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Commentary: Treating ER+ Breast Cancer and Brain Metastases, July 2022
The clinical benefit of fulvestrant as a second-line treatment after tumor progression with CDK4/6i-based therapy has been discouraging, highlighting an unmet need for a better SERD in this space.1 Multiple oral SERD are currently in trials. The EMERALD trial is a phase 3 study that randomly assigned 477 patients with ER+/HER2- mBC in a 1:1 ratio to elacestrant, an oral SERD, vs standard of care (SOC) endocrine therapy (ET). Enrolled patients had received one to two prior ET and one or less chemotherapy treatments in the metastatic disease settings. All patients had prior treatment with a CDK4/6i. Fulvestrant-naive patients were required to have fulvestrant as the SOC ET. In contrast, patients previously treated with fulvestrant received an AI, the selection of which was based on prior AI therapy. Primary endpoints were progression-free survival (PFS) in all patients and in patients with detectable ESR1 mutation. The median PFS in the elacestrant arm was 2.8 months vs 1.9 months in the control arm [hazard ratio (HR) 0.70; 95% CI 0.55-0.88; P = .002]. The 6-month PFS was 34% vs 20% in all patients and 41% vs 19% in patients with detectable ESR1 mutation, favoring the elacestrant arm. In the subgroup analysis among patients who received fulvestrant in the control arm, the 6-month PFS was 34% vs 21% in all patients and 41% vs 19% in patients with ESR1 mutation. Grade 3 or 4 adverse events developed in 27% patients in the elacestrant arm compared with 20% in the SOC arm. More patients in the elacestrant arm developed nausea, vomiting, and liver function abnormalities compared with patients in the SOC arm.
This is the first phase 3 trial demonstrating statistically significant prolongation of PFS associated with an oral SERD compared with SOC ET in patients with ER+/HER2- mBC who had prior treatment with a CDK4/6i. A new drug application has been submitted to the US Food and Drug Administration based on this data. If approved, elacestrant may be favored over fulvestrant as the standard ET for ER+/HER2- mBC after progression on a CDK4/6i-based therapy.
Patients with breast cancer brain metastasis (BrM) have a poor prognosis. Systemic therapies with good central nervous system (CNS) permeability and strong activity against BrM are much needed. An exploratory subset of the phase 3 BEACON trial demonstrated improvement in overall survival (OS) with etirinotecan pegol, a long-acting polymer conjugate of irinotecan, compared with physicians' choice chemotherapy in patients with mBC with treated and stable BrMs.2
Based on this data, a large phase 3 study (the ATTAIN study) was conducted. Patients with mBC with treated and stable BrM (n = 178) were randomly assigned to receive etirinotecan pegol vs physicians' choice of chemotherapy (eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel, or nab-paclitaxel). The primary endpoint of OS was similar in both groups (etirinotecan pegol 7.8 months; chemotherapy 7.5 months; HR 0.90; 95% CI 0.61-1.33; P = .60). Median PFS for mBC with CNS metastases (etirinotecan pegol vs chemotherapy) were 3.9 vs 3.3 months (HR 0.59; 95% CI 0.33-1.05; P = .07) and for non-CNS metastases were 2.8 vs 1.9 months (HR 0.72; 95% CI 0.45-1.16; P = .18). Adverse events were grade 3 or 4 in 57% patients receiving etirinotecan pegol compared with 64% receiving SOC chemotherapy.
This trial failed to meet its primary endpoint. The possible explanations proposed by the investigators are a protocol amendment that reduced the power of the trial to 80%, some key differences in the patient population in the ATTAIN trial compared with the BEACON trial, and the possibility of the BEACON trial exploratory analysis result being a false positive. The OS of around 7 months highlights the unmet need for better systemic therapy for patients with BrM breast cancer, especially those with HER2- breast cancer.
Additional References
- Lindeman GJ, Fernando TM, Bowen R, et al. VERONICA: Randomized phase II study of fulvestrant and venetoclax in ER-positive metastatic breast cancer post-CDK4/6 inhibitors – Efficacy, safety, and biomarker results. Clin Cancer Res. 2022 (June 21). Doi: 10.1158/1078-0432.CCR-21-3811
- Cortés J, Rugo HS, Awada A, et al. Prolonged survival in patients with breast cancer and a history of brain metastases: Results of a preplanned subgroup analysis from the randomized phase III BEACON trial. Breast Cancer Res Treat. 2017;165:329-341. Doi: 10.1007/s10549-017-4304-7
The clinical benefit of fulvestrant as a second-line treatment after tumor progression with CDK4/6i-based therapy has been discouraging, highlighting an unmet need for a better SERD in this space.1 Multiple oral SERD are currently in trials. The EMERALD trial is a phase 3 study that randomly assigned 477 patients with ER+/HER2- mBC in a 1:1 ratio to elacestrant, an oral SERD, vs standard of care (SOC) endocrine therapy (ET). Enrolled patients had received one to two prior ET and one or less chemotherapy treatments in the metastatic disease settings. All patients had prior treatment with a CDK4/6i. Fulvestrant-naive patients were required to have fulvestrant as the SOC ET. In contrast, patients previously treated with fulvestrant received an AI, the selection of which was based on prior AI therapy. Primary endpoints were progression-free survival (PFS) in all patients and in patients with detectable ESR1 mutation. The median PFS in the elacestrant arm was 2.8 months vs 1.9 months in the control arm [hazard ratio (HR) 0.70; 95% CI 0.55-0.88; P = .002]. The 6-month PFS was 34% vs 20% in all patients and 41% vs 19% in patients with detectable ESR1 mutation, favoring the elacestrant arm. In the subgroup analysis among patients who received fulvestrant in the control arm, the 6-month PFS was 34% vs 21% in all patients and 41% vs 19% in patients with ESR1 mutation. Grade 3 or 4 adverse events developed in 27% patients in the elacestrant arm compared with 20% in the SOC arm. More patients in the elacestrant arm developed nausea, vomiting, and liver function abnormalities compared with patients in the SOC arm.
This is the first phase 3 trial demonstrating statistically significant prolongation of PFS associated with an oral SERD compared with SOC ET in patients with ER+/HER2- mBC who had prior treatment with a CDK4/6i. A new drug application has been submitted to the US Food and Drug Administration based on this data. If approved, elacestrant may be favored over fulvestrant as the standard ET for ER+/HER2- mBC after progression on a CDK4/6i-based therapy.
Patients with breast cancer brain metastasis (BrM) have a poor prognosis. Systemic therapies with good central nervous system (CNS) permeability and strong activity against BrM are much needed. An exploratory subset of the phase 3 BEACON trial demonstrated improvement in overall survival (OS) with etirinotecan pegol, a long-acting polymer conjugate of irinotecan, compared with physicians' choice chemotherapy in patients with mBC with treated and stable BrMs.2
Based on this data, a large phase 3 study (the ATTAIN study) was conducted. Patients with mBC with treated and stable BrM (n = 178) were randomly assigned to receive etirinotecan pegol vs physicians' choice of chemotherapy (eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel, or nab-paclitaxel). The primary endpoint of OS was similar in both groups (etirinotecan pegol 7.8 months; chemotherapy 7.5 months; HR 0.90; 95% CI 0.61-1.33; P = .60). Median PFS for mBC with CNS metastases (etirinotecan pegol vs chemotherapy) were 3.9 vs 3.3 months (HR 0.59; 95% CI 0.33-1.05; P = .07) and for non-CNS metastases were 2.8 vs 1.9 months (HR 0.72; 95% CI 0.45-1.16; P = .18). Adverse events were grade 3 or 4 in 57% patients receiving etirinotecan pegol compared with 64% receiving SOC chemotherapy.
This trial failed to meet its primary endpoint. The possible explanations proposed by the investigators are a protocol amendment that reduced the power of the trial to 80%, some key differences in the patient population in the ATTAIN trial compared with the BEACON trial, and the possibility of the BEACON trial exploratory analysis result being a false positive. The OS of around 7 months highlights the unmet need for better systemic therapy for patients with BrM breast cancer, especially those with HER2- breast cancer.
Additional References
- Lindeman GJ, Fernando TM, Bowen R, et al. VERONICA: Randomized phase II study of fulvestrant and venetoclax in ER-positive metastatic breast cancer post-CDK4/6 inhibitors – Efficacy, safety, and biomarker results. Clin Cancer Res. 2022 (June 21). Doi: 10.1158/1078-0432.CCR-21-3811
- Cortés J, Rugo HS, Awada A, et al. Prolonged survival in patients with breast cancer and a history of brain metastases: Results of a preplanned subgroup analysis from the randomized phase III BEACON trial. Breast Cancer Res Treat. 2017;165:329-341. Doi: 10.1007/s10549-017-4304-7
The clinical benefit of fulvestrant as a second-line treatment after tumor progression with CDK4/6i-based therapy has been discouraging, highlighting an unmet need for a better SERD in this space.1 Multiple oral SERD are currently in trials. The EMERALD trial is a phase 3 study that randomly assigned 477 patients with ER+/HER2- mBC in a 1:1 ratio to elacestrant, an oral SERD, vs standard of care (SOC) endocrine therapy (ET). Enrolled patients had received one to two prior ET and one or less chemotherapy treatments in the metastatic disease settings. All patients had prior treatment with a CDK4/6i. Fulvestrant-naive patients were required to have fulvestrant as the SOC ET. In contrast, patients previously treated with fulvestrant received an AI, the selection of which was based on prior AI therapy. Primary endpoints were progression-free survival (PFS) in all patients and in patients with detectable ESR1 mutation. The median PFS in the elacestrant arm was 2.8 months vs 1.9 months in the control arm [hazard ratio (HR) 0.70; 95% CI 0.55-0.88; P = .002]. The 6-month PFS was 34% vs 20% in all patients and 41% vs 19% in patients with detectable ESR1 mutation, favoring the elacestrant arm. In the subgroup analysis among patients who received fulvestrant in the control arm, the 6-month PFS was 34% vs 21% in all patients and 41% vs 19% in patients with ESR1 mutation. Grade 3 or 4 adverse events developed in 27% patients in the elacestrant arm compared with 20% in the SOC arm. More patients in the elacestrant arm developed nausea, vomiting, and liver function abnormalities compared with patients in the SOC arm.
This is the first phase 3 trial demonstrating statistically significant prolongation of PFS associated with an oral SERD compared with SOC ET in patients with ER+/HER2- mBC who had prior treatment with a CDK4/6i. A new drug application has been submitted to the US Food and Drug Administration based on this data. If approved, elacestrant may be favored over fulvestrant as the standard ET for ER+/HER2- mBC after progression on a CDK4/6i-based therapy.
Patients with breast cancer brain metastasis (BrM) have a poor prognosis. Systemic therapies with good central nervous system (CNS) permeability and strong activity against BrM are much needed. An exploratory subset of the phase 3 BEACON trial demonstrated improvement in overall survival (OS) with etirinotecan pegol, a long-acting polymer conjugate of irinotecan, compared with physicians' choice chemotherapy in patients with mBC with treated and stable BrMs.2
Based on this data, a large phase 3 study (the ATTAIN study) was conducted. Patients with mBC with treated and stable BrM (n = 178) were randomly assigned to receive etirinotecan pegol vs physicians' choice of chemotherapy (eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel, or nab-paclitaxel). The primary endpoint of OS was similar in both groups (etirinotecan pegol 7.8 months; chemotherapy 7.5 months; HR 0.90; 95% CI 0.61-1.33; P = .60). Median PFS for mBC with CNS metastases (etirinotecan pegol vs chemotherapy) were 3.9 vs 3.3 months (HR 0.59; 95% CI 0.33-1.05; P = .07) and for non-CNS metastases were 2.8 vs 1.9 months (HR 0.72; 95% CI 0.45-1.16; P = .18). Adverse events were grade 3 or 4 in 57% patients receiving etirinotecan pegol compared with 64% receiving SOC chemotherapy.
This trial failed to meet its primary endpoint. The possible explanations proposed by the investigators are a protocol amendment that reduced the power of the trial to 80%, some key differences in the patient population in the ATTAIN trial compared with the BEACON trial, and the possibility of the BEACON trial exploratory analysis result being a false positive. The OS of around 7 months highlights the unmet need for better systemic therapy for patients with BrM breast cancer, especially those with HER2- breast cancer.
Additional References
- Lindeman GJ, Fernando TM, Bowen R, et al. VERONICA: Randomized phase II study of fulvestrant and venetoclax in ER-positive metastatic breast cancer post-CDK4/6 inhibitors – Efficacy, safety, and biomarker results. Clin Cancer Res. 2022 (June 21). Doi: 10.1158/1078-0432.CCR-21-3811
- Cortés J, Rugo HS, Awada A, et al. Prolonged survival in patients with breast cancer and a history of brain metastases: Results of a preplanned subgroup analysis from the randomized phase III BEACON trial. Breast Cancer Res Treat. 2017;165:329-341. Doi: 10.1007/s10549-017-4304-7
Scientists find brain mechanism behind age-related memory loss
Scientists at Johns Hopkins University have identified a mechanism in the brain behind age-related memory loss, expanding our knowledge of the inner workings of the aging brain and possibly opening the door to new Alzheimer’s treatments.
The researchers looked at the hippocampus, a part of the brain thought to store long-term memories.
Neurons there are responsible for a pair of memory functions – called pattern separation and pattern completion – that work together in young, healthy brains. These functions can swing out of balance with age, impacting memory.
