se is not sufficient to increase serum 25-hydroxyvitamin D. Rather, increased synthesis by the skin or increased dietary intake are the most relevant factors for the nutritional status of this vitamin.

“A recent systematic review looking at the relationship between vitamin D levels and weight loss via caloric restriction and exercise showed a small but significant effect in the sense that weight loss increases vitamin D levels. However, other meta-analyses have not found significant results in this area,” she said.

“In my opinion, these results depend on how long the intervention is performed. If a lot of weight is lost in a short time frame, vitamin D is released into the adipose tissue, a process that doesn’t have any significant impact on the nutritional status of this vitamin. Generally, the effect of this relationship is small (1.5 ng/mL) and of little clinical relevance. Moreover, many systematic reviews have analyzed this relationship following bariatric surgery and have also come up with inconclusive results,” Dr. Bretón added.

What role do treatments play in correcting vitamin D deficiency? Dr. Bretón explained that studies that have examined how fortified foods affect obesity show that though these foods don’t cause significant weight changes, they do affect fat mass and waist circumference. This finding suggests that fortified foods have some impact, not necessarily on weight but perhaps on adiposity.

“To rightly value all this data, one has to pay special attention to the environment and the context where the research took place (children or adults, baseline vitamin D levels, and so on). If fortified foods are directly supplemented with cholecalciferol, the results are very inconsistent. We therefore cannot say that treatment with vitamin D can reduce body weight and adiposity,” she said.

When it comes to the complications from obesity, studies of vitamin D supplementation, cancer, and cardiovascular disease did not find any beneficial effect on preventing these pathologies.

For obesity’s impact on vitamin D supplementation, it is known that the levels achieved are lower in patients with obesity compared with patients of normal weight. “Compared with other interventions, however, these levels (15.27 ng/mL) are clinically relevant,” she noted.
 

Future Directions

Dr. Bretón explained that all this evidence has revealed many debates regarding the association of vitamin D levels with obesity. “For example, it appears that obesity could predict low vitamin D levels (not necessarily a deficiency). In turn, these low levels could cause obesity, especially during embryonic development, when programming of adipocyte physiology is taking place.”

Dr. Bretón sees many confounding factors that will need to be elucidated in the future. “One factor is that we aren’t sure whether the patient we’re seeing has vitamin D deficiency or if other factors are in play, like time since weight loss, laboratory technique used to measure vitamin D, nutritional status, geographic location, time of year when the test is performed, et cetera. You also have to assess other factors having to do with obesity, like how adiposity is being measured and whether BMI reflects that adiposity.”

Last, the expert reviewed the major research efforts underway that are based on evidence that vitamin D is associated with insulin resistance. Studies are being performed on pancreatic function, the role of vitamin D levels in ovarian physiology related to insulin resistance (specifically, the role of hyperandrogenism), adipose tissue (vitamin D receptor expression, volumetric dilution), and other components of metabolic syndrome to determine how this vitamin’s status influences the renin-angiotensin system, apoptosis, and cardiovascular risk.

“There is also plenty of research going on surrounding metabolic liver disease, which has a lot to do with the microbiota. So, they’re studying the relationship between vitamin D and dysbiosis, especially regarding local immunomodulation in the gut in relation to the microbiota,” she added.

Another area of research is cancer, focusing primarily on analyzing the nutritional status of vitamin D in relation to the microbiome and how this status may affect the therapeutic effect of chemotherapy and radiation therapy. “It would be interesting to find out whether the effect of immunotherapy varies depending on the patient’s vitamin D status,” concluded Dr. Bretón.

Dr. Bretón’s lecture at the 64th Congress of the SEEN was sponsored by the Foundation for Analysis and Social Studies (FAES).

This article was translated from the Medscape Spanish edition.  A version of this article appeared on Medscape.com.

MADRID — The role of vitamin D in the risk for overweight and obesity has been the subject of multiple studies. Though there’s still not enough evidence to reach a decisive conclusion, several ongoing debates are setting the stage for future research.

Irene Bretón, MD, PhD, discussed these debates in a presentation titled “Vitamin D Deficiency and Obesity: Cause or Consequence?” delivered at the 64th Congress of the Spanish Society of Endocrinology and Nutrition (SEEN). Dr. Bretón is president of the Foundation of the Spanish Society of Endocrinology and Nutrition.

“Vitamin D deficiency can arise from different causes. The percentage that can be attributed to solar radiation is extremely variable. Some studies put it at 80%, while others suggest lower figures. Many diseases have also been associated with vitamin D deficiency or with low vitamin D levels (which are not always at the level of deficiency). Nonetheless, we still have a lot to learn about these associations,” she said.

Dr. Bretón pointed out that many of these studies overlook parathyroid hormone testing. “I also think it’s more appropriate to discuss nutritional status of vitamin D as opposed to serum levels, because these data can be misleading. It would be interesting to focus more on vitamin D metabolism and not just plasma levels.”
 

Vitamin Deficiency 

To answer whether obesity and its complications could be related to low vitamin D levels, Dr. Bretón pointed to this vitamin’s profile in various regions of the world and called attention to the fact that none of the studies on this topic include populations with roughly adequate levels of this vitamin.

“This highlights the prevalence of vitamin D deficiency worldwide. It affects approximately 50% of the population, has been described in all age groups, and affects both men and women — particularly pregnant women and those in menopause — and older adults,” said Dr. Bretón.

She also cited the figures backing this fact: 88% have 25-hydroxyvitamin D levels < 30 ng/mL, 37% have levels < 20 ng/mL, and 7% have levels < 10 ng/mL.

“These percentages have brought us to consider their potential link to the current obesity epidemic. Studies in humans have observed a relationship between low plasma levels and markers for obesity and adiposity. Free 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D are known to be reduced in obesity, and treatments to correct vitamin D deficiency are less effective in people with the disease,” she noted.

Regarding the impact in “the opposite direction,” that is, whether obesity affects the nutritional status of vitamin D, Bretón explained that observational studies have generally found a relationship between overweight and obesity and lower plasma levels of vitamin D. “Data from these studies show that each kg/m² increase in [body mass index (BMI)] is associated with a 1.15% decrease in 25-hydroxyvitamin D. These studies also show that the prevalence of vitamin D deficiency is 35% higher in patients with obesity and 24% higher in those that are overweight compared with individuals of normal weight. A relationship has been observed between vitamin D deficiency and body fat percentage in men and women and in all age groups,” explained Dr. Bretón.

Dr. Bretón noted that the diseases most closely associated with obesity are type 2 diabetes, hypertension, ischemic heart disease, cancer (colon, breast, prostate, and ovarian), inflammatory liver disease, asthma, and inflammatory diseases.
 

Mechanisms Involved

Dr. Bretón reviewed the latest evidence on the mechanisms involved in the relationship between obesity and vitamin D deficiency. “People with obesity may experience less solar exposure (more of their body is covered, or they spend more time indoors), but reduced exposure to the sun is known to have less of an influence on vitamin D levels. Studies where people were given radiation to test how their plasma levels of vitamin D respond have found that there is a smaller effect in people with obesity, and that the effect is inversely correlated with BMI: the higher the BMI, the less vitamin D levels increase under exposure to solar radiation.”

Another mechanism is sequestration in adipose tissue, which is the largest reservoir of vitamin D in the body. Nevertheless, factors such as vitamin D concentration in this tissue, regulation of local metabolism, and vitamin uptake and release are less understood. It is therefore unclear whether this mechanism acts to regulate plasma levels.

“This is why severe vitamin D deficiencies (and deficiencies of other fat-soluble vitamins) that occur after bariatric surgery are often not seen in the first year after surgery but develop much later, when the vitamin that has accumulated in adipose tissue is released as weight is lost,” said Dr. Bretón.

“On the other hand, the volumetric dilution in blood that occurs in relation to total body fat content may explain the variability of plasma levels and the response to treatment. Predictive equations have been described,” she explained.
 

The Prenatal Stage

Dr. Bretón mentioned that the best setting for studying the impact of vitamin D and preventing future obesity is during the initial stages of life, when adipogenesis and fetal programming are occurring.

“Studies in animals have shown how maternal vitamin D deficiency (due to nongenetic or nonepigenetic mechanisms) leads to changes in adipogenesis and programming of adipose reserves. A fetal or perinatal environment with low vitamin D levels programs all these mechanisms differently, and not just adipogenesis and adipocyte differentiation in utero,” she added.

Various mechanisms involved in vitamin D deficiency as a cause of obesity are currently being studied in the prenatal setting. One such mechanism is the interaction between the vitamin D receptor and 1 alpha–hydroxylase, which are present in the adipose tissue and help modulate lipid metabolism.

“The vitamin D receptor is particularly expressed in the early stages of adipocyte differentiation, but its expression drops off as the differentiation process continues. Vitamin D receptor knockout mice have a slender phenotype and are resistant to diet-induced obesity. They also accumulate less fat with age and a high-fat diet,” explained Dr. Bretón.

“However, vitamin D also influences the production of inflammatory adipokines in these early stages of life. It specifically plays a central role in modulating the inflammatory response in adipose tissue. These anti-inflammatory effects appear to be mediated by inhibition of [NF–kappa B] and MAPK signaling pathways. All of this suggests that vitamin D influences both adipogenesis and how the adipose tissue functions,” she added.
 

Weight Loss 

When considering the link between vitamin D and obesity in the context of weight loss, Dr. Bretón explained that studies in this area suggest that weight loss per se is not sufficient to increase serum 25-hydroxyvitamin D. Rather, increased synthesis by the skin or increased dietary intake are the most relevant factors for the nutritional status of this vitamin.

“A recent systematic review looking at the relationship between vitamin D levels and weight loss via caloric restriction and exercise showed a small but significant effect in the sense that weight loss increases vitamin D levels. However, other meta-analyses have not found significant results in this area,” she said.

“In my opinion, these results depend on how long the intervention is performed. If a lot of weight is lost in a short time frame, vitamin D is released into the adipose tissue, a process that doesn’t have any significant impact on the nutritional status of this vitamin. Generally, the effect of this relationship is small (1.5 ng/mL) and of little clinical relevance. Moreover, many systematic reviews have analyzed this relationship following bariatric surgery and have also come up with inconclusive results,” Dr. Bretón added.

What role do treatments play in correcting vitamin D deficiency? Dr. Bretón explained that studies that have examined how fortified foods affect obesity show that though these foods don’t cause significant weight changes, they do affect fat mass and waist circumference. This finding suggests that fortified foods have some impact, not necessarily on weight but perhaps on adiposity.

“To rightly value all this data, one has to pay special attention to the environment and the context where the research took place (children or adults, baseline vitamin D levels, and so on). If fortified foods are directly supplemented with cholecalciferol, the results are very inconsistent. We therefore cannot say that treatment with vitamin D can reduce body weight and adiposity,” she said.

When it comes to the complications from obesity, studies of vitamin D supplementation, cancer, and cardiovascular disease did not find any beneficial effect on preventing these pathologies.

For obesity’s impact on vitamin D supplementation, it is known that the levels achieved are lower in patients with obesity compared with patients of normal weight. “Compared with other interventions, however, these levels (15.27 ng/mL) are clinically relevant,” she noted.
 

Future Directions

Dr. Bretón explained that all this evidence has revealed many debates regarding the association of vitamin D levels with obesity. “For example, it appears that obesity could predict low vitamin D levels (not necessarily a deficiency). In turn, these low levels could cause obesity, especially during embryonic development, when programming of adipocyte physiology is taking place.”

Dr. Bretón sees many confounding factors that will need to be elucidated in the future. “One factor is that we aren’t sure whether the patient we’re seeing has vitamin D deficiency or if other factors are in play, like time since weight loss, laboratory technique used to measure vitamin D, nutritional status, geographic location, time of year when the test is performed, et cetera. You also have to assess other factors having to do with obesity, like how adiposity is being measured and whether BMI reflects that adiposity.”

Last, the expert reviewed the major research efforts underway that are based on evidence that vitamin D is associated with insulin resistance. Studies are being performed on pancreatic function, the role of vitamin D levels in ovarian physiology related to insulin resistance (specifically, the role of hyperandrogenism), adipose tissue (vitamin D receptor expression, volumetric dilution), and other components of metabolic syndrome to determine how this vitamin’s status influences the renin-angiotensin system, apoptosis, and cardiovascular risk.

“There is also plenty of research going on surrounding metabolic liver disease, which has a lot to do with the microbiota. So, they’re studying the relationship between vitamin D and dysbiosis, especially regarding local immunomodulation in the gut in relation to the microbiota,” she added.

Another area of research is cancer, focusing primarily on analyzing the nutritional status of vitamin D in relation to the microbiome and how this status may affect the therapeutic effect of chemotherapy and radiation therapy. “It would be interesting to find out whether the effect of immunotherapy varies depending on the patient’s vitamin D status,” concluded Dr. Bretón.

Dr. Bretón’s lecture at the 64th Congress of the SEEN was sponsored by the Foundation for Analysis and Social Studies (FAES).

This article was translated from the Medscape Spanish edition.  A version of this article appeared on Medscape.com.

SAN ANTONIO — Women 65-70 years old are often offered the option of skipping radiation after lumpectomy for hormone receptor–positive early-stage breast cancer and moving straight to endocrine therapy.

The recurrence rate with and without radiation is well known so women can be counseled accurately about their options. For some, the 10% risk of recurrence at 10 years without radiation seems reasonable, for others it does not.

Omitting radiation for older postmenopausal women is “very reasonable to offer so long as they are willing to accept the risk,” said Reshma Jagsi, MD, chief of radiation oncology at Emory University, Atlanta.

The option, however, isn’t generally offered to postmenopausal women younger than 65 years old because their risk from skipping adjuvant radiation isn’t known, but that’s about to change.

Several teams are investigating the issue, including one led by Dr. Jagsi, who presented her and her colleagues’ latest results at the San Antonio Breast Cancer Symposium.

In the single-arm IDEA [Individualized Decisions for Endocrine therapy Alone] study, 200 women 50-69 years old with pT1N0 unifocal hormone receptor–positive, HER2-negative invasive breast cancer agreed to the approach when it was offered to them following lumpectomy with sentinel lymph node biopsy. The mean tumor size was 10 mm with margins of at least 2 mm.

The women were at low risk for recurrence, with recurrence risk scores no higher than 18 points on the Oncotype DX 21-gene assay; the mean score was 11 points.

Radiation would have been the usual next step after lumpectomy, but instead the patients went directly to endocrine therapy for 5 years, with adherence above 80%.

At 5 years, the results are “promising,” Dr. Jagsi said at the meeting. Overall and breast cancer–specific survival were both 100%, and the recurrence rate was just 1%, with two recurrences before the 5-year point. The women were a mean of 62 years old.

A similar single-arm trial, LUMINA, recently reported comparable results.

Dr. Jagsi called the findings of the studies “reassuring,” but cautioned that it will be a while before younger postmenopausal women can be offered radiation-free treatment like their older peers.

Even though the results suggest “that this might well be a really good idea,” longer follow-up and randomized data are needed “before we change the standard of care,” she said.

Of concern, for instance, is that there were six additional recurrences in the IDEA study past the 5-year mark, for a total of three recurrences among the 60 women 50-59 years old (5%) and five among the 140 women 60-69 years old (3.6%). Five of the recurrent cases were adherent to endocrine therapy.

