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Mitchel is a reporter for MDedge based in the Philadelphia area. He started with the company in 1992, when it was International Medical News Group (IMNG), and has since covered a range of medical specialties. Mitchel trained as a virologist at Roswell Park Memorial Institute in Buffalo, and then worked briefly as a researcher at Boston Children's Hospital before pivoting to journalism as a AAAS Mass Media Fellow in 1980. His first reporting job was with Science Digest magazine, and from the mid-1980s to early-1990s he was a reporter with Medical World News. @mitchelzoler
Risk score predicts rehospitalization after heart surgery
PHOENIX – A simple, five-element formula can help identify the patients undergoing heart surgery who face the greatest risk for a hospital readmission within 30 days following discharge from their index hospitalization.
The surgeons who developed this formula hope to use it in an investigational program that will target intensified management resources in postsurgical patients who face the highest readmission risk, to cut rehospitalizations and better improve their clinical status and quality of life.
The analysis that produced this formula also documented that the worst offender for triggering rehospitalizations following heart surgery is fluid overload, the proximate readmission cause for 23% of postsurgical patients, Dr. Arman Kilic said at the annual meeting of the Society of Thoracic Surgeons. The next most common cause was infection, which led to 20% of readmissions, followed by arrhythmias, responsible for 8% of readmissions, said Dr. Kilic, a thoracic surgeon at the University of Pennsylvania in Philadelphia.
Because fluid overload, often in the form of pleural effusion, is such an important driver of rehospitalizations, a more targeted management program would include better titration of diuretic treatment to patients following heart surgery, thoracentesis, and closer monitoring of clinical features that flag fluid overload such as weight.
“The volume overload issue is where the money is. If we can reduce that, it could really impact readmissions,” Dr. Kilic said in an interview.
An investigational program to target rehospitalization risk in heart surgery patients is planned at Johns Hopkins Hospital in Baltimore, where Dr. Kilic worked when he performed this analysis. Surgeons at Johns Hopkins are now in the process of getting funding for this pilot program, said Dr. John V. Conte Jr., professor of surgery and director of mechanical circulatory support at Johns Hopkins and a collaborator with Dr. Kilic on developing the risk formula.
“We’ll tailor postoperative follow-up. We’ll get high-risk patients back to the clinic sooner, and we’ll send nurse practitioners to see them to make sure they’re taking their medications and are getting weighed daily,” Dr. Conte said in an interview. “When a patient has heart surgery, they typically retain about 5-10 pounds of fluid. Patients with good renal function give up that fluid easily, but others are difficult to diurese. Many patients go home before they have been fully diuresed, and we need to follow these patients and transition them better to out-of-hospital care.”
He noted that other situations also come up that unnecessarily drive patients back to the hospital when an alternative and less expensive intervention might be equally effective. For example, some patients return to the hospital out of concern for how their chest wound is healing. Instead of being rehospitalized, such patients could be reassured by having them send a nurse a photo of their wound or by coming to an outpatient clinic.
“We need to engage more often with recently discharged patients,” Dr. Conte said in an interview. “Discharging them doesn’t mean separating them from the health care system; it should mean interacting with patients in a different way” that produces better outcomes and patient satisfaction for less money. Developing improved ways to manage recent heart surgery patients following discharge becomes even more critical later this year when, in July, the Centers for Medicare & Medicaid Services adds 30-day readmissions following coronary artery bypass grafting (CABG) to its list of procedures that can generate a penalty to hospitals if they exceed U.S. norms for readmission rates.
The risk model developed by Dr. Kilic, Dr. Conte, and their associates used data collected from 5,360 heart surgery patients treated at Johns Hopkins during 2008-2013. Nearly half the patients underwent isolated CABG, and 20% had isolated valve surgery. Overall, 585 patients (11%) had a hospital readmission within 30 days of their index discharge. One limitation of the analysis was it used data only on readmissions back to Johns Hopkins Hospital.
The researchers used data from three-quarters of the database to derive the risk formula, and from the remaining 25% of the database to validate the formula. A multivariate analysis of demographic and clinical characteristics that significantly linked with an elevated risk for readmissions identified five factors that independently made a significant contribution to readmission risk. The researchers assigned each of these five factors points depending on its relative contribution to readmission risk in the adjusted model: Severe chronic lung disease received 6 points; placement of a ventricular assist device received 5 points, while other types of heart surgery that was not CABG or valve surgery received 4 points (isolated CABG, isolated valve, or combined CABG and valve surgery received 0 points); development of acute renal failure postoperatively but before index discharge received 4 points; an index length of stay beyond 7 days received 4 points; and African American race received 3 points. The maximum number of points a patient could receive was 22.
Patients with a score of 0 had a 6% rate of a 30-day readmission; those with a score of 22 had a 63% readmission rate. For simplicity, Dr. Kilic suggested dividing patients into three categories based on their readmission risk score: Low-risk patients with a score of 0 had a readmission risk of 6%, medium-risk patients with a score of 1-10 had a readmission risk of 12%, and high-risk patients with a score of 11 or more had a readmission risk of 31%. The researchers found a 96% correlation when comparing these predicted readmission risk rates based on the derivation-subgroup analysis with the actual readmission rates seen in the validation subgroup of their database. The targeted risk-management program planned by Dr. Conte would primarily focus on high-risk patients.
Dr. Kilic and Dr. Conte said they had no relevant financial disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
Dr. Kilic's data illustrates common factors resulting in rehospitalization after cardiac surgery. Fastidious fluid management in these patients and others is critical to reduce hospital readmissions. A further point to consider is that many pleural effusions, especially those on the left side, are due to retained hemothorax rather than fluid overload. In those instances, early surgical intervention with video-assisted thoracoscopic surgery, rather than prolonged diuresis, would be optimal.
Dr. Francis J. Podbielski, FCCP, serves on the editorial advisory board for CHEST Physician.
Dr. Kilic's data illustrates common factors resulting in rehospitalization after cardiac surgery. Fastidious fluid management in these patients and others is critical to reduce hospital readmissions. A further point to consider is that many pleural effusions, especially those on the left side, are due to retained hemothorax rather than fluid overload. In those instances, early surgical intervention with video-assisted thoracoscopic surgery, rather than prolonged diuresis, would be optimal.
Dr. Francis J. Podbielski, FCCP, serves on the editorial advisory board for CHEST Physician.
Dr. Kilic's data illustrates common factors resulting in rehospitalization after cardiac surgery. Fastidious fluid management in these patients and others is critical to reduce hospital readmissions. A further point to consider is that many pleural effusions, especially those on the left side, are due to retained hemothorax rather than fluid overload. In those instances, early surgical intervention with video-assisted thoracoscopic surgery, rather than prolonged diuresis, would be optimal.
Dr. Francis J. Podbielski, FCCP, serves on the editorial advisory board for CHEST Physician.
PHOENIX – A simple, five-element formula can help identify the patients undergoing heart surgery who face the greatest risk for a hospital readmission within 30 days following discharge from their index hospitalization.
The surgeons who developed this formula hope to use it in an investigational program that will target intensified management resources in postsurgical patients who face the highest readmission risk, to cut rehospitalizations and better improve their clinical status and quality of life.
The analysis that produced this formula also documented that the worst offender for triggering rehospitalizations following heart surgery is fluid overload, the proximate readmission cause for 23% of postsurgical patients, Dr. Arman Kilic said at the annual meeting of the Society of Thoracic Surgeons. The next most common cause was infection, which led to 20% of readmissions, followed by arrhythmias, responsible for 8% of readmissions, said Dr. Kilic, a thoracic surgeon at the University of Pennsylvania in Philadelphia.
Because fluid overload, often in the form of pleural effusion, is such an important driver of rehospitalizations, a more targeted management program would include better titration of diuretic treatment to patients following heart surgery, thoracentesis, and closer monitoring of clinical features that flag fluid overload such as weight.
“The volume overload issue is where the money is. If we can reduce that, it could really impact readmissions,” Dr. Kilic said in an interview.
An investigational program to target rehospitalization risk in heart surgery patients is planned at Johns Hopkins Hospital in Baltimore, where Dr. Kilic worked when he performed this analysis. Surgeons at Johns Hopkins are now in the process of getting funding for this pilot program, said Dr. John V. Conte Jr., professor of surgery and director of mechanical circulatory support at Johns Hopkins and a collaborator with Dr. Kilic on developing the risk formula.
“We’ll tailor postoperative follow-up. We’ll get high-risk patients back to the clinic sooner, and we’ll send nurse practitioners to see them to make sure they’re taking their medications and are getting weighed daily,” Dr. Conte said in an interview. “When a patient has heart surgery, they typically retain about 5-10 pounds of fluid. Patients with good renal function give up that fluid easily, but others are difficult to diurese. Many patients go home before they have been fully diuresed, and we need to follow these patients and transition them better to out-of-hospital care.”
He noted that other situations also come up that unnecessarily drive patients back to the hospital when an alternative and less expensive intervention might be equally effective. For example, some patients return to the hospital out of concern for how their chest wound is healing. Instead of being rehospitalized, such patients could be reassured by having them send a nurse a photo of their wound or by coming to an outpatient clinic.
“We need to engage more often with recently discharged patients,” Dr. Conte said in an interview. “Discharging them doesn’t mean separating them from the health care system; it should mean interacting with patients in a different way” that produces better outcomes and patient satisfaction for less money. Developing improved ways to manage recent heart surgery patients following discharge becomes even more critical later this year when, in July, the Centers for Medicare & Medicaid Services adds 30-day readmissions following coronary artery bypass grafting (CABG) to its list of procedures that can generate a penalty to hospitals if they exceed U.S. norms for readmission rates.
The risk model developed by Dr. Kilic, Dr. Conte, and their associates used data collected from 5,360 heart surgery patients treated at Johns Hopkins during 2008-2013. Nearly half the patients underwent isolated CABG, and 20% had isolated valve surgery. Overall, 585 patients (11%) had a hospital readmission within 30 days of their index discharge. One limitation of the analysis was it used data only on readmissions back to Johns Hopkins Hospital.
The researchers used data from three-quarters of the database to derive the risk formula, and from the remaining 25% of the database to validate the formula. A multivariate analysis of demographic and clinical characteristics that significantly linked with an elevated risk for readmissions identified five factors that independently made a significant contribution to readmission risk. The researchers assigned each of these five factors points depending on its relative contribution to readmission risk in the adjusted model: Severe chronic lung disease received 6 points; placement of a ventricular assist device received 5 points, while other types of heart surgery that was not CABG or valve surgery received 4 points (isolated CABG, isolated valve, or combined CABG and valve surgery received 0 points); development of acute renal failure postoperatively but before index discharge received 4 points; an index length of stay beyond 7 days received 4 points; and African American race received 3 points. The maximum number of points a patient could receive was 22.
Patients with a score of 0 had a 6% rate of a 30-day readmission; those with a score of 22 had a 63% readmission rate. For simplicity, Dr. Kilic suggested dividing patients into three categories based on their readmission risk score: Low-risk patients with a score of 0 had a readmission risk of 6%, medium-risk patients with a score of 1-10 had a readmission risk of 12%, and high-risk patients with a score of 11 or more had a readmission risk of 31%. The researchers found a 96% correlation when comparing these predicted readmission risk rates based on the derivation-subgroup analysis with the actual readmission rates seen in the validation subgroup of their database. The targeted risk-management program planned by Dr. Conte would primarily focus on high-risk patients.