The Johns Hopkins team may have discovered what causes this imbalance. Their findings – reported in a paper in the journal Current Biology – may not only help us improve dementia treatments, but even prevent or delay a loss of thinking skills in the first place, the researchers say.
Pattern separation vs. pattern completion
To understand how the hippocampus changes with age, the researchers looked at rats’ brains. In rats and in humans, pattern separation and pattern completion are present, controlled by neurons in the hippocampus.
As the name suggests, pattern completion is when you take a few details or fragments of information – a few notes of music, or the start of a famous movie quote – and your brain retrieves the full memory. Pattern separation, on the other hand, is being able to tell similar observations or experiences apart (like two visits to the same restaurant) to be stored as separate memories.
These functions occur along a gradient across a tiny region called CA3. That gradient, the study found, disappears with aging, said lead study author Hey-Kyoung Lee, PhD, an assistant research scientist at the university’s Zanvyl Krieger Mind/Brain Institute. “The main consequence of the loss,” Dr. Lee said, “is that pattern completion becomes more dominant in rats as they age.”
What’s happening in the brain
Neurons responsible for pattern completion occupy the “distal” end of CA3, while those in charge of pattern separation reside at the “proximal” end. Dr. Lee said prior studies had not examined the proximal and distal regions separately, as she and her team did in this study.
What was surprising, said Dr. Lee, “was that hyperactivity in aging was observed toward the proximal CA3 region, not the expected distal region.” Contrary to their expectations, that hyperactivity did not enhance function in that area but rather dampened it. Hence: “There is diminished pattern separation and augmented pattern completion,” she said.
– they may recall a certain restaurant they’d been to but not be able to separate what happened during one visit versus another.
Why do some older adults stay sharp?
That memory impairment does not happen to everyone, and it doesn’t happen to all rats either. In fact, the researchers found that some older rats performed spatial-learning tasks as well as young rats did – even though their brains were already beginning to favor pattern completion.
If we can better understand why this happens, we may uncover new therapies for age-related memory loss, Dr. Lee said.
Coauthor Michela Gallagher’s team previously demonstrated that the anti-epilepsy drug levetiracetam improves memory performance by reducing hyperactivity in the hippocampus.
The extra detail this study adds may allow scientists to better aim such drugs in the future, Dr. Lee speculated. “It would give us better control of where we could possibly target the deficits we see.”
A version of this article first appeared on WebMD.com.
Scientists at Johns Hopkins University have identified a mechanism in the brain behind age-related memory loss, expanding our knowledge of the inner workings of the aging brain and possibly opening the door to new Alzheimer’s treatments.
The researchers looked at the hippocampus, a part of the brain thought to store long-term memories.
Neurons there are responsible for a pair of memory functions – called pattern separation and pattern completion – that work together in young, healthy brains. These functions can swing out of balance with age, impacting memory.
The Johns Hopkins team may have discovered what causes this imbalance. Their findings – reported in a paper in the journal Current Biology – may not only help us improve dementia treatments, but even prevent or delay a loss of thinking skills in the first place, the researchers say.
Pattern separation vs. pattern completion
To understand how the hippocampus changes with age, the researchers looked at rats’ brains. In rats and in humans, pattern separation and pattern completion are present, controlled by neurons in the hippocampus.
As the name suggests, pattern completion is when you take a few details or fragments of information – a few notes of music, or the start of a famous movie quote – and your brain retrieves the full memory. Pattern separation, on the other hand, is being able to tell similar observations or experiences apart (like two visits to the same restaurant) to be stored as separate memories.
These functions occur along a gradient across a tiny region called CA3. That gradient, the study found, disappears with aging, said lead study author Hey-Kyoung Lee, PhD, an assistant research scientist at the university’s Zanvyl Krieger Mind/Brain Institute. “The main consequence of the loss,” Dr. Lee said, “is that pattern completion becomes more dominant in rats as they age.”
What’s happening in the brain
Neurons responsible for pattern completion occupy the “distal” end of CA3, while those in charge of pattern separation reside at the “proximal” end. Dr. Lee said prior studies had not examined the proximal and distal regions separately, as she and her team did in this study.
What was surprising, said Dr. Lee, “was that hyperactivity in aging was observed toward the proximal CA3 region, not the expected distal region.” Contrary to their expectations, that hyperactivity did not enhance function in that area but rather dampened it. Hence: “There is diminished pattern separation and augmented pattern completion,” she said.
– they may recall a certain restaurant they’d been to but not be able to separate what happened during one visit versus another.
Why do some older adults stay sharp?
That memory impairment does not happen to everyone, and it doesn’t happen to all rats either. In fact, the researchers found that some older rats performed spatial-learning tasks as well as young rats did – even though their brains were already beginning to favor pattern completion.
If we can better understand why this happens, we may uncover new therapies for age-related memory loss, Dr. Lee said.
Coauthor Michela Gallagher’s team previously demonstrated that the anti-epilepsy drug levetiracetam improves memory performance by reducing hyperactivity in the hippocampus.
The extra detail this study adds may allow scientists to better aim such drugs in the future, Dr. Lee speculated. “It would give us better control of where we could possibly target the deficits we see.”
A version of this article first appeared on WebMD.com.
Scientists at Johns Hopkins University have identified a mechanism in the brain behind age-related memory loss, expanding our knowledge of the inner workings of the aging brain and possibly opening the door to new Alzheimer’s treatments.
The researchers looked at the hippocampus, a part of the brain thought to store long-term memories.
Neurons there are responsible for a pair of memory functions – called pattern separation and pattern completion – that work together in young, healthy brains. These functions can swing out of balance with age, impacting memory.
The Johns Hopkins team may have discovered what causes this imbalance. Their findings – reported in a paper in the journal Current Biology – may not only help us improve dementia treatments, but even prevent or delay a loss of thinking skills in the first place, the researchers say.
Pattern separation vs. pattern completion
To understand how the hippocampus changes with age, the researchers looked at rats’ brains. In rats and in humans, pattern separation and pattern completion are present, controlled by neurons in the hippocampus.
As the name suggests, pattern completion is when you take a few details or fragments of information – a few notes of music, or the start of a famous movie quote – and your brain retrieves the full memory. Pattern separation, on the other hand, is being able to tell similar observations or experiences apart (like two visits to the same restaurant) to be stored as separate memories.
These functions occur along a gradient across a tiny region called CA3. That gradient, the study found, disappears with aging, said lead study author Hey-Kyoung Lee, PhD, an assistant research scientist at the university’s Zanvyl Krieger Mind/Brain Institute. “The main consequence of the loss,” Dr. Lee said, “is that pattern completion becomes more dominant in rats as they age.”
What’s happening in the brain
Neurons responsible for pattern completion occupy the “distal” end of CA3, while those in charge of pattern separation reside at the “proximal” end. Dr. Lee said prior studies had not examined the proximal and distal regions separately, as she and her team did in this study.
What was surprising, said Dr. Lee, “was that hyperactivity in aging was observed toward the proximal CA3 region, not the expected distal region.” Contrary to their expectations, that hyperactivity did not enhance function in that area but rather dampened it. Hence: “There is diminished pattern separation and augmented pattern completion,” she said.
– they may recall a certain restaurant they’d been to but not be able to separate what happened during one visit versus another.
Why do some older adults stay sharp?
That memory impairment does not happen to everyone, and it doesn’t happen to all rats either. In fact, the researchers found that some older rats performed spatial-learning tasks as well as young rats did – even though their brains were already beginning to favor pattern completion.
If we can better understand why this happens, we may uncover new therapies for age-related memory loss, Dr. Lee said.
Coauthor Michela Gallagher’s team previously demonstrated that the anti-epilepsy drug levetiracetam improves memory performance by reducing hyperactivity in the hippocampus.
The extra detail this study adds may allow scientists to better aim such drugs in the future, Dr. Lee speculated. “It would give us better control of where we could possibly target the deficits we see.”
A version of this article first appeared on WebMD.com.
FROM CURRENT BIOLOGY
Can bone density scans help predict dementia risk?
, new research suggests.
In an analysis of more than 900 study participants, women in their 70s with more advanced abdominal aortic calcification (AAC) seen on lateral spine images during dual-energy x-ray absorptiometry (DXA) had a two- to fourfold higher risk for late-life dementia than those with low AAC.
This finding was independent of cardiovascular risk factors and apolipoprotein E (APOE ) genotype.
“While these results are exciting, we now need to undertake further large screening studies in older men and women using this approach to show that the findings are generalizable to older men and can identify people with greater cognitive decline,” coinvestigator Marc Sim, PhD, Edith Cowan University, Joondalup, Australia, said in an interview.
“This will hopefully open the door to studies of early disease-modifying interventions,” Sim said.
The findings were published online in The Lancet Regional Health – Western Pacific.
AAC and cognition
Late-life dementia occurring after age 80 is increasingly common because of both vascular and nonvascular risk factors.
Two recent studies in middle-aged and older men and women showed that AAC identified on bone densitometry was associated with poorer cognition, suggesting it may be related to cognitive decline and increased dementia risk.
This provided the rationale for the current study, Dr. Sim noted.
The researchers assessed AAC using DXA lateral spine images captured in the late 1990s in a prospective cohort of 958 older women who were participating in an osteoporosis study.
AAC was classified into established low, moderate, and extensive categories. At baseline, all women were aged 70 and older, and 45% had low AAC, 36% had moderate AAC, and 19% had extensive AAC.
Over 14.5 years, 150 women (15.7%) had a late-life hospitalization and/or died.
Improved risk prediction
Results showed that, compared with women who had low AAC, women with moderate and extensive AAC were more likely to experience late-life dementia hospitalization (9.3% low, 15.5% moderate, and 18.3% extensive) and death (2.8%, 8.3%, and 9.4%, respectively).
After multivariable adjustment, women with moderate AAC had a two- and threefold increased relative risk for late-life dementia hospitalization or death, compared with their peers who had low AAC.
Women with extensive AAC had a two- and fourfold increase in the adjusted relative risk for late-life dementia hospitalization or death.
“To our knowledge this is the first time it has been shown that AAC from these scans is related to late-life dementia,” Dr. Sim said.
“We demonstrated that AAC improved risk prediction in addition to cardiovascular risk factors and APOE genotype, a genetic risk factor for Alzheimer’s disease, the major form of dementia,” he added.
Dr. Sim noted “these additional lateral spine images” can be taken at the same time that hip and spine bone density tests are done.
“This provides an opportunity to identify AAC in large numbers of people,” he said.
He cautioned, however, that further studies with detailed dementia-related phenotypes, brain imaging, and measures of cognition are needed to confirm whether AAC will add value to dementia risk prediction.
‘Not surprising’
Commenting on the findings for this article, Claire Sexton, DPhil, senior director of scientific programs and outreach at the Alzheimer’s Association, Chicago, noted that AAC is a marker of atherosclerosis and is associated with vascular health outcomes.
Therefore, it is “not surprising it would be associated with dementia too. There’s been previous research linking atherosclerosis and Alzheimer’s disease,” Dr. Sexton said.
“What’s novel about this research is that it’s looking at AAC specifically, which can be identified through a relatively simple test that is already in widespread use,” she added.
Dr. Sexton noted that “much more research” is now needed in larger, more diverse populations in order to better understand the link between AAC and dementia – and whether bone density testing may be an appropriate dementia-screening tool.
“The good news is vascular conditions like atherosclerosis can be managed through lifestyle changes like eating a healthy diet and getting regular exercise. And research tells us what’s good for the heart is good for the brain,” Dr. Sexton said.
The study was funded by Kidney Health Australia, Healthway Health Promotion Foundation of Western Australia, Sir Charles Gairdner Hospital Research Advisory Committee Grant, and the National Health and Medical Research Council of Australia. Dr. Sim and Dr. Sexton have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests.
In an analysis of more than 900 study participants, women in their 70s with more advanced abdominal aortic calcification (AAC) seen on lateral spine images during dual-energy x-ray absorptiometry (DXA) had a two- to fourfold higher risk for late-life dementia than those with low AAC.
This finding was independent of cardiovascular risk factors and apolipoprotein E (APOE ) genotype.
“While these results are exciting, we now need to undertake further large screening studies in older men and women using this approach to show that the findings are generalizable to older men and can identify people with greater cognitive decline,” coinvestigator Marc Sim, PhD, Edith Cowan University, Joondalup, Australia, said in an interview.
“This will hopefully open the door to studies of early disease-modifying interventions,” Sim said.
The findings were published online in The Lancet Regional Health – Western Pacific.
AAC and cognition
Late-life dementia occurring after age 80 is increasingly common because of both vascular and nonvascular risk factors.
Two recent studies in middle-aged and older men and women showed that AAC identified on bone densitometry was associated with poorer cognition, suggesting it may be related to cognitive decline and increased dementia risk.
This provided the rationale for the current study, Dr. Sim noted.
The researchers assessed AAC using DXA lateral spine images captured in the late 1990s in a prospective cohort of 958 older women who were participating in an osteoporosis study.
AAC was classified into established low, moderate, and extensive categories. At baseline, all women were aged 70 and older, and 45% had low AAC, 36% had moderate AAC, and 19% had extensive AAC.
Over 14.5 years, 150 women (15.7%) had a late-life hospitalization and/or died.
Improved risk prediction
Results showed that, compared with women who had low AAC, women with moderate and extensive AAC were more likely to experience late-life dementia hospitalization (9.3% low, 15.5% moderate, and 18.3% extensive) and death (2.8%, 8.3%, and 9.4%, respectively).