Also, so few women in IDEA have passed the 5-year mark that “we can’t [conclude] anything” about long-term relapse risks, Dr. Jagsi said. Besides that, skipping radiation for such women at this point is “not reasonable,” Dr. Jagsi added.

Carlos Arteaga, MD, director of the UT Southwestern Simmons Cancer Center, Dallas, agreed.

“I think we have to wait. We have randomized studies that will test this in a formal way. Be that as it may, this provides the basis for a conversation physicians can have with patients because this could be an option” at some point, said Dr. Arteaga, who moderated Dr. Jagsi’s presentation.

“This is a big step in trying not to do too much for patients who don’t need it,” Virginia Kaklamani, MD, leader of the breast cancer program at UT Health San Antonio, said in an interview.

IDEA was published in the Journal of Clinical Oncology to coincide with Dr. Jagsi’s presentation.

The study was funded by the Susan G. Komen Breast Cancer Foundation and the University of Michigan Rogel Cancer Center. Dr. Jagsi has stock in Equity Quotient and research support form Genentech. Disclosure information for Arteaga was not available. Dr. Kaklamani has extensive industry ties, including being a speaker for Pfizer, Genentech, Novartis, and AstraZeneca.

SAN ANTONIO — Women 65-70 years old are often offered the option of skipping radiation after lumpectomy for hormone receptor–positive early-stage breast cancer and moving straight to endocrine therapy.

The recurrence rate with and without radiation is well known so women can be counseled accurately about their options. For some, the 10% risk of recurrence at 10 years without radiation seems reasonable, for others it does not.

Omitting radiation for older postmenopausal women is “very reasonable to offer so long as they are willing to accept the risk,” said Reshma Jagsi, MD, chief of radiation oncology at Emory University, Atlanta.

The option, however, isn’t generally offered to postmenopausal women younger than 65 years old because their risk from skipping adjuvant radiation isn’t known, but that’s about to change.

Several teams are investigating the issue, including one led by Dr. Jagsi, who presented her and her colleagues’ latest results at the San Antonio Breast Cancer Symposium.

In the single-arm IDEA [Individualized Decisions for Endocrine therapy Alone] study, 200 women 50-69 years old with pT1N0 unifocal hormone receptor–positive, HER2-negative invasive breast cancer agreed to the approach when it was offered to them following lumpectomy with sentinel lymph node biopsy. The mean tumor size was 10 mm with margins of at least 2 mm.

The women were at low risk for recurrence, with recurrence risk scores no higher than 18 points on the Oncotype DX 21-gene assay; the mean score was 11 points.

Radiation would have been the usual next step after lumpectomy, but instead the patients went directly to endocrine therapy for 5 years, with adherence above 80%.

At 5 years, the results are “promising,” Dr. Jagsi said at the meeting. Overall and breast cancer–specific survival were both 100%, and the recurrence rate was just 1%, with two recurrences before the 5-year point. The women were a mean of 62 years old.

A similar single-arm trial, LUMINA, recently reported comparable results.

Dr. Jagsi called the findings of the studies “reassuring,” but cautioned that it will be a while before younger postmenopausal women can be offered radiation-free treatment like their older peers.

Even though the results suggest “that this might well be a really good idea,” longer follow-up and randomized data are needed “before we change the standard of care,” she said.

Of concern, for instance, is that there were six additional recurrences in the IDEA study past the 5-year mark, for a total of three recurrences among the 60 women 50-59 years old (5%) and five among the 140 women 60-69 years old (3.6%). Five of the recurrent cases were adherent to endocrine therapy.

Also, so few women in IDEA have passed the 5-year mark that “we can’t [conclude] anything” about long-term relapse risks, Dr. Jagsi said. Besides that, skipping radiation for such women at this point is “not reasonable,” Dr. Jagsi added.

Carlos Arteaga, MD, director of the UT Southwestern Simmons Cancer Center, Dallas, agreed.

“I think we have to wait. We have randomized studies that will test this in a formal way. Be that as it may, this provides the basis for a conversation physicians can have with patients because this could be an option” at some point, said Dr. Arteaga, who moderated Dr. Jagsi’s presentation.

“This is a big step in trying not to do too much for patients who don’t need it,” Virginia Kaklamani, MD, leader of the breast cancer program at UT Health San Antonio, said in an interview.

IDEA was published in the Journal of Clinical Oncology to coincide with Dr. Jagsi’s presentation.

The study was funded by the Susan G. Komen Breast Cancer Foundation and the University of Michigan Rogel Cancer Center. Dr. Jagsi has stock in Equity Quotient and research support form Genentech. Disclosure information for Arteaga was not available. Dr. Kaklamani has extensive industry ties, including being a speaker for Pfizer, Genentech, Novartis, and AstraZeneca.

SAN ANTONIO — Women 65-70 years old are often offered the option of skipping radiation after lumpectomy for hormone receptor–positive early-stage breast cancer and moving straight to endocrine therapy.

The recurrence rate with and without radiation is well known so women can be counseled accurately about their options. For some, the 10% risk of recurrence at 10 years without radiation seems reasonable, for others it does not.

Omitting radiation for older postmenopausal women is “very reasonable to offer so long as they are willing to accept the risk,” said Reshma Jagsi, MD, chief of radiation oncology at Emory University, Atlanta.

The option, however, isn’t generally offered to postmenopausal women younger than 65 years old because their risk from skipping adjuvant radiation isn’t known, but that’s about to change.

Several teams are investigating the issue, including one led by Dr. Jagsi, who presented her and her colleagues’ latest results at the San Antonio Breast Cancer Symposium.

In the single-arm IDEA [Individualized Decisions for Endocrine therapy Alone] study, 200 women 50-69 years old with pT1N0 unifocal hormone receptor–positive, HER2-negative invasive breast cancer agreed to the approach when it was offered to them following lumpectomy with sentinel lymph node biopsy. The mean tumor size was 10 mm with margins of at least 2 mm.

The women were at low risk for recurrence, with recurrence risk scores no higher than 18 points on the Oncotype DX 21-gene assay; the mean score was 11 points.

Radiation would have been the usual next step after lumpectomy, but instead the patients went directly to endocrine therapy for 5 years, with adherence above 80%.

At 5 years, the results are “promising,” Dr. Jagsi said at the meeting. Overall and breast cancer–specific survival were both 100%, and the recurrence rate was just 1%, with two recurrences before the 5-year point. The women were a mean of 62 years old.

A similar single-arm trial, LUMINA, recently reported comparable results.

Dr. Jagsi called the findings of the studies “reassuring,” but cautioned that it will be a while before younger postmenopausal women can be offered radiation-free treatment like their older peers.

Even though the results suggest “that this might well be a really good idea,” longer follow-up and randomized data are needed “before we change the standard of care,” she said.

Of concern, for instance, is that there were six additional recurrences in the IDEA study past the 5-year mark, for a total of three recurrences among the 60 women 50-59 years old (5%) and five among the 140 women 60-69 years old (3.6%). Five of the recurrent cases were adherent to endocrine therapy.

Also, so few women in IDEA have passed the 5-year mark that “we can’t [conclude] anything” about long-term relapse risks, Dr. Jagsi said. Besides that, skipping radiation for such women at this point is “not reasonable,” Dr. Jagsi added.

Carlos Arteaga, MD, director of the UT Southwestern Simmons Cancer Center, Dallas, agreed.

“I think we have to wait. We have randomized studies that will test this in a formal way. Be that as it may, this provides the basis for a conversation physicians can have with patients because this could be an option” at some point, said Dr. Arteaga, who moderated Dr. Jagsi’s presentation.

“This is a big step in trying not to do too much for patients who don’t need it,” Virginia Kaklamani, MD, leader of the breast cancer program at UT Health San Antonio, said in an interview.

IDEA was published in the Journal of Clinical Oncology to coincide with Dr. Jagsi’s presentation.

The study was funded by the Susan G. Komen Breast Cancer Foundation and the University of Michigan Rogel Cancer Center. Dr. Jagsi has stock in Equity Quotient and research support form Genentech. Disclosure information for Arteaga was not available. Dr. Kaklamani has extensive industry ties, including being a speaker for Pfizer, Genentech, Novartis, and AstraZeneca.

SAN ANTONIO — Sleep problems are common in women with breast cancer and often associated with poorer physical and mental health, a new study finds. Poor sleep quality and short sleep duration in particular were associated with poorer mental well-being.

“It’s important to ask patients [with breast cancer] about sleep and provide targeted interventions to improve sleep, when needed, to improve quality of life,” Lin Yang, PhD, with Cancer Care Alberta and University of Calgary, Canada, said in an interview.

The growing population of breast cancer survivors, particularly in developed countries, is burdened by a high prevalence of sleep problems, affecting more than half of the survivors, Dr. Yang said at the San Antonio Breast Cancer Symposium. 

The AMBER cohort study delved into how sleep health aspects, including sleep duration, timing, and quality, relate to the physical and mental well-being of women recently diagnosed with breast cancer. 

The study recruited 1409 women with newly diagnosed early-stage breast cancer from Edmonton and Calgary, Canada, between 2012 and 2019. 

The women completed the Pittsburgh Sleep Quality Index (PSQI) to assess habitual sleep duration and timing as well as sleep latency, efficiency, disturbance, medication, and daytime dysfunction and version two of the Short Form-36 (SF-36) to assess physical and mental well-being. 

Multivariable linear regressions were used to estimate the association of sleep characteristics with physical and mental well-being, adjusting for sociodemographic, disease, clinical, and lifestyle behavior factors.

Among the total patient cohort (mean age, 55 years), 41% experienced either short sleep duration (less than 6 h/d) or long sleep duration (more than 9 h/d), and the same percentage also reported regularly going to bed after 11 PM.

Of note, said Dr. Yang, in the multivariable model, short sleep duration was significantly associated with poorer mental well-being (beta-coefficient, -3.6; 95% CI, -4.7 to -2.4) but not poorer physical well-being (beta-coefficient, -1.5; 95% CI, -2.3 to -0.7). 

Sleep timing didn’t appear to have a meaningful impact on quality of life. 

However, poor sleep quality, measured through various metrics like sleep efficiency, disturbances, medication use, and daytime dysfunction, correlated with reduced physical and mental well-being, Dr. Yang said. 

She noted that targeted interventions to improve sleep health may lead to improvements in the quality of life among women with newly diagnosed breast cancer.

“Sleep is something we don’t necessarily think about in patients with breast cancer,” said Don Dizon, MD, with Brown University, Providence, Rhode Island, discussant for the study presentation.

However, this study shows the “clinical significance” of sleep, he said. “Notably 35% of this population is taking a sleeping pill.” 

Dr. Yang is an editorial board member of the Journal of Healthy Eating and Active Living. Dr. Dizon receives consulting fees from Astra Zeneca, Glaxo Smith Kline, Kronos Bio, and Pfizer and industry grant support from Bristol-Myers Squibb.

A version of this article appeared on Medscape.com.

SAN ANTONIO — Sleep problems are common in women with breast cancer and often associated with poorer physical and mental health, a new study finds. Poor sleep quality and short sleep duration in particular were associated with poorer mental well-being.

“It’s important to ask patients [with breast cancer] about sleep and provide targeted interventions to improve sleep, when needed, to improve quality of life,” Lin Yang, PhD, with Cancer Care Alberta and University of Calgary, Canada, said in an interview.

The growing population of breast cancer survivors, particularly in developed countries, is burdened by a high prevalence of sleep problems, affecting more than half of the survivors, Dr. Yang said at the San Antonio Breast Cancer Symposium. 

The AMBER cohort study delved into how sleep health aspects, including sleep duration, timing, and quality, relate to the physical and mental well-being of women recently diagnosed with breast cancer. 

The study recruited 1409 women with newly diagnosed early-stage breast cancer from Edmonton and Calgary, Canada, between 2012 and 2019. 

The women completed the Pittsburgh Sleep Quality Index (PSQI) to assess habitual sleep duration and timing as well as sleep latency, efficiency, disturbance, medication, and daytime dysfunction and version two of the Short Form-36 (SF-36) to assess physical and mental well-being. 

Multivariable linear regressions were used to estimate the association of sleep characteristics with physical and mental well-being, adjusting for sociodemographic, disease, clinical, and lifestyle behavior factors.

Among the total patient cohort (mean age, 55 years), 41% experienced either short sleep duration (less than 6 h/d) or long sleep duration (more than 9 h/d), and the same percentage also reported regularly going to bed after 11 PM.

Of note, said Dr. Yang, in the multivariable model, short sleep duration was significantly associated with poorer mental well-being (beta-coefficient, -3.6; 95% CI, -4.7 to -2.4) but not poorer physical well-being (beta-coefficient, -1.5; 95% CI, -2.3 to -0.7). 

Sleep timing didn’t appear to have a meaningful impact on quality of life. 

However, poor sleep quality, measured through various metrics like sleep efficiency, disturbances, medication use, and daytime dysfunction, correlated with reduced physical and mental well-being, Dr. Yang said. 

She noted that targeted interventions to improve sleep health may lead to improvements in the quality of life among women with newly diagnosed breast cancer.

“Sleep is something we don’t necessarily think about in patients with breast cancer,” said Don Dizon, MD, with Brown University, Providence, Rhode Island, discussant for the study presentation.

However, this study shows the “clinical significance” of sleep, he said. “Notably 35% of this population is taking a sleeping pill.” 

Dr. Yang is an editorial board member of the Journal of Healthy Eating and Active Living. Dr. Dizon receives consulting fees from Astra Zeneca, Glaxo Smith Kline, Kronos Bio, and Pfizer and industry grant support from Bristol-Myers Squibb.

A version of this article appeared on Medscape.com.

SAN ANTONIO — Sleep problems are common in women with breast cancer and often associated with poorer physical and mental health, a new study finds. Poor sleep quality and short sleep duration in particular were associated with poorer mental well-being.

“It’s important to ask patients [with breast cancer] about sleep and provide targeted interventions to improve sleep, when needed, to improve quality of life,” Lin Yang, PhD, with Cancer Care Alberta and University of Calgary, Canada, said in an interview.

The growing population of breast cancer survivors, particularly in developed countries, is burdened by a high prevalence of sleep problems, affecting more than half of the survivors, Dr. Yang said at the San Antonio Breast Cancer Symposium. 

The AMBER cohort study delved into how sleep health aspects, including sleep duration, timing, and quality, relate to the physical and mental well-being of women recently diagnosed with breast cancer. 

The study recruited 1409 women with newly diagnosed early-stage breast cancer from Edmonton and Calgary, Canada, between 2012 and 2019. 

The women completed the Pittsburgh Sleep Quality Index (PSQI) to assess habitual sleep duration and timing as well as sleep latency, efficiency, disturbance, medication, and daytime dysfunction and version two of the Short Form-36 (SF-36) to assess physical and mental well-being. 

Multivariable linear regressions were used to estimate the association of sleep characteristics with physical and mental well-being, adjusting for sociodemographic, disease, clinical, and lifestyle behavior factors.

Among the total patient cohort (mean age, 55 years), 41% experienced either short sleep duration (less than 6 h/d) or long sleep duration (more than 9 h/d), and the same percentage also reported regularly going to bed after 11 PM.