Dr. Kilic and Dr. Conte said they had no relevant financial disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
PHOENIX – A simple, five-element formula can help identify the patients undergoing heart surgery who face the greatest risk for a hospital readmission within 30 days following discharge from their index hospitalization.
The surgeons who developed this formula hope to use it in an investigational program that will target intensified management resources in postsurgical patients who face the highest readmission risk, to cut rehospitalizations and better improve their clinical status and quality of life.
The analysis that produced this formula also documented that the worst offender for triggering rehospitalizations following heart surgery is fluid overload, the proximate readmission cause for 23% of postsurgical patients, Dr. Arman Kilic said at the annual meeting of the Society of Thoracic Surgeons. The next most common cause was infection, which led to 20% of readmissions, followed by arrhythmias, responsible for 8% of readmissions, said Dr. Kilic, a thoracic surgeon at the University of Pennsylvania in Philadelphia.
Because fluid overload, often in the form of pleural effusion, is such an important driver of rehospitalizations, a more targeted management program would include better titration of diuretic treatment to patients following heart surgery, thoracentesis, and closer monitoring of clinical features that flag fluid overload such as weight.
“The volume overload issue is where the money is. If we can reduce that, it could really impact readmissions,” Dr. Kilic said in an interview.
An investigational program to target rehospitalization risk in heart surgery patients is planned at Johns Hopkins Hospital in Baltimore, where Dr. Kilic worked when he performed this analysis. Surgeons at Johns Hopkins are now in the process of getting funding for this pilot program, said Dr. John V. Conte Jr., professor of surgery and director of mechanical circulatory support at Johns Hopkins and a collaborator with Dr. Kilic on developing the risk formula.
“We’ll tailor postoperative follow-up. We’ll get high-risk patients back to the clinic sooner, and we’ll send nurse practitioners to see them to make sure they’re taking their medications and are getting weighed daily,” Dr. Conte said in an interview. “When a patient has heart surgery, they typically retain about 5-10 pounds of fluid. Patients with good renal function give up that fluid easily, but others are difficult to diurese. Many patients go home before they have been fully diuresed, and we need to follow these patients and transition them better to out-of-hospital care.”
He noted that other situations also come up that unnecessarily drive patients back to the hospital when an alternative and less expensive intervention might be equally effective. For example, some patients return to the hospital out of concern for how their chest wound is healing. Instead of being rehospitalized, such patients could be reassured by having them send a nurse a photo of their wound or by coming to an outpatient clinic.
“We need to engage more often with recently discharged patients,” Dr. Conte said in an interview. “Discharging them doesn’t mean separating them from the health care system; it should mean interacting with patients in a different way” that produces better outcomes and patient satisfaction for less money. Developing improved ways to manage recent heart surgery patients following discharge becomes even more critical later this year when, in July, the Centers for Medicare & Medicaid Services adds 30-day readmissions following coronary artery bypass grafting (CABG) to its list of procedures that can generate a penalty to hospitals if they exceed U.S. norms for readmission rates.
The risk model developed by Dr. Kilic, Dr. Conte, and their associates used data collected from 5,360 heart surgery patients treated at Johns Hopkins during 2008-2013. Nearly half the patients underwent isolated CABG, and 20% had isolated valve surgery. Overall, 585 patients (11%) had a hospital readmission within 30 days of their index discharge. One limitation of the analysis was it used data only on readmissions back to Johns Hopkins Hospital.
The researchers used data from three-quarters of the database to derive the risk formula, and from the remaining 25% of the database to validate the formula. A multivariate analysis of demographic and clinical characteristics that significantly linked with an elevated risk for readmissions identified five factors that independently made a significant contribution to readmission risk. The researchers assigned each of these five factors points depending on its relative contribution to readmission risk in the adjusted model: Severe chronic lung disease received 6 points; placement of a ventricular assist device received 5 points, while other types of heart surgery that was not CABG or valve surgery received 4 points (isolated CABG, isolated valve, or combined CABG and valve surgery received 0 points); development of acute renal failure postoperatively but before index discharge received 4 points; an index length of stay beyond 7 days received 4 points; and African American race received 3 points. The maximum number of points a patient could receive was 22.
Patients with a score of 0 had a 6% rate of a 30-day readmission; those with a score of 22 had a 63% readmission rate. For simplicity, Dr. Kilic suggested dividing patients into three categories based on their readmission risk score: Low-risk patients with a score of 0 had a readmission risk of 6%, medium-risk patients with a score of 1-10 had a readmission risk of 12%, and high-risk patients with a score of 11 or more had a readmission risk of 31%. The researchers found a 96% correlation when comparing these predicted readmission risk rates based on the derivation-subgroup analysis with the actual readmission rates seen in the validation subgroup of their database. The targeted risk-management program planned by Dr. Conte would primarily focus on high-risk patients.
Dr. Kilic and Dr. Conte said they had no relevant financial disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
Key clinical point: A risk score predicted which heart surgery patients faced the greatest risk for hospital readmission within 30 days of their index discharge.
Major finding: Patients with a 0 score had a 6% 30-day readmission rate; a high score of 22 linked with a 63% rate.
Data source: A review of 5,360 heart surgery patients treated at one U.S. center.
Disclosures: Dr. Kilic and Dr. Conte said they had no relevant financial disclosures.
Antidepressants Tied to Lower Dementia Mortality
MADRID – Elderly patients who develop dementia often are on an antidepressant when dementia is diagnosed, and unexpectedly antidepressant use during the 3 years preceding diagnosis of dementia was linked with a significantly reduced mortality risk, Dr. Daniela Enache reported at the meeting, sponsored by the European Psychiatric Association.
Elderly Swedish patients who took an antidepressant for at least 1 year during the 3 years prior to their dementia diagnosis had a 13% relative reduction in mortality, compared with similar new-dementia patients who had not been on an antidepressant. The researchers tracked mortality for a median of 2.1 years following dementia diagnosis in 20,050 Swedes with a new dementia diagnosis using records from 2007-2013, said Dr. Enache, a psychiatrist and neurogeriatics researcher at the Karolinska Institute in Stockholm. The analysis adjusted for differences in age, sex, mental state, number of drugs used, and living conditions.
The protective effect from 3 years of antidepressant use was strongest in people who went on to develop Alzheimer’s disease, the most common form of dementia in the study affecting 36% of all people who developed dementia. The findings also documented the relatively frequent antidepressant use by elderly people who develop dementia. In the series of people with newly diagnosed dementia of any type, 25% were on an antidepressant at the time of their dementia diagnosis, and 4,325 (22%) had used an antidepressant at least once during the 3 years prior to their diagnosis; 1,128 (6%) of the people diagnosed with dementia had used an antidepressant during all 3 years preceding their diagnosis.
Dr. Enache admitted that it was not clear why antidepressant treatment would have this mortality effect. One possibility is that the mortality benefit came from the action of antidepressants on behavioral symptoms. Or antidepressants could have a biological effect, such as reducing production of amyloid beta or affecting neurogenesis and brain plasticity. A third possibility is that antidepressant use is a marker for overall better health care.
Whatever the explanation, the finding provides reassurance that antidepressant treatment is safe in elderly patients who are at risk of developing dementia, she noted. And patients newly diagnosed with dementia should be screened for depression, although Dr. Enache stressed that antidepressants can be prescribed for other reasons, such as anxiety or behavior problems.
All types of antidepressants had this mortality effect: tricyclics, selective serotonin reuptake inhibitors, and other types. Use of antidepressants was roughly similar across various dementia diagnoses, ranging from 22% of patients with mixed dementia and 23% of those with Alzheimer’s disease to a high of 32% among patients with Parkinson’s disease dementia.
The researchers used data collected in the national Swedish Dementia Registry, which includes about 90% of patients treated at Swedish memory clinics, along with data from the national Prescribed Drug Registry. The average age at time of dementia diagnosis was 78 years. Following Alzheimer’s disease, the other most common diagnoses were mixed dementia, in 25%, and vascular dementia, in 19%.
Dr. Enache had no disclosures.
These were quite surprising findings: a mortality reduction linked with antidepressant treatment, Dr. Reinhard Heun said in an interview. We’ll see if someone can replicate this. Perhaps the finding was caused by an unadjusted selection bias, or an effect from a comorbidity. Or it could be that patients on antidepressants also received better health care. Seeing a mortality benefit is difficult to explain.
 |
| Mitchel L. Zoler/Frontline Medical News Dr. Reinhard Heun |
Hypothesizing an actual causal link between antidepressant use and reduced mortality in patients recently diagnosed with dementia would mean that antidepressants have an effect on underlying dementia pathology. That seems unlikely. Treatment of depression in elderly patients is primarily focused on improving patients’ quality of life, and there is good evidence that antidepressant treatment achieves that. Improving quality of life is a much more realistic goal for antidepressant therapy than improving survival.
Dr. Heun is professor of psychiatry at Royal Derby (England) Hospital. He had no relevant disclosures.
These were quite surprising findings: a mortality reduction linked with antidepressant treatment, Dr. Reinhard Heun said in an interview. We’ll see if someone can replicate this. Perhaps the finding was caused by an unadjusted selection bias, or an effect from a comorbidity. Or it could be that patients on antidepressants also received better health care. Seeing a mortality benefit is difficult to explain.
|
| Mitchel L. Zoler/Frontline Medical News Dr. Reinhard Heun |
Hypothesizing an actual causal link between antidepressant use and reduced mortality in patients recently diagnosed with dementia would mean that antidepressants have an effect on underlying dementia pathology. That seems unlikely. Treatment of depression in elderly patients is primarily focused on improving patients’ quality of life, and there is good evidence that antidepressant treatment achieves that. Improving quality of life is a much more realistic goal for antidepressant therapy than improving survival.
Dr. Heun is professor of psychiatry at Royal Derby (England) Hospital. He had no relevant disclosures.
These were quite surprising findings: a mortality reduction linked with antidepressant treatment, Dr. Reinhard Heun said in an interview. We’ll see if someone can replicate this. Perhaps the finding was caused by an unadjusted selection bias, or an effect from a comorbidity. Or it could be that patients on antidepressants also received better health care. Seeing a mortality benefit is difficult to explain.
|
| Mitchel L. Zoler/Frontline Medical News Dr. Reinhard Heun |
Hypothesizing an actual causal link between antidepressant use and reduced mortality in patients recently diagnosed with dementia would mean that antidepressants have an effect on underlying dementia pathology. That seems unlikely. Treatment of depression in elderly patients is primarily focused on improving patients’ quality of life, and there is good evidence that antidepressant treatment achieves that. Improving quality of life is a much more realistic goal for antidepressant therapy than improving survival.
Dr. Heun is professor of psychiatry at Royal Derby (England) Hospital. He had no relevant disclosures.
MADRID – Elderly patients who develop dementia often are on an antidepressant when dementia is diagnosed, and unexpectedly antidepressant use during the 3 years preceding diagnosis of dementia was linked with a significantly reduced mortality risk, Dr. Daniela Enache reported at the meeting, sponsored by the European Psychiatric Association.
Elderly Swedish patients who took an antidepressant for at least 1 year during the 3 years prior to their dementia diagnosis had a 13% relative reduction in mortality, compared with similar new-dementia patients who had not been on an antidepressant. The researchers tracked mortality for a median of 2.1 years following dementia diagnosis in 20,050 Swedes with a new dementia diagnosis using records from 2007-2013, said Dr. Enache, a psychiatrist and neurogeriatics researcher at the Karolinska Institute in Stockholm. The analysis adjusted for differences in age, sex, mental state, number of drugs used, and living conditions.