After multivariable adjustment, women with moderate AAC had a two- and threefold increased relative risk for late-life dementia hospitalization or death, compared with their peers who had low AAC.
Women with extensive AAC had a two- and fourfold increase in the adjusted relative risk for late-life dementia hospitalization or death.
“To our knowledge this is the first time it has been shown that AAC from these scans is related to late-life dementia,” Dr. Sim said.
“We demonstrated that AAC improved risk prediction in addition to cardiovascular risk factors and APOE genotype, a genetic risk factor for Alzheimer’s disease, the major form of dementia,” he added.
Dr. Sim noted “these additional lateral spine images” can be taken at the same time that hip and spine bone density tests are done.
“This provides an opportunity to identify AAC in large numbers of people,” he said.
He cautioned, however, that further studies with detailed dementia-related phenotypes, brain imaging, and measures of cognition are needed to confirm whether AAC will add value to dementia risk prediction.
‘Not surprising’
Commenting on the findings for this article, Claire Sexton, DPhil, senior director of scientific programs and outreach at the Alzheimer’s Association, Chicago, noted that AAC is a marker of atherosclerosis and is associated with vascular health outcomes.
Therefore, it is “not surprising it would be associated with dementia too. There’s been previous research linking atherosclerosis and Alzheimer’s disease,” Dr. Sexton said.
“What’s novel about this research is that it’s looking at AAC specifically, which can be identified through a relatively simple test that is already in widespread use,” she added.
Dr. Sexton noted that “much more research” is now needed in larger, more diverse populations in order to better understand the link between AAC and dementia – and whether bone density testing may be an appropriate dementia-screening tool.
“The good news is vascular conditions like atherosclerosis can be managed through lifestyle changes like eating a healthy diet and getting regular exercise. And research tells us what’s good for the heart is good for the brain,” Dr. Sexton said.
The study was funded by Kidney Health Australia, Healthway Health Promotion Foundation of Western Australia, Sir Charles Gairdner Hospital Research Advisory Committee Grant, and the National Health and Medical Research Council of Australia. Dr. Sim and Dr. Sexton have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests.
In an analysis of more than 900 study participants, women in their 70s with more advanced abdominal aortic calcification (AAC) seen on lateral spine images during dual-energy x-ray absorptiometry (DXA) had a two- to fourfold higher risk for late-life dementia than those with low AAC.
This finding was independent of cardiovascular risk factors and apolipoprotein E (APOE ) genotype.
“While these results are exciting, we now need to undertake further large screening studies in older men and women using this approach to show that the findings are generalizable to older men and can identify people with greater cognitive decline,” coinvestigator Marc Sim, PhD, Edith Cowan University, Joondalup, Australia, said in an interview.
“This will hopefully open the door to studies of early disease-modifying interventions,” Sim said.
The findings were published online in The Lancet Regional Health – Western Pacific.
AAC and cognition
Late-life dementia occurring after age 80 is increasingly common because of both vascular and nonvascular risk factors.
Two recent studies in middle-aged and older men and women showed that AAC identified on bone densitometry was associated with poorer cognition, suggesting it may be related to cognitive decline and increased dementia risk.
This provided the rationale for the current study, Dr. Sim noted.
The researchers assessed AAC using DXA lateral spine images captured in the late 1990s in a prospective cohort of 958 older women who were participating in an osteoporosis study.
AAC was classified into established low, moderate, and extensive categories. At baseline, all women were aged 70 and older, and 45% had low AAC, 36% had moderate AAC, and 19% had extensive AAC.
Over 14.5 years, 150 women (15.7%) had a late-life hospitalization and/or died.
Improved risk prediction
Results showed that, compared with women who had low AAC, women with moderate and extensive AAC were more likely to experience late-life dementia hospitalization (9.3% low, 15.5% moderate, and 18.3% extensive) and death (2.8%, 8.3%, and 9.4%, respectively).
After multivariable adjustment, women with moderate AAC had a two- and threefold increased relative risk for late-life dementia hospitalization or death, compared with their peers who had low AAC.
Women with extensive AAC had a two- and fourfold increase in the adjusted relative risk for late-life dementia hospitalization or death.
“To our knowledge this is the first time it has been shown that AAC from these scans is related to late-life dementia,” Dr. Sim said.
“We demonstrated that AAC improved risk prediction in addition to cardiovascular risk factors and APOE genotype, a genetic risk factor for Alzheimer’s disease, the major form of dementia,” he added.
Dr. Sim noted “these additional lateral spine images” can be taken at the same time that hip and spine bone density tests are done.
“This provides an opportunity to identify AAC in large numbers of people,” he said.
He cautioned, however, that further studies with detailed dementia-related phenotypes, brain imaging, and measures of cognition are needed to confirm whether AAC will add value to dementia risk prediction.
‘Not surprising’
Commenting on the findings for this article, Claire Sexton, DPhil, senior director of scientific programs and outreach at the Alzheimer’s Association, Chicago, noted that AAC is a marker of atherosclerosis and is associated with vascular health outcomes.
Therefore, it is “not surprising it would be associated with dementia too. There’s been previous research linking atherosclerosis and Alzheimer’s disease,” Dr. Sexton said.
“What’s novel about this research is that it’s looking at AAC specifically, which can be identified through a relatively simple test that is already in widespread use,” she added.
Dr. Sexton noted that “much more research” is now needed in larger, more diverse populations in order to better understand the link between AAC and dementia – and whether bone density testing may be an appropriate dementia-screening tool.
“The good news is vascular conditions like atherosclerosis can be managed through lifestyle changes like eating a healthy diet and getting regular exercise. And research tells us what’s good for the heart is good for the brain,” Dr. Sexton said.
The study was funded by Kidney Health Australia, Healthway Health Promotion Foundation of Western Australia, Sir Charles Gairdner Hospital Research Advisory Committee Grant, and the National Health and Medical Research Council of Australia. Dr. Sim and Dr. Sexton have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE LANCET REGIONAL HEALTH – WESTERN PACIFIC
Cancer may increase risk of type 2 diabetes
most notably pancreatic malignancies.
“Our study demonstrates that there is an elevated risk of developing diabetes if a person is affected by lung, pancreatic, breast, brain, urinary tract, or uterine cancers,” said Lykke Sylow, PhD, associate professor in the Molecular Metabolism in Cancer and Ageing Group at the University of Copenhagen, in a statement.
“It is great to see such a large, well-designed study confirm the findings of previous smaller studies and observations,” said Elias S. Siraj, MD, the David L. Bernd Distinguished Chair for EVMS-Sentara Cardiovascular Diabetes Program at Eastern Virginia Medical School in Norfolk, when asked for comment by this news organization. Dr. Siraj also noted that “in clinical care we do observe that many patients develop diabetes after being diagnosed with cancer although one needs a well-designed study to confirm that observation.”
Diabetes risk highest with pancreatic cancer
Type 2 diabetes at the time of cancer diagnosis is known to increase cancer-specific and all-cause mortality, but not much is known about whether cancer is a risk factor for type 2 diabetes, the researchers state in their study, published in Diabetes Care.
Dr. Sylow and colleagues from the Steno Diabetes Center Copenhagen, Rigshospitalet, analyzed a database consisting of 112 million blood samples from 1.3 million Danes from 2000 to 2015. They looked at cancer cases with an incidence of more than 1,000 and excluded individuals with diabetes prior to cancer diagnosis.
They found an increased risk of new-onset type 2 diabetes for all cancers (hazard ratio, 1.09; 95% confidence interval, 1.03-1.14). For pancreatic cancer, the hazard ratio rose to 5.0 (95% CI, 3.62-6.90), for brain and nervous system cancers the hazard ratio was 1.54 (95% CI, 1.22-1.95), and for uterine cancer the hazard ratio was 1.41 (95% CI, 1.10-1.84).
The link with pancreatic cancer was not surprising, said Dr. Sylow.
Dr. Siraj agreed, noting that a few studies have shown a strong association. “It has also been observed for years that many patients with pancreatic cancer may present with new-onset diabetes,” he said. “The mechanism is not clearly understood but could include a direct damage of the beta cells by the pancreatic cancer or could be due to a paraneoplastic secretion of special factors by the cancer that can affect beta-cell function or insulin resistance,” said Dr. Siraj, who is also professor and chief of endocrinology and director of the Strelitz Diabetes Center at Eastern Virginia Medical School.
The higher diabetes risk associated with brain and nervous system cancers has not been previously described and is “an intriguing finding,” he said.
In their statement, the Danish investigators said there is nothing in their research to suggest why some cancers are associated with a higher risk of new-onset type 2 diabetes, but they offered some theories, including that chemotherapeutics and perhaps the cancer, itself, may contribute.
“We know that cancer cells are able to secrete substances that can affect organs and possibility contribute to an increased incidence of diabetes,” said Dr. Sylow in the statement.
Increased mortality risk in those with cancer and type 2 diabetes
Dr. Sylow and colleagues also analyzed mortality in a subset of 28,308 patients with cancer who were still alive 2 years after diagnosis. They documented a 21% higher rate of all-cause mortality in these patients compared with those who did not have new-onset type 2 diabetes.
“We do not know enough about the patients who were diagnosed with type 2 diabetes, but we think our findings illustrate a potential new area of intervention in the cancer clinic,” Dr. Sylow said. However, the findings still require replication before drawing any definite conclusions, she added.
Christoffer Johansen, MD, PhD, DMSc, of Rigshospitalet, said in the statement that it might be prudent to screen patients with lung, breast, brain, uterine, and urinary tract cancers for diabetes. “Early intervention could have an impact on certain cancer patients,” said Dr. Johansen.
Dr. Siraj said he would urge oncologists to routinely monitor blood glucose levels during cancer treatment and as part of long-term surveillance, and to consider the potential risk of new-onset diabetes when choosing a cancer therapy. If diabetes is diagnosed, clinicians should be sure that it’s managed by a primary care physician or endocrinologist, “as proper treatment may contribute to better outcomes of the cancer,” said Dr. Siraj.
Endocrinologists should consider the possibility of pancreatic cancer if someone with few risk factors for type 2 diabetes has a new-onset diagnosis, he said. And they should aim for good glycemic control in those with new-onset type 2 diabetes, as it may lead to better cancer outcomes, he said.
Dr. Sylow has reported grant support from the Novo Nordisk Foundation and Independent Research Fund Denmark. Dr. Johansen has reported serving as an educator for Janssen and Pfizer. Coauthors have received grant support from the Danish Cancer Society and served as consultants, on advisory boards, or as educators for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Incyte, GSK, MSD, Mundipharma, Novartis, Novo Nordisk, Pfizer, and Sanofi.
A version of this article first appeared on Medscape.com.
most notably pancreatic malignancies.
“Our study demonstrates that there is an elevated risk of developing diabetes if a person is affected by lung, pancreatic, breast, brain, urinary tract, or uterine cancers,” said Lykke Sylow, PhD, associate professor in the Molecular Metabolism in Cancer and Ageing Group at the University of Copenhagen, in a statement.
“It is great to see such a large, well-designed study confirm the findings of previous smaller studies and observations,” said Elias S. Siraj, MD, the David L. Bernd Distinguished Chair for EVMS-Sentara Cardiovascular Diabetes Program at Eastern Virginia Medical School in Norfolk, when asked for comment by this news organization. Dr. Siraj also noted that “in clinical care we do observe that many patients develop diabetes after being diagnosed with cancer although one needs a well-designed study to confirm that observation.”
Diabetes risk highest with pancreatic cancer
Type 2 diabetes at the time of cancer diagnosis is known to increase cancer-specific and all-cause mortality, but not much is known about whether cancer is a risk factor for type 2 diabetes, the researchers state in their study, published in Diabetes Care.
Dr. Sylow and colleagues from the Steno Diabetes Center Copenhagen, Rigshospitalet, analyzed a database consisting of 112 million blood samples from 1.3 million Danes from 2000 to 2015. They looked at cancer cases with an incidence of more than 1,000 and excluded individuals with diabetes prior to cancer diagnosis.
They found an increased risk of new-onset type 2 diabetes for all cancers (hazard ratio, 1.09; 95% confidence interval, 1.03-1.14). For pancreatic cancer, the hazard ratio rose to 5.0 (95% CI, 3.62-6.90), for brain and nervous system cancers the hazard ratio was 1.54 (95% CI, 1.22-1.95), and for uterine cancer the hazard ratio was 1.41 (95% CI, 1.10-1.84).
The link with pancreatic cancer was not surprising, said Dr. Sylow.
Dr. Siraj agreed, noting that a few studies have shown a strong association. “It has also been observed for years that many patients with pancreatic cancer may present with new-onset diabetes,” he said. “The mechanism is not clearly understood but could include a direct damage of the beta cells by the pancreatic cancer or could be due to a paraneoplastic secretion of special factors by the cancer that can affect beta-cell function or insulin resistance,” said Dr. Siraj, who is also professor and chief of endocrinology and director of the Strelitz Diabetes Center at Eastern Virginia Medical School.
The higher diabetes risk associated with brain and nervous system cancers has not been previously described and is “an intriguing finding,” he said.
In their statement, the Danish investigators said there is nothing in their research to suggest why some cancers are associated with a higher risk of new-onset type 2 diabetes, but they offered some theories, including that chemotherapeutics and perhaps the cancer, itself, may contribute.
“We know that cancer cells are able to secrete substances that can affect organs and possibility contribute to an increased incidence of diabetes,” said Dr. Sylow in the statement.