Of note, said Dr. Yang, in the multivariable model, short sleep duration was significantly associated with poorer mental well-being (beta-coefficient, -3.6; 95% CI, -4.7 to -2.4) but not poorer physical well-being (beta-coefficient, -1.5; 95% CI, -2.3 to -0.7). 

Sleep timing didn’t appear to have a meaningful impact on quality of life. 

However, poor sleep quality, measured through various metrics like sleep efficiency, disturbances, medication use, and daytime dysfunction, correlated with reduced physical and mental well-being, Dr. Yang said. 

She noted that targeted interventions to improve sleep health may lead to improvements in the quality of life among women with newly diagnosed breast cancer.

“Sleep is something we don’t necessarily think about in patients with breast cancer,” said Don Dizon, MD, with Brown University, Providence, Rhode Island, discussant for the study presentation.

However, this study shows the “clinical significance” of sleep, he said. “Notably 35% of this population is taking a sleeping pill.” 

Dr. Yang is an editorial board member of the Journal of Healthy Eating and Active Living. Dr. Dizon receives consulting fees from Astra Zeneca, Glaxo Smith Kline, Kronos Bio, and Pfizer and industry grant support from Bristol-Myers Squibb.

A version of this article appeared on Medscape.com.

SAN ANTONIO — There’s a long-standing debate in breast oncology about what to do when positive axillary lymph nodes turn negative after neoadjuvant chemotherapy.

Do patients still need regional nodal irradiation or can they skip it? 

Currently, it’s about a 50/50 split among oncologists, according to breast cancer surgeon Eleftherios P. Mamounas, MD, medical director of the Comprehensive Breast Program at the Orlando Health Cancer Institute in Florida.

Until now, Dr. Mamounas’s own institution has opted for regional irradiation just to be on the safe side, but he said that’s going to change in the wake of a multicenter trial he presented at the San Antonio Breast Cancer Symposium. 

Dr. Mamounas led a team that randomized 1556 women equally to either regional nodal irradiation or no nodal irradiation following surgery, which was lumpectomy in just over half the subjects and mastectomy in the rest. 

Women were a median of 52 years old. Almost 60% had T2 disease and the rest were split about evenly between T1 and T3 disease. Nearly a quarter of the tumors were triple-negative, and over half were HER2 positive.

In the regional nodal irradiation arm, women who had mastectomies had chest wall irradiation in addition to regional nodal irradiation, while women who underwent lumpectomies had whole breast irradiation with regional nodal irradiation. In the no-irradiation group, mastectomies were followed by observation and lumpectomies by whole breast irradiation alone. 

All the women had positive axillary lymph nodes (N1) on needle biopsies at baseline that were found to be free of cancer at surgery (ypN0) following neoadjuvant chemotherapy. Neoadjuvant therapy consisted of at least 8 weeks of chemotherapy plus anti-HER2 therapy for HER2-positive patients. 

Dr. Mamounas and colleagues observed no meaningful differences in outcomes between the two groups: 92.7% of women in the nodal irradiation arm and 91.8% in the no-irradiation arm were free from invasive recurrences 5 years after surgery.

Patients in both groups demonstrated similar 5-year disease-free survival and overall survival. The 5-year disease-free survival was 88.5% without and 88.3% with regional nodal irradiation and 5-year overall survival was 94% without and 93.6% with regional nodal irradiation.

The team did not observe study-related deaths or unexpected toxicities. Overall, 6.5% of patients without regional nodal irradiation developed grade 3 toxicity vs. 10% of patients with irradiation. Grade 4 toxicity was rare, occurring in 0.1% of patients in the no-irradiation group vs. 0.5% in the irradiation group.

The trial answers “a very important question,” according to Kate Lathrop, MD, a breast medical oncologist at UT Health San Antonio, who moderated the presentation. 

The trial results were “highly awaited” because “we didn’t have the data to make these” decisions, Dr. Lathrop said. 

Knowing these patients do just as well without regional nodal irradiation is “going to change a lot of opinions,” said Dr. Lathrop, because we can avoid subjecting patients to unnecessary toxicity, including lymphedema with regional nodal irradiation as well as problems with breast reconstruction after mastectomy.

Because recurrences can still occur after 5 years, Dr. Mamounas’s team will continue to follow the women, but he believes “it’s very unlikely that long-term distant disease-free survival will change.” 

Based on the study, “we will omit” regional nodal irradiation for women who fit the study criteria, Dr. Mamounas said.

When asked if women should ask their doctors about skipping regional nodal irradiation, Dr. Mamounas said “absolutely.” 

“I think it requires a discussion at this point,” he explained. “Based on the data, it’s a reasonable conclusion that radiotherapy can be avoided” in many cases, such as in lower-stage women with one initially positive node. 

Dr. Mamounas said he thinks patients will be interested in the approach “because they are really looking to avoid radiotherapy” if they can. 

The work was funded by the National Cancer Institute. Dr. Mamounas has been a consultant and speaker for Genentech, Merck, and an adviser for TerSera Therapeutics, Biotheranostics Inc., and Sanofi. He owns stock in Moderna. Dr. Lathrop is a consultant for Pfizer, GE Healthcare, and Biotheranostics, and a speaker for Biotheranostics.
 

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

SAN ANTONIO — There’s a long-standing debate in breast oncology about what to do when positive axillary lymph nodes turn negative after neoadjuvant chemotherapy.

Do patients still need regional nodal irradiation or can they skip it? 

Currently, it’s about a 50/50 split among oncologists, according to breast cancer surgeon Eleftherios P. Mamounas, MD, medical director of the Comprehensive Breast Program at the Orlando Health Cancer Institute in Florida.

Until now, Dr. Mamounas’s own institution has opted for regional irradiation just to be on the safe side, but he said that’s going to change in the wake of a multicenter trial he presented at the San Antonio Breast Cancer Symposium. 

Dr. Mamounas led a team that randomized 1556 women equally to either regional nodal irradiation or no nodal irradiation following surgery, which was lumpectomy in just over half the subjects and mastectomy in the rest. 

Women were a median of 52 years old. Almost 60% had T2 disease and the rest were split about evenly between T1 and T3 disease. Nearly a quarter of the tumors were triple-negative, and over half were HER2 positive.

In the regional nodal irradiation arm, women who had mastectomies had chest wall irradiation in addition to regional nodal irradiation, while women who underwent lumpectomies had whole breast irradiation with regional nodal irradiation. In the no-irradiation group, mastectomies were followed by observation and lumpectomies by whole breast irradiation alone. 

All the women had positive axillary lymph nodes (N1) on needle biopsies at baseline that were found to be free of cancer at surgery (ypN0) following neoadjuvant chemotherapy. Neoadjuvant therapy consisted of at least 8 weeks of chemotherapy plus anti-HER2 therapy for HER2-positive patients. 

Dr. Mamounas and colleagues observed no meaningful differences in outcomes between the two groups: 92.7% of women in the nodal irradiation arm and 91.8% in the no-irradiation arm were free from invasive recurrences 5 years after surgery.

Patients in both groups demonstrated similar 5-year disease-free survival and overall survival. The 5-year disease-free survival was 88.5% without and 88.3% with regional nodal irradiation and 5-year overall survival was 94% without and 93.6% with regional nodal irradiation.

The team did not observe study-related deaths or unexpected toxicities. Overall, 6.5% of patients without regional nodal irradiation developed grade 3 toxicity vs. 10% of patients with irradiation. Grade 4 toxicity was rare, occurring in 0.1% of patients in the no-irradiation group vs. 0.5% in the irradiation group.

The trial answers “a very important question,” according to Kate Lathrop, MD, a breast medical oncologist at UT Health San Antonio, who moderated the presentation. 

The trial results were “highly awaited” because “we didn’t have the data to make these” decisions, Dr. Lathrop said. 

Knowing these patients do just as well without regional nodal irradiation is “going to change a lot of opinions,” said Dr. Lathrop, because we can avoid subjecting patients to unnecessary toxicity, including lymphedema with regional nodal irradiation as well as problems with breast reconstruction after mastectomy.

Because recurrences can still occur after 5 years, Dr. Mamounas’s team will continue to follow the women, but he believes “it’s very unlikely that long-term distant disease-free survival will change.” 

Based on the study, “we will omit” regional nodal irradiation for women who fit the study criteria, Dr. Mamounas said.

When asked if women should ask their doctors about skipping regional nodal irradiation, Dr. Mamounas said “absolutely.” 

“I think it requires a discussion at this point,” he explained. “Based on the data, it’s a reasonable conclusion that radiotherapy can be avoided” in many cases, such as in lower-stage women with one initially positive node. 

Dr. Mamounas said he thinks patients will be interested in the approach “because they are really looking to avoid radiotherapy” if they can. 

The work was funded by the National Cancer Institute. Dr. Mamounas has been a consultant and speaker for Genentech, Merck, and an adviser for TerSera Therapeutics, Biotheranostics Inc., and Sanofi. He owns stock in Moderna. Dr. Lathrop is a consultant for Pfizer, GE Healthcare, and Biotheranostics, and a speaker for Biotheranostics.
 

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

SAN ANTONIO — There’s a long-standing debate in breast oncology about what to do when positive axillary lymph nodes turn negative after neoadjuvant chemotherapy.

Do patients still need regional nodal irradiation or can they skip it? 

Currently, it’s about a 50/50 split among oncologists, according to breast cancer surgeon Eleftherios P. Mamounas, MD, medical director of the Comprehensive Breast Program at the Orlando Health Cancer Institute in Florida.

Until now, Dr. Mamounas’s own institution has opted for regional irradiation just to be on the safe side, but he said that’s going to change in the wake of a multicenter trial he presented at the San Antonio Breast Cancer Symposium. 

Dr. Mamounas led a team that randomized 1556 women equally to either regional nodal irradiation or no nodal irradiation following surgery, which was lumpectomy in just over half the subjects and mastectomy in the rest. 

Women were a median of 52 years old. Almost 60% had T2 disease and the rest were split about evenly between T1 and T3 disease. Nearly a quarter of the tumors were triple-negative, and over half were HER2 positive.

In the regional nodal irradiation arm, women who had mastectomies had chest wall irradiation in addition to regional nodal irradiation, while women who underwent lumpectomies had whole breast irradiation with regional nodal irradiation. In the no-irradiation group, mastectomies were followed by observation and lumpectomies by whole breast irradiation alone. 

All the women had positive axillary lymph nodes (N1) on needle biopsies at baseline that were found to be free of cancer at surgery (ypN0) following neoadjuvant chemotherapy. Neoadjuvant therapy consisted of at least 8 weeks of chemotherapy plus anti-HER2 therapy for HER2-positive patients. 

Dr. Mamounas and colleagues observed no meaningful differences in outcomes between the two groups: 92.7% of women in the nodal irradiation arm and 91.8% in the no-irradiation arm were free from invasive recurrences 5 years after surgery.

Patients in both groups demonstrated similar 5-year disease-free survival and overall survival. The 5-year disease-free survival was 88.5% without and 88.3% with regional nodal irradiation and 5-year overall survival was 94% without and 93.6% with regional nodal irradiation.

The team did not observe study-related deaths or unexpected toxicities. Overall, 6.5% of patients without regional nodal irradiation developed grade 3 toxicity vs. 10% of patients with irradiation. Grade 4 toxicity was rare, occurring in 0.1% of patients in the no-irradiation group vs. 0.5% in the irradiation group.

The trial answers “a very important question,” according to Kate Lathrop, MD, a breast medical oncologist at UT Health San Antonio, who moderated the presentation. 

The trial results were “highly awaited” because “we didn’t have the data to make these” decisions, Dr. Lathrop said. 

Knowing these patients do just as well without regional nodal irradiation is “going to change a lot of opinions,” said Dr. Lathrop, because we can avoid subjecting patients to unnecessary toxicity, including lymphedema with regional nodal irradiation as well as problems with breast reconstruction after mastectomy.

Because recurrences can still occur after 5 years, Dr. Mamounas’s team will continue to follow the women, but he believes “it’s very unlikely that long-term distant disease-free survival will change.” 

Based on the study, “we will omit” regional nodal irradiation for women who fit the study criteria, Dr. Mamounas said.

When asked if women should ask their doctors about skipping regional nodal irradiation, Dr. Mamounas said “absolutely.” 

“I think it requires a discussion at this point,” he explained. “Based on the data, it’s a reasonable conclusion that radiotherapy can be avoided” in many cases, such as in lower-stage women with one initially positive node. 

Dr. Mamounas said he thinks patients will be interested in the approach “because they are really looking to avoid radiotherapy” if they can. 

The work was funded by the National Cancer Institute. Dr. Mamounas has been a consultant and speaker for Genentech, Merck, and an adviser for TerSera Therapeutics, Biotheranostics Inc., and Sanofi. He owns stock in Moderna. Dr. Lathrop is a consultant for Pfizer, GE Healthcare, and Biotheranostics, and a speaker for Biotheranostics.
 

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

SAN ANTONIO — Breast cancer care can cause significant financial stress for patients, but certain interventions may help patients cope with these financial burdens, new survey findings show. 

Almost half of patients surveyed reported a “significant” or “catastrophic” financial burden related to their breast cancer care. But patients also found a range of resources helpful for minimizing this burden, including direct assistance programs that reduce the cost of medications, grants from nonprofits that can cover cancer-related expenses, as well as programs that offer free or low-cost transportation to medical appointments. 

Financial toxicity remains a “pervasive problem in the breast cancer community and we really need to go to the next step, which is designing patient-centered, patient-facing interventions to make improvements,” Fumiko Chino, MD, with Memorial Sloan Kettering Cancer Center in New York City, said when presenting the survey results at the San Antonio Breast Cancer Symposium. 

A growing body of evidence shows that cancer care, especially for breast cancer, can take a heavy financial toll on patients. However, routine screening for financial toxicity is not necessarily a routine part of clinical care, and providers may not know the types of financial assistance patients value most, Dr. Chino explained.

Dr. Chino and colleagues surveyed 1437 women with breast cancer about their level of financial distress as well as the specific interventions or education initiatives they found most helpful.

Most patients (60%) were White, 27% were Hispanic, and 8% Black. Three quarters of patients were on active treatments, 89% had nonmetastatic disease, and 11% had metastatic disease.

Overall, 47% of patients reported a significant or catastrophic financial burden related to their breast cancer diagnosis and care. This burden was higher for those with metastatic disease (61% vs 45%).

Patients assessed 10 strategies for coping with the financial burdens of care. The top-rated interventions included patient assistance programs offered by pharmaceutical or medical test companies, rated highly by 32% of respondents, and grants from nonprofits, rated highly by 31% of respondents. Patients also found financial assistance departments at cancer centers or hospitals helpful (29%); coupons and savings cards to reduce the cost of prescription drugs (28%); and programs that provide free or low-cost transportation to medical appointments (28%).

In terms of education, respondents said having a checklist of questions to ask their oncology team as well as a list of breast cancer-specific financial grants to apply for would be especially helpful when navigating the financial burdens of breast cancer care.

These preferences, however, did vary by race/ethnicity and disease status. Hispanic patients, for instance, found patient assistance programs offered by companies and cancer centers as well as transportation assistance more helpful than other groups. 

Patients with metastatic disease found patient assistance programs offered by medical companies particularly helpful compared with patients with nonmetastatic disease. And compared with patients with metastatic disease, those with nonmetastatic breast cancer found assistance through clinical trials and professional medical billing advocates helpful.