The protective effect from 3 years of antidepressant use was strongest in people who went on to develop Alzheimer’s disease, the most common form of dementia in the study affecting 36% of all people who developed dementia. The findings also documented the relatively frequent antidepressant use by elderly people who develop dementia. In the series of people with newly diagnosed dementia of any type, 25% were on an antidepressant at the time of their dementia diagnosis, and 4,325 (22%) had used an antidepressant at least once during the 3 years prior to their diagnosis; 1,128 (6%) of the people diagnosed with dementia had used an antidepressant during all 3 years preceding their diagnosis.
Dr. Enache admitted that it was not clear why antidepressant treatment would have this mortality effect. One possibility is that the mortality benefit came from the action of antidepressants on behavioral symptoms. Or antidepressants could have a biological effect, such as reducing production of amyloid beta or affecting neurogenesis and brain plasticity. A third possibility is that antidepressant use is a marker for overall better health care.
Whatever the explanation, the finding provides reassurance that antidepressant treatment is safe in elderly patients who are at risk of developing dementia, she noted. And patients newly diagnosed with dementia should be screened for depression, although Dr. Enache stressed that antidepressants can be prescribed for other reasons, such as anxiety or behavior problems.
All types of antidepressants had this mortality effect: tricyclics, selective serotonin reuptake inhibitors, and other types. Use of antidepressants was roughly similar across various dementia diagnoses, ranging from 22% of patients with mixed dementia and 23% of those with Alzheimer’s disease to a high of 32% among patients with Parkinson’s disease dementia.
The researchers used data collected in the national Swedish Dementia Registry, which includes about 90% of patients treated at Swedish memory clinics, along with data from the national Prescribed Drug Registry. The average age at time of dementia diagnosis was 78 years. Following Alzheimer’s disease, the other most common diagnoses were mixed dementia, in 25%, and vascular dementia, in 19%.
Dr. Enache had no disclosures.
MADRID – Elderly patients who develop dementia often are on an antidepressant when dementia is diagnosed, and unexpectedly antidepressant use during the 3 years preceding diagnosis of dementia was linked with a significantly reduced mortality risk, Dr. Daniela Enache reported at the meeting, sponsored by the European Psychiatric Association.
Elderly Swedish patients who took an antidepressant for at least 1 year during the 3 years prior to their dementia diagnosis had a 13% relative reduction in mortality, compared with similar new-dementia patients who had not been on an antidepressant. The researchers tracked mortality for a median of 2.1 years following dementia diagnosis in 20,050 Swedes with a new dementia diagnosis using records from 2007-2013, said Dr. Enache, a psychiatrist and neurogeriatics researcher at the Karolinska Institute in Stockholm. The analysis adjusted for differences in age, sex, mental state, number of drugs used, and living conditions.
The protective effect from 3 years of antidepressant use was strongest in people who went on to develop Alzheimer’s disease, the most common form of dementia in the study affecting 36% of all people who developed dementia. The findings also documented the relatively frequent antidepressant use by elderly people who develop dementia. In the series of people with newly diagnosed dementia of any type, 25% were on an antidepressant at the time of their dementia diagnosis, and 4,325 (22%) had used an antidepressant at least once during the 3 years prior to their diagnosis; 1,128 (6%) of the people diagnosed with dementia had used an antidepressant during all 3 years preceding their diagnosis.
Dr. Enache admitted that it was not clear why antidepressant treatment would have this mortality effect. One possibility is that the mortality benefit came from the action of antidepressants on behavioral symptoms. Or antidepressants could have a biological effect, such as reducing production of amyloid beta or affecting neurogenesis and brain plasticity. A third possibility is that antidepressant use is a marker for overall better health care.
Whatever the explanation, the finding provides reassurance that antidepressant treatment is safe in elderly patients who are at risk of developing dementia, she noted. And patients newly diagnosed with dementia should be screened for depression, although Dr. Enache stressed that antidepressants can be prescribed for other reasons, such as anxiety or behavior problems.
All types of antidepressants had this mortality effect: tricyclics, selective serotonin reuptake inhibitors, and other types. Use of antidepressants was roughly similar across various dementia diagnoses, ranging from 22% of patients with mixed dementia and 23% of those with Alzheimer’s disease to a high of 32% among patients with Parkinson’s disease dementia.
The researchers used data collected in the national Swedish Dementia Registry, which includes about 90% of patients treated at Swedish memory clinics, along with data from the national Prescribed Drug Registry. The average age at time of dementia diagnosis was 78 years. Following Alzheimer’s disease, the other most common diagnoses were mixed dementia, in 25%, and vascular dementia, in 19%.
Dr. Enache had no disclosures.
AT THE EUROPEAN CONGRESS OF PSYCHIATRY
Antidepressants tied to lower dementia mortality
MADRID – Elderly patients who develop dementia often are on an antidepressant when dementia is diagnosed, and unexpectedly antidepressant use during the 3 years preceding diagnosis of dementia was linked with a significantly reduced mortality risk, Dr. Daniela Enache reported at the meeting, sponsored by the European Psychiatric Association.
Elderly Swedish patients who took an antidepressant for at least 1 year during the 3 years prior to their dementia diagnosis had a 13% relative reduction in mortality, compared with similar new-dementia patients who had not been on an antidepressant. The researchers tracked mortality for a median of 2.1 years following dementia diagnosis in 20,050 Swedes with a new dementia diagnosis using records from 2007-2013, said Dr. Enache, a psychiatrist and neurogeriatics researcher at the Karolinska Institute in Stockholm. The analysis adjusted for differences in age, sex, mental state, number of drugs used, and living conditions.
The protective effect from 3 years of antidepressant use was strongest in people who went on to develop Alzheimer’s disease, the most common form of dementia in the study affecting 36% of all people who developed dementia. The findings also documented the relatively frequent antidepressant use by elderly people who develop dementia. In the series of people with newly diagnosed dementia of any type, 25% were on an antidepressant at the time of their dementia diagnosis, and 4,325 (22%) had used an antidepressant at least once during the 3 years prior to their diagnosis; 1,128 (6%) of the people diagnosed with dementia had used an antidepressant during all 3 years preceding their diagnosis.
Dr. Enache admitted that it was not clear why antidepressant treatment would have this mortality effect. One possibility is that the mortality benefit came from the action of antidepressants on behavioral symptoms. Or antidepressants could have a biological effect, such as reducing production of amyloid beta or affecting neurogenesis and brain plasticity. A third possibility is that antidepressant use is a marker for overall better health care.
Whatever the explanation, the finding provides reassurance that antidepressant treatment is safe in elderly patients who are at risk of developing dementia, she noted. And patients newly diagnosed with dementia should be screened for depression, although Dr. Enache stressed that antidepressants can be prescribed for other reasons, such as anxiety or behavior problems.
All types of antidepressants had this mortality effect: tricyclics, selective serotonin reuptake inhibitors, and other types. Use of antidepressants was roughly similar across various dementia diagnoses, ranging from 22% of patients with mixed dementia and 23% of those with Alzheimer’s disease to a high of 32% among patients with Parkinson’s disease dementia.
The researchers used data collected in the national Swedish Dementia Registry, which includes about 90% of patients treated at Swedish memory clinics, along with data from the national Prescribed Drug Registry. The average age at time of dementia diagnosis was 78 years. Following Alzheimer’s disease, the other most common diagnoses were mixed dementia, in 25%, and vascular dementia, in 19%.
Dr. Enache had no disclosures.
On Twitter @mitchelzoler
These were quite surprising findings: a mortality reduction linked with antidepressant treatment, Dr. Reinhard Heun said in an interview. We’ll see if someone can replicate this. Perhaps the finding was caused by an unadjusted selection bias, or an effect from a comorbidity. Or it could be that patients on antidepressants also received better health care. Seeing a mortality benefit is difficult to explain.
|
| Mitchel L. Zoler/Frontline Medical News Dr. Reinhard Heun |
Hypothesizing an actual causal link between antidepressant use and reduced mortality in patients recently diagnosed with dementia would mean that antidepressants have an effect on underlying dementia pathology. That seems unlikely. Treatment of depression in elderly patients is primarily focused on improving patients’ quality of life, and there is good evidence that antidepressant treatment achieves that. Improving quality of life is a much more realistic goal for antidepressant therapy than improving survival.
Dr. Heun is professor of psychiatry at Royal Derby (England) Hospital. He had no relevant disclosures.
These were quite surprising findings: a mortality reduction linked with antidepressant treatment, Dr. Reinhard Heun said in an interview. We’ll see if someone can replicate this. Perhaps the finding was caused by an unadjusted selection bias, or an effect from a comorbidity. Or it could be that patients on antidepressants also received better health care. Seeing a mortality benefit is difficult to explain.
|
| Mitchel L. Zoler/Frontline Medical News Dr. Reinhard Heun |
Hypothesizing an actual causal link between antidepressant use and reduced mortality in patients recently diagnosed with dementia would mean that antidepressants have an effect on underlying dementia pathology. That seems unlikely. Treatment of depression in elderly patients is primarily focused on improving patients’ quality of life, and there is good evidence that antidepressant treatment achieves that. Improving quality of life is a much more realistic goal for antidepressant therapy than improving survival.
Dr. Heun is professor of psychiatry at Royal Derby (England) Hospital. He had no relevant disclosures.
These were quite surprising findings: a mortality reduction linked with antidepressant treatment, Dr. Reinhard Heun said in an interview. We’ll see if someone can replicate this. Perhaps the finding was caused by an unadjusted selection bias, or an effect from a comorbidity. Or it could be that patients on antidepressants also received better health care. Seeing a mortality benefit is difficult to explain.
|
| Mitchel L. Zoler/Frontline Medical News Dr. Reinhard Heun |
Hypothesizing an actual causal link between antidepressant use and reduced mortality in patients recently diagnosed with dementia would mean that antidepressants have an effect on underlying dementia pathology. That seems unlikely. Treatment of depression in elderly patients is primarily focused on improving patients’ quality of life, and there is good evidence that antidepressant treatment achieves that. Improving quality of life is a much more realistic goal for antidepressant therapy than improving survival.
Dr. Heun is professor of psychiatry at Royal Derby (England) Hospital. He had no relevant disclosures.
MADRID – Elderly patients who develop dementia often are on an antidepressant when dementia is diagnosed, and unexpectedly antidepressant use during the 3 years preceding diagnosis of dementia was linked with a significantly reduced mortality risk, Dr. Daniela Enache reported at the meeting, sponsored by the European Psychiatric Association.
Elderly Swedish patients who took an antidepressant for at least 1 year during the 3 years prior to their dementia diagnosis had a 13% relative reduction in mortality, compared with similar new-dementia patients who had not been on an antidepressant. The researchers tracked mortality for a median of 2.1 years following dementia diagnosis in 20,050 Swedes with a new dementia diagnosis using records from 2007-2013, said Dr. Enache, a psychiatrist and neurogeriatics researcher at the Karolinska Institute in Stockholm. The analysis adjusted for differences in age, sex, mental state, number of drugs used, and living conditions.
The protective effect from 3 years of antidepressant use was strongest in people who went on to develop Alzheimer’s disease, the most common form of dementia in the study affecting 36% of all people who developed dementia. The findings also documented the relatively frequent antidepressant use by elderly people who develop dementia. In the series of people with newly diagnosed dementia of any type, 25% were on an antidepressant at the time of their dementia diagnosis, and 4,325 (22%) had used an antidepressant at least once during the 3 years prior to their diagnosis; 1,128 (6%) of the people diagnosed with dementia had used an antidepressant during all 3 years preceding their diagnosis.