Increased mortality risk in those with cancer and type 2 diabetes
Dr. Sylow and colleagues also analyzed mortality in a subset of 28,308 patients with cancer who were still alive 2 years after diagnosis. They documented a 21% higher rate of all-cause mortality in these patients compared with those who did not have new-onset type 2 diabetes.
“We do not know enough about the patients who were diagnosed with type 2 diabetes, but we think our findings illustrate a potential new area of intervention in the cancer clinic,” Dr. Sylow said. However, the findings still require replication before drawing any definite conclusions, she added.
Christoffer Johansen, MD, PhD, DMSc, of Rigshospitalet, said in the statement that it might be prudent to screen patients with lung, breast, brain, uterine, and urinary tract cancers for diabetes. “Early intervention could have an impact on certain cancer patients,” said Dr. Johansen.
Dr. Siraj said he would urge oncologists to routinely monitor blood glucose levels during cancer treatment and as part of long-term surveillance, and to consider the potential risk of new-onset diabetes when choosing a cancer therapy. If diabetes is diagnosed, clinicians should be sure that it’s managed by a primary care physician or endocrinologist, “as proper treatment may contribute to better outcomes of the cancer,” said Dr. Siraj.
Endocrinologists should consider the possibility of pancreatic cancer if someone with few risk factors for type 2 diabetes has a new-onset diagnosis, he said. And they should aim for good glycemic control in those with new-onset type 2 diabetes, as it may lead to better cancer outcomes, he said.
Dr. Sylow has reported grant support from the Novo Nordisk Foundation and Independent Research Fund Denmark. Dr. Johansen has reported serving as an educator for Janssen and Pfizer. Coauthors have received grant support from the Danish Cancer Society and served as consultants, on advisory boards, or as educators for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Incyte, GSK, MSD, Mundipharma, Novartis, Novo Nordisk, Pfizer, and Sanofi.
A version of this article first appeared on Medscape.com.
most notably pancreatic malignancies.
“Our study demonstrates that there is an elevated risk of developing diabetes if a person is affected by lung, pancreatic, breast, brain, urinary tract, or uterine cancers,” said Lykke Sylow, PhD, associate professor in the Molecular Metabolism in Cancer and Ageing Group at the University of Copenhagen, in a statement.
“It is great to see such a large, well-designed study confirm the findings of previous smaller studies and observations,” said Elias S. Siraj, MD, the David L. Bernd Distinguished Chair for EVMS-Sentara Cardiovascular Diabetes Program at Eastern Virginia Medical School in Norfolk, when asked for comment by this news organization. Dr. Siraj also noted that “in clinical care we do observe that many patients develop diabetes after being diagnosed with cancer although one needs a well-designed study to confirm that observation.”
Diabetes risk highest with pancreatic cancer
Type 2 diabetes at the time of cancer diagnosis is known to increase cancer-specific and all-cause mortality, but not much is known about whether cancer is a risk factor for type 2 diabetes, the researchers state in their study, published in Diabetes Care.
Dr. Sylow and colleagues from the Steno Diabetes Center Copenhagen, Rigshospitalet, analyzed a database consisting of 112 million blood samples from 1.3 million Danes from 2000 to 2015. They looked at cancer cases with an incidence of more than 1,000 and excluded individuals with diabetes prior to cancer diagnosis.
They found an increased risk of new-onset type 2 diabetes for all cancers (hazard ratio, 1.09; 95% confidence interval, 1.03-1.14). For pancreatic cancer, the hazard ratio rose to 5.0 (95% CI, 3.62-6.90), for brain and nervous system cancers the hazard ratio was 1.54 (95% CI, 1.22-1.95), and for uterine cancer the hazard ratio was 1.41 (95% CI, 1.10-1.84).
The link with pancreatic cancer was not surprising, said Dr. Sylow.
Dr. Siraj agreed, noting that a few studies have shown a strong association. “It has also been observed for years that many patients with pancreatic cancer may present with new-onset diabetes,” he said. “The mechanism is not clearly understood but could include a direct damage of the beta cells by the pancreatic cancer or could be due to a paraneoplastic secretion of special factors by the cancer that can affect beta-cell function or insulin resistance,” said Dr. Siraj, who is also professor and chief of endocrinology and director of the Strelitz Diabetes Center at Eastern Virginia Medical School.
The higher diabetes risk associated with brain and nervous system cancers has not been previously described and is “an intriguing finding,” he said.
In their statement, the Danish investigators said there is nothing in their research to suggest why some cancers are associated with a higher risk of new-onset type 2 diabetes, but they offered some theories, including that chemotherapeutics and perhaps the cancer, itself, may contribute.
“We know that cancer cells are able to secrete substances that can affect organs and possibility contribute to an increased incidence of diabetes,” said Dr. Sylow in the statement.
Increased mortality risk in those with cancer and type 2 diabetes
Dr. Sylow and colleagues also analyzed mortality in a subset of 28,308 patients with cancer who were still alive 2 years after diagnosis. They documented a 21% higher rate of all-cause mortality in these patients compared with those who did not have new-onset type 2 diabetes.
“We do not know enough about the patients who were diagnosed with type 2 diabetes, but we think our findings illustrate a potential new area of intervention in the cancer clinic,” Dr. Sylow said. However, the findings still require replication before drawing any definite conclusions, she added.
Christoffer Johansen, MD, PhD, DMSc, of Rigshospitalet, said in the statement that it might be prudent to screen patients with lung, breast, brain, uterine, and urinary tract cancers for diabetes. “Early intervention could have an impact on certain cancer patients,” said Dr. Johansen.
Dr. Siraj said he would urge oncologists to routinely monitor blood glucose levels during cancer treatment and as part of long-term surveillance, and to consider the potential risk of new-onset diabetes when choosing a cancer therapy. If diabetes is diagnosed, clinicians should be sure that it’s managed by a primary care physician or endocrinologist, “as proper treatment may contribute to better outcomes of the cancer,” said Dr. Siraj.
Endocrinologists should consider the possibility of pancreatic cancer if someone with few risk factors for type 2 diabetes has a new-onset diagnosis, he said. And they should aim for good glycemic control in those with new-onset type 2 diabetes, as it may lead to better cancer outcomes, he said.
Dr. Sylow has reported grant support from the Novo Nordisk Foundation and Independent Research Fund Denmark. Dr. Johansen has reported serving as an educator for Janssen and Pfizer. Coauthors have received grant support from the Danish Cancer Society and served as consultants, on advisory boards, or as educators for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Incyte, GSK, MSD, Mundipharma, Novartis, Novo Nordisk, Pfizer, and Sanofi.
A version of this article first appeared on Medscape.com.
FROM DIABETES CARE
First-ever Huntington staging system may jump-start drug development for early-stage disease
Researchers liken the Huntington’s disease Integrated Staging System (HD-ISS) to the system currently used to stage cancer. It groups patients according to their underlying biological, clinical, and functional characteristics.
It also includes criteria to biologically define Huntington’s disease stages across the entire disease spectrum, from birth to death, which is something that has not been done before. For now, the HD-ISS is only intended for research, but it could one day be modified for use in the clinic, investigators wrote.
“This systematization is of critical importance to select the most appropriate target population for clinical trials and studies,” said co-investigator Cristina Sampaio, MD, chief medical officer at the CHDI Foundation, Princeton, N.J.
“By providing a methodology to precisely define cases early in the neurodegenerative process, the HD-ISS will be instrumental in conducting trials in the very early disease stages,” Dr. Sampaio added.
The position paper was published in the July issue of the Lancet Neurology.
New approach needed
There is no approved therapy to slow Huntington’s disease progression. Clinical trials currently enroll patients with demonstrable symptoms, which limits the ability to test therapeutics that could delay or prevent neurodegeneration.
Huntington’s disease is rare, occurring in about 2.7 per 100,000 individuals worldwide. It is caused by a mutation in the HTT gene involving a DNA segment known as a CAG trinucleotide repeat.
Currently, Huntington’s disease is diagnosed on the basis of clinical signs that emerge late in the disease course, an approach developed before the discovery of the HTT gene and the development of the genetic test for the CAG mutation.
The disease phase prior to diagnosis has been described as presymptomatic, premanifest, or prodromal. However, the three terms have varying definitions that make it difficult to compare study results across trials.
Because drug development had focused on the overt motor sign phase of the disease, there was no real need for an evidence-based staging system that classified disease phases from birth, the investigators noted.
“Now, the research community and regulators recognize that it is critical to conduct trials early in the disease when no signs or overt symptoms are measurable,” Dr. Sampaio said.
Defining disease stages
Work on the staging system was done through the Huntington’s Disease Regulatory Science Consortium, an international project begun in 2018 among biotech and pharma companies, academic institutions, and nonprofit research and advocacy organizations.
Overall, more than 50 clinicians and researchers were involved in developing the HD-ISS.
Using modeling data from four large observational studies that included patients with Huntington’s disease and control groups, researchers identified four different stages of Huntington’s disease:
- Stage 0: Begins at birth with identification of HTT gene mutations but no detectable pathologic changes.
- Stage 1: Begins when biomarker changes are detected via MRI by a volume decrease in six brain areas.
- Stage 2: Begins when clinical signs of Huntington’s disease are present, as determined through motor and cognitive assessments.
- Stage 3: Begins when functional decline is evident, with worsening on the Independence Scale and the Total Functional Capacity of the Unified Huntington’s Disease Rating Scale.
Applying the HD-ISS to clinical trials requires the collection of information routinely recorded in Huntington’s disease research, as well as some additional data, but researchers say its application is straightforward.
The HD-ISS uses a numerical staging system similar to that used in the U.S. Food and Drug Administration’s guidance for Alzheimer’s disease (AD) and integrates the prodromal, presymptomatic, or premanifest phase of the disease. This distinguishes it from earlier classification systems.
The HD-ISS can be adapted if new Huntington’s disease biomarkers are identified.
“As research results are generated, this will further validate the HD-ISS and potentially lead to the development of a derivative, and possibly simplified, system for clinical practice,” Dr. Sampaio said.
The new system goes further than a more recent proposal from the Movement Disorder Society task force, which addresses earlier stages in Huntington’s disease but doesn’t consider objective biomarker data.
Question of timing
Commenting on the findings, Erin Furr-Stimming, MD, neurologist and director of the Huntington’s Disease Society of America Center of Excellence with McGovern Medical School, UTHealth, Houston, said targeting early-stage disease will be key.
“Similar to more common neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease, there is a period of at least a decade when changes are occurring in the nervous system, prior to the manifestation of clinical symptoms and signs significant enough to warrant a clinical diagnosis,” Dr. Furr-Stimming said.
She noted that multiple trials of disease-modifying agents for Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease have failed for a multitude of reasons, “but one consistent question that is relevant to all these diseases is that of timing: Should we intervene and test these therapies earlier?
“The premanifest or prodromal period may be the ideal time to intervene with a disease-modifying therapy, prior to onset of any neurodegeneration,” Dr. Furr-Stimming said.
The CHDI Foundation provided financial support to the Critical Path Institute for the Huntington’s Disease Regulatory Science Consortium, including all working group efforts. Dr. Sampio is an employee of and receives salary from CHDI Management. She has also received consultancy honorariums (unrelated to HD) from Pfizer, Kyowa Kirin, vTv Therapeutics, GW Pharmaceuticals, Neuraly, Neuroderm, Green Valley Pharmaceuticals, and Pinteon Pharmaceuticals. A full list of disclosures for the other researchers is in the original article. Dr. Furr-Stimming reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Researchers liken the Huntington’s disease Integrated Staging System (HD-ISS) to the system currently used to stage cancer. It groups patients according to their underlying biological, clinical, and functional characteristics.
It also includes criteria to biologically define Huntington’s disease stages across the entire disease spectrum, from birth to death, which is something that has not been done before. For now, the HD-ISS is only intended for research, but it could one day be modified for use in the clinic, investigators wrote.
“This systematization is of critical importance to select the most appropriate target population for clinical trials and studies,” said co-investigator Cristina Sampaio, MD, chief medical officer at the CHDI Foundation, Princeton, N.J.
“By providing a methodology to precisely define cases early in the neurodegenerative process, the HD-ISS will be instrumental in conducting trials in the very early disease stages,” Dr. Sampaio added.
The position paper was published in the July issue of the Lancet Neurology.
New approach needed
There is no approved therapy to slow Huntington’s disease progression. Clinical trials currently enroll patients with demonstrable symptoms, which limits the ability to test therapeutics that could delay or prevent neurodegeneration.
Huntington’s disease is rare, occurring in about 2.7 per 100,000 individuals worldwide. It is caused by a mutation in the HTT gene involving a DNA segment known as a CAG trinucleotide repeat.
Currently, Huntington’s disease is diagnosed on the basis of clinical signs that emerge late in the disease course, an approach developed before the discovery of the HTT gene and the development of the genetic test for the CAG mutation.
The disease phase prior to diagnosis has been described as presymptomatic, premanifest, or prodromal. However, the three terms have varying definitions that make it difficult to compare study results across trials.
Because drug development had focused on the overt motor sign phase of the disease, there was no real need for an evidence-based staging system that classified disease phases from birth, the investigators noted.
“Now, the research community and regulators recognize that it is critical to conduct trials early in the disease when no signs or overt symptoms are measurable,” Dr. Sampaio said.
Defining disease stages
Work on the staging system was done through the Huntington’s Disease Regulatory Science Consortium, an international project begun in 2018 among biotech and pharma companies, academic institutions, and nonprofit research and advocacy organizations.
Overall, more than 50 clinicians and researchers were involved in developing the HD-ISS.