This study confirms the high rates of financial burden in women with breast cancer and clearly demonstrates that intervention preferences vary by sociodemographic and clinical characteristics, study discussant Claire C. Conley, PhD, from Georgetown University, Washington, DC, commented.

“This highlights that one size really doesn’t fit all when it comes to those financial burden interventions,” Dr. Conley said. “We need to think about factors at the patient level, the organizational level, and the environment level.”

The study had no commercial funding. Dr. Chino and Dr. Conley have disclosed no relevant financial relationships.

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

SAN ANTONIO — Breast cancer care can cause significant financial stress for patients, but certain interventions may help patients cope with these financial burdens, new survey findings show. 

Almost half of patients surveyed reported a “significant” or “catastrophic” financial burden related to their breast cancer care. But patients also found a range of resources helpful for minimizing this burden, including direct assistance programs that reduce the cost of medications, grants from nonprofits that can cover cancer-related expenses, as well as programs that offer free or low-cost transportation to medical appointments. 

Financial toxicity remains a “pervasive problem in the breast cancer community and we really need to go to the next step, which is designing patient-centered, patient-facing interventions to make improvements,” Fumiko Chino, MD, with Memorial Sloan Kettering Cancer Center in New York City, said when presenting the survey results at the San Antonio Breast Cancer Symposium. 

A growing body of evidence shows that cancer care, especially for breast cancer, can take a heavy financial toll on patients. However, routine screening for financial toxicity is not necessarily a routine part of clinical care, and providers may not know the types of financial assistance patients value most, Dr. Chino explained.

Dr. Chino and colleagues surveyed 1437 women with breast cancer about their level of financial distress as well as the specific interventions or education initiatives they found most helpful.

Most patients (60%) were White, 27% were Hispanic, and 8% Black. Three quarters of patients were on active treatments, 89% had nonmetastatic disease, and 11% had metastatic disease.

Overall, 47% of patients reported a significant or catastrophic financial burden related to their breast cancer diagnosis and care. This burden was higher for those with metastatic disease (61% vs 45%).

Patients assessed 10 strategies for coping with the financial burdens of care. The top-rated interventions included patient assistance programs offered by pharmaceutical or medical test companies, rated highly by 32% of respondents, and grants from nonprofits, rated highly by 31% of respondents. Patients also found financial assistance departments at cancer centers or hospitals helpful (29%); coupons and savings cards to reduce the cost of prescription drugs (28%); and programs that provide free or low-cost transportation to medical appointments (28%).

In terms of education, respondents said having a checklist of questions to ask their oncology team as well as a list of breast cancer-specific financial grants to apply for would be especially helpful when navigating the financial burdens of breast cancer care.

These preferences, however, did vary by race/ethnicity and disease status. Hispanic patients, for instance, found patient assistance programs offered by companies and cancer centers as well as transportation assistance more helpful than other groups. 

Patients with metastatic disease found patient assistance programs offered by medical companies particularly helpful compared with patients with nonmetastatic disease. And compared with patients with metastatic disease, those with nonmetastatic breast cancer found assistance through clinical trials and professional medical billing advocates helpful.

This study confirms the high rates of financial burden in women with breast cancer and clearly demonstrates that intervention preferences vary by sociodemographic and clinical characteristics, study discussant Claire C. Conley, PhD, from Georgetown University, Washington, DC, commented.

“This highlights that one size really doesn’t fit all when it comes to those financial burden interventions,” Dr. Conley said. “We need to think about factors at the patient level, the organizational level, and the environment level.”

The study had no commercial funding. Dr. Chino and Dr. Conley have disclosed no relevant financial relationships.

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

SAN ANTONIO — Breast cancer care can cause significant financial stress for patients, but certain interventions may help patients cope with these financial burdens, new survey findings show. 

Almost half of patients surveyed reported a “significant” or “catastrophic” financial burden related to their breast cancer care. But patients also found a range of resources helpful for minimizing this burden, including direct assistance programs that reduce the cost of medications, grants from nonprofits that can cover cancer-related expenses, as well as programs that offer free or low-cost transportation to medical appointments. 

Financial toxicity remains a “pervasive problem in the breast cancer community and we really need to go to the next step, which is designing patient-centered, patient-facing interventions to make improvements,” Fumiko Chino, MD, with Memorial Sloan Kettering Cancer Center in New York City, said when presenting the survey results at the San Antonio Breast Cancer Symposium. 

A growing body of evidence shows that cancer care, especially for breast cancer, can take a heavy financial toll on patients. However, routine screening for financial toxicity is not necessarily a routine part of clinical care, and providers may not know the types of financial assistance patients value most, Dr. Chino explained.

Dr. Chino and colleagues surveyed 1437 women with breast cancer about their level of financial distress as well as the specific interventions or education initiatives they found most helpful.

Most patients (60%) were White, 27% were Hispanic, and 8% Black. Three quarters of patients were on active treatments, 89% had nonmetastatic disease, and 11% had metastatic disease.

Overall, 47% of patients reported a significant or catastrophic financial burden related to their breast cancer diagnosis and care. This burden was higher for those with metastatic disease (61% vs 45%).

Patients assessed 10 strategies for coping with the financial burdens of care. The top-rated interventions included patient assistance programs offered by pharmaceutical or medical test companies, rated highly by 32% of respondents, and grants from nonprofits, rated highly by 31% of respondents. Patients also found financial assistance departments at cancer centers or hospitals helpful (29%); coupons and savings cards to reduce the cost of prescription drugs (28%); and programs that provide free or low-cost transportation to medical appointments (28%).

In terms of education, respondents said having a checklist of questions to ask their oncology team as well as a list of breast cancer-specific financial grants to apply for would be especially helpful when navigating the financial burdens of breast cancer care.

These preferences, however, did vary by race/ethnicity and disease status. Hispanic patients, for instance, found patient assistance programs offered by companies and cancer centers as well as transportation assistance more helpful than other groups. 

Patients with metastatic disease found patient assistance programs offered by medical companies particularly helpful compared with patients with nonmetastatic disease. And compared with patients with metastatic disease, those with nonmetastatic breast cancer found assistance through clinical trials and professional medical billing advocates helpful.

This study confirms the high rates of financial burden in women with breast cancer and clearly demonstrates that intervention preferences vary by sociodemographic and clinical characteristics, study discussant Claire C. Conley, PhD, from Georgetown University, Washington, DC, commented.

“This highlights that one size really doesn’t fit all when it comes to those financial burden interventions,” Dr. Conley said. “We need to think about factors at the patient level, the organizational level, and the environment level.”

The study had no commercial funding. Dr. Chino and Dr. Conley have disclosed no relevant financial relationships.

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

ORLANDO — Older people with epilepsy who live in deprived neighborhoods with lower socioeconomic status, fewer educational opportunities, and less access to health care have poorer memory, executive function, and processing speed than those living in more affluent areas, early research suggests.

Seniors with epilepsy present with multiple comorbidities, including, for example, hypertension and diabetes, and they are at increased risk of developing dementia, said study investigator Anny Reyes, PhD, a postdoctoral scholar at the University of California at San Diego.

Past research has shown neighborhood disadvantage is associated with numerous adverse health outcomes, including an increased risk for developing Alzheimer’s disease and related dementias (ADRD).

“We already know epilepsy on its own increases risks for dementia, and when you add disadvantaged to that, it’s going to increase the risk even more,” said Dr. Reyes.

Neurologists should ask their older patients with epilepsy, many of whom live alone, about food insecurity and access to resources “not just within the hospital system but also within their community,” she said.

The findings were presented at the annual meeting of the American Epilepsy Society.
 

Proxy Measure of Disadvantage

The incidence and prevalence of epilepsy increases with age. Older adults represent the fastest growing segment of individuals with epilepsy, said Dr. Reyes.

The new study included 40 patients with focal epilepsy, average age 67 years, from three areas: San Diego, California; Madison, Wisconsin; and Cleveland, Ohio.

Researchers collected clinical and sociodemographic information as well as vascular biomarkers. They also gathered individual-level data, including income, parental education levels, details on childhood upbringing, etc.

Using residential addresses, investigators determined the area deprivation index (ADI) value for study participants. The ADI is a proxy measure for neighborhood-level socioeconomic disadvantage that captures factors such a poverty, employment, housing, and education opportunities.

ADI values range from 1 to 10, with a higher number indicating greater neighborhood disadvantage. About 30% of the cohort had an ADI decile greater than 6.

Researchers divided subjects into Most Disadvantaged (ADI greater than 7) and Least Disadvantaged (AD 7 or less). The two groups were similar with regard to age, education level, and race/ethnicity.

But those from the most disadvantaged areas were younger, taking more antiseizure medications, had fewer years of education, lower levels of father’s education, less personal and family income, and were less likely to be diagnosed with hypertension.

Study subjects completed neuropsychological testing, including:

• Measures of learning (Rey Auditory Verbal Learning Test [RAVLT] Learning Over Trials; Wechsler Memory Scale 4th Edition [WMS-4] Logical Memory [LM] Story B immediate; and WMS-4 Visual Reproduction [VR] immediate)
• Memory (RAVLT delayed recall, WMS-4 LM delayed recall, and WMS-4 VR delayed recall)
• Language (Multilingual Naming Test, Auditory Naming Test, and animal fluency)
• Executive function/processing speed (Letter fluency and Trail-Making Test Parts A and B)

The study found a correlation between higher ADI (most disadvantaged) and poorer performance on learning (Spearman rho: -0.433; 95% CI -0.664 to -0.126; P = .006), memory (r = -0.496; 95% CI -0.707 to -0.205; P = .001), and executive function/processes speed (r = -0.315; 95% CI -0.577 to 0.006; P = .048), but no significant association with language.

Looking at individual-level data, the study found memory and processing speed “were driving the relationship, and again, patients had worse performance when they were coming from the most disadvantaged neighborhoods,” said Dr. Reyes.

The investigators also examined mood, including depression and anxiety, and subjective complaints of cognitive problems. “We found those patients residing in the most disadvantaged neighborhoods complained more about memory problems,” she said.

The results underscore the need for community-level interventions “that could provide resources in support of these older adults and their families and connect them to services we know are good for brain health,” said Dr. Reyes.

Alzheimer’s disease experts “have done a really good job of this, but this is new for epilepsy,” she added. “This gives us a great opportunity to kind of bridge the worlds of dementia and epilepsy.”
 

Novel Research

Commenting on the research, Rani Sarkis, MD, assistant professor of neurology, Brigham and Women’s Hospital, Boston, said the study is “very useful” as it ties social determinants of health to cognition.

“We have not been doing that” in people with epilepsy, he said.

The study, one of the first to look at the link between disadvantaged neighborhoods and cognitive impairment, “has very important” public health implications, including the need to consider access to activities that promote cognitive resilience and other brain health initiatives, said Dr. Sarkis.

Another larger study that looked at neighborhood deprivation and cognition in epilepsy was also presented at the AES meeting and published earlier this year in the journal Neurology.

That study included 800 patients with pharmaco-resistant temporal lobe epilepsy being evaluated for surgery at the Cleveland Clinic, mean age about 38 years. It examined numerous cognitive domains as well as depression and anxiety in relation to ADI generated by patient addresses and split into quintiles from least to most disadvantaged.

After controlling for covariants, the study found scores for all cognitive domains were significantly worse in the most disadvantaged quintile except for executive function, which was close to reaching significance (P = .052), said lead author Robyn M. Busch, PhD, a clinical neuropsychologist in the Epilepsy Center, Department of Neurology, Cleveland Clinic.

The study also found people in the most disadvantaged areas had more symptoms of depression and anxiety compared with people in the least disadvantaged areas, said Busch.
 

A Complex Issue

Although the exact mechanism tying disadvantaged areas to cognition in epilepsy isn’t fully understood, having less access to health care and educational opportunities, poor nutrition, and being under chronic stress “are all things that affect the brain,” said Dr. Busch.

“This is super complex and it’s going to be really difficult to tease apart, but we’d like to look at imaging data to see if it’s something structural, if there are functional changes in the brain or something that might help us understand this better.”

But it’s also possible that having epilepsy “might be pushing people into environments” that offer fewer employment and educational opportunities and less access to resources, she said.

The study authors and Dr. Sarkis report no relevant financial relationships.

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

ORLANDO — Older people with epilepsy who live in deprived neighborhoods with lower socioeconomic status, fewer educational opportunities, and less access to health care have poorer memory, executive function, and processing speed than those living in more affluent areas, early research suggests.

Seniors with epilepsy present with multiple comorbidities, including, for example, hypertension and diabetes, and they are at increased risk of developing dementia, said study investigator Anny Reyes, PhD, a postdoctoral scholar at the University of California at San Diego.

Past research has shown neighborhood disadvantage is associated with numerous adverse health outcomes, including an increased risk for developing Alzheimer’s disease and related dementias (ADRD).

“We already know epilepsy on its own increases risks for dementia, and when you add disadvantaged to that, it’s going to increase the risk even more,” said Dr. Reyes.

Neurologists should ask their older patients with epilepsy, many of whom live alone, about food insecurity and access to resources “not just within the hospital system but also within their community,” she said.

The findings were presented at the annual meeting of the American Epilepsy Society.
 

Proxy Measure of Disadvantage

The incidence and prevalence of epilepsy increases with age. Older adults represent the fastest growing segment of individuals with epilepsy, said Dr. Reyes.

The new study included 40 patients with focal epilepsy, average age 67 years, from three areas: San Diego, California; Madison, Wisconsin; and Cleveland, Ohio.

Researchers collected clinical and sociodemographic information as well as vascular biomarkers. They also gathered individual-level data, including income, parental education levels, details on childhood upbringing, etc.

Using residential addresses, investigators determined the area deprivation index (ADI) value for study participants. The ADI is a proxy measure for neighborhood-level socioeconomic disadvantage that captures factors such a poverty, employment, housing, and education opportunities.

ADI values range from 1 to 10, with a higher number indicating greater neighborhood disadvantage. About 30% of the cohort had an ADI decile greater than 6.

Researchers divided subjects into Most Disadvantaged (ADI greater than 7) and Least Disadvantaged (AD 7 or less). The two groups were similar with regard to age, education level, and race/ethnicity.

But those from the most disadvantaged areas were younger, taking more antiseizure medications, had fewer years of education, lower levels of father’s education, less personal and family income, and were less likely to be diagnosed with hypertension.

Study subjects completed neuropsychological testing, including:

• Measures of learning (Rey Auditory Verbal Learning Test [RAVLT] Learning Over Trials; Wechsler Memory Scale 4th Edition [WMS-4] Logical Memory [LM] Story B immediate; and WMS-4 Visual Reproduction [VR] immediate)
• Memory (RAVLT delayed recall, WMS-4 LM delayed recall, and WMS-4 VR delayed recall)
• Language (Multilingual Naming Test, Auditory Naming Test, and animal fluency)
• Executive function/processing speed (Letter fluency and Trail-Making Test Parts A and B)

The study found a correlation between higher ADI (most disadvantaged) and poorer performance on learning (Spearman rho: -0.433; 95% CI -0.664 to -0.126; P = .006), memory (r = -0.496; 95% CI -0.707 to -0.205; P = .001), and executive function/processes speed (r = -0.315; 95% CI -0.577 to 0.006; P = .048), but no significant association with language.