Dr. Enache admitted that it was not clear why antidepressant treatment would have this mortality effect. One possibility is that the mortality benefit came from the action of antidepressants on behavioral symptoms. Or antidepressants could have a biological effect, such as reducing production of amyloid beta or affecting neurogenesis and brain plasticity. A third possibility is that antidepressant use is a marker for overall better health care.
Whatever the explanation, the finding provides reassurance that antidepressant treatment is safe in elderly patients who are at risk of developing dementia, she noted. And patients newly diagnosed with dementia should be screened for depression, although Dr. Enache stressed that antidepressants can be prescribed for other reasons, such as anxiety or behavior problems.
All types of antidepressants had this mortality effect: tricyclics, selective serotonin reuptake inhibitors, and other types. Use of antidepressants was roughly similar across various dementia diagnoses, ranging from 22% of patients with mixed dementia and 23% of those with Alzheimer’s disease to a high of 32% among patients with Parkinson’s disease dementia.
The researchers used data collected in the national Swedish Dementia Registry, which includes about 90% of patients treated at Swedish memory clinics, along with data from the national Prescribed Drug Registry. The average age at time of dementia diagnosis was 78 years. Following Alzheimer’s disease, the other most common diagnoses were mixed dementia, in 25%, and vascular dementia, in 19%.
Dr. Enache had no disclosures.
On Twitter @mitchelzoler
MADRID – Elderly patients who develop dementia often are on an antidepressant when dementia is diagnosed, and unexpectedly antidepressant use during the 3 years preceding diagnosis of dementia was linked with a significantly reduced mortality risk, Dr. Daniela Enache reported at the meeting, sponsored by the European Psychiatric Association.
Elderly Swedish patients who took an antidepressant for at least 1 year during the 3 years prior to their dementia diagnosis had a 13% relative reduction in mortality, compared with similar new-dementia patients who had not been on an antidepressant. The researchers tracked mortality for a median of 2.1 years following dementia diagnosis in 20,050 Swedes with a new dementia diagnosis using records from 2007-2013, said Dr. Enache, a psychiatrist and neurogeriatics researcher at the Karolinska Institute in Stockholm. The analysis adjusted for differences in age, sex, mental state, number of drugs used, and living conditions.
The protective effect from 3 years of antidepressant use was strongest in people who went on to develop Alzheimer’s disease, the most common form of dementia in the study affecting 36% of all people who developed dementia. The findings also documented the relatively frequent antidepressant use by elderly people who develop dementia. In the series of people with newly diagnosed dementia of any type, 25% were on an antidepressant at the time of their dementia diagnosis, and 4,325 (22%) had used an antidepressant at least once during the 3 years prior to their diagnosis; 1,128 (6%) of the people diagnosed with dementia had used an antidepressant during all 3 years preceding their diagnosis.
Dr. Enache admitted that it was not clear why antidepressant treatment would have this mortality effect. One possibility is that the mortality benefit came from the action of antidepressants on behavioral symptoms. Or antidepressants could have a biological effect, such as reducing production of amyloid beta or affecting neurogenesis and brain plasticity. A third possibility is that antidepressant use is a marker for overall better health care.
Whatever the explanation, the finding provides reassurance that antidepressant treatment is safe in elderly patients who are at risk of developing dementia, she noted. And patients newly diagnosed with dementia should be screened for depression, although Dr. Enache stressed that antidepressants can be prescribed for other reasons, such as anxiety or behavior problems.
All types of antidepressants had this mortality effect: tricyclics, selective serotonin reuptake inhibitors, and other types. Use of antidepressants was roughly similar across various dementia diagnoses, ranging from 22% of patients with mixed dementia and 23% of those with Alzheimer’s disease to a high of 32% among patients with Parkinson’s disease dementia.
The researchers used data collected in the national Swedish Dementia Registry, which includes about 90% of patients treated at Swedish memory clinics, along with data from the national Prescribed Drug Registry. The average age at time of dementia diagnosis was 78 years. Following Alzheimer’s disease, the other most common diagnoses were mixed dementia, in 25%, and vascular dementia, in 19%.
Dr. Enache had no disclosures.
On Twitter @mitchelzoler
AT THE EUROPEAN CONGRESS OF PSYCHIATRY
Key clinical point: People on antidepressants during the 3 years prior to a new diagnosis of dementia had significantly reduced mortality during 2 years following the dementia diagnosis.
Major finding: All-cause mortality dropped by a relative 13% when people received an antidepressant prior to a dementia diagnosis.
Data source: Review of Swedish national registries for 20,050 new dementia diagnoses.
Disclosures: Dr. Enache had no disclosures.
Exploratory analysis provides support for Recurrence Score
AMSTERDAM – A 21-gene expression assessment tool may identify selected breast cancer patients who can safely forgo adjuvant chemotherapy, according to an exploratory analysis of data collected on Recurrence Scores and 5-year disease-free survival in a multicenter German trial primarily designed to compare different chemotherapy regimens.
Recurrence Score joined nodal status, stage, and grade as one of the four prognostic factors that each significantly linked with 5-year disease-free survival in a multivariate-adjusted analysis of 2,642 women with HER2-negative and hormone-receptor positive primary breast cancer, Dr. Oleg Gluz said at the European Breast Cancer Congress. Patients with a low Recurrence Score of 0-11 (on a scale of 0-100) had a 94% rate of disease-free survival during a median 55 months of follow-up when the vast majority of these patients received hormonal therapy only and no chemotherapy, said Dr. Gluz, an oncologist at the Breast Center Niederrhein of Evangelical Hospital Bethesda in Moenchengladbach, Germany. The Recurrence Score is calculated based on results from a RNA-based gene expression test known as Oncotype DX.
A Recurrence Score gene expression profile of 0-11 occurred in 18% of the screened patients, and 86% of these patients accepted the option of no chemotherapy. An additional 30% of the study group had a Recurrence Score of 12-18, and 30% had a score of 19-25, and all these patients with scores of 12-25 collectively had a 94% rate of disease-free survival following chemotherapy during a median 55 months of follow-up. Assigning all these patients with scores of 12-25 likely represents “overtreatment” for patients who also had negative lymph nodes or minimal lymph node involvement, Dr. Gluz said. In the remaining 22% of patients, who had Recurrence Scores of 26 or greater at baseline, the rate of disease-free survival after chemotherapy with a median 55 -month follow-up was 84%, Dr. Gluz reported.
These findings were consistent with an earlier report of disease-free survival after a median 3-year follow-up in the same patients, who were randomized to different chemotherapy alternatives in the PlanB trial, a phase III study primarily designed to assess the relative efficacy and safety of two chemotherapy alternatives in patients with high-risk clinical features including either positive lymph nodes or a high-risk clinical profile despite having negative lymph nodes (J Clin Oncol. 2016 Feb 29. doi: 10.1200/JCO.2015.63.5383). They were also consistent with published 5-year disease-free survival results from a prospective evaluation of the Recurrence Score in more than 10,000 women with node-negative, hormone receptor–positive, HER2-negative breast cancer in the Trial Assigning Individualized Options for Treatment (TAILORx) study (New Engl J Med. 2015 Nov 19;373 [21]:2005-14).
“These results are interesting and provocative, but are not yet practice changing because in these high-risk patients with hormone receptor–positive tumors, relapses can occur several years after treatment so we need to wait for longer follow-up,” commented Dr. Angelo Di Leo, head of medical oncology at Prato (Italy) Hospital. He also cited the need to wait for results from several prospective, randomized trials now in progress that are more directly addressing the role of genetic profiling in predicting patient prognosis and treatment responses.
On Twitter @mitchelzoler
The key question about the genetic signatures of breast cancers obtained using tests like the Recurrence Score is whether gene-expression profiles provide useful information about the efficacy of currently-available treatment options. Before we start using assessment tools like Recurrence Score we need to see their value proven in prospective, randomized trials.
 |
| Mitchel L. Zoler/Frontline Medical News Dr. Jonas Bergh |
Our patients face a significant risk from recurrence if we prematurely use analyses like the Recurrence Score to guide treatment decisions. The 5-year median follow-up reported by Dr. Gluz is too short to produce completely reliable results.
I am concerned about the potential for undertreating patients by withholding chemotherapy from patients with a low Recurrence Score who also have one to three positive lymph nodes. We must intelligently balance the appeal of avoiding potentially toxic chemotherapy regimens against the risk for recurrence that patients could face if they don’t receive the chemotherapy regimen they require.
Dr. Jonas Bergh is a professor of oncology-pathology at the Karolinska Institute in Stockholm. He had no relevant disclosures. He made these comments as designated discussant for Dr. Gluz’s report.
The key question about the genetic signatures of breast cancers obtained using tests like the Recurrence Score is whether gene-expression profiles provide useful information about the efficacy of currently-available treatment options. Before we start using assessment tools like Recurrence Score we need to see their value proven in prospective, randomized trials.
|
| Mitchel L. Zoler/Frontline Medical News Dr. Jonas Bergh |
Our patients face a significant risk from recurrence if we prematurely use analyses like the Recurrence Score to guide treatment decisions. The 5-year median follow-up reported by Dr. Gluz is too short to produce completely reliable results.
I am concerned about the potential for undertreating patients by withholding chemotherapy from patients with a low Recurrence Score who also have one to three positive lymph nodes. We must intelligently balance the appeal of avoiding potentially toxic chemotherapy regimens against the risk for recurrence that patients could face if they don’t receive the chemotherapy regimen they require.
Dr. Jonas Bergh is a professor of oncology-pathology at the Karolinska Institute in Stockholm. He had no relevant disclosures. He made these comments as designated discussant for Dr. Gluz’s report.
The key question about the genetic signatures of breast cancers obtained using tests like the Recurrence Score is whether gene-expression profiles provide useful information about the efficacy of currently-available treatment options. Before we start using assessment tools like Recurrence Score we need to see their value proven in prospective, randomized trials.
|
| Mitchel L. Zoler/Frontline Medical News Dr. Jonas Bergh |
Our patients face a significant risk from recurrence if we prematurely use analyses like the Recurrence Score to guide treatment decisions. The 5-year median follow-up reported by Dr. Gluz is too short to produce completely reliable results.
I am concerned about the potential for undertreating patients by withholding chemotherapy from patients with a low Recurrence Score who also have one to three positive lymph nodes. We must intelligently balance the appeal of avoiding potentially toxic chemotherapy regimens against the risk for recurrence that patients could face if they don’t receive the chemotherapy regimen they require.
Dr. Jonas Bergh is a professor of oncology-pathology at the Karolinska Institute in Stockholm. He had no relevant disclosures. He made these comments as designated discussant for Dr. Gluz’s report.
AMSTERDAM – A 21-gene expression assessment tool may identify selected breast cancer patients who can safely forgo adjuvant chemotherapy, according to an exploratory analysis of data collected on Recurrence Scores and 5-year disease-free survival in a multicenter German trial primarily designed to compare different chemotherapy regimens.
Recurrence Score joined nodal status, stage, and grade as one of the four prognostic factors that each significantly linked with 5-year disease-free survival in a multivariate-adjusted analysis of 2,642 women with HER2-negative and hormone-receptor positive primary breast cancer, Dr. Oleg Gluz said at the European Breast Cancer Congress. Patients with a low Recurrence Score of 0-11 (on a scale of 0-100) had a 94% rate of disease-free survival during a median 55 months of follow-up when the vast majority of these patients received hormonal therapy only and no chemotherapy, said Dr. Gluz, an oncologist at the Breast Center Niederrhein of Evangelical Hospital Bethesda in Moenchengladbach, Germany. The Recurrence Score is calculated based on results from a RNA-based gene expression test known as Oncotype DX.