Using modeling data from four large observational studies that included patients with Huntington’s disease and control groups, researchers identified four different stages of Huntington’s disease:
- Stage 0: Begins at birth with identification of HTT gene mutations but no detectable pathologic changes.
- Stage 1: Begins when biomarker changes are detected via MRI by a volume decrease in six brain areas.
- Stage 2: Begins when clinical signs of Huntington’s disease are present, as determined through motor and cognitive assessments.
- Stage 3: Begins when functional decline is evident, with worsening on the Independence Scale and the Total Functional Capacity of the Unified Huntington’s Disease Rating Scale.
Applying the HD-ISS to clinical trials requires the collection of information routinely recorded in Huntington’s disease research, as well as some additional data, but researchers say its application is straightforward.
The HD-ISS uses a numerical staging system similar to that used in the U.S. Food and Drug Administration’s guidance for Alzheimer’s disease (AD) and integrates the prodromal, presymptomatic, or premanifest phase of the disease. This distinguishes it from earlier classification systems.
The HD-ISS can be adapted if new Huntington’s disease biomarkers are identified.
“As research results are generated, this will further validate the HD-ISS and potentially lead to the development of a derivative, and possibly simplified, system for clinical practice,” Dr. Sampaio said.
The new system goes further than a more recent proposal from the Movement Disorder Society task force, which addresses earlier stages in Huntington’s disease but doesn’t consider objective biomarker data.
Question of timing
Commenting on the findings, Erin Furr-Stimming, MD, neurologist and director of the Huntington’s Disease Society of America Center of Excellence with McGovern Medical School, UTHealth, Houston, said targeting early-stage disease will be key.
“Similar to more common neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease, there is a period of at least a decade when changes are occurring in the nervous system, prior to the manifestation of clinical symptoms and signs significant enough to warrant a clinical diagnosis,” Dr. Furr-Stimming said.
She noted that multiple trials of disease-modifying agents for Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease have failed for a multitude of reasons, “but one consistent question that is relevant to all these diseases is that of timing: Should we intervene and test these therapies earlier?
“The premanifest or prodromal period may be the ideal time to intervene with a disease-modifying therapy, prior to onset of any neurodegeneration,” Dr. Furr-Stimming said.
The CHDI Foundation provided financial support to the Critical Path Institute for the Huntington’s Disease Regulatory Science Consortium, including all working group efforts. Dr. Sampio is an employee of and receives salary from CHDI Management. She has also received consultancy honorariums (unrelated to HD) from Pfizer, Kyowa Kirin, vTv Therapeutics, GW Pharmaceuticals, Neuraly, Neuroderm, Green Valley Pharmaceuticals, and Pinteon Pharmaceuticals. A full list of disclosures for the other researchers is in the original article. Dr. Furr-Stimming reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Researchers liken the Huntington’s disease Integrated Staging System (HD-ISS) to the system currently used to stage cancer. It groups patients according to their underlying biological, clinical, and functional characteristics.
It also includes criteria to biologically define Huntington’s disease stages across the entire disease spectrum, from birth to death, which is something that has not been done before. For now, the HD-ISS is only intended for research, but it could one day be modified for use in the clinic, investigators wrote.
“This systematization is of critical importance to select the most appropriate target population for clinical trials and studies,” said co-investigator Cristina Sampaio, MD, chief medical officer at the CHDI Foundation, Princeton, N.J.
“By providing a methodology to precisely define cases early in the neurodegenerative process, the HD-ISS will be instrumental in conducting trials in the very early disease stages,” Dr. Sampaio added.
The position paper was published in the July issue of the Lancet Neurology.
New approach needed
There is no approved therapy to slow Huntington’s disease progression. Clinical trials currently enroll patients with demonstrable symptoms, which limits the ability to test therapeutics that could delay or prevent neurodegeneration.
Huntington’s disease is rare, occurring in about 2.7 per 100,000 individuals worldwide. It is caused by a mutation in the HTT gene involving a DNA segment known as a CAG trinucleotide repeat.
Currently, Huntington’s disease is diagnosed on the basis of clinical signs that emerge late in the disease course, an approach developed before the discovery of the HTT gene and the development of the genetic test for the CAG mutation.
The disease phase prior to diagnosis has been described as presymptomatic, premanifest, or prodromal. However, the three terms have varying definitions that make it difficult to compare study results across trials.
Because drug development had focused on the overt motor sign phase of the disease, there was no real need for an evidence-based staging system that classified disease phases from birth, the investigators noted.
“Now, the research community and regulators recognize that it is critical to conduct trials early in the disease when no signs or overt symptoms are measurable,” Dr. Sampaio said.
Defining disease stages
Work on the staging system was done through the Huntington’s Disease Regulatory Science Consortium, an international project begun in 2018 among biotech and pharma companies, academic institutions, and nonprofit research and advocacy organizations.
Overall, more than 50 clinicians and researchers were involved in developing the HD-ISS.
Using modeling data from four large observational studies that included patients with Huntington’s disease and control groups, researchers identified four different stages of Huntington’s disease:
- Stage 0: Begins at birth with identification of HTT gene mutations but no detectable pathologic changes.
- Stage 1: Begins when biomarker changes are detected via MRI by a volume decrease in six brain areas.
- Stage 2: Begins when clinical signs of Huntington’s disease are present, as determined through motor and cognitive assessments.
- Stage 3: Begins when functional decline is evident, with worsening on the Independence Scale and the Total Functional Capacity of the Unified Huntington’s Disease Rating Scale.
Applying the HD-ISS to clinical trials requires the collection of information routinely recorded in Huntington’s disease research, as well as some additional data, but researchers say its application is straightforward.
The HD-ISS uses a numerical staging system similar to that used in the U.S. Food and Drug Administration’s guidance for Alzheimer’s disease (AD) and integrates the prodromal, presymptomatic, or premanifest phase of the disease. This distinguishes it from earlier classification systems.
The HD-ISS can be adapted if new Huntington’s disease biomarkers are identified.
“As research results are generated, this will further validate the HD-ISS and potentially lead to the development of a derivative, and possibly simplified, system for clinical practice,” Dr. Sampaio said.
The new system goes further than a more recent proposal from the Movement Disorder Society task force, which addresses earlier stages in Huntington’s disease but doesn’t consider objective biomarker data.
Question of timing
Commenting on the findings, Erin Furr-Stimming, MD, neurologist and director of the Huntington’s Disease Society of America Center of Excellence with McGovern Medical School, UTHealth, Houston, said targeting early-stage disease will be key.
“Similar to more common neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease, there is a period of at least a decade when changes are occurring in the nervous system, prior to the manifestation of clinical symptoms and signs significant enough to warrant a clinical diagnosis,” Dr. Furr-Stimming said.
She noted that multiple trials of disease-modifying agents for Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease have failed for a multitude of reasons, “but one consistent question that is relevant to all these diseases is that of timing: Should we intervene and test these therapies earlier?
“The premanifest or prodromal period may be the ideal time to intervene with a disease-modifying therapy, prior to onset of any neurodegeneration,” Dr. Furr-Stimming said.
The CHDI Foundation provided financial support to the Critical Path Institute for the Huntington’s Disease Regulatory Science Consortium, including all working group efforts. Dr. Sampio is an employee of and receives salary from CHDI Management. She has also received consultancy honorariums (unrelated to HD) from Pfizer, Kyowa Kirin, vTv Therapeutics, GW Pharmaceuticals, Neuraly, Neuroderm, Green Valley Pharmaceuticals, and Pinteon Pharmaceuticals. A full list of disclosures for the other researchers is in the original article. Dr. Furr-Stimming reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE LANCET NEUROLOGY
Mobile devices ‘addictive by design’: Obesity is one of many health effects
Wireless devices, like smart phones and tablets, appear to induce compulsive or even addictive use in many individuals, leading to adverse health consequences that are likely to be curtailed only through often difficult behavior modification, according to a pediatric endocrinologist’s take on the problem.
While the summary was based in part on the analysis of 234 published papers drawn from the medical literature, the lead author, Nidhi Gupta, MD, said the data reinforce her own clinical experience.
“As a pediatric endocrinologist, the trend in smartphone-associated health disorders, such as obesity, sleep, and behavior issues, worries me,” Dr. Gupta, director of KAP Pediatric Endocrinology, Nashville, Tenn., said at the annual meeting of the Endocrine Society.
Based on her search of the medical literature, the available data raise concern. In one study she cited, for example, each hour per day of screen time was found to translate into a body mass index increase of 0.5 to 0.7 kg/m2 (P < .001).
With this type of progressive rise in BMI comes prediabetes, dyslipidemia, and other metabolic disorders associated with major health risks, including cardiovascular disease. And there are others. Dr. Gupta cited data suggesting screen time before bed disturbs sleep, which has its own set of health risks.
“When I say health, it includes physical health, mental health, and emotional health,” said Dr. Gupta.
In the U.S. and other countries with a growing obesity epidemic, lack of physical activity and unhealthy eating are widely considered the major culprits. Excessive screen time contributes to both.
“When we are engaged with our devices, we are often snacking subconsciously and not very mindful that we are making unhealthy choices,” Dr. Gupta said.
The problem is that there is a vicious circle. Compulsive use of devices follows the same loop as other types of addictive behaviors, according to Dr. Gupta. She traced overuse of wireless devices to the dopaminergic system, which is a powerful neuroendocrine-mediated process of craving, response, and reward.
Like fat, sugar, and salt, which provoke a neuroendocrine reward signal, the chimes and buzzes of a cell phone provide their own cues for reward in the form of a dopamine surge. As a result, these become the “triggers of an irresistible and irrational urge to check our device that makes the dopamine go high in our brain,” Dr. Gupta explained.
Although the vicious cycle can be thwarted by turning off the device, Dr. Gupta characterized this as “impractical” when smartphones are so vital to daily communication. Rather, Dr. Gupta advocated a program of moderation, reserving the phone for useful tasks without succumbing to the siren song of apps that waste time.
The most conspicuous culprit is social media, which Dr. Gupta considers to be among the most Pavlovian triggers of cell phone addiction. However, she acknowledged that participation in social media has its justifications.
“I, myself, use social media for my own branding and marketing,” Dr. Gupta said.
The problem that users have is distinguishing between screen time that does and does not have value, according to Dr. Gupta. She indicated that many of those overusing their smart devices are being driven by the dopaminergic reward system, which is generally divorced from the real goals of life, such as personal satisfaction and activity that is rewarding monetarily or in other ways.
“I am not asking for these devices to be thrown out the window. I am advocating for moderation, balance, and real-life engagement,” Dr. Gupta said at the meeting, held in Atlanta and virtually.
She outlined a long list of practical suggestions, including turning off the alarms, chimes, and messages that engage the user into the vicious dopaminergic-reward system loop. She suggested mindfulness so that the user can distinguish between valuable device use and activity that is simply procrastination.
“The devices are designed to be addictive. They are designed to manipulate our brain,” she said. “Eliminate the reward. Let’s try to make our devices boring, unappealing, or enticing so that they only work as tools.”
The medical literature is filled with data that support the potential harms of excessive screen use, leading many others to make some of the same points. In 2017, Thomas N. Robinson, MD, professor of child health at Stanford (Calif.) University, reviewed data showing an association between screen media exposure and obesity in children and adolescents.
“This is an area crying out for more research,” Dr. Robinson said in an interview. The problem of screen time, sedentary behavior, and weight gain has been an issue since the television was invented, which was the point he made in his 2017 paper, but he agreed that the problem is only getting worse.
“Digital technology has become ubiquitous, touching nearly every aspect of people’s lives,” he said. Yet, as evidence grows that overuse of this technology can be harmful, it is creating a problem without a clear solution.
“There are few data about the efficacy of specific strategies to reduce harmful impacts of digital screen use,” he said.
While some of the solutions that Dr. Gupta described make sense, they are more easily described than executed. The dopaminergic reward system is strong and largely experienced subconsciously. Recruiting patients to recognize that dopaminergic rewards are not rewards in any true sense is already a challenge. Enlisting patients to take the difficult steps to avoid the behavioral cues might be even more difficult.
Dr. Gupta and Dr. Robinson report no potential conflicts of interest.
Wireless devices, like smart phones and tablets, appear to induce compulsive or even addictive use in many individuals, leading to adverse health consequences that are likely to be curtailed only through often difficult behavior modification, according to a pediatric endocrinologist’s take on the problem.
While the summary was based in part on the analysis of 234 published papers drawn from the medical literature, the lead author, Nidhi Gupta, MD, said the data reinforce her own clinical experience.
“As a pediatric endocrinologist, the trend in smartphone-associated health disorders, such as obesity, sleep, and behavior issues, worries me,” Dr. Gupta, director of KAP Pediatric Endocrinology, Nashville, Tenn., said at the annual meeting of the Endocrine Society.
Based on her search of the medical literature, the available data raise concern. In one study she cited, for example, each hour per day of screen time was found to translate into a body mass index increase of 0.5 to 0.7 kg/m2 (P < .001).
With this type of progressive rise in BMI comes prediabetes, dyslipidemia, and other metabolic disorders associated with major health risks, including cardiovascular disease. And there are others. Dr. Gupta cited data suggesting screen time before bed disturbs sleep, which has its own set of health risks.
“When I say health, it includes physical health, mental health, and emotional health,” said Dr. Gupta.
In the U.S. and other countries with a growing obesity epidemic, lack of physical activity and unhealthy eating are widely considered the major culprits. Excessive screen time contributes to both.