Looking at individual-level data, the study found memory and processing speed “were driving the relationship, and again, patients had worse performance when they were coming from the most disadvantaged neighborhoods,” said Dr. Reyes.

The investigators also examined mood, including depression and anxiety, and subjective complaints of cognitive problems. “We found those patients residing in the most disadvantaged neighborhoods complained more about memory problems,” she said.

The results underscore the need for community-level interventions “that could provide resources in support of these older adults and their families and connect them to services we know are good for brain health,” said Dr. Reyes.

Alzheimer’s disease experts “have done a really good job of this, but this is new for epilepsy,” she added. “This gives us a great opportunity to kind of bridge the worlds of dementia and epilepsy.”
 

Novel Research

Commenting on the research, Rani Sarkis, MD, assistant professor of neurology, Brigham and Women’s Hospital, Boston, said the study is “very useful” as it ties social determinants of health to cognition.

“We have not been doing that” in people with epilepsy, he said.

The study, one of the first to look at the link between disadvantaged neighborhoods and cognitive impairment, “has very important” public health implications, including the need to consider access to activities that promote cognitive resilience and other brain health initiatives, said Dr. Sarkis.

Another larger study that looked at neighborhood deprivation and cognition in epilepsy was also presented at the AES meeting and published earlier this year in the journal Neurology.

That study included 800 patients with pharmaco-resistant temporal lobe epilepsy being evaluated for surgery at the Cleveland Clinic, mean age about 38 years. It examined numerous cognitive domains as well as depression and anxiety in relation to ADI generated by patient addresses and split into quintiles from least to most disadvantaged.

After controlling for covariants, the study found scores for all cognitive domains were significantly worse in the most disadvantaged quintile except for executive function, which was close to reaching significance (P = .052), said lead author Robyn M. Busch, PhD, a clinical neuropsychologist in the Epilepsy Center, Department of Neurology, Cleveland Clinic.

The study also found people in the most disadvantaged areas had more symptoms of depression and anxiety compared with people in the least disadvantaged areas, said Busch.
 

A Complex Issue

Although the exact mechanism tying disadvantaged areas to cognition in epilepsy isn’t fully understood, having less access to health care and educational opportunities, poor nutrition, and being under chronic stress “are all things that affect the brain,” said Dr. Busch.

“This is super complex and it’s going to be really difficult to tease apart, but we’d like to look at imaging data to see if it’s something structural, if there are functional changes in the brain or something that might help us understand this better.”

But it’s also possible that having epilepsy “might be pushing people into environments” that offer fewer employment and educational opportunities and less access to resources, she said.

The study authors and Dr. Sarkis report no relevant financial relationships.

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

ORLANDO — Older people with epilepsy who live in deprived neighborhoods with lower socioeconomic status, fewer educational opportunities, and less access to health care have poorer memory, executive function, and processing speed than those living in more affluent areas, early research suggests.

Seniors with epilepsy present with multiple comorbidities, including, for example, hypertension and diabetes, and they are at increased risk of developing dementia, said study investigator Anny Reyes, PhD, a postdoctoral scholar at the University of California at San Diego.

Past research has shown neighborhood disadvantage is associated with numerous adverse health outcomes, including an increased risk for developing Alzheimer’s disease and related dementias (ADRD).

“We already know epilepsy on its own increases risks for dementia, and when you add disadvantaged to that, it’s going to increase the risk even more,” said Dr. Reyes.

Neurologists should ask their older patients with epilepsy, many of whom live alone, about food insecurity and access to resources “not just within the hospital system but also within their community,” she said.

The findings were presented at the annual meeting of the American Epilepsy Society.
 

Proxy Measure of Disadvantage

The incidence and prevalence of epilepsy increases with age. Older adults represent the fastest growing segment of individuals with epilepsy, said Dr. Reyes.

The new study included 40 patients with focal epilepsy, average age 67 years, from three areas: San Diego, California; Madison, Wisconsin; and Cleveland, Ohio.

Researchers collected clinical and sociodemographic information as well as vascular biomarkers. They also gathered individual-level data, including income, parental education levels, details on childhood upbringing, etc.

Using residential addresses, investigators determined the area deprivation index (ADI) value for study participants. The ADI is a proxy measure for neighborhood-level socioeconomic disadvantage that captures factors such a poverty, employment, housing, and education opportunities.

ADI values range from 1 to 10, with a higher number indicating greater neighborhood disadvantage. About 30% of the cohort had an ADI decile greater than 6.

Researchers divided subjects into Most Disadvantaged (ADI greater than 7) and Least Disadvantaged (AD 7 or less). The two groups were similar with regard to age, education level, and race/ethnicity.

But those from the most disadvantaged areas were younger, taking more antiseizure medications, had fewer years of education, lower levels of father’s education, less personal and family income, and were less likely to be diagnosed with hypertension.

Study subjects completed neuropsychological testing, including:

• Measures of learning (Rey Auditory Verbal Learning Test [RAVLT] Learning Over Trials; Wechsler Memory Scale 4th Edition [WMS-4] Logical Memory [LM] Story B immediate; and WMS-4 Visual Reproduction [VR] immediate)
• Memory (RAVLT delayed recall, WMS-4 LM delayed recall, and WMS-4 VR delayed recall)
• Language (Multilingual Naming Test, Auditory Naming Test, and animal fluency)
• Executive function/processing speed (Letter fluency and Trail-Making Test Parts A and B)

The study found a correlation between higher ADI (most disadvantaged) and poorer performance on learning (Spearman rho: -0.433; 95% CI -0.664 to -0.126; P = .006), memory (r = -0.496; 95% CI -0.707 to -0.205; P = .001), and executive function/processes speed (r = -0.315; 95% CI -0.577 to 0.006; P = .048), but no significant association with language.

Looking at individual-level data, the study found memory and processing speed “were driving the relationship, and again, patients had worse performance when they were coming from the most disadvantaged neighborhoods,” said Dr. Reyes.

The investigators also examined mood, including depression and anxiety, and subjective complaints of cognitive problems. “We found those patients residing in the most disadvantaged neighborhoods complained more about memory problems,” she said.

The results underscore the need for community-level interventions “that could provide resources in support of these older adults and their families and connect them to services we know are good for brain health,” said Dr. Reyes.

Alzheimer’s disease experts “have done a really good job of this, but this is new for epilepsy,” she added. “This gives us a great opportunity to kind of bridge the worlds of dementia and epilepsy.”
 

Novel Research

Commenting on the research, Rani Sarkis, MD, assistant professor of neurology, Brigham and Women’s Hospital, Boston, said the study is “very useful” as it ties social determinants of health to cognition.

“We have not been doing that” in people with epilepsy, he said.

The study, one of the first to look at the link between disadvantaged neighborhoods and cognitive impairment, “has very important” public health implications, including the need to consider access to activities that promote cognitive resilience and other brain health initiatives, said Dr. Sarkis.

Another larger study that looked at neighborhood deprivation and cognition in epilepsy was also presented at the AES meeting and published earlier this year in the journal Neurology.

That study included 800 patients with pharmaco-resistant temporal lobe epilepsy being evaluated for surgery at the Cleveland Clinic, mean age about 38 years. It examined numerous cognitive domains as well as depression and anxiety in relation to ADI generated by patient addresses and split into quintiles from least to most disadvantaged.

After controlling for covariants, the study found scores for all cognitive domains were significantly worse in the most disadvantaged quintile except for executive function, which was close to reaching significance (P = .052), said lead author Robyn M. Busch, PhD, a clinical neuropsychologist in the Epilepsy Center, Department of Neurology, Cleveland Clinic.

The study also found people in the most disadvantaged areas had more symptoms of depression and anxiety compared with people in the least disadvantaged areas, said Busch.
 

A Complex Issue

Although the exact mechanism tying disadvantaged areas to cognition in epilepsy isn’t fully understood, having less access to health care and educational opportunities, poor nutrition, and being under chronic stress “are all things that affect the brain,” said Dr. Busch.

“This is super complex and it’s going to be really difficult to tease apart, but we’d like to look at imaging data to see if it’s something structural, if there are functional changes in the brain or something that might help us understand this better.”

But it’s also possible that having epilepsy “might be pushing people into environments” that offer fewer employment and educational opportunities and less access to resources, she said.

The study authors and Dr. Sarkis report no relevant financial relationships.

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

ORLANDO — Genetic testing is warranted in patients with epilepsy of unknown origin, new research suggests. Investigators found that pathogenic genetic variants were identified in over 40% of patients with epilepsy of unknown cause who underwent genetic testing.

Such testing is particularly beneficial for those with early-onset epilepsy and those with comorbid developmental delay, said study investigator Yi Li, MD, PhD, clinical assistant professor, Department of Neurology & Neurological Sciences, Stanford University School of Medicine, Stanford, California. 

But every patient with epilepsy of unknown etiology needs to consider genetic testing as part of their standard workup.

Dr. Li noted research showing that a diagnosis of a genetic epilepsy leads to alteration of treatment in about 20% of cases — for example, starting a specific antiseizure medication or avoiding a treatment such as a sodium channel blocker in patients diagnosed with Dravet syndrome. A genetic diagnosis also may make patients eligible for clinical trials investigating gene therapies. 

Genetic testing results may end a long and exhausting “diagnostic odyssey” that families have been on, she said. Patients often wait more than a decade to get genetic testing, the study found.

The findings were presented at the annual meeting of the American Epilepsy Society.
 

Major Delays

About 20%-30% of epilepsy is caused by acquired conditions such as stroke, tumor, or head injury. The remaining 70%-80% is believed to be due to one or more genetic factors.

Genetic testing has become standard for children with early-onset epilepsy, but it’s not common practice among adults with the condition — at least not yet.

The retrospective study involved a chart review of patient electronic health records from 2018-2023. Researchers used the Stanford electronic health record Cohort Discovery tool (STARR) database to identify 286 patients over age 16 years with epilepsy who had records of genetic testing.

Of the 286 patients, 148 were male and 138 female, and mean age was approximately 30 years. Among those with known epilepsy types, 53.6% had focal epilepsy and 28.8% had generalized epilpesy.

The mean age of seizure onset was 11.9 years, but the mean age at genetic testing was 25.1 years. “There’s a gap of about 13 or 14 years for genetic workup after a patient has a first seizure,” said Dr. Li.

Such a “huge delay” means patients may miss out on “potential precision treatment choices,” she said.

And having a diagnosis can connect patients to others with the same condition as well as to related organizations and communities that offer support, she added.

Types of genetic testing identified in the study included panel testing, which looks at the genes associated with epilepsy; whole exome sequencing (WES), which includes all 20,000 genes in one test; and microarray testing, which assesses missing sections of chromosomes. WES had the highest diagnostic yield (48%), followed by genetic panel testing (32.7%) and microarray testing (20.9%).

These tests collectively identified pathogenic variants in 40.9% of patients. In addition, test results showed that 53.10% of patients had variants of uncertain significance.

In the full cohort, the most commonly identified variants were mutations in TSC1 (which causes tuberous sclerosis, SCN1A (which causes Dravet syndrome), and MECP2. Among patients with seizure onset after age 1 year, MECP2 and DEPDC5 were the two most commonly identified pathogenic variants.

Researchers examined factors possibly associated with a higher risk for genetic epilepsy, including family history, comorbid developmental delay, febrile seizures, status epilepticus, perinatal injury, and seizure onset age. In an adjusted analysis, comorbid developmental delay (estimate 2.338; 95% confidence interval [CI], 1.402-3.900; P =.001) and seizure onset before 1 year (estimate 2.365; 95% CI, 1.282-4.366; P =.006) predicted higher yield of pathogenic variants related to epilepsy.

Dr. Li noted that study participants with a family history of epilepsy were not more likely to test positive for a genetic link, so doctors shouldn’t rule out testing in patients if there’s no family history.

Both the International League Against Epilepsy (ILAE) and the National Society of Genetic Counselors (NSGC) recommend genetic testing in adult epilepsy patients, with the AES endorsing the NSGC guideline.

Although testing is becoming increasingly accessible, insurance companies don’t always cover the cost.

Dr. Li said she hopes her research raises awareness among clinicians that there’s more they can do to improve care for epilepsy patients. “We should offer patients genetic testing if we don’t have a clear etiology.”
 

Valuable Evidence

Commenting on the research findings, Annapurna Poduri, MD, MPH, director, Epilepsy Genetics Program, Boston Children’s Hospital, Boston, Massachusetts, said this research “is incredibly important.”

“What’s really telling about this study and others that have come up over the last few years is they’re real-world retrospective studies, so they’re looking back at patients who have been seen over many, many years.”

The research provides clinicians, insurance companies, and others with evidence that genetic testing is “valuable and can actually improve outcomes,” said Dr. Poduri.

She noted that 20 years ago, there were only a handful of genes identified as being involved with epilepsy, most related to sodium or potassium channels. But since then, “the technology has just raced ahead” to the point where now “dozens of genes” have been identified.

Not only does knowing the genetic basis of epilepsy improve management, but it offers families some peace of mind. “They blame themselves” for their loved one’s condition, said Dr. Poduri. “They may worry it was something they did in pregnancy; for example, maybe it was because [they] didn’t take that vitamin one day.”

Diagnostic certainty also means that patients “don’t have to do more tests which might be invasive” and unnecessarily costly.

Drs. Li and Poduri report no relevant conflicts of interest.

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

ORLANDO — Genetic testing is warranted in patients with epilepsy of unknown origin, new research suggests. Investigators found that pathogenic genetic variants were identified in over 40% of patients with epilepsy of unknown cause who underwent genetic testing.

Such testing is particularly beneficial for those with early-onset epilepsy and those with comorbid developmental delay, said study investigator Yi Li, MD, PhD, clinical assistant professor, Department of Neurology & Neurological Sciences, Stanford University School of Medicine, Stanford, California. 

But every patient with epilepsy of unknown etiology needs to consider genetic testing as part of their standard workup.

Dr. Li noted research showing that a diagnosis of a genetic epilepsy leads to alteration of treatment in about 20% of cases — for example, starting a specific antiseizure medication or avoiding a treatment such as a sodium channel blocker in patients diagnosed with Dravet syndrome. A genetic diagnosis also may make patients eligible for clinical trials investigating gene therapies. 

Genetic testing results may end a long and exhausting “diagnostic odyssey” that families have been on, she said. Patients often wait more than a decade to get genetic testing, the study found.

The findings were presented at the annual meeting of the American Epilepsy Society.
 

Major Delays

About 20%-30% of epilepsy is caused by acquired conditions such as stroke, tumor, or head injury. The remaining 70%-80% is believed to be due to one or more genetic factors.

Genetic testing has become standard for children with early-onset epilepsy, but it’s not common practice among adults with the condition — at least not yet.

The retrospective study involved a chart review of patient electronic health records from 2018-2023. Researchers used the Stanford electronic health record Cohort Discovery tool (STARR) database to identify 286 patients over age 16 years with epilepsy who had records of genetic testing.

Of the 286 patients, 148 were male and 138 female, and mean age was approximately 30 years. Among those with known epilepsy types, 53.6% had focal epilepsy and 28.8% had generalized epilpesy.

The mean age of seizure onset was 11.9 years, but the mean age at genetic testing was 25.1 years. “There’s a gap of about 13 or 14 years for genetic workup after a patient has a first seizure,” said Dr. Li.

Such a “huge delay” means patients may miss out on “potential precision treatment choices,” she said.