A Recurrence Score gene expression profile of 0-11 occurred in 18% of the screened patients, and 86% of these patients accepted the option of no chemotherapy. An additional 30% of the study group had a Recurrence Score of 12-18, and 30% had a score of 19-25, and all these patients with scores of 12-25 collectively had a 94% rate of disease-free survival following chemotherapy during a median 55 months of follow-up. Assigning all these patients with scores of 12-25 likely represents “overtreatment” for patients who also had negative lymph nodes or minimal lymph node involvement, Dr. Gluz said. In the remaining 22% of patients, who had Recurrence Scores of 26 or greater at baseline, the rate of disease-free survival after chemotherapy with a median 55 -month follow-up was 84%, Dr. Gluz reported.
These findings were consistent with an earlier report of disease-free survival after a median 3-year follow-up in the same patients, who were randomized to different chemotherapy alternatives in the PlanB trial, a phase III study primarily designed to assess the relative efficacy and safety of two chemotherapy alternatives in patients with high-risk clinical features including either positive lymph nodes or a high-risk clinical profile despite having negative lymph nodes (J Clin Oncol. 2016 Feb 29. doi: 10.1200/JCO.2015.63.5383). They were also consistent with published 5-year disease-free survival results from a prospective evaluation of the Recurrence Score in more than 10,000 women with node-negative, hormone receptor–positive, HER2-negative breast cancer in the Trial Assigning Individualized Options for Treatment (TAILORx) study (New Engl J Med. 2015 Nov 19;373 [21]:2005-14).
“These results are interesting and provocative, but are not yet practice changing because in these high-risk patients with hormone receptor–positive tumors, relapses can occur several years after treatment so we need to wait for longer follow-up,” commented Dr. Angelo Di Leo, head of medical oncology at Prato (Italy) Hospital. He also cited the need to wait for results from several prospective, randomized trials now in progress that are more directly addressing the role of genetic profiling in predicting patient prognosis and treatment responses.
On Twitter @mitchelzoler
AMSTERDAM – A 21-gene expression assessment tool may identify selected breast cancer patients who can safely forgo adjuvant chemotherapy, according to an exploratory analysis of data collected on Recurrence Scores and 5-year disease-free survival in a multicenter German trial primarily designed to compare different chemotherapy regimens.
Recurrence Score joined nodal status, stage, and grade as one of the four prognostic factors that each significantly linked with 5-year disease-free survival in a multivariate-adjusted analysis of 2,642 women with HER2-negative and hormone-receptor positive primary breast cancer, Dr. Oleg Gluz said at the European Breast Cancer Congress. Patients with a low Recurrence Score of 0-11 (on a scale of 0-100) had a 94% rate of disease-free survival during a median 55 months of follow-up when the vast majority of these patients received hormonal therapy only and no chemotherapy, said Dr. Gluz, an oncologist at the Breast Center Niederrhein of Evangelical Hospital Bethesda in Moenchengladbach, Germany. The Recurrence Score is calculated based on results from a RNA-based gene expression test known as Oncotype DX.
A Recurrence Score gene expression profile of 0-11 occurred in 18% of the screened patients, and 86% of these patients accepted the option of no chemotherapy. An additional 30% of the study group had a Recurrence Score of 12-18, and 30% had a score of 19-25, and all these patients with scores of 12-25 collectively had a 94% rate of disease-free survival following chemotherapy during a median 55 months of follow-up. Assigning all these patients with scores of 12-25 likely represents “overtreatment” for patients who also had negative lymph nodes or minimal lymph node involvement, Dr. Gluz said. In the remaining 22% of patients, who had Recurrence Scores of 26 or greater at baseline, the rate of disease-free survival after chemotherapy with a median 55 -month follow-up was 84%, Dr. Gluz reported.
These findings were consistent with an earlier report of disease-free survival after a median 3-year follow-up in the same patients, who were randomized to different chemotherapy alternatives in the PlanB trial, a phase III study primarily designed to assess the relative efficacy and safety of two chemotherapy alternatives in patients with high-risk clinical features including either positive lymph nodes or a high-risk clinical profile despite having negative lymph nodes (J Clin Oncol. 2016 Feb 29. doi: 10.1200/JCO.2015.63.5383). They were also consistent with published 5-year disease-free survival results from a prospective evaluation of the Recurrence Score in more than 10,000 women with node-negative, hormone receptor–positive, HER2-negative breast cancer in the Trial Assigning Individualized Options for Treatment (TAILORx) study (New Engl J Med. 2015 Nov 19;373 [21]:2005-14).
“These results are interesting and provocative, but are not yet practice changing because in these high-risk patients with hormone receptor–positive tumors, relapses can occur several years after treatment so we need to wait for longer follow-up,” commented Dr. Angelo Di Leo, head of medical oncology at Prato (Italy) Hospital. He also cited the need to wait for results from several prospective, randomized trials now in progress that are more directly addressing the role of genetic profiling in predicting patient prognosis and treatment responses.
On Twitter @mitchelzoler
AT EBCC10
Key clinical point: A commercialized assessment of gene expression, the Recurrence Score, identified high-risk breast cancer patients who could forgo chemotherapy and receive hormonal treatment only and still have a good level of 5-year recurrence-free survival.
Major finding: Patients with a Recurrence Score of 0-11 had a 94% 5-year disease-free survival rate while largely avoiding chemotherapy.
Data source: The Plan B study, which included 2,642 German patients with hormone receptor–positive, HER2-negative breast cancer.
Disclosures: The Plan B trial was sponsored by Sanofi-Aventis, Amgen, and Genomic Health, the company that markets the Recurrence Score assay. Dr. Gluz said that he has been a speaker on behalf of Genomic Health and Nanostring. Dr. Di Leo said that he has been a lecturer on behalf of Genomic Health and has been a lecturer or advisor for seven drug companies.
Lifestyle Intervention Blocks Antipsychotic-associated Weight Gain
MADRID – The weight gain most patients have when first starting treatment with antipsychotic medications is not inevitable.
A 12-week intervention program designed to promote exercise and a healthy diet largely blunted a big weight gain by 16 adolescents and young adults starting treatment after an initial diagnosis of psychosis in a controlled study at a single Australian center. Later follow-up further showed that a majority of participants in the program remained mostly free of excess weight 2 years after the life-style intervention, Dr. Philip B. Ward said at the meeting sponsored by the European Psychiatric Association.
Implementing this type of intervention is very important because antipsychotic-induced weight gain launches young psychiatric patients into a middle age that often includes metabolic syndrome, type 2 diabetes, and a significantly increased risk for cardiovascular disease events, said Dr. Ward, a psychiatrist at the University of New South Wales in Sydney.
He reported results from a pilot program, Keeping the Body in Mind, run at one of the university’s community clinics that gave newly-diagnosed psychiatric patients aged 15-25 years regular instruction in diet, food shopping, and cooking and in an exercise class that included individualized coaching over the course of 12 weeks. At the end of the program, average weight gain relative to baseline weight was 1.8 kg among 16 patients in the intervention group and 7.8 kg among 12 patients who received standard care at a different community clinic. (Early Interv Psychiatry. 2015. doi: 10.1111/eip.12230).
Expressed another way, 2 of the 16 participating patients (13%) had a clinically significant (at least 7%) weight gain during the 12-week program, compared with 9 of the 12 (75%) of patients with a significant weight gain in the control group.
To assess the durability of this effect, Dr. Ward and his associates did follow-up 2 years later on 12 of the participants, who showed an average 1.3-kg weight gain after 2 years, compared with their weight at the time they entered the program, Dr Ward reported. Based on this success, the university’s psychiatric clinics are now expanding the program to make it available to all patients starting treatment on antipsychotic medications, about 80 patients a year, Dr. Ward said in an interview.
Although Dr. Ward stressed the importance of lifestyle intervention, he noted that the antipsychotic drug selected for treatment can also affect the magnitude of acute weight gain. Two drugs that seem to pose some of the lowest weight-gain risks are aripiprazole and ziprasidone.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
MADRID – The weight gain most patients have when first starting treatment with antipsychotic medications is not inevitable.
A 12-week intervention program designed to promote exercise and a healthy diet largely blunted a big weight gain by 16 adolescents and young adults starting treatment after an initial diagnosis of psychosis in a controlled study at a single Australian center. Later follow-up further showed that a majority of participants in the program remained mostly free of excess weight 2 years after the life-style intervention, Dr. Philip B. Ward said at the meeting sponsored by the European Psychiatric Association.
Implementing this type of intervention is very important because antipsychotic-induced weight gain launches young psychiatric patients into a middle age that often includes metabolic syndrome, type 2 diabetes, and a significantly increased risk for cardiovascular disease events, said Dr. Ward, a psychiatrist at the University of New South Wales in Sydney.
He reported results from a pilot program, Keeping the Body in Mind, run at one of the university’s community clinics that gave newly-diagnosed psychiatric patients aged 15-25 years regular instruction in diet, food shopping, and cooking and in an exercise class that included individualized coaching over the course of 12 weeks. At the end of the program, average weight gain relative to baseline weight was 1.8 kg among 16 patients in the intervention group and 7.8 kg among 12 patients who received standard care at a different community clinic. (Early Interv Psychiatry. 2015. doi: 10.1111/eip.12230).
Expressed another way, 2 of the 16 participating patients (13%) had a clinically significant (at least 7%) weight gain during the 12-week program, compared with 9 of the 12 (75%) of patients with a significant weight gain in the control group.
To assess the durability of this effect, Dr. Ward and his associates did follow-up 2 years later on 12 of the participants, who showed an average 1.3-kg weight gain after 2 years, compared with their weight at the time they entered the program, Dr Ward reported. Based on this success, the university’s psychiatric clinics are now expanding the program to make it available to all patients starting treatment on antipsychotic medications, about 80 patients a year, Dr. Ward said in an interview.
Although Dr. Ward stressed the importance of lifestyle intervention, he noted that the antipsychotic drug selected for treatment can also affect the magnitude of acute weight gain. Two drugs that seem to pose some of the lowest weight-gain risks are aripiprazole and ziprasidone.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
MADRID – The weight gain most patients have when first starting treatment with antipsychotic medications is not inevitable.
A 12-week intervention program designed to promote exercise and a healthy diet largely blunted a big weight gain by 16 adolescents and young adults starting treatment after an initial diagnosis of psychosis in a controlled study at a single Australian center. Later follow-up further showed that a majority of participants in the program remained mostly free of excess weight 2 years after the life-style intervention, Dr. Philip B. Ward said at the meeting sponsored by the European Psychiatric Association.
Implementing this type of intervention is very important because antipsychotic-induced weight gain launches young psychiatric patients into a middle age that often includes metabolic syndrome, type 2 diabetes, and a significantly increased risk for cardiovascular disease events, said Dr. Ward, a psychiatrist at the University of New South Wales in Sydney.
He reported results from a pilot program, Keeping the Body in Mind, run at one of the university’s community clinics that gave newly-diagnosed psychiatric patients aged 15-25 years regular instruction in diet, food shopping, and cooking and in an exercise class that included individualized coaching over the course of 12 weeks. At the end of the program, average weight gain relative to baseline weight was 1.8 kg among 16 patients in the intervention group and 7.8 kg among 12 patients who received standard care at a different community clinic. (Early Interv Psychiatry. 2015. doi: 10.1111/eip.12230).