“When we are engaged with our devices, we are often snacking subconsciously and not very mindful that we are making unhealthy choices,” Dr. Gupta said.
The problem is that there is a vicious circle. Compulsive use of devices follows the same loop as other types of addictive behaviors, according to Dr. Gupta. She traced overuse of wireless devices to the dopaminergic system, which is a powerful neuroendocrine-mediated process of craving, response, and reward.
Like fat, sugar, and salt, which provoke a neuroendocrine reward signal, the chimes and buzzes of a cell phone provide their own cues for reward in the form of a dopamine surge. As a result, these become the “triggers of an irresistible and irrational urge to check our device that makes the dopamine go high in our brain,” Dr. Gupta explained.
Although the vicious cycle can be thwarted by turning off the device, Dr. Gupta characterized this as “impractical” when smartphones are so vital to daily communication. Rather, Dr. Gupta advocated a program of moderation, reserving the phone for useful tasks without succumbing to the siren song of apps that waste time.
The most conspicuous culprit is social media, which Dr. Gupta considers to be among the most Pavlovian triggers of cell phone addiction. However, she acknowledged that participation in social media has its justifications.
“I, myself, use social media for my own branding and marketing,” Dr. Gupta said.
The problem that users have is distinguishing between screen time that does and does not have value, according to Dr. Gupta. She indicated that many of those overusing their smart devices are being driven by the dopaminergic reward system, which is generally divorced from the real goals of life, such as personal satisfaction and activity that is rewarding monetarily or in other ways.
“I am not asking for these devices to be thrown out the window. I am advocating for moderation, balance, and real-life engagement,” Dr. Gupta said at the meeting, held in Atlanta and virtually.
She outlined a long list of practical suggestions, including turning off the alarms, chimes, and messages that engage the user into the vicious dopaminergic-reward system loop. She suggested mindfulness so that the user can distinguish between valuable device use and activity that is simply procrastination.
“The devices are designed to be addictive. They are designed to manipulate our brain,” she said. “Eliminate the reward. Let’s try to make our devices boring, unappealing, or enticing so that they only work as tools.”
The medical literature is filled with data that support the potential harms of excessive screen use, leading many others to make some of the same points. In 2017, Thomas N. Robinson, MD, professor of child health at Stanford (Calif.) University, reviewed data showing an association between screen media exposure and obesity in children and adolescents.
“This is an area crying out for more research,” Dr. Robinson said in an interview. The problem of screen time, sedentary behavior, and weight gain has been an issue since the television was invented, which was the point he made in his 2017 paper, but he agreed that the problem is only getting worse.
“Digital technology has become ubiquitous, touching nearly every aspect of people’s lives,” he said. Yet, as evidence grows that overuse of this technology can be harmful, it is creating a problem without a clear solution.
“There are few data about the efficacy of specific strategies to reduce harmful impacts of digital screen use,” he said.
While some of the solutions that Dr. Gupta described make sense, they are more easily described than executed. The dopaminergic reward system is strong and largely experienced subconsciously. Recruiting patients to recognize that dopaminergic rewards are not rewards in any true sense is already a challenge. Enlisting patients to take the difficult steps to avoid the behavioral cues might be even more difficult.
Dr. Gupta and Dr. Robinson report no potential conflicts of interest.
Wireless devices, like smart phones and tablets, appear to induce compulsive or even addictive use in many individuals, leading to adverse health consequences that are likely to be curtailed only through often difficult behavior modification, according to a pediatric endocrinologist’s take on the problem.
While the summary was based in part on the analysis of 234 published papers drawn from the medical literature, the lead author, Nidhi Gupta, MD, said the data reinforce her own clinical experience.
“As a pediatric endocrinologist, the trend in smartphone-associated health disorders, such as obesity, sleep, and behavior issues, worries me,” Dr. Gupta, director of KAP Pediatric Endocrinology, Nashville, Tenn., said at the annual meeting of the Endocrine Society.
Based on her search of the medical literature, the available data raise concern. In one study she cited, for example, each hour per day of screen time was found to translate into a body mass index increase of 0.5 to 0.7 kg/m2 (P < .001).
With this type of progressive rise in BMI comes prediabetes, dyslipidemia, and other metabolic disorders associated with major health risks, including cardiovascular disease. And there are others. Dr. Gupta cited data suggesting screen time before bed disturbs sleep, which has its own set of health risks.
“When I say health, it includes physical health, mental health, and emotional health,” said Dr. Gupta.
In the U.S. and other countries with a growing obesity epidemic, lack of physical activity and unhealthy eating are widely considered the major culprits. Excessive screen time contributes to both.
“When we are engaged with our devices, we are often snacking subconsciously and not very mindful that we are making unhealthy choices,” Dr. Gupta said.
The problem is that there is a vicious circle. Compulsive use of devices follows the same loop as other types of addictive behaviors, according to Dr. Gupta. She traced overuse of wireless devices to the dopaminergic system, which is a powerful neuroendocrine-mediated process of craving, response, and reward.
Like fat, sugar, and salt, which provoke a neuroendocrine reward signal, the chimes and buzzes of a cell phone provide their own cues for reward in the form of a dopamine surge. As a result, these become the “triggers of an irresistible and irrational urge to check our device that makes the dopamine go high in our brain,” Dr. Gupta explained.
Although the vicious cycle can be thwarted by turning off the device, Dr. Gupta characterized this as “impractical” when smartphones are so vital to daily communication. Rather, Dr. Gupta advocated a program of moderation, reserving the phone for useful tasks without succumbing to the siren song of apps that waste time.
The most conspicuous culprit is social media, which Dr. Gupta considers to be among the most Pavlovian triggers of cell phone addiction. However, she acknowledged that participation in social media has its justifications.
“I, myself, use social media for my own branding and marketing,” Dr. Gupta said.
The problem that users have is distinguishing between screen time that does and does not have value, according to Dr. Gupta. She indicated that many of those overusing their smart devices are being driven by the dopaminergic reward system, which is generally divorced from the real goals of life, such as personal satisfaction and activity that is rewarding monetarily or in other ways.
“I am not asking for these devices to be thrown out the window. I am advocating for moderation, balance, and real-life engagement,” Dr. Gupta said at the meeting, held in Atlanta and virtually.
She outlined a long list of practical suggestions, including turning off the alarms, chimes, and messages that engage the user into the vicious dopaminergic-reward system loop. She suggested mindfulness so that the user can distinguish between valuable device use and activity that is simply procrastination.
“The devices are designed to be addictive. They are designed to manipulate our brain,” she said. “Eliminate the reward. Let’s try to make our devices boring, unappealing, or enticing so that they only work as tools.”
The medical literature is filled with data that support the potential harms of excessive screen use, leading many others to make some of the same points. In 2017, Thomas N. Robinson, MD, professor of child health at Stanford (Calif.) University, reviewed data showing an association between screen media exposure and obesity in children and adolescents.
“This is an area crying out for more research,” Dr. Robinson said in an interview. The problem of screen time, sedentary behavior, and weight gain has been an issue since the television was invented, which was the point he made in his 2017 paper, but he agreed that the problem is only getting worse.
“Digital technology has become ubiquitous, touching nearly every aspect of people’s lives,” he said. Yet, as evidence grows that overuse of this technology can be harmful, it is creating a problem without a clear solution.
“There are few data about the efficacy of specific strategies to reduce harmful impacts of digital screen use,” he said.
While some of the solutions that Dr. Gupta described make sense, they are more easily described than executed. The dopaminergic reward system is strong and largely experienced subconsciously. Recruiting patients to recognize that dopaminergic rewards are not rewards in any true sense is already a challenge. Enlisting patients to take the difficult steps to avoid the behavioral cues might be even more difficult.
Dr. Gupta and Dr. Robinson report no potential conflicts of interest.
FROM ENDO 2022
Food insecurity drives poor glycemic control
People with diabetes who had a poor-quality diet and food insecurity were significantly more likely to have poor glycemic and cholesterol control than were those with a healthier diet and food security, based on data from a national study of more than 2,000 individuals.
The American Diabetes Association recommends a high-quality diet for people with diabetes (PWD) to achieve treatment goals; however, roughly 18% of PWD in the United States are food insecure and/or have a poor-quality diet, Sarah S. Casagrande, PhD, of DLH Corporation, Silver Spring, Md., and colleagues wrote in a poster presented at the annual scientific sessions of the ADA in New Orleans.
To examine the impact of food insecurity and diet quality on diabetes and lipid management, the researchers reviewed data from 2,075 adults with self-reported diabetes who completed the National Health and Nutrition Examination Surveys between 2013 and 2018.
Diet quality was divided into quartiles based on the 2015 Healthy Eating Index. Food insecurity was assessed using a standard 10-item questionnaire including questions about running out of food and not being able to afford more, reducing meal sizes, eating less or not at all, and going hungry because of lack of money for food.
The logistic regression analysis controlled for factors including sociodemographics, health care use, smoking, diabetes medications, blood pressure medication use, cholesterol medication use, and body mass index.
Overall, 17.6% of the participants were food insecure and had a low-quality diet, 14.2% were food insecure with a high-quality diet, 33.1% were food secure with a low-quality diet, and 35.2% were food secure with a high-quality diet.
PWD in the food insecure/low-quality diet group were significantly more likely to be younger, non-Hispanic black or Hispanic, and uninsured compared to those in the food secure/high-quality diet group (P < .001 for all).
When the researchers examined glycemic control, they found that PWD in the food insecurity/low-quality diet groups were significantly more likely than were those with food security/high-quality diets to have hemoglobin A1c of at least 7.0% (adjusted odds ratio, 1.85), A1c of at least 8.0% (aOR, 1.79), low HDL cholesterol (aOR, 1.69), and high triglycerides (aOR, 3.26).
PWD with food insecurity but a high-quality diet also were significantly more likely than were those with food security and a high quality diet to have A1c of at least 7.0% (aOR, 1.69), A1c of at least 8.0% (aOR, 1.83), and high triglycerides (aOR, 2.44). PWD with food security but a low-quality diet were significantly more likely than was the food security/high-quality diet group to have A1c of at least 7% (aOR, 1.55).
The study findings were limited by several factors including the cross-sectional design, reliance on self-reports, and inability to distinguish between type 1 and type 2 diabetes, the researchers wrote.
However, the results were strengthened by the large, nationally representative sample and the inclusion of multiple clinical outcomes in the patient assessment, they said.
The results suggest that food insecurity had a significant impact on both glycemic control and cholesterol management independent of diet quality, the researchers noted. Based on these findings, health care providers treating PWD may wish to assess their patients’ food security status, and “interventions could address disparities in food security,” they concluded.
Food insecurity a growing problem
“With more communities being pushed into state of war, drought, and famine globally, it is important to track impact of food insecurity and low quality food on common medical conditions like diabetes in our vulnerable communities,” Romesh K. Khardori, MD, professor of medicine: endocrinology, and metabolism at Eastern Virginia Medical School, Norfolk, said in an interview.
Dr. Khardori, who was not involved in the study, said he was not surprised by the current study findings.
“Type of food, amount of food, and quality of food have been stressed in diabetes management for more than 100 years,” he said. “Organizations charged with recommendations, such as the ADA and American Dietetic Association, have regularly updated their recommendations,” he noted. “It was not surprising, therefore, to find food insecurity and low quality tied to poor glycemic control.”
The take-home message for clinicians is to consider the availability and quality of food that their patients are exposed to when evaluating barriers to proper glycemic control, Dr. Khardori emphasized.
However, additional research is needed to explore whether the prescription of a sufficient amount of good quality food would alleviate the adverse impact seen in the current study, he said.
The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. The researchers and Dr. Khardori had no financial conflicts to disclose.
People with diabetes who had a poor-quality diet and food insecurity were significantly more likely to have poor glycemic and cholesterol control than were those with a healthier diet and food security, based on data from a national study of more than 2,000 individuals.
The American Diabetes Association recommends a high-quality diet for people with diabetes (PWD) to achieve treatment goals; however, roughly 18% of PWD in the United States are food insecure and/or have a poor-quality diet, Sarah S. Casagrande, PhD, of DLH Corporation, Silver Spring, Md., and colleagues wrote in a poster presented at the annual scientific sessions of the ADA in New Orleans.
To examine the impact of food insecurity and diet quality on diabetes and lipid management, the researchers reviewed data from 2,075 adults with self-reported diabetes who completed the National Health and Nutrition Examination Surveys between 2013 and 2018.
Diet quality was divided into quartiles based on the 2015 Healthy Eating Index. Food insecurity was assessed using a standard 10-item questionnaire including questions about running out of food and not being able to afford more, reducing meal sizes, eating less or not at all, and going hungry because of lack of money for food.
The logistic regression analysis controlled for factors including sociodemographics, health care use, smoking, diabetes medications, blood pressure medication use, cholesterol medication use, and body mass index.
Overall, 17.6% of the participants were food insecure and had a low-quality diet, 14.2% were food insecure with a high-quality diet, 33.1% were food secure with a low-quality diet, and 35.2% were food secure with a high-quality diet.
PWD in the food insecure/low-quality diet group were significantly more likely to be younger, non-Hispanic black or Hispanic, and uninsured compared to those in the food secure/high-quality diet group (P < .001 for all).
When the researchers examined glycemic control, they found that PWD in the food insecurity/low-quality diet groups were significantly more likely than were those with food security/high-quality diets to have hemoglobin A1c of at least 7.0% (adjusted odds ratio, 1.85), A1c of at least 8.0% (aOR, 1.79), low HDL cholesterol (aOR, 1.69), and high triglycerides (aOR, 3.26).