And having a diagnosis can connect patients to others with the same condition as well as to related organizations and communities that offer support, she added.

Types of genetic testing identified in the study included panel testing, which looks at the genes associated with epilepsy; whole exome sequencing (WES), which includes all 20,000 genes in one test; and microarray testing, which assesses missing sections of chromosomes. WES had the highest diagnostic yield (48%), followed by genetic panel testing (32.7%) and microarray testing (20.9%).

These tests collectively identified pathogenic variants in 40.9% of patients. In addition, test results showed that 53.10% of patients had variants of uncertain significance.

In the full cohort, the most commonly identified variants were mutations in TSC1 (which causes tuberous sclerosis, SCN1A (which causes Dravet syndrome), and MECP2. Among patients with seizure onset after age 1 year, MECP2 and DEPDC5 were the two most commonly identified pathogenic variants.

Researchers examined factors possibly associated with a higher risk for genetic epilepsy, including family history, comorbid developmental delay, febrile seizures, status epilepticus, perinatal injury, and seizure onset age. In an adjusted analysis, comorbid developmental delay (estimate 2.338; 95% confidence interval [CI], 1.402-3.900; P =.001) and seizure onset before 1 year (estimate 2.365; 95% CI, 1.282-4.366; P =.006) predicted higher yield of pathogenic variants related to epilepsy.

Dr. Li noted that study participants with a family history of epilepsy were not more likely to test positive for a genetic link, so doctors shouldn’t rule out testing in patients if there’s no family history.

Both the International League Against Epilepsy (ILAE) and the National Society of Genetic Counselors (NSGC) recommend genetic testing in adult epilepsy patients, with the AES endorsing the NSGC guideline.

Although testing is becoming increasingly accessible, insurance companies don’t always cover the cost.

Dr. Li said she hopes her research raises awareness among clinicians that there’s more they can do to improve care for epilepsy patients. “We should offer patients genetic testing if we don’t have a clear etiology.”
 

Valuable Evidence

Commenting on the research findings, Annapurna Poduri, MD, MPH, director, Epilepsy Genetics Program, Boston Children’s Hospital, Boston, Massachusetts, said this research “is incredibly important.”

“What’s really telling about this study and others that have come up over the last few years is they’re real-world retrospective studies, so they’re looking back at patients who have been seen over many, many years.”

The research provides clinicians, insurance companies, and others with evidence that genetic testing is “valuable and can actually improve outcomes,” said Dr. Poduri.

She noted that 20 years ago, there were only a handful of genes identified as being involved with epilepsy, most related to sodium or potassium channels. But since then, “the technology has just raced ahead” to the point where now “dozens of genes” have been identified.

Not only does knowing the genetic basis of epilepsy improve management, but it offers families some peace of mind. “They blame themselves” for their loved one’s condition, said Dr. Poduri. “They may worry it was something they did in pregnancy; for example, maybe it was because [they] didn’t take that vitamin one day.”

Diagnostic certainty also means that patients “don’t have to do more tests which might be invasive” and unnecessarily costly.

Drs. Li and Poduri report no relevant conflicts of interest.

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

ORLANDO — Genetic testing is warranted in patients with epilepsy of unknown origin, new research suggests. Investigators found that pathogenic genetic variants were identified in over 40% of patients with epilepsy of unknown cause who underwent genetic testing.

Such testing is particularly beneficial for those with early-onset epilepsy and those with comorbid developmental delay, said study investigator Yi Li, MD, PhD, clinical assistant professor, Department of Neurology & Neurological Sciences, Stanford University School of Medicine, Stanford, California. 

But every patient with epilepsy of unknown etiology needs to consider genetic testing as part of their standard workup.

Dr. Li noted research showing that a diagnosis of a genetic epilepsy leads to alteration of treatment in about 20% of cases — for example, starting a specific antiseizure medication or avoiding a treatment such as a sodium channel blocker in patients diagnosed with Dravet syndrome. A genetic diagnosis also may make patients eligible for clinical trials investigating gene therapies. 

Genetic testing results may end a long and exhausting “diagnostic odyssey” that families have been on, she said. Patients often wait more than a decade to get genetic testing, the study found.

The findings were presented at the annual meeting of the American Epilepsy Society.
 

Major Delays

About 20%-30% of epilepsy is caused by acquired conditions such as stroke, tumor, or head injury. The remaining 70%-80% is believed to be due to one or more genetic factors.

Genetic testing has become standard for children with early-onset epilepsy, but it’s not common practice among adults with the condition — at least not yet.

The retrospective study involved a chart review of patient electronic health records from 2018-2023. Researchers used the Stanford electronic health record Cohort Discovery tool (STARR) database to identify 286 patients over age 16 years with epilepsy who had records of genetic testing.

Of the 286 patients, 148 were male and 138 female, and mean age was approximately 30 years. Among those with known epilepsy types, 53.6% had focal epilepsy and 28.8% had generalized epilpesy.

The mean age of seizure onset was 11.9 years, but the mean age at genetic testing was 25.1 years. “There’s a gap of about 13 or 14 years for genetic workup after a patient has a first seizure,” said Dr. Li.

Such a “huge delay” means patients may miss out on “potential precision treatment choices,” she said.

And having a diagnosis can connect patients to others with the same condition as well as to related organizations and communities that offer support, she added.

Types of genetic testing identified in the study included panel testing, which looks at the genes associated with epilepsy; whole exome sequencing (WES), which includes all 20,000 genes in one test; and microarray testing, which assesses missing sections of chromosomes. WES had the highest diagnostic yield (48%), followed by genetic panel testing (32.7%) and microarray testing (20.9%).

These tests collectively identified pathogenic variants in 40.9% of patients. In addition, test results showed that 53.10% of patients had variants of uncertain significance.

In the full cohort, the most commonly identified variants were mutations in TSC1 (which causes tuberous sclerosis, SCN1A (which causes Dravet syndrome), and MECP2. Among patients with seizure onset after age 1 year, MECP2 and DEPDC5 were the two most commonly identified pathogenic variants.

Researchers examined factors possibly associated with a higher risk for genetic epilepsy, including family history, comorbid developmental delay, febrile seizures, status epilepticus, perinatal injury, and seizure onset age. In an adjusted analysis, comorbid developmental delay (estimate 2.338; 95% confidence interval [CI], 1.402-3.900; P =.001) and seizure onset before 1 year (estimate 2.365; 95% CI, 1.282-4.366; P =.006) predicted higher yield of pathogenic variants related to epilepsy.

Dr. Li noted that study participants with a family history of epilepsy were not more likely to test positive for a genetic link, so doctors shouldn’t rule out testing in patients if there’s no family history.

Both the International League Against Epilepsy (ILAE) and the National Society of Genetic Counselors (NSGC) recommend genetic testing in adult epilepsy patients, with the AES endorsing the NSGC guideline.

Although testing is becoming increasingly accessible, insurance companies don’t always cover the cost.

Dr. Li said she hopes her research raises awareness among clinicians that there’s more they can do to improve care for epilepsy patients. “We should offer patients genetic testing if we don’t have a clear etiology.”
 

Valuable Evidence

Commenting on the research findings, Annapurna Poduri, MD, MPH, director, Epilepsy Genetics Program, Boston Children’s Hospital, Boston, Massachusetts, said this research “is incredibly important.”

“What’s really telling about this study and others that have come up over the last few years is they’re real-world retrospective studies, so they’re looking back at patients who have been seen over many, many years.”

The research provides clinicians, insurance companies, and others with evidence that genetic testing is “valuable and can actually improve outcomes,” said Dr. Poduri.

She noted that 20 years ago, there were only a handful of genes identified as being involved with epilepsy, most related to sodium or potassium channels. But since then, “the technology has just raced ahead” to the point where now “dozens of genes” have been identified.

Not only does knowing the genetic basis of epilepsy improve management, but it offers families some peace of mind. “They blame themselves” for their loved one’s condition, said Dr. Poduri. “They may worry it was something they did in pregnancy; for example, maybe it was because [they] didn’t take that vitamin one day.”

Diagnostic certainty also means that patients “don’t have to do more tests which might be invasive” and unnecessarily costly.

Drs. Li and Poduri report no relevant conflicts of interest.

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

For patients with chronic migraine, combination therapy with anti-CGRP monoclonal antibodies and onabotulinumtoxinA may be more effective than monotherapy, possibly owing to the synergistic mechanism of action of the two agents, a new study suggests.

“People with chronic migraine may be the toughest to treat. They have the greatest disability, and often insurance companies would prefer monotherapy, but in these patients, sometimes using a multifaceted approach and using different drugs that target different pathophysiologies of migraine can probably provide greater benefit in terms of reducing the frequency and severity of the headaches,” study investigator MaryAnn Mays, MD, staff neurologist at the Headache and Facial Pain Clinic in the Neurologic Institute, Cleveland Clinic, Cleveland, Ohio, said in an interview.

The findings were presented at the annual meeting of the American Headache Society.
 

Fewer Migraine Days

OnabotulinumtodxinA (onabot) has been shown to selectively inhibit unmyelinated C-fibers but not A-delta-meningeal nociceptors. Anti-CGRP mAb therapies have been shown to prevent the activation of A-delta-fibers but not C-fibers, said Dr. Mays.

For the study, the investigators reviewed the electronic medical records of 194 patients who had been concurrently treated with anti-CGRP mAbs and onabot. Most (86.6%) were women; ages ranged from 36 to 65 years, and at baseline, they had been having an average of 28 (+4.6) monthly migraine days (MMDs).

The number of MMDs were assessed at two periods: 3 months after monotherapy with an anti-CGRP mAb or onabot injections, and 3 months after combined therapy.

Monotherapy reduced the average number of MMDs from 28 to 18.6, for a reduction of 9.4 days (P > .0001).

After initiation of combined therapy, the average number of MMDs decreased further, from 18.6 MMDs to 12.1 MMDs (P > .0001).

In all, the combination of onabot and anti-CGRP mAbs resulted in a total MMD reduction of 15.8 (P > .0001).

In addition, most patients (68%) reported a 50% or greater reduction in MMDs, and 46.4% reported a 75% or greater reduction.
 

Great News for Patients

Commenting for this article, Rashmi B. Halker Singh, MD, associate professor of neurology at Mayo Clinic, Scottsdale, Arizona, said the study findings “support what we see in clinical practice and what we suspected from preclinical data.”

Single-agent treatment is not sufficient for many patients. Data confirming the benefit of dual therapy will provide more evidence to insurance companies of the need for coverage.

“We have lots of individuals for whom single treatment is not sufficient and who need this combination of treatment, and it is often denied by insurance. There are preclinical data suggesting synergy, but insurance says it is experimental, so the claims get denied. This leaves patients having to choose which drug they want to continue with, and that’s really heartbreaking,” Dr. Halker Singh said.

The importance of this study is that it adds more data to support evidence-based therapies for migraine and to help patients get the treatment they need, she added.

Dr. Mays reports financial relationships with AbbVie, Amgen, and Teva. Dr. Halker Singh reports no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

For patients with chronic migraine, combination therapy with anti-CGRP monoclonal antibodies and onabotulinumtoxinA may be more effective than monotherapy, possibly owing to the synergistic mechanism of action of the two agents, a new study suggests.

“People with chronic migraine may be the toughest to treat. They have the greatest disability, and often insurance companies would prefer monotherapy, but in these patients, sometimes using a multifaceted approach and using different drugs that target different pathophysiologies of migraine can probably provide greater benefit in terms of reducing the frequency and severity of the headaches,” study investigator MaryAnn Mays, MD, staff neurologist at the Headache and Facial Pain Clinic in the Neurologic Institute, Cleveland Clinic, Cleveland, Ohio, said in an interview.

The findings were presented at the annual meeting of the American Headache Society.
 

Fewer Migraine Days

OnabotulinumtodxinA (onabot) has been shown to selectively inhibit unmyelinated C-fibers but not A-delta-meningeal nociceptors. Anti-CGRP mAb therapies have been shown to prevent the activation of A-delta-fibers but not C-fibers, said Dr. Mays.

For the study, the investigators reviewed the electronic medical records of 194 patients who had been concurrently treated with anti-CGRP mAbs and onabot. Most (86.6%) were women; ages ranged from 36 to 65 years, and at baseline, they had been having an average of 28 (+4.6) monthly migraine days (MMDs).

The number of MMDs were assessed at two periods: 3 months after monotherapy with an anti-CGRP mAb or onabot injections, and 3 months after combined therapy.

Monotherapy reduced the average number of MMDs from 28 to 18.6, for a reduction of 9.4 days (P > .0001).

After initiation of combined therapy, the average number of MMDs decreased further, from 18.6 MMDs to 12.1 MMDs (P > .0001).

In all, the combination of onabot and anti-CGRP mAbs resulted in a total MMD reduction of 15.8 (P > .0001).

In addition, most patients (68%) reported a 50% or greater reduction in MMDs, and 46.4% reported a 75% or greater reduction.
 

Great News for Patients

Commenting for this article, Rashmi B. Halker Singh, MD, associate professor of neurology at Mayo Clinic, Scottsdale, Arizona, said the study findings “support what we see in clinical practice and what we suspected from preclinical data.”

Single-agent treatment is not sufficient for many patients. Data confirming the benefit of dual therapy will provide more evidence to insurance companies of the need for coverage.

“We have lots of individuals for whom single treatment is not sufficient and who need this combination of treatment, and it is often denied by insurance. There are preclinical data suggesting synergy, but insurance says it is experimental, so the claims get denied. This leaves patients having to choose which drug they want to continue with, and that’s really heartbreaking,” Dr. Halker Singh said.

The importance of this study is that it adds more data to support evidence-based therapies for migraine and to help patients get the treatment they need, she added.

Dr. Mays reports financial relationships with AbbVie, Amgen, and Teva. Dr. Halker Singh reports no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

For patients with chronic migraine, combination therapy with anti-CGRP monoclonal antibodies and onabotulinumtoxinA may be more effective than monotherapy, possibly owing to the synergistic mechanism of action of the two agents, a new study suggests.

“People with chronic migraine may be the toughest to treat. They have the greatest disability, and often insurance companies would prefer monotherapy, but in these patients, sometimes using a multifaceted approach and using different drugs that target different pathophysiologies of migraine can probably provide greater benefit in terms of reducing the frequency and severity of the headaches,” study investigator MaryAnn Mays, MD, staff neurologist at the Headache and Facial Pain Clinic in the Neurologic Institute, Cleveland Clinic, Cleveland, Ohio, said in an interview.

The findings were presented at the annual meeting of the American Headache Society.
 

Fewer Migraine Days

OnabotulinumtodxinA (onabot) has been shown to selectively inhibit unmyelinated C-fibers but not A-delta-meningeal nociceptors. Anti-CGRP mAb therapies have been shown to prevent the activation of A-delta-fibers but not C-fibers, said Dr. Mays.

For the study, the investigators reviewed the electronic medical records of 194 patients who had been concurrently treated with anti-CGRP mAbs and onabot. Most (86.6%) were women; ages ranged from 36 to 65 years, and at baseline, they had been having an average of 28 (+4.6) monthly migraine days (MMDs).

The number of MMDs were assessed at two periods: 3 months after monotherapy with an anti-CGRP mAb or onabot injections, and 3 months after combined therapy.