Expressed another way, 2 of the 16 participating patients (13%) had a clinically significant (at least 7%) weight gain during the 12-week program, compared with 9 of the 12 (75%) of patients with a significant weight gain in the control group.
To assess the durability of this effect, Dr. Ward and his associates did follow-up 2 years later on 12 of the participants, who showed an average 1.3-kg weight gain after 2 years, compared with their weight at the time they entered the program, Dr Ward reported. Based on this success, the university’s psychiatric clinics are now expanding the program to make it available to all patients starting treatment on antipsychotic medications, about 80 patients a year, Dr. Ward said in an interview.
Although Dr. Ward stressed the importance of lifestyle intervention, he noted that the antipsychotic drug selected for treatment can also affect the magnitude of acute weight gain. Two drugs that seem to pose some of the lowest weight-gain risks are aripiprazole and ziprasidone.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT THE EUROPEAN CONGRESS OF PSYCHIATRY
VIDEO: Lifestyle intervention blocks antipsychotic-associated weight gain
MADRID – The weight gain most patients have when first starting treatment with antipsychotic medications is not inevitable.
A 12-week intervention program designed to promote exercise and a healthy diet largely blunted a big weight gain by 16 adolescents and young adults starting treatment after an initial diagnosis of psychosis in a controlled study at a single Australian center. Later follow-up further showed that a majority of participants in the program remained mostly free of excess weight 2 years after the life-style intervention, Dr. Philip B. Ward said at the meeting sponsored by the European Psychiatric Association.
Implementing this type of intervention is very important because antipsychotic-induced weight gain launches young psychiatric patients into a middle age that often includes metabolic syndrome, type 2 diabetes, and a significantly increased risk for cardiovascular disease events, said Dr. Ward, a psychiatrist at the University of New South Wales in Sydney.
He reported results from a pilot program, Keeping the Body in Mind, run at one of the university’s community clinics that gave newly-diagnosed psychiatric patients aged 15-25 years regular instruction in diet, food shopping, and cooking and in an exercise class that included individualized coaching over the course of 12 weeks. At the end of the program, average weight gain relative to baseline weight was 1.8 kg among 16 patients in the intervention group and 7.8 kg among 12 patients who received standard care at a different community clinic. (Early Interv Psychiatry. 2015. doi: 10.1111/eip.12230).
Expressed another way, 2 of the 16 participating patients (13%) had a clinically significant (at least 7%) weight gain during the 12-week program, compared with 9 of the 12 (75%) of patients with a significant weight gain in the control group.
To assess the durability of this effect, Dr. Ward and his associates did follow-up 2 years later on 12 of the participants, who showed an average 1.3-kg weight gain after 2 years, compared with their weight at the time they entered the program, Dr Ward reported. Based on this success, the university’s psychiatric clinics are now expanding the program to make it available to all patients starting treatment on antipsychotic medications, about 80 patients a year, Dr. Ward said in an interview.
Although Dr. Ward stressed the importance of lifestyle intervention, he noted that the antipsychotic drug selected for treatment can also affect the magnitude of acute weight gain. Two drugs that seem to pose some of the lowest weight-gain risks are aripiprazole and ziprasidone.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
MADRID – The weight gain most patients have when first starting treatment with antipsychotic medications is not inevitable.
A 12-week intervention program designed to promote exercise and a healthy diet largely blunted a big weight gain by 16 adolescents and young adults starting treatment after an initial diagnosis of psychosis in a controlled study at a single Australian center. Later follow-up further showed that a majority of participants in the program remained mostly free of excess weight 2 years after the life-style intervention, Dr. Philip B. Ward said at the meeting sponsored by the European Psychiatric Association.
Implementing this type of intervention is very important because antipsychotic-induced weight gain launches young psychiatric patients into a middle age that often includes metabolic syndrome, type 2 diabetes, and a significantly increased risk for cardiovascular disease events, said Dr. Ward, a psychiatrist at the University of New South Wales in Sydney.
He reported results from a pilot program, Keeping the Body in Mind, run at one of the university’s community clinics that gave newly-diagnosed psychiatric patients aged 15-25 years regular instruction in diet, food shopping, and cooking and in an exercise class that included individualized coaching over the course of 12 weeks. At the end of the program, average weight gain relative to baseline weight was 1.8 kg among 16 patients in the intervention group and 7.8 kg among 12 patients who received standard care at a different community clinic. (Early Interv Psychiatry. 2015. doi: 10.1111/eip.12230).
Expressed another way, 2 of the 16 participating patients (13%) had a clinically significant (at least 7%) weight gain during the 12-week program, compared with 9 of the 12 (75%) of patients with a significant weight gain in the control group.
To assess the durability of this effect, Dr. Ward and his associates did follow-up 2 years later on 12 of the participants, who showed an average 1.3-kg weight gain after 2 years, compared with their weight at the time they entered the program, Dr Ward reported. Based on this success, the university’s psychiatric clinics are now expanding the program to make it available to all patients starting treatment on antipsychotic medications, about 80 patients a year, Dr. Ward said in an interview.
Although Dr. Ward stressed the importance of lifestyle intervention, he noted that the antipsychotic drug selected for treatment can also affect the magnitude of acute weight gain. Two drugs that seem to pose some of the lowest weight-gain risks are aripiprazole and ziprasidone.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
MADRID – The weight gain most patients have when first starting treatment with antipsychotic medications is not inevitable.
A 12-week intervention program designed to promote exercise and a healthy diet largely blunted a big weight gain by 16 adolescents and young adults starting treatment after an initial diagnosis of psychosis in a controlled study at a single Australian center. Later follow-up further showed that a majority of participants in the program remained mostly free of excess weight 2 years after the life-style intervention, Dr. Philip B. Ward said at the meeting sponsored by the European Psychiatric Association.
Implementing this type of intervention is very important because antipsychotic-induced weight gain launches young psychiatric patients into a middle age that often includes metabolic syndrome, type 2 diabetes, and a significantly increased risk for cardiovascular disease events, said Dr. Ward, a psychiatrist at the University of New South Wales in Sydney.
He reported results from a pilot program, Keeping the Body in Mind, run at one of the university’s community clinics that gave newly-diagnosed psychiatric patients aged 15-25 years regular instruction in diet, food shopping, and cooking and in an exercise class that included individualized coaching over the course of 12 weeks. At the end of the program, average weight gain relative to baseline weight was 1.8 kg among 16 patients in the intervention group and 7.8 kg among 12 patients who received standard care at a different community clinic. (Early Interv Psychiatry. 2015. doi: 10.1111/eip.12230).
Expressed another way, 2 of the 16 participating patients (13%) had a clinically significant (at least 7%) weight gain during the 12-week program, compared with 9 of the 12 (75%) of patients with a significant weight gain in the control group.
To assess the durability of this effect, Dr. Ward and his associates did follow-up 2 years later on 12 of the participants, who showed an average 1.3-kg weight gain after 2 years, compared with their weight at the time they entered the program, Dr Ward reported. Based on this success, the university’s psychiatric clinics are now expanding the program to make it available to all patients starting treatment on antipsychotic medications, about 80 patients a year, Dr. Ward said in an interview.
Although Dr. Ward stressed the importance of lifestyle intervention, he noted that the antipsychotic drug selected for treatment can also affect the magnitude of acute weight gain. Two drugs that seem to pose some of the lowest weight-gain risks are aripiprazole and ziprasidone.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
AT THE EUROPEAN CONGRESS OF PSYCHIATRY
Key clinical point: Most adolescents and young adults who participated in a lifestyle intervention when they began receiving an antipsychotic medication avoided acute weight gain.
Major finding: At 2-year follow-up, the average weight gain by program participants was 1.3 kg above baseline weight.
Data source: Sixteen adolescent and young-adult patients newly diagnosed with psychosis treated at one Australian center.
Disclosures: Dr. Ward had no disclosures.
Brexpiprazole combined analysis shows schizophrenia safety, efficacy
MADRID – Brexpiprazole, a new drug for treatment of schizophrenia that received Food and Drug Administration marketing approval in July 2015, showed good efficacy for patients with acute schizophrenia as well as a good safety profile in a combined analysis from three phase III trials that compared the drug against placebo.
“The incidence of withdrawals due to adverse effects was lower with brexpiprazole administered as 2-4 mg/day than with placebo, and the incidence of activating and sedating effects with brexpiprazole was low, Catherine Weiss, Ph.D., reported at the meeting, sponsored by the European Psychiatric Association.
“For long-term treatment, the lower level of sedation from treatment with brexpiprazole is an advantage,” said Dr. Weiss, director of global medical affairs for Otsuka, the company that is marketing brexpiprazole (Rexulti) along with a partner company, Lundbeck.
“We hope that brexpiprazole will be suitable for outpatients with schizophrenia who still have the potential to function in the community, to work and have relationships. Our data show that brexpiprazole prevents schizophrenia relapses and is very well tolerated,” said Dr. Emmanuelle Weiller, a senior medical adviser with Lundbeck in Copenhagen.
In its announcement of the marketing approval for brexpiprazole last year, the FDA did not include any description of how the drug works. But according to a statement from Lundbeck, the efficacy of brexpiprazole may be mediated by partial or full agonist activity at certain serotonin or dopamine receptors. The drug also has high affinity for certain noradrenaline alpha receptors.
The FDA based its approval for treatment of adults with schizophrenia (the drug was simultaneously also approved for adjunctive treatment of adults with major depressive disorder) on the results from two pivotal trials that both were published last year (Am Psychiatry. 2015 Sept 1;172[9]:870-80 and Schizophr Res. 2015 May;164[1-3]:127-35).
Dr. Weiss’ combined analysis used data collected in both of these trials as well as in a third trial, the results of which were reported in a separate talk during the same meeting session. The third brexpiprazole trial randomized 468 adults with schizophrenia to one of three treatment groups: patients who received a flexible brexpiprazole dosage, patients who received placebo, and patients randomized to treatment with quetiapine XR, a subgroup that served as an active reference arm but not a comparator arm.
The combined analysis focused on the 868 patients in any of the three trials who received either 2 mg or 4 mg of brexpiprazole daily and its comparison to 517 patients who received placebo during 6 weeks of treatment. The combined results showed an overall, average incremental reduction in the positive and negative syndrome scale (PANSS) score of 5.8 with brexpiprazole treatment compared with placebo, a statistically significant difference, Dr. Weiss reported. Treatment with brexpiprazole for 6 weeks also produced significant improvements compared with placebo for three secondary efficacy measures: clinical global impression of severity, clinical global impression of improvement, and personal and social performance.
The safety analysis showed that treatment-emergent adverse events leading to withdrawal from treatment occurred in 8% of patients on brexpiprazole and in 13% of those on placebo. None of the most common treatment-emergent adverse effects were substantially more common in the brexpiprazole-treated patients, compared with those on placebo.
Brexpiprazole’s likely role right now is as an alternative maintenance drug for patients whose schizophrenia is either not adequately controlled by an older agent, or for patients who experience intolerable adverse effects on an older drug and would like an alternative drug that does not interfere as much with their usual activities, Dr. Weiller said in an interview.
Dr. Weiss is an employee of Otsuka. Dr. Weiller is an employee of Lundbeck. Otsuka and Lundbeck funded these drug studies.