PWD with food insecurity but a high-quality diet also were significantly more likely than were those with food security and a high quality diet to have A1c of at least 7.0% (aOR, 1.69), A1c of at least 8.0% (aOR, 1.83), and high triglycerides (aOR, 2.44). PWD with food security but a low-quality diet were significantly more likely than was the food security/high-quality diet group to have A1c of at least 7% (aOR, 1.55).
The study findings were limited by several factors including the cross-sectional design, reliance on self-reports, and inability to distinguish between type 1 and type 2 diabetes, the researchers wrote.
However, the results were strengthened by the large, nationally representative sample and the inclusion of multiple clinical outcomes in the patient assessment, they said.
The results suggest that food insecurity had a significant impact on both glycemic control and cholesterol management independent of diet quality, the researchers noted. Based on these findings, health care providers treating PWD may wish to assess their patients’ food security status, and “interventions could address disparities in food security,” they concluded.
Food insecurity a growing problem
“With more communities being pushed into state of war, drought, and famine globally, it is important to track impact of food insecurity and low quality food on common medical conditions like diabetes in our vulnerable communities,” Romesh K. Khardori, MD, professor of medicine: endocrinology, and metabolism at Eastern Virginia Medical School, Norfolk, said in an interview.
Dr. Khardori, who was not involved in the study, said he was not surprised by the current study findings.
“Type of food, amount of food, and quality of food have been stressed in diabetes management for more than 100 years,” he said. “Organizations charged with recommendations, such as the ADA and American Dietetic Association, have regularly updated their recommendations,” he noted. “It was not surprising, therefore, to find food insecurity and low quality tied to poor glycemic control.”
The take-home message for clinicians is to consider the availability and quality of food that their patients are exposed to when evaluating barriers to proper glycemic control, Dr. Khardori emphasized.
However, additional research is needed to explore whether the prescription of a sufficient amount of good quality food would alleviate the adverse impact seen in the current study, he said.
The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. The researchers and Dr. Khardori had no financial conflicts to disclose.
People with diabetes who had a poor-quality diet and food insecurity were significantly more likely to have poor glycemic and cholesterol control than were those with a healthier diet and food security, based on data from a national study of more than 2,000 individuals.
The American Diabetes Association recommends a high-quality diet for people with diabetes (PWD) to achieve treatment goals; however, roughly 18% of PWD in the United States are food insecure and/or have a poor-quality diet, Sarah S. Casagrande, PhD, of DLH Corporation, Silver Spring, Md., and colleagues wrote in a poster presented at the annual scientific sessions of the ADA in New Orleans.
To examine the impact of food insecurity and diet quality on diabetes and lipid management, the researchers reviewed data from 2,075 adults with self-reported diabetes who completed the National Health and Nutrition Examination Surveys between 2013 and 2018.
Diet quality was divided into quartiles based on the 2015 Healthy Eating Index. Food insecurity was assessed using a standard 10-item questionnaire including questions about running out of food and not being able to afford more, reducing meal sizes, eating less or not at all, and going hungry because of lack of money for food.
The logistic regression analysis controlled for factors including sociodemographics, health care use, smoking, diabetes medications, blood pressure medication use, cholesterol medication use, and body mass index.
Overall, 17.6% of the participants were food insecure and had a low-quality diet, 14.2% were food insecure with a high-quality diet, 33.1% were food secure with a low-quality diet, and 35.2% were food secure with a high-quality diet.
PWD in the food insecure/low-quality diet group were significantly more likely to be younger, non-Hispanic black or Hispanic, and uninsured compared to those in the food secure/high-quality diet group (P < .001 for all).
When the researchers examined glycemic control, they found that PWD in the food insecurity/low-quality diet groups were significantly more likely than were those with food security/high-quality diets to have hemoglobin A1c of at least 7.0% (adjusted odds ratio, 1.85), A1c of at least 8.0% (aOR, 1.79), low HDL cholesterol (aOR, 1.69), and high triglycerides (aOR, 3.26).
PWD with food insecurity but a high-quality diet also were significantly more likely than were those with food security and a high quality diet to have A1c of at least 7.0% (aOR, 1.69), A1c of at least 8.0% (aOR, 1.83), and high triglycerides (aOR, 2.44). PWD with food security but a low-quality diet were significantly more likely than was the food security/high-quality diet group to have A1c of at least 7% (aOR, 1.55).
The study findings were limited by several factors including the cross-sectional design, reliance on self-reports, and inability to distinguish between type 1 and type 2 diabetes, the researchers wrote.
However, the results were strengthened by the large, nationally representative sample and the inclusion of multiple clinical outcomes in the patient assessment, they said.
The results suggest that food insecurity had a significant impact on both glycemic control and cholesterol management independent of diet quality, the researchers noted. Based on these findings, health care providers treating PWD may wish to assess their patients’ food security status, and “interventions could address disparities in food security,” they concluded.
Food insecurity a growing problem
“With more communities being pushed into state of war, drought, and famine globally, it is important to track impact of food insecurity and low quality food on common medical conditions like diabetes in our vulnerable communities,” Romesh K. Khardori, MD, professor of medicine: endocrinology, and metabolism at Eastern Virginia Medical School, Norfolk, said in an interview.
Dr. Khardori, who was not involved in the study, said he was not surprised by the current study findings.
“Type of food, amount of food, and quality of food have been stressed in diabetes management for more than 100 years,” he said. “Organizations charged with recommendations, such as the ADA and American Dietetic Association, have regularly updated their recommendations,” he noted. “It was not surprising, therefore, to find food insecurity and low quality tied to poor glycemic control.”
The take-home message for clinicians is to consider the availability and quality of food that their patients are exposed to when evaluating barriers to proper glycemic control, Dr. Khardori emphasized.
However, additional research is needed to explore whether the prescription of a sufficient amount of good quality food would alleviate the adverse impact seen in the current study, he said.
The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. The researchers and Dr. Khardori had no financial conflicts to disclose.
FROM ADA 2022
ACC/AHA issue clinical lexicon for complications of COVID-19
The American College of Cardiology and the American Heart Association have jointly issued a comprehensive set of data standards to help clarify definitions of the cardiovascular (CV) and non-CV complications of COVID-19.
It’s the work of the ACC/AHA Task Force on Clinical Data Standards and has been endorsed by the Heart Failure Society of America and Society for Cardiac Angiography and Interventions.
There is increased importance to understanding the acute and long-term impact of COVID-19 on CV health, the writing group notes. Until now, however, there has not been “clarity or consensus” on definitions of CV conditions related to COVID-19, with different diagnostic terminologies being used for overlapping conditions, such as “myocardial injury,” “myocarditis,” “type Il myocardial infarction,” “stress cardiomyopathy,” and “inflammatory cardiomyopathy,” they point out.
“We, as a research community, did some things right and some things wrong surrounding the COVID pandemic,” Sandeep Das, MD, MPH, vice chair of the writing group, noted in an interview with this news organization.
“The things that we really did right is that everybody responded with enthusiasm, kind of all hands on deck with a massive crisis response, and that was fantastic,” Dr. Das said.
“However, because of the need to hurry, we didn’t structure and organize in the way that we typically would for something that was sort of a slow burn kind of problem rather than an emergency. One of the consequences of that was fragmentation of how things are collected, reported, et cetera, and that leads to confusion,” he added.
The report was published simultaneously June 23 in the Journal of the American College of Cardiology and Circulation: Cardiovascular Quality and Outcomes.
A necessary but not glamorous project
The new data standards for COVID-19 will help standardize definitions and set the framework to capture and better understand how COVID-19 affects CV health.
“It wasn’t exactly a glamorous-type project but, at the same time, it’s super necessary to kind of get everybody on the same page and working together,” Dr. Das said.
Broad agreement on common vocabulary and definitions will help with efforts to pool or compare data from electronic health records, clinical registries, administrative datasets, and other databases, and determine whether these data apply to clinical practice and research endeavors, the writing group says.
They considered data elements relevant to the full range of care provided to COVID-19 patients in all care settings. Among the key items included in the document are:
- Case definitions for confirmed, probable, and suspected acute COVID-19, as well as postacute sequelae of COVID-19.
- Definitions for acute CV complications related to COVID-19, including acute myocardial injury, heart failure, shock, arrhythmia, thromboembolic complications, and .
- Data elements related to COVID-19 vaccination status, comorbidities, and preexisting CV conditions.
- Definitions for postacute CV sequelae of SARS-CoV-2 infection and long-term CV complications of COVID-19.
- Data elements for CV mortality during acute COVID-19.
- Data elements for non-CV complications to help document severity of illness and other competing diagnoses and complications that might affect CV outcomes.
- A list of symptoms and signs related to COVID-19 and CV complications.
- Data elements for diagnostic and therapeutic strategies for COVID-19 and CV conditions.
- A discussion of advanced therapies, including , extracorporeal membrane oxygenation, and end-of-life management strategies.
These data standards will be useful for researchers, registry developers, and clinicians, and they are proposed as a framework for ICD-10 code development of COVID-19–related CV conditions, the writing group says.
The standards are also of “great importance” to patients, clinicians, investigators, scientists, administrators, public health officials, policymakers, and payers, the group says.
Dr. Das said that, although there is no formal plan in place to update the document, he could see sections that might be refined.
“For example, there’s a nice long list of all the various variants, and unfortunately, I suspect that that is going to change and evolve over time,” Dr. Das told this news organization.
“We tried very hard not to include things like specifying specific treatments so we didn’t get proscriptive. We wanted to make it descriptive, so hopefully it will stand the test of time pretty well,” he added.
This research had no commercial funding. The writing group has no relevant disclosures.
A version of this article first appeared on Medscape.com.
The American College of Cardiology and the American Heart Association have jointly issued a comprehensive set of data standards to help clarify definitions of the cardiovascular (CV) and non-CV complications of COVID-19.
It’s the work of the ACC/AHA Task Force on Clinical Data Standards and has been endorsed by the Heart Failure Society of America and Society for Cardiac Angiography and Interventions.
There is increased importance to understanding the acute and long-term impact of COVID-19 on CV health, the writing group notes. Until now, however, there has not been “clarity or consensus” on definitions of CV conditions related to COVID-19, with different diagnostic terminologies being used for overlapping conditions, such as “myocardial injury,” “myocarditis,” “type Il myocardial infarction,” “stress cardiomyopathy,” and “inflammatory cardiomyopathy,” they point out.
“We, as a research community, did some things right and some things wrong surrounding the COVID pandemic,” Sandeep Das, MD, MPH, vice chair of the writing group, noted in an interview with this news organization.
“The things that we really did right is that everybody responded with enthusiasm, kind of all hands on deck with a massive crisis response, and that was fantastic,” Dr. Das said.
“However, because of the need to hurry, we didn’t structure and organize in the way that we typically would for something that was sort of a slow burn kind of problem rather than an emergency. One of the consequences of that was fragmentation of how things are collected, reported, et cetera, and that leads to confusion,” he added.
The report was published simultaneously June 23 in the Journal of the American College of Cardiology and Circulation: Cardiovascular Quality and Outcomes.
A necessary but not glamorous project
The new data standards for COVID-19 will help standardize definitions and set the framework to capture and better understand how COVID-19 affects CV health.
“It wasn’t exactly a glamorous-type project but, at the same time, it’s super necessary to kind of get everybody on the same page and working together,” Dr. Das said.
Broad agreement on common vocabulary and definitions will help with efforts to pool or compare data from electronic health records, clinical registries, administrative datasets, and other databases, and determine whether these data apply to clinical practice and research endeavors, the writing group says.
They considered data elements relevant to the full range of care provided to COVID-19 patients in all care settings. Among the key items included in the document are:
- Case definitions for confirmed, probable, and suspected acute COVID-19, as well as postacute sequelae of COVID-19.
- Definitions for acute CV complications related to COVID-19, including acute myocardial injury, heart failure, shock, arrhythmia, thromboembolic complications, and .
- Data elements related to COVID-19 vaccination status, comorbidities, and preexisting CV conditions.
- Definitions for postacute CV sequelae of SARS-CoV-2 infection and long-term CV complications of COVID-19.
- Data elements for CV mortality during acute COVID-19.
- Data elements for non-CV complications to help document severity of illness and other competing diagnoses and complications that might affect CV outcomes.
- A list of symptoms and signs related to COVID-19 and CV complications.
- Data elements for diagnostic and therapeutic strategies for COVID-19 and CV conditions.
- A discussion of advanced therapies, including , extracorporeal membrane oxygenation, and end-of-life management strategies.
These data standards will be useful for researchers, registry developers, and clinicians, and they are proposed as a framework for ICD-10 code development of COVID-19–related CV conditions, the writing group says.
The standards are also of “great importance” to patients, clinicians, investigators, scientists, administrators, public health officials, policymakers, and payers, the group says.
Dr. Das said that, although there is no formal plan in place to update the document, he could see sections that might be refined.
“For example, there’s a nice long list of all the various variants, and unfortunately, I suspect that that is going to change and evolve over time,” Dr. Das told this news organization.
“We tried very hard not to include things like specifying specific treatments so we didn’t get proscriptive. We wanted to make it descriptive, so hopefully it will stand the test of time pretty well,” he added.
This research had no commercial funding. The writing group has no relevant disclosures.
A version of this article first appeared on Medscape.com.
The American College of Cardiology and the American Heart Association have jointly issued a comprehensive set of data standards to help clarify definitions of the cardiovascular (CV) and non-CV complications of COVID-19.