Monotherapy reduced the average number of MMDs from 28 to 18.6, for a reduction of 9.4 days (P > .0001).

After initiation of combined therapy, the average number of MMDs decreased further, from 18.6 MMDs to 12.1 MMDs (P > .0001).

In all, the combination of onabot and anti-CGRP mAbs resulted in a total MMD reduction of 15.8 (P > .0001).

In addition, most patients (68%) reported a 50% or greater reduction in MMDs, and 46.4% reported a 75% or greater reduction.
 

Great News for Patients

Commenting for this article, Rashmi B. Halker Singh, MD, associate professor of neurology at Mayo Clinic, Scottsdale, Arizona, said the study findings “support what we see in clinical practice and what we suspected from preclinical data.”

Single-agent treatment is not sufficient for many patients. Data confirming the benefit of dual therapy will provide more evidence to insurance companies of the need for coverage.

“We have lots of individuals for whom single treatment is not sufficient and who need this combination of treatment, and it is often denied by insurance. There are preclinical data suggesting synergy, but insurance says it is experimental, so the claims get denied. This leaves patients having to choose which drug they want to continue with, and that’s really heartbreaking,” Dr. Halker Singh said.

The importance of this study is that it adds more data to support evidence-based therapies for migraine and to help patients get the treatment they need, she added.

Dr. Mays reports financial relationships with AbbVie, Amgen, and Teva. Dr. Halker Singh reports no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

SAN ANTONIO – In previously treated patients with locally advanced unresectable or metastatic HER2-positive breast cancer, tucatinib (Tukysa, Seagen) and trastuzumab emtansine (Kadcyla, T-DM1, Genentech) improved progression-free survival (PFS) versus T-DM1 alone, according to results from the phase III HER2CLIMB-02 study. A subanalysis of patients with brain metastases at baseline also showed an improvement in this population.

Brain metastases are common HER2+ breast cancer, and this is associated with poor outcomes, according to Sara A. Hurvitz, MD, who presented the study at the San Antonio Breast Cancer Symposium. There are few treatment options available for this population.

“Adding tucatinib to TDM-1 significantly improved progression free survival in patients with previously treated HER2+ advanced disease. The types of adverse events were consistent with previous reporting, and this is the second randomized study which included patients with brain metastases to demonstrate that a tucatinib-based regimen delays disease progression in this disease setting,” said Dr. Hurvitz, professor and head of the division of hematology and oncology at the University of Washington Department of Medicine and senior vice president and director of the Clinical Research Division at Fred Hutchinson Cancer Center.

Both tucatinib and TDM-1 target the HER2 receptor. T-DM1 is an antibody-drug conjugate (ADC) of trastuzumab (Herceptin) and the drug emtansine that has received FDA approval as monotherapy for both early- and late-stage HER2-positive breast cancer. Tucatinib is a small-molecule HER2 inhibitor and has efficacy against disease progression in the central nervous system, which is unusual among HER2-targeted therapies.

The earlier HER2CLIMB trial showed improved outcomes among heavily pretreated patients — including those with brain metastases — when tucatinib was added to trastuzumab and capecitabine (Xeloda, Genentech). In 2020, the FDA approved the combination for advanced unresectable or metastatic HER2-positive breast cancer, including brain metastases.

To determine if tucatinib could also improve responses when combined with a trastuzumab-based ADC, the researchers randomized 463 patients to tucatinib plus T-DM1 or placebo plus T-DM1. Nearly half (44.1%) of patients had brain metastases at baseline. Over a median follow-up of 24.4 months, the combination group had a 24% lower risk of progression or death (hazard ratio [HR], 0.76; P = .0163) and a longer median progression-free survival (9.5 months versus 7.4 months).

The PFS benefit was also seen in patients with baseline brain metastases (HR, 0.64; 95% CI, 0.46-0.89]). An insufficient number of survival events had occurred at the interim analysis to determine OS at the time of the presentation.

There was no statistically significant difference in overall response rate in the intervention arm. Treatment-emergent adverse events (TEAEs) that were more common in the tucatinib arm included nausea (65.4% vs. 49.4%), diarrhea (56.7% vs. 26.6%), and fatigue (48.9% vs. 37.3%). Grade 3 or higher TEAEs in the tucatinib arm included alanine and aspartate aminotransferase elevations (16.5% for both), versus 2.6% in the control arm for both. TEAEs associated treatment discontinuation occurred among 22.1% in the tucatinib arm and 11.6% in the control arm. TEAEs that led to mortality occurred in 1.3% of the tucatinib group and 0.9% of the control arm.

“I think tucatinib really does contain level one evidence for use in the setting of CNS metastases. There’s not yet data that has replaced that, so I will continue to consider using it in the second line setting, as it’s currently indicated in the presence of brain metastases. Without brain metastases, based on [the DESTINY-Breast03 trial], I’d probably opt for [trastuzumab deroxtecan], which is still the standard,” said Dr. Hurvitz.

Following the talk, Valentina Guarneri, MD, PhD, served as a discussant. She underscored the clinical need for treatment of patients with brain metastases.

“Brain metastases represent a devastating event for our patients and remain an unmet need considering that all of these patients will eventually require local therapies, with potentially debilitating sequelae. Since optimal therapy for these patients should not be an afterthought, clinical trials taking the risk of including these patients must be valued,” said Dr. Guarneri, professor of oncology at the University of Padua in Italy.

She acknowledged the success of the dual HER2 inhibitor strategy, and said it opens up avenues for combinations with novel antibody-drug conjugates. “HER2CLIMB-02 is unlikely to change the current algorithm, but it reinforces the role of tucatinib in the treatment of HER2+ metastatic breast cancer. The data further support studies in the early disease setting aiming to prevent the development of brain metastases,” said Dr. Guarneri.

The study was funded by Seagen. Dr. Hurvitz has received research funding from Ambrx, Arvinas, AstraZeneca, Bayer, Celcuity, CytomX Therapeutics, Daiichi Sankyo, Dantari Inc., Dignitana, Genentech, (Roche), G1 Therapeutics, Gilead Sciences Inc., Greenwich LifeSciences Inc., GSK, Immunomedics, Eli Lilly and Company, Loxo Oncology, MacroGenics, Novartis, OBI Pharma Inc., Orinove Inc., Orum Therapeutics, Pfizer, Phoenix Molecular Designs, Pieris Pharmaceuticals Inc., Puma Biotechnology, Radius Health, Sanofi, Seagen, and Zymeworks; has received royalties from McGraw Hill, Sage Publications, Wiley, and Wolters Kluwer; has served on the data and safety monitoring board for Alliance Foundation Trials LLC, Atossa Therapeutics, and the Quantum Leap Healthcare Collaborative; and has received honoraria from the Vaniam Group and OncLive. Her husband holds stock in ROMTech. Dr. Guarneri has been a member of the advisory boards for AstraZeneca, Daiichi Sankyo, Eisai, Eli Lilly, Exact Sciences, Gilead, Merck Serono, MSD, Novartis, Pfizer, Olema Oncology, and Pierre Fabre. She has been an invited speaker for AstraZeneca, Daiichi Sankyo, Eli Lilly, Exact Sciences, Gilead, GSK Novartis, and Zentiva.

SAN ANTONIO – In previously treated patients with locally advanced unresectable or metastatic HER2-positive breast cancer, tucatinib (Tukysa, Seagen) and trastuzumab emtansine (Kadcyla, T-DM1, Genentech) improved progression-free survival (PFS) versus T-DM1 alone, according to results from the phase III HER2CLIMB-02 study. A subanalysis of patients with brain metastases at baseline also showed an improvement in this population.

Brain metastases are common HER2+ breast cancer, and this is associated with poor outcomes, according to Sara A. Hurvitz, MD, who presented the study at the San Antonio Breast Cancer Symposium. There are few treatment options available for this population.

“Adding tucatinib to TDM-1 significantly improved progression free survival in patients with previously treated HER2+ advanced disease. The types of adverse events were consistent with previous reporting, and this is the second randomized study which included patients with brain metastases to demonstrate that a tucatinib-based regimen delays disease progression in this disease setting,” said Dr. Hurvitz, professor and head of the division of hematology and oncology at the University of Washington Department of Medicine and senior vice president and director of the Clinical Research Division at Fred Hutchinson Cancer Center.

Both tucatinib and TDM-1 target the HER2 receptor. T-DM1 is an antibody-drug conjugate (ADC) of trastuzumab (Herceptin) and the drug emtansine that has received FDA approval as monotherapy for both early- and late-stage HER2-positive breast cancer. Tucatinib is a small-molecule HER2 inhibitor and has efficacy against disease progression in the central nervous system, which is unusual among HER2-targeted therapies.

The earlier HER2CLIMB trial showed improved outcomes among heavily pretreated patients — including those with brain metastases — when tucatinib was added to trastuzumab and capecitabine (Xeloda, Genentech). In 2020, the FDA approved the combination for advanced unresectable or metastatic HER2-positive breast cancer, including brain metastases.

To determine if tucatinib could also improve responses when combined with a trastuzumab-based ADC, the researchers randomized 463 patients to tucatinib plus T-DM1 or placebo plus T-DM1. Nearly half (44.1%) of patients had brain metastases at baseline. Over a median follow-up of 24.4 months, the combination group had a 24% lower risk of progression or death (hazard ratio [HR], 0.76; P = .0163) and a longer median progression-free survival (9.5 months versus 7.4 months).

The PFS benefit was also seen in patients with baseline brain metastases (HR, 0.64; 95% CI, 0.46-0.89]). An insufficient number of survival events had occurred at the interim analysis to determine OS at the time of the presentation.

There was no statistically significant difference in overall response rate in the intervention arm. Treatment-emergent adverse events (TEAEs) that were more common in the tucatinib arm included nausea (65.4% vs. 49.4%), diarrhea (56.7% vs. 26.6%), and fatigue (48.9% vs. 37.3%). Grade 3 or higher TEAEs in the tucatinib arm included alanine and aspartate aminotransferase elevations (16.5% for both), versus 2.6% in the control arm for both. TEAEs associated treatment discontinuation occurred among 22.1% in the tucatinib arm and 11.6% in the control arm. TEAEs that led to mortality occurred in 1.3% of the tucatinib group and 0.9% of the control arm.

“I think tucatinib really does contain level one evidence for use in the setting of CNS metastases. There’s not yet data that has replaced that, so I will continue to consider using it in the second line setting, as it’s currently indicated in the presence of brain metastases. Without brain metastases, based on [the DESTINY-Breast03 trial], I’d probably opt for [trastuzumab deroxtecan], which is still the standard,” said Dr. Hurvitz.

Following the talk, Valentina Guarneri, MD, PhD, served as a discussant. She underscored the clinical need for treatment of patients with brain metastases.

“Brain metastases represent a devastating event for our patients and remain an unmet need considering that all of these patients will eventually require local therapies, with potentially debilitating sequelae. Since optimal therapy for these patients should not be an afterthought, clinical trials taking the risk of including these patients must be valued,” said Dr. Guarneri, professor of oncology at the University of Padua in Italy.

She acknowledged the success of the dual HER2 inhibitor strategy, and said it opens up avenues for combinations with novel antibody-drug conjugates. “HER2CLIMB-02 is unlikely to change the current algorithm, but it reinforces the role of tucatinib in the treatment of HER2+ metastatic breast cancer. The data further support studies in the early disease setting aiming to prevent the development of brain metastases,” said Dr. Guarneri.

The study was funded by Seagen. Dr. Hurvitz has received research funding from Ambrx, Arvinas, AstraZeneca, Bayer, Celcuity, CytomX Therapeutics, Daiichi Sankyo, Dantari Inc., Dignitana, Genentech, (Roche), G1 Therapeutics, Gilead Sciences Inc., Greenwich LifeSciences Inc., GSK, Immunomedics, Eli Lilly and Company, Loxo Oncology, MacroGenics, Novartis, OBI Pharma Inc., Orinove Inc., Orum Therapeutics, Pfizer, Phoenix Molecular Designs, Pieris Pharmaceuticals Inc., Puma Biotechnology, Radius Health, Sanofi, Seagen, and Zymeworks; has received royalties from McGraw Hill, Sage Publications, Wiley, and Wolters Kluwer; has served on the data and safety monitoring board for Alliance Foundation Trials LLC, Atossa Therapeutics, and the Quantum Leap Healthcare Collaborative; and has received honoraria from the Vaniam Group and OncLive. Her husband holds stock in ROMTech. Dr. Guarneri has been a member of the advisory boards for AstraZeneca, Daiichi Sankyo, Eisai, Eli Lilly, Exact Sciences, Gilead, Merck Serono, MSD, Novartis, Pfizer, Olema Oncology, and Pierre Fabre. She has been an invited speaker for AstraZeneca, Daiichi Sankyo, Eli Lilly, Exact Sciences, Gilead, GSK Novartis, and Zentiva.

SAN ANTONIO – In previously treated patients with locally advanced unresectable or metastatic HER2-positive breast cancer, tucatinib (Tukysa, Seagen) and trastuzumab emtansine (Kadcyla, T-DM1, Genentech) improved progression-free survival (PFS) versus T-DM1 alone, according to results from the phase III HER2CLIMB-02 study. A subanalysis of patients with brain metastases at baseline also showed an improvement in this population.

Brain metastases are common HER2+ breast cancer, and this is associated with poor outcomes, according to Sara A. Hurvitz, MD, who presented the study at the San Antonio Breast Cancer Symposium. There are few treatment options available for this population.

“Adding tucatinib to TDM-1 significantly improved progression free survival in patients with previously treated HER2+ advanced disease. The types of adverse events were consistent with previous reporting, and this is the second randomized study which included patients with brain metastases to demonstrate that a tucatinib-based regimen delays disease progression in this disease setting,” said Dr. Hurvitz, professor and head of the division of hematology and oncology at the University of Washington Department of Medicine and senior vice president and director of the Clinical Research Division at Fred Hutchinson Cancer Center.

Both tucatinib and TDM-1 target the HER2 receptor. T-DM1 is an antibody-drug conjugate (ADC) of trastuzumab (Herceptin) and the drug emtansine that has received FDA approval as monotherapy for both early- and late-stage HER2-positive breast cancer. Tucatinib is a small-molecule HER2 inhibitor and has efficacy against disease progression in the central nervous system, which is unusual among HER2-targeted therapies.

The earlier HER2CLIMB trial showed improved outcomes among heavily pretreated patients — including those with brain metastases — when tucatinib was added to trastuzumab and capecitabine (Xeloda, Genentech). In 2020, the FDA approved the combination for advanced unresectable or metastatic HER2-positive breast cancer, including brain metastases.

To determine if tucatinib could also improve responses when combined with a trastuzumab-based ADC, the researchers randomized 463 patients to tucatinib plus T-DM1 or placebo plus T-DM1. Nearly half (44.1%) of patients had brain metastases at baseline. Over a median follow-up of 24.4 months, the combination group had a 24% lower risk of progression or death (hazard ratio [HR], 0.76; P = .0163) and a longer median progression-free survival (9.5 months versus 7.4 months).

The PFS benefit was also seen in patients with baseline brain metastases (HR, 0.64; 95% CI, 0.46-0.89]). An insufficient number of survival events had occurred at the interim analysis to determine OS at the time of the presentation.