On Twitter @mitchelzoler
MADRID – Brexpiprazole, a new drug for treatment of schizophrenia that received Food and Drug Administration marketing approval in July 2015, showed good efficacy for patients with acute schizophrenia as well as a good safety profile in a combined analysis from three phase III trials that compared the drug against placebo.
“The incidence of withdrawals due to adverse effects was lower with brexpiprazole administered as 2-4 mg/day than with placebo, and the incidence of activating and sedating effects with brexpiprazole was low, Catherine Weiss, Ph.D., reported at the meeting, sponsored by the European Psychiatric Association.
“For long-term treatment, the lower level of sedation from treatment with brexpiprazole is an advantage,” said Dr. Weiss, director of global medical affairs for Otsuka, the company that is marketing brexpiprazole (Rexulti) along with a partner company, Lundbeck.
“We hope that brexpiprazole will be suitable for outpatients with schizophrenia who still have the potential to function in the community, to work and have relationships. Our data show that brexpiprazole prevents schizophrenia relapses and is very well tolerated,” said Dr. Emmanuelle Weiller, a senior medical adviser with Lundbeck in Copenhagen.
In its announcement of the marketing approval for brexpiprazole last year, the FDA did not include any description of how the drug works. But according to a statement from Lundbeck, the efficacy of brexpiprazole may be mediated by partial or full agonist activity at certain serotonin or dopamine receptors. The drug also has high affinity for certain noradrenaline alpha receptors.
The FDA based its approval for treatment of adults with schizophrenia (the drug was simultaneously also approved for adjunctive treatment of adults with major depressive disorder) on the results from two pivotal trials that both were published last year (Am Psychiatry. 2015 Sept 1;172[9]:870-80 and Schizophr Res. 2015 May;164[1-3]:127-35).
Dr. Weiss’ combined analysis used data collected in both of these trials as well as in a third trial, the results of which were reported in a separate talk during the same meeting session. The third brexpiprazole trial randomized 468 adults with schizophrenia to one of three treatment groups: patients who received a flexible brexpiprazole dosage, patients who received placebo, and patients randomized to treatment with quetiapine XR, a subgroup that served as an active reference arm but not a comparator arm.
The combined analysis focused on the 868 patients in any of the three trials who received either 2 mg or 4 mg of brexpiprazole daily and its comparison to 517 patients who received placebo during 6 weeks of treatment. The combined results showed an overall, average incremental reduction in the positive and negative syndrome scale (PANSS) score of 5.8 with brexpiprazole treatment compared with placebo, a statistically significant difference, Dr. Weiss reported. Treatment with brexpiprazole for 6 weeks also produced significant improvements compared with placebo for three secondary efficacy measures: clinical global impression of severity, clinical global impression of improvement, and personal and social performance.
The safety analysis showed that treatment-emergent adverse events leading to withdrawal from treatment occurred in 8% of patients on brexpiprazole and in 13% of those on placebo. None of the most common treatment-emergent adverse effects were substantially more common in the brexpiprazole-treated patients, compared with those on placebo.
Brexpiprazole’s likely role right now is as an alternative maintenance drug for patients whose schizophrenia is either not adequately controlled by an older agent, or for patients who experience intolerable adverse effects on an older drug and would like an alternative drug that does not interfere as much with their usual activities, Dr. Weiller said in an interview.
Dr. Weiss is an employee of Otsuka. Dr. Weiller is an employee of Lundbeck. Otsuka and Lundbeck funded these drug studies.
On Twitter @mitchelzoler
MADRID – Brexpiprazole, a new drug for treatment of schizophrenia that received Food and Drug Administration marketing approval in July 2015, showed good efficacy for patients with acute schizophrenia as well as a good safety profile in a combined analysis from three phase III trials that compared the drug against placebo.
“The incidence of withdrawals due to adverse effects was lower with brexpiprazole administered as 2-4 mg/day than with placebo, and the incidence of activating and sedating effects with brexpiprazole was low, Catherine Weiss, Ph.D., reported at the meeting, sponsored by the European Psychiatric Association.
“For long-term treatment, the lower level of sedation from treatment with brexpiprazole is an advantage,” said Dr. Weiss, director of global medical affairs for Otsuka, the company that is marketing brexpiprazole (Rexulti) along with a partner company, Lundbeck.
“We hope that brexpiprazole will be suitable for outpatients with schizophrenia who still have the potential to function in the community, to work and have relationships. Our data show that brexpiprazole prevents schizophrenia relapses and is very well tolerated,” said Dr. Emmanuelle Weiller, a senior medical adviser with Lundbeck in Copenhagen.
In its announcement of the marketing approval for brexpiprazole last year, the FDA did not include any description of how the drug works. But according to a statement from Lundbeck, the efficacy of brexpiprazole may be mediated by partial or full agonist activity at certain serotonin or dopamine receptors. The drug also has high affinity for certain noradrenaline alpha receptors.
The FDA based its approval for treatment of adults with schizophrenia (the drug was simultaneously also approved for adjunctive treatment of adults with major depressive disorder) on the results from two pivotal trials that both were published last year (Am Psychiatry. 2015 Sept 1;172[9]:870-80 and Schizophr Res. 2015 May;164[1-3]:127-35).
Dr. Weiss’ combined analysis used data collected in both of these trials as well as in a third trial, the results of which were reported in a separate talk during the same meeting session. The third brexpiprazole trial randomized 468 adults with schizophrenia to one of three treatment groups: patients who received a flexible brexpiprazole dosage, patients who received placebo, and patients randomized to treatment with quetiapine XR, a subgroup that served as an active reference arm but not a comparator arm.
The combined analysis focused on the 868 patients in any of the three trials who received either 2 mg or 4 mg of brexpiprazole daily and its comparison to 517 patients who received placebo during 6 weeks of treatment. The combined results showed an overall, average incremental reduction in the positive and negative syndrome scale (PANSS) score of 5.8 with brexpiprazole treatment compared with placebo, a statistically significant difference, Dr. Weiss reported. Treatment with brexpiprazole for 6 weeks also produced significant improvements compared with placebo for three secondary efficacy measures: clinical global impression of severity, clinical global impression of improvement, and personal and social performance.
The safety analysis showed that treatment-emergent adverse events leading to withdrawal from treatment occurred in 8% of patients on brexpiprazole and in 13% of those on placebo. None of the most common treatment-emergent adverse effects were substantially more common in the brexpiprazole-treated patients, compared with those on placebo.
Brexpiprazole’s likely role right now is as an alternative maintenance drug for patients whose schizophrenia is either not adequately controlled by an older agent, or for patients who experience intolerable adverse effects on an older drug and would like an alternative drug that does not interfere as much with their usual activities, Dr. Weiller said in an interview.
Dr. Weiss is an employee of Otsuka. Dr. Weiller is an employee of Lundbeck. Otsuka and Lundbeck funded these drug studies.
On Twitter @mitchelzoler
AT THE EUROPEAN CONGRESS OF PSYCHIATRY
Key clinical point: A combined analysis of data from three phase III trials confirmed brexpiprazole’s safety and efficacy for adults with schizophrenia.
Major finding: Brexpiprazole treatment for 6 weeks produced an average 5.8-point incremental reduction in the positive and negative syndrome scale score, compared with placebo.
Data source: Combined analysis of three phase III trials that together included 868 patients treated with brexpiprazole and 517 who received placebo.
Disclosures: Dr. Weiss is an employee of Otsuka. Dr. Weiller is an employee of Lundbeck. Otsuka and Lundbeck together market brexpiprazole (Rexulti) and funded these drug studies.
Dose-dense chemotherapy boosts premenopausal breast cancer survival
AMSTERDAM – Premenopausal women with breast cancer at high risk for recurrence had a significantly improved 10-year rate of overall survival when they received a dose-dense chemotherapy regimen, compared with women treated with a standard dosage schedule.
This post hoc analysis of 1,549 premenopausal patients, a subgroup drawn from two separate trials run a decade apart, helps further confirm the benefit of the dose-dense approach in this population. “I think that European practice will now change,” based on this new analysis plus other recent findings from smaller studies, predicted Dr. Matteo Lambertini, who reported the analysis at the European Breast Cancer Congress.
“Dose-dense adjuvant chemotherapy may be considered the preferred treatment option and should be proposed to all high-risk, premenopausal breast cancer patients who are candidates for chemotherapy,” said Dr. Lambertini of Azienda University Hospital in Genoa, Italy. Although dose-dense regimens are common in U.S. practice for these patients and used at certain European Centers, many other European cancer programs still use standard-dose chemotherapy, he said.
The findings also showed that when treatment induced amenorrhea, it had no bearing on subsequent survival, and that the dose-dense regimen did not cause amenorrhea.
The analysis run by Dr. Lambertini and his associates pieced together data from premenopausal women who formed subgroups in two large Italian trials of dose-dense regimens as adjuvant chemotherapy for women of all ages with early-stage breast cancer: the Mammella InterGruppo (MIG) 1 trial and the Gruppo Italiano Mammella (GIM) 2 trial. MIG1 randomized 1,214 patients with early-stage breast cancer to standard chemotherapy given in 3-week cycles or in dose-dense 2-week cycles. At a median 10-year follow-up, the results showed a nonsignificant difference in overall survival between the two arms; the findings primarily demonstrated the safety of the dose-dense regimen (J Nat Cancer Inst. 2005 Dec 7;97 [23]:1724-33). GIM2 randomized 2,019 patients with early-stage breast cancer to the same alternatives, standard chemotherapy administered either every 2 or every 3 weeks and followed them for a median of 7 years. Its results showed a statistically significant improvement in disease-free survival after 5 years with the dose-dense regimen (Lancet. 2015 May 9;385[9980]:1863-72).
All patients in both studies routinely received ongoing treatment with a granulocyte colony–stimulating factor analogue during chemotherapy to help avoid the development of anemia or leukopenia.
Dr. Lambertini’s analysis focused on the 1,549 women from both studies who were premenopausal at the time they received treatment, with more than half of these patients younger than 45 years old. In this population, treatment with the dose-dense regimen resulted in a statistically significant increased rate of 10-year overall survival, expressed as a 29% reduced hazard ratio for death with dose-dense treatment (P = .021), he reported. The benefit was greatest in women with hormone receptor–negative tumors, with a hazard ratio for death reduced by 35% among women with a hormone receptor–negative tumor; overall mortality fell by 22% after a dose-dense regimen, compared with women who received chemotherapy with a standard interval between treatments.
The analysis also showed no impact from development of amenorrhea, with a nonsignificant hazard ratio of 16% separating the mortality rates in women who developed treatment-related amenorrhea and those who did not.
“This meta-analysis provides important information that has the potential to change and improve treatment of breast cancer in premenopausal patients,” commented Dr. Fátima Cardoso, director of the breast unit at the Champalimaud Clinical Center, Lisbon. The new findings “give us evidence-based answers as to whether or not dose-dense chemotherapy can be used in these patients without increasing their risk of treatment-induced amenorrhea, as well as showing a survival benefit,” Dr. Cardoso said in a written statement.
On Twitter@mitchelzoler
This analysis confirms the appropriateness of dose-dense chemotherapy regimens for premenopausal patients, an approach that is already routinely used in women with high-risk breast cancer who require chemotherapy. Dose-dense regimens are currently used more widely in the United States than in Europe, but these new findings should help further convince European oncologists to use dose-dense treatment schedules. The disadvantage of these regimens is that they involve more clinic visits and are more costly.
One of the factors increasing the cost is the need for greater bone marrow support by concurrent treatment with a granulocyte colony–stimulating factor analogue. It is important to have data like these to convince payers that dose-dense regimens are worth their extra cost.