It’s the work of the ACC/AHA Task Force on Clinical Data Standards and has been endorsed by the Heart Failure Society of America and Society for Cardiac Angiography and Interventions.
There is increased importance to understanding the acute and long-term impact of COVID-19 on CV health, the writing group notes. Until now, however, there has not been “clarity or consensus” on definitions of CV conditions related to COVID-19, with different diagnostic terminologies being used for overlapping conditions, such as “myocardial injury,” “myocarditis,” “type Il myocardial infarction,” “stress cardiomyopathy,” and “inflammatory cardiomyopathy,” they point out.
“We, as a research community, did some things right and some things wrong surrounding the COVID pandemic,” Sandeep Das, MD, MPH, vice chair of the writing group, noted in an interview with this news organization.
“The things that we really did right is that everybody responded with enthusiasm, kind of all hands on deck with a massive crisis response, and that was fantastic,” Dr. Das said.
“However, because of the need to hurry, we didn’t structure and organize in the way that we typically would for something that was sort of a slow burn kind of problem rather than an emergency. One of the consequences of that was fragmentation of how things are collected, reported, et cetera, and that leads to confusion,” he added.
The report was published simultaneously June 23 in the Journal of the American College of Cardiology and Circulation: Cardiovascular Quality and Outcomes.
A necessary but not glamorous project
The new data standards for COVID-19 will help standardize definitions and set the framework to capture and better understand how COVID-19 affects CV health.
“It wasn’t exactly a glamorous-type project but, at the same time, it’s super necessary to kind of get everybody on the same page and working together,” Dr. Das said.
Broad agreement on common vocabulary and definitions will help with efforts to pool or compare data from electronic health records, clinical registries, administrative datasets, and other databases, and determine whether these data apply to clinical practice and research endeavors, the writing group says.
They considered data elements relevant to the full range of care provided to COVID-19 patients in all care settings. Among the key items included in the document are:
- Case definitions for confirmed, probable, and suspected acute COVID-19, as well as postacute sequelae of COVID-19.
- Definitions for acute CV complications related to COVID-19, including acute myocardial injury, heart failure, shock, arrhythmia, thromboembolic complications, and .
- Data elements related to COVID-19 vaccination status, comorbidities, and preexisting CV conditions.
- Definitions for postacute CV sequelae of SARS-CoV-2 infection and long-term CV complications of COVID-19.
- Data elements for CV mortality during acute COVID-19.
- Data elements for non-CV complications to help document severity of illness and other competing diagnoses and complications that might affect CV outcomes.
- A list of symptoms and signs related to COVID-19 and CV complications.
- Data elements for diagnostic and therapeutic strategies for COVID-19 and CV conditions.
- A discussion of advanced therapies, including , extracorporeal membrane oxygenation, and end-of-life management strategies.
These data standards will be useful for researchers, registry developers, and clinicians, and they are proposed as a framework for ICD-10 code development of COVID-19–related CV conditions, the writing group says.
The standards are also of “great importance” to patients, clinicians, investigators, scientists, administrators, public health officials, policymakers, and payers, the group says.
Dr. Das said that, although there is no formal plan in place to update the document, he could see sections that might be refined.
“For example, there’s a nice long list of all the various variants, and unfortunately, I suspect that that is going to change and evolve over time,” Dr. Das told this news organization.
“We tried very hard not to include things like specifying specific treatments so we didn’t get proscriptive. We wanted to make it descriptive, so hopefully it will stand the test of time pretty well,” he added.
This research had no commercial funding. The writing group has no relevant disclosures.
A version of this article first appeared on Medscape.com.
Highlights in Early Breast Cancer From the 2022 American Society of Clinical Oncology Annual Meeting
Dr Ann Partridge from the Dana-Farber Cancer Institute in Boston, Massachusetts, highlights important new data in early breast cancer presented at American Society of Clinical Oncology (ASCO) 2022.
Dr Partridge begins with promising results from the NeoSTAR study, which looked at the use of the novel antibody-drug conjugate (ADC) sacituzumab govitecan in the neoadjuvant setting. This is the first trial of an ADC in patients with triple-negative breast cancer (TNBC) and demonstrated single-agent efficacy in localized TNBC.
Next, Dr Partridge discusses the 8-year post-trial follow-up of the ASTRRA study, which randomly assigned patients to 5 years of tamoxifen or 5 years of tamoxifen plus 2 years of ovarian suppression. The findings demonstrated consistent survival advantage and suggest that adding ovarian function suppression to tamoxifen should be considered for those who remain in a premenopausal state or resume ovarian function after chemotherapy.
Looking to potential new biomarkers for risk recurrence, Dr Partridge reports on provocative data from the CHiRP study. The investigators looked at the use of circulating tumor DNA to identify minimal residual disease and predict clinical outcomes in high-risk, early-stage HR+ breast cancer. Although additional research is needed, Dr Partridge is encouraged that in the near future, the use of circulating DNA technology will help guide therapeutic decisions in early breast cancer.
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Ann H. Partridge, MD, MPH, Professor of Medicine; Vice Chair of Medical Oncology, Department of Breast Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts
Ann H. Partridge, MD, MPH, has disclosed no relevant financial relationships.
Dr Ann Partridge from the Dana-Farber Cancer Institute in Boston, Massachusetts, highlights important new data in early breast cancer presented at American Society of Clinical Oncology (ASCO) 2022.
Dr Partridge begins with promising results from the NeoSTAR study, which looked at the use of the novel antibody-drug conjugate (ADC) sacituzumab govitecan in the neoadjuvant setting. This is the first trial of an ADC in patients with triple-negative breast cancer (TNBC) and demonstrated single-agent efficacy in localized TNBC.
Next, Dr Partridge discusses the 8-year post-trial follow-up of the ASTRRA study, which randomly assigned patients to 5 years of tamoxifen or 5 years of tamoxifen plus 2 years of ovarian suppression. The findings demonstrated consistent survival advantage and suggest that adding ovarian function suppression to tamoxifen should be considered for those who remain in a premenopausal state or resume ovarian function after chemotherapy.
Looking to potential new biomarkers for risk recurrence, Dr Partridge reports on provocative data from the CHiRP study. The investigators looked at the use of circulating tumor DNA to identify minimal residual disease and predict clinical outcomes in high-risk, early-stage HR+ breast cancer. Although additional research is needed, Dr Partridge is encouraged that in the near future, the use of circulating DNA technology will help guide therapeutic decisions in early breast cancer.
--
Ann H. Partridge, MD, MPH, Professor of Medicine; Vice Chair of Medical Oncology, Department of Breast Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts
Ann H. Partridge, MD, MPH, has disclosed no relevant financial relationships.
Dr Ann Partridge from the Dana-Farber Cancer Institute in Boston, Massachusetts, highlights important new data in early breast cancer presented at American Society of Clinical Oncology (ASCO) 2022.
Dr Partridge begins with promising results from the NeoSTAR study, which looked at the use of the novel antibody-drug conjugate (ADC) sacituzumab govitecan in the neoadjuvant setting. This is the first trial of an ADC in patients with triple-negative breast cancer (TNBC) and demonstrated single-agent efficacy in localized TNBC.
Next, Dr Partridge discusses the 8-year post-trial follow-up of the ASTRRA study, which randomly assigned patients to 5 years of tamoxifen or 5 years of tamoxifen plus 2 years of ovarian suppression. The findings demonstrated consistent survival advantage and suggest that adding ovarian function suppression to tamoxifen should be considered for those who remain in a premenopausal state or resume ovarian function after chemotherapy.
Looking to potential new biomarkers for risk recurrence, Dr Partridge reports on provocative data from the CHiRP study. The investigators looked at the use of circulating tumor DNA to identify minimal residual disease and predict clinical outcomes in high-risk, early-stage HR+ breast cancer. Although additional research is needed, Dr Partridge is encouraged that in the near future, the use of circulating DNA technology will help guide therapeutic decisions in early breast cancer.
--
Ann H. Partridge, MD, MPH, Professor of Medicine; Vice Chair of Medical Oncology, Department of Breast Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts
Ann H. Partridge, MD, MPH, has disclosed no relevant financial relationships.
Key Abstracts in Metastatic Breast Cancer From the 2022 American Society of Clinical Oncology Annual Meeting
Dr Harold J. Burstein, from the Dana-Farber Cancer Institute in Boston, Massachusetts, reports on important abstracts in the management of metastatic breast cancer from the 2022 American Society of Clinical Oncology (ASCO) annual meeting.
Dr Burstein first highlights results from the NRG-BR002 trial, a randomized phase 2 study comparing standard therapy vs standard therapy in combination with focal stereotactic radiation treatment for oligometastatic disease in up to four sites. Investigators reported no impact on progression-free or overall survival.
Exciting results from the DESTINY-Breast04 trial were a "showstopper," according to Dr Burstein. Investigators reported prolonged progression-free survival and overall survival in patients with HER2-low unresectable and/or metastatic disease with the use of the antibody-drug conjugate trastuzumab deruxtecan compared with physicians' choice of standard single-agent chemotherapy, advancing a new treatment option for the large subset of patients with HER2-low disease.
Next, Dr Burstein discusses results from the TROPiCS-02 trial, which compared another antibody-drug conjugate, sacituzumab govitecan, with standard chemotherapy in patients with ER+/HER- breast cancer. A statistically significant benefit was reported, although the progression-free survival at just 6 weeks was relatively modest.
Finally, Dr Burstein reports on interesting data from the MAINTAIN study, a phase 2 randomized trial looking at maintenance CDK4/6 inhibition after progression on initial treatment. Results suggest that switching endocrine therapy and continuing treatment with CDK4/6 inhibitor ribociclib beyond progression may be of clinical value to patients.
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Harold J. Burstein, MD, PhD, Professor, Department of Medicine, Harvard Medical School; Medical Oncologist, Dana-Farber Cancer Institute, Brigham & Women's Hospital, Boston, Massachusetts
Harold J. Burstein, MD, PhD, has disclosed no relevant financial relationships.
Dr Harold J. Burstein, from the Dana-Farber Cancer Institute in Boston, Massachusetts, reports on important abstracts in the management of metastatic breast cancer from the 2022 American Society of Clinical Oncology (ASCO) annual meeting.
Dr Burstein first highlights results from the NRG-BR002 trial, a randomized phase 2 study comparing standard therapy vs standard therapy in combination with focal stereotactic radiation treatment for oligometastatic disease in up to four sites. Investigators reported no impact on progression-free or overall survival.
Exciting results from the DESTINY-Breast04 trial were a "showstopper," according to Dr Burstein. Investigators reported prolonged progression-free survival and overall survival in patients with HER2-low unresectable and/or metastatic disease with the use of the antibody-drug conjugate trastuzumab deruxtecan compared with physicians' choice of standard single-agent chemotherapy, advancing a new treatment option for the large subset of patients with HER2-low disease.
Next, Dr Burstein discusses results from the TROPiCS-02 trial, which compared another antibody-drug conjugate, sacituzumab govitecan, with standard chemotherapy in patients with ER+/HER- breast cancer. A statistically significant benefit was reported, although the progression-free survival at just 6 weeks was relatively modest.
Finally, Dr Burstein reports on interesting data from the MAINTAIN study, a phase 2 randomized trial looking at maintenance CDK4/6 inhibition after progression on initial treatment. Results suggest that switching endocrine therapy and continuing treatment with CDK4/6 inhibitor ribociclib beyond progression may be of clinical value to patients.
--
Harold J. Burstein, MD, PhD, Professor, Department of Medicine, Harvard Medical School; Medical Oncologist, Dana-Farber Cancer Institute, Brigham & Women's Hospital, Boston, Massachusetts
Harold J. Burstein, MD, PhD, has disclosed no relevant financial relationships.
Dr Harold J. Burstein, from the Dana-Farber Cancer Institute in Boston, Massachusetts, reports on important abstracts in the management of metastatic breast cancer from the 2022 American Society of Clinical Oncology (ASCO) annual meeting.
Dr Burstein first highlights results from the NRG-BR002 trial, a randomized phase 2 study comparing standard therapy vs standard therapy in combination with focal stereotactic radiation treatment for oligometastatic disease in up to four sites. Investigators reported no impact on progression-free or overall survival.
Exciting results from the DESTINY-Breast04 trial were a "showstopper," according to Dr Burstein. Investigators reported prolonged progression-free survival and overall survival in patients with HER2-low unresectable and/or metastatic disease with the use of the antibody-drug conjugate trastuzumab deruxtecan compared with physicians' choice of standard single-agent chemotherapy, advancing a new treatment option for the large subset of patients with HER2-low disease.
Next, Dr Burstein discusses results from the TROPiCS-02 trial, which compared another antibody-drug conjugate, sacituzumab govitecan, with standard chemotherapy in patients with ER+/HER- breast cancer. A statistically significant benefit was reported, although the progression-free survival at just 6 weeks was relatively modest.
Finally, Dr Burstein reports on interesting data from the MAINTAIN study, a phase 2 randomized trial looking at maintenance CDK4/6 inhibition after progression on initial treatment. Results suggest that switching endocrine therapy and continuing treatment with CDK4/6 inhibitor ribociclib beyond progression may be of clinical value to patients.
--
Harold J. Burstein, MD, PhD, Professor, Department of Medicine, Harvard Medical School; Medical Oncologist, Dana-Farber Cancer Institute, Brigham & Women's Hospital, Boston, Massachusetts
Harold J. Burstein, MD, PhD, has disclosed no relevant financial relationships.