There was no statistically significant difference in overall response rate in the intervention arm. Treatment-emergent adverse events (TEAEs) that were more common in the tucatinib arm included nausea (65.4% vs. 49.4%), diarrhea (56.7% vs. 26.6%), and fatigue (48.9% vs. 37.3%). Grade 3 or higher TEAEs in the tucatinib arm included alanine and aspartate aminotransferase elevations (16.5% for both), versus 2.6% in the control arm for both. TEAEs associated treatment discontinuation occurred among 22.1% in the tucatinib arm and 11.6% in the control arm. TEAEs that led to mortality occurred in 1.3% of the tucatinib group and 0.9% of the control arm.

“I think tucatinib really does contain level one evidence for use in the setting of CNS metastases. There’s not yet data that has replaced that, so I will continue to consider using it in the second line setting, as it’s currently indicated in the presence of brain metastases. Without brain metastases, based on [the DESTINY-Breast03 trial], I’d probably opt for [trastuzumab deroxtecan], which is still the standard,” said Dr. Hurvitz.

Following the talk, Valentina Guarneri, MD, PhD, served as a discussant. She underscored the clinical need for treatment of patients with brain metastases.

“Brain metastases represent a devastating event for our patients and remain an unmet need considering that all of these patients will eventually require local therapies, with potentially debilitating sequelae. Since optimal therapy for these patients should not be an afterthought, clinical trials taking the risk of including these patients must be valued,” said Dr. Guarneri, professor of oncology at the University of Padua in Italy.

She acknowledged the success of the dual HER2 inhibitor strategy, and said it opens up avenues for combinations with novel antibody-drug conjugates. “HER2CLIMB-02 is unlikely to change the current algorithm, but it reinforces the role of tucatinib in the treatment of HER2+ metastatic breast cancer. The data further support studies in the early disease setting aiming to prevent the development of brain metastases,” said Dr. Guarneri.

The study was funded by Seagen. Dr. Hurvitz has received research funding from Ambrx, Arvinas, AstraZeneca, Bayer, Celcuity, CytomX Therapeutics, Daiichi Sankyo, Dantari Inc., Dignitana, Genentech, (Roche), G1 Therapeutics, Gilead Sciences Inc., Greenwich LifeSciences Inc., GSK, Immunomedics, Eli Lilly and Company, Loxo Oncology, MacroGenics, Novartis, OBI Pharma Inc., Orinove Inc., Orum Therapeutics, Pfizer, Phoenix Molecular Designs, Pieris Pharmaceuticals Inc., Puma Biotechnology, Radius Health, Sanofi, Seagen, and Zymeworks; has received royalties from McGraw Hill, Sage Publications, Wiley, and Wolters Kluwer; has served on the data and safety monitoring board for Alliance Foundation Trials LLC, Atossa Therapeutics, and the Quantum Leap Healthcare Collaborative; and has received honoraria from the Vaniam Group and OncLive. Her husband holds stock in ROMTech. Dr. Guarneri has been a member of the advisory boards for AstraZeneca, Daiichi Sankyo, Eisai, Eli Lilly, Exact Sciences, Gilead, Merck Serono, MSD, Novartis, Pfizer, Olema Oncology, and Pierre Fabre. She has been an invited speaker for AstraZeneca, Daiichi Sankyo, Eli Lilly, Exact Sciences, Gilead, GSK Novartis, and Zentiva.

BARCELONA, SPAIN — Around half of all patients with chronic headache or migraine overuse their medication, leading to aggravated or new types of headaches. “Medication overuse headache” is the third most frequent type of headache, affecting some 60 million people or around 1% of the world’s population.

“It’s a big problem,” Sait Ashina, MD, of Beth Israel Deaconess Medical Center, Boston, Massachusetts, told the audience in an opening plenary at the 17th European Headache Congress in Barcelona. “But it’s important to distinguish between medication overuse, which is a behavior, and medication overuse headache, which is a distinct secondary order condition.”

Medication overuse headache is characterized by an increasing headache frequency and progressive use of short-term medication and is recognized as a major factor in the shift from episodic to chronic headache.

It is often underrecognized; however, educating doctors and patients is a crucial element of effective treatment. Recognition that headache medication is being overused is a crucial first step to treatment, followed by advising the patient to discontinue the medication. But this poses its own problems, as it can cause withdrawal symptoms.

According to a longitudinal population-based study published in 2008, most patients overuse acetaminophen or paracetamol, followed by nonsteroidal anti-inflammatory drugs and 5-hydroxytriptamine agonists (triptans) and, in the United States, barbiturates and opioids.
 

What’s the Best Treatment Strategy?

Medication overuse headache is often treated by complete withdrawal from medication, but the withdrawal symptoms can be severe. They include nausea and vomiting, arterial hypertension, tachycardia, sleep disturbances, anxiety, and restlessness, with their duration and severity depending solely on the type of headache medication that has been overused.

There is, however, no consensus on how best to treat medication overuse headache — withdrawal plus preventive treatment, preventive treatment without withdrawal, and withdrawal with optional preventive treatment 2 months after withdrawal. The findings showed that all three strategies were effective. But the research team concluded that withdrawal combined with preventive medication from the start of withdrawal was the recommended approach.

The electronic headache diary has proved to be very useful, as it can aid accurate diagnosis by providing clear insights into a patient’s condition. Information from the diary is more reliable than self-reports because patients often underestimate the frequency of their headaches, migraines, and use of medication.

Patients who are treated for medication overuse headache tend to have a high relapse rate. So, the electronic headache diary can also be very useful for follow-up by alerting patients and clinicians when headaches and medication overuse are increasing again.

“After diagnosing medication overuse or medication overuse headache, we advise our patients to discontinue the medication,” said Judith Pijpers of Leiden University Medical School, the Netherlands. “This provides clinically relevant improvements in headache frequency in a majority of patients and a significant reduction in headache days.”

In 2019, Dr. Pijpers and her colleagues published the results of a double-blind randomized controlled trial showing that botulinum toxin A, which is widely used to treat chronic migraine, has no additional benefit over acute withdrawal in patients with chronic migraine and medication overuse.

“We saw no difference between the groups during both the double-blind and the open label phase,” said Dr. Pijpers. “And that is why we do not give patients botulinum toxin A during withdrawal.”

A further trial within the botox study showed modest benefits for behavioral intervention by a headache nurse comprising education, motivational interviewing, and value-based activity planning during withdrawal therapy.

Patients can be stratified to some extent based on the type of headache they have and the medication they are taking for it.

“You can predict [a patient’s response] to some extent from the type of medication they overuse and the type of underlying primary headache,” Dr. Pijpers said in an interview.

“Those with underlying tension-type headache have different withdrawal symptoms than those with underlying migraine, and the withdrawal symptoms tend to be somewhat shorter if a patient overuses triptans compared to analgesics.”
 

Predicting Patients’ Responses to Migraine Medication

Dr. Pijpers and her colleagues recently published the results of a cohort study suggesting that cutaneous allodynia may predict how patients with migraine respond to withdrawal therapy. Nearly 75% of the 173 patients enrolled in the study reported experiencing allodynia — pain caused by a stimulus that does not normally cause pain. The study showed that absence of allodynia was predictive of a good outcome for patients after withdrawal therapy and of reversion from chronic to episodic migraine.

The ability to accurately predict patients’ responses could pave the way for personalized treatments of medication overuse headache.
 

A version of this article appeared in Medscape.com.

BARCELONA, SPAIN — Around half of all patients with chronic headache or migraine overuse their medication, leading to aggravated or new types of headaches. “Medication overuse headache” is the third most frequent type of headache, affecting some 60 million people or around 1% of the world’s population.

“It’s a big problem,” Sait Ashina, MD, of Beth Israel Deaconess Medical Center, Boston, Massachusetts, told the audience in an opening plenary at the 17th European Headache Congress in Barcelona. “But it’s important to distinguish between medication overuse, which is a behavior, and medication overuse headache, which is a distinct secondary order condition.”

Medication overuse headache is characterized by an increasing headache frequency and progressive use of short-term medication and is recognized as a major factor in the shift from episodic to chronic headache.

It is often underrecognized; however, educating doctors and patients is a crucial element of effective treatment. Recognition that headache medication is being overused is a crucial first step to treatment, followed by advising the patient to discontinue the medication. But this poses its own problems, as it can cause withdrawal symptoms.

According to a longitudinal population-based study published in 2008, most patients overuse acetaminophen or paracetamol, followed by nonsteroidal anti-inflammatory drugs and 5-hydroxytriptamine agonists (triptans) and, in the United States, barbiturates and opioids.
 

What’s the Best Treatment Strategy?

Medication overuse headache is often treated by complete withdrawal from medication, but the withdrawal symptoms can be severe. They include nausea and vomiting, arterial hypertension, tachycardia, sleep disturbances, anxiety, and restlessness, with their duration and severity depending solely on the type of headache medication that has been overused.

There is, however, no consensus on how best to treat medication overuse headache — withdrawal plus preventive treatment, preventive treatment without withdrawal, and withdrawal with optional preventive treatment 2 months after withdrawal. The findings showed that all three strategies were effective. But the research team concluded that withdrawal combined with preventive medication from the start of withdrawal was the recommended approach.

The electronic headache diary has proved to be very useful, as it can aid accurate diagnosis by providing clear insights into a patient’s condition. Information from the diary is more reliable than self-reports because patients often underestimate the frequency of their headaches, migraines, and use of medication.

Patients who are treated for medication overuse headache tend to have a high relapse rate. So, the electronic headache diary can also be very useful for follow-up by alerting patients and clinicians when headaches and medication overuse are increasing again.

“After diagnosing medication overuse or medication overuse headache, we advise our patients to discontinue the medication,” said Judith Pijpers of Leiden University Medical School, the Netherlands. “This provides clinically relevant improvements in headache frequency in a majority of patients and a significant reduction in headache days.”

In 2019, Dr. Pijpers and her colleagues published the results of a double-blind randomized controlled trial showing that botulinum toxin A, which is widely used to treat chronic migraine, has no additional benefit over acute withdrawal in patients with chronic migraine and medication overuse.

“We saw no difference between the groups during both the double-blind and the open label phase,” said Dr. Pijpers. “And that is why we do not give patients botulinum toxin A during withdrawal.”

A further trial within the botox study showed modest benefits for behavioral intervention by a headache nurse comprising education, motivational interviewing, and value-based activity planning during withdrawal therapy.

Patients can be stratified to some extent based on the type of headache they have and the medication they are taking for it.

“You can predict [a patient’s response] to some extent from the type of medication they overuse and the type of underlying primary headache,” Dr. Pijpers said in an interview.

“Those with underlying tension-type headache have different withdrawal symptoms than those with underlying migraine, and the withdrawal symptoms tend to be somewhat shorter if a patient overuses triptans compared to analgesics.”
 

Predicting Patients’ Responses to Migraine Medication

Dr. Pijpers and her colleagues recently published the results of a cohort study suggesting that cutaneous allodynia may predict how patients with migraine respond to withdrawal therapy. Nearly 75% of the 173 patients enrolled in the study reported experiencing allodynia — pain caused by a stimulus that does not normally cause pain. The study showed that absence of allodynia was predictive of a good outcome for patients after withdrawal therapy and of reversion from chronic to episodic migraine.

The ability to accurately predict patients’ responses could pave the way for personalized treatments of medication overuse headache.
 

A version of this article appeared in Medscape.com.

BARCELONA, SPAIN — Around half of all patients with chronic headache or migraine overuse their medication, leading to aggravated or new types of headaches. “Medication overuse headache” is the third most frequent type of headache, affecting some 60 million people or around 1% of the world’s population.

“It’s a big problem,” Sait Ashina, MD, of Beth Israel Deaconess Medical Center, Boston, Massachusetts, told the audience in an opening plenary at the 17th European Headache Congress in Barcelona. “But it’s important to distinguish between medication overuse, which is a behavior, and medication overuse headache, which is a distinct secondary order condition.”

Medication overuse headache is characterized by an increasing headache frequency and progressive use of short-term medication and is recognized as a major factor in the shift from episodic to chronic headache.

It is often underrecognized; however, educating doctors and patients is a crucial element of effective treatment. Recognition that headache medication is being overused is a crucial first step to treatment, followed by advising the patient to discontinue the medication. But this poses its own problems, as it can cause withdrawal symptoms.

According to a longitudinal population-based study published in 2008, most patients overuse acetaminophen or paracetamol, followed by nonsteroidal anti-inflammatory drugs and 5-hydroxytriptamine agonists (triptans) and, in the United States, barbiturates and opioids.
 

What’s the Best Treatment Strategy?

Medication overuse headache is often treated by complete withdrawal from medication, but the withdrawal symptoms can be severe. They include nausea and vomiting, arterial hypertension, tachycardia, sleep disturbances, anxiety, and restlessness, with their duration and severity depending solely on the type of headache medication that has been overused.

There is, however, no consensus on how best to treat medication overuse headache — withdrawal plus preventive treatment, preventive treatment without withdrawal, and withdrawal with optional preventive treatment 2 months after withdrawal. The findings showed that all three strategies were effective. But the research team concluded that withdrawal combined with preventive medication from the start of withdrawal was the recommended approach.

The electronic headache diary has proved to be very useful, as it can aid accurate diagnosis by providing clear insights into a patient’s condition. Information from the diary is more reliable than self-reports because patients often underestimate the frequency of their headaches, migraines, and use of medication.

Patients who are treated for medication overuse headache tend to have a high relapse rate. So, the electronic headache diary can also be very useful for follow-up by alerting patients and clinicians when headaches and medication overuse are increasing again.

“After diagnosing medication overuse or medication overuse headache, we advise our patients to discontinue the medication,” said Judith Pijpers of Leiden University Medical School, the Netherlands. “This provides clinically relevant improvements in headache frequency in a majority of patients and a significant reduction in headache days.”

In 2019, Dr. Pijpers and her colleagues published the results of a double-blind randomized controlled trial showing that botulinum toxin A, which is widely used to treat chronic migraine, has no additional benefit over acute withdrawal in patients with chronic migraine and medication overuse.

“We saw no difference between the groups during both the double-blind and the open label phase,” said Dr. Pijpers. “And that is why we do not give patients botulinum toxin A during withdrawal.”

A further trial within the botox study showed modest benefits for behavioral intervention by a headache nurse comprising education, motivational interviewing, and value-based activity planning during withdrawal therapy.

Patients can be stratified to some extent based on the type of headache they have and the medication they are taking for it.

“You can predict [a patient’s response] to some extent from the type of medication they overuse and the type of underlying primary headache,” Dr. Pijpers said in an interview.

“Those with underlying tension-type headache have different withdrawal symptoms than those with underlying migraine, and the withdrawal symptoms tend to be somewhat shorter if a patient overuses triptans compared to analgesics.”
 

Predicting Patients’ Responses to Migraine Medication

Dr. Pijpers and her colleagues recently published the results of a cohort study suggesting that cutaneous allodynia may predict how patients with migraine respond to withdrawal therapy. Nearly 75% of the 173 patients enrolled in the study reported experiencing allodynia — pain caused by a stimulus that does not normally cause pain. The study showed that absence of allodynia was predictive of a good outcome for patients after withdrawal therapy and of reversion from chronic to episodic migraine.

The ability to accurately predict patients’ responses could pave the way for personalized treatments of medication overuse headache.
 

A version of this article appeared in Medscape.com.