By focusing specifically on premenopausal women, this analysis also showed that dose-dense regimens do not trigger more episodes of amenorrhea, nor were episodes of amenorrhea needed to get the greatest survival benefit.
Dr. Emiel J.T. Rutgers is a surgical oncologist and clinical director of the Netherlands Cancer Institute in Amsterdam. He had no relevant financial disclosures. He made these comments during a video interview with this news organization.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
This analysis confirms the appropriateness of dose-dense chemotherapy regimens for premenopausal patients, an approach that is already routinely used in women with high-risk breast cancer who require chemotherapy. Dose-dense regimens are currently used more widely in the United States than in Europe, but these new findings should help further convince European oncologists to use dose-dense treatment schedules. The disadvantage of these regimens is that they involve more clinic visits and are more costly.
One of the factors increasing the cost is the need for greater bone marrow support by concurrent treatment with a granulocyte colony–stimulating factor analogue. It is important to have data like these to convince payers that dose-dense regimens are worth their extra cost.
By focusing specifically on premenopausal women, this analysis also showed that dose-dense regimens do not trigger more episodes of amenorrhea, nor were episodes of amenorrhea needed to get the greatest survival benefit.
Dr. Emiel J.T. Rutgers is a surgical oncologist and clinical director of the Netherlands Cancer Institute in Amsterdam. He had no relevant financial disclosures. He made these comments during a video interview with this news organization.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
This analysis confirms the appropriateness of dose-dense chemotherapy regimens for premenopausal patients, an approach that is already routinely used in women with high-risk breast cancer who require chemotherapy. Dose-dense regimens are currently used more widely in the United States than in Europe, but these new findings should help further convince European oncologists to use dose-dense treatment schedules. The disadvantage of these regimens is that they involve more clinic visits and are more costly.
One of the factors increasing the cost is the need for greater bone marrow support by concurrent treatment with a granulocyte colony–stimulating factor analogue. It is important to have data like these to convince payers that dose-dense regimens are worth their extra cost.
By focusing specifically on premenopausal women, this analysis also showed that dose-dense regimens do not trigger more episodes of amenorrhea, nor were episodes of amenorrhea needed to get the greatest survival benefit.
Dr. Emiel J.T. Rutgers is a surgical oncologist and clinical director of the Netherlands Cancer Institute in Amsterdam. He had no relevant financial disclosures. He made these comments during a video interview with this news organization.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AMSTERDAM – Premenopausal women with breast cancer at high risk for recurrence had a significantly improved 10-year rate of overall survival when they received a dose-dense chemotherapy regimen, compared with women treated with a standard dosage schedule.
This post hoc analysis of 1,549 premenopausal patients, a subgroup drawn from two separate trials run a decade apart, helps further confirm the benefit of the dose-dense approach in this population. “I think that European practice will now change,” based on this new analysis plus other recent findings from smaller studies, predicted Dr. Matteo Lambertini, who reported the analysis at the European Breast Cancer Congress.
“Dose-dense adjuvant chemotherapy may be considered the preferred treatment option and should be proposed to all high-risk, premenopausal breast cancer patients who are candidates for chemotherapy,” said Dr. Lambertini of Azienda University Hospital in Genoa, Italy. Although dose-dense regimens are common in U.S. practice for these patients and used at certain European Centers, many other European cancer programs still use standard-dose chemotherapy, he said.
The findings also showed that when treatment induced amenorrhea, it had no bearing on subsequent survival, and that the dose-dense regimen did not cause amenorrhea.
The analysis run by Dr. Lambertini and his associates pieced together data from premenopausal women who formed subgroups in two large Italian trials of dose-dense regimens as adjuvant chemotherapy for women of all ages with early-stage breast cancer: the Mammella InterGruppo (MIG) 1 trial and the Gruppo Italiano Mammella (GIM) 2 trial. MIG1 randomized 1,214 patients with early-stage breast cancer to standard chemotherapy given in 3-week cycles or in dose-dense 2-week cycles. At a median 10-year follow-up, the results showed a nonsignificant difference in overall survival between the two arms; the findings primarily demonstrated the safety of the dose-dense regimen (J Nat Cancer Inst. 2005 Dec 7;97 [23]:1724-33). GIM2 randomized 2,019 patients with early-stage breast cancer to the same alternatives, standard chemotherapy administered either every 2 or every 3 weeks and followed them for a median of 7 years. Its results showed a statistically significant improvement in disease-free survival after 5 years with the dose-dense regimen (Lancet. 2015 May 9;385[9980]:1863-72).
All patients in both studies routinely received ongoing treatment with a granulocyte colony–stimulating factor analogue during chemotherapy to help avoid the development of anemia or leukopenia.
Dr. Lambertini’s analysis focused on the 1,549 women from both studies who were premenopausal at the time they received treatment, with more than half of these patients younger than 45 years old. In this population, treatment with the dose-dense regimen resulted in a statistically significant increased rate of 10-year overall survival, expressed as a 29% reduced hazard ratio for death with dose-dense treatment (P = .021), he reported. The benefit was greatest in women with hormone receptor–negative tumors, with a hazard ratio for death reduced by 35% among women with a hormone receptor–negative tumor; overall mortality fell by 22% after a dose-dense regimen, compared with women who received chemotherapy with a standard interval between treatments.
The analysis also showed no impact from development of amenorrhea, with a nonsignificant hazard ratio of 16% separating the mortality rates in women who developed treatment-related amenorrhea and those who did not.
“This meta-analysis provides important information that has the potential to change and improve treatment of breast cancer in premenopausal patients,” commented Dr. Fátima Cardoso, director of the breast unit at the Champalimaud Clinical Center, Lisbon. The new findings “give us evidence-based answers as to whether or not dose-dense chemotherapy can be used in these patients without increasing their risk of treatment-induced amenorrhea, as well as showing a survival benefit,” Dr. Cardoso said in a written statement.
On Twitter@mitchelzoler
AMSTERDAM – Premenopausal women with breast cancer at high risk for recurrence had a significantly improved 10-year rate of overall survival when they received a dose-dense chemotherapy regimen, compared with women treated with a standard dosage schedule.
This post hoc analysis of 1,549 premenopausal patients, a subgroup drawn from two separate trials run a decade apart, helps further confirm the benefit of the dose-dense approach in this population. “I think that European practice will now change,” based on this new analysis plus other recent findings from smaller studies, predicted Dr. Matteo Lambertini, who reported the analysis at the European Breast Cancer Congress.
“Dose-dense adjuvant chemotherapy may be considered the preferred treatment option and should be proposed to all high-risk, premenopausal breast cancer patients who are candidates for chemotherapy,” said Dr. Lambertini of Azienda University Hospital in Genoa, Italy. Although dose-dense regimens are common in U.S. practice for these patients and used at certain European Centers, many other European cancer programs still use standard-dose chemotherapy, he said.
The findings also showed that when treatment induced amenorrhea, it had no bearing on subsequent survival, and that the dose-dense regimen did not cause amenorrhea.
The analysis run by Dr. Lambertini and his associates pieced together data from premenopausal women who formed subgroups in two large Italian trials of dose-dense regimens as adjuvant chemotherapy for women of all ages with early-stage breast cancer: the Mammella InterGruppo (MIG) 1 trial and the Gruppo Italiano Mammella (GIM) 2 trial. MIG1 randomized 1,214 patients with early-stage breast cancer to standard chemotherapy given in 3-week cycles or in dose-dense 2-week cycles. At a median 10-year follow-up, the results showed a nonsignificant difference in overall survival between the two arms; the findings primarily demonstrated the safety of the dose-dense regimen (J Nat Cancer Inst. 2005 Dec 7;97 [23]:1724-33). GIM2 randomized 2,019 patients with early-stage breast cancer to the same alternatives, standard chemotherapy administered either every 2 or every 3 weeks and followed them for a median of 7 years. Its results showed a statistically significant improvement in disease-free survival after 5 years with the dose-dense regimen (Lancet. 2015 May 9;385[9980]:1863-72).
All patients in both studies routinely received ongoing treatment with a granulocyte colony–stimulating factor analogue during chemotherapy to help avoid the development of anemia or leukopenia.
Dr. Lambertini’s analysis focused on the 1,549 women from both studies who were premenopausal at the time they received treatment, with more than half of these patients younger than 45 years old. In this population, treatment with the dose-dense regimen resulted in a statistically significant increased rate of 10-year overall survival, expressed as a 29% reduced hazard ratio for death with dose-dense treatment (P = .021), he reported. The benefit was greatest in women with hormone receptor–negative tumors, with a hazard ratio for death reduced by 35% among women with a hormone receptor–negative tumor; overall mortality fell by 22% after a dose-dense regimen, compared with women who received chemotherapy with a standard interval between treatments.
The analysis also showed no impact from development of amenorrhea, with a nonsignificant hazard ratio of 16% separating the mortality rates in women who developed treatment-related amenorrhea and those who did not.
“This meta-analysis provides important information that has the potential to change and improve treatment of breast cancer in premenopausal patients,” commented Dr. Fátima Cardoso, director of the breast unit at the Champalimaud Clinical Center, Lisbon. The new findings “give us evidence-based answers as to whether or not dose-dense chemotherapy can be used in these patients without increasing their risk of treatment-induced amenorrhea, as well as showing a survival benefit,” Dr. Cardoso said in a written statement.
On Twitter@mitchelzoler
AT EBCC10
Key clinical point: Premenopausal women with breast cancer at high risk for recurrence had a significantly improved rate of overall 10-year survival following a dose-dense chemotherapy regimen, compared with women who received a standard-treatment schedule.
Major finding: The mortality hazard ratio fell by 29% (P = .021) with dose-dense treatment, compared with standard chemotherapy.
Data source: A post hoc subgroup analysis of data collected from two large Italian chemotherapy trials that together included 1,549 premenopausal breast cancer patients.
Disclosures: Dr. Lambertini and Dr. Cardoso had no relevant financial disclosures.
VIDEO: Focused breast cancer radiation maintains efficacy, cuts AEs
AMSTERDAM – Modifying the standard radiation dosage to women with early-stage breast cancer so that the tumor-bed dosage remained the same but eliminated the dosage delivered to surrounding breast tissue led to similar 5-year efficacy and reduced adverse effects in a multicenter U.K. trial that involved more than 2,000 patients.
“Partial-breast radiotherapy was noninferior to whole-breast radiotherpy for reducing local recurrences and reduced the severity of overall breast appearance and breast hardness,” Dr. Charlotte Coles said at the European Breast Cancer Congress. “I consider this practice changing,” concluded Dr. Coles of Cambridge (England) University Hospitals.
While some experts at the meeting agreed with Dr. Coles’ assessment of the findings, others took a more skeptical view, focusing on the median follow-up of just 5 years.
“There is still some question about the long-term results for local recurrence rates,” said Dr. Robert Mansel, professor of surgical oncology at Cardiff (Wales) University. In addition, “the rationale for doing this is to reduce side effects to the whole breast, but the results showed little difference in side effects” between women who received the standard radiation dosage and those who received a reduced dosage, “so the rationale for doing this is not quite there,” said Dr. Mansel, the session’s designated discussant.
The Intensity Modulated Partial Breast Radiotherapy for Women with Early Breast Cancer (IMPORT LOW) trial enrolled 2,018 patients with early breast cancer at 30 U.K. centers during 2007-2010. Patients underwent breast conservation surgery and were at least 50 years old, had a tumor of 3 cm or less, had an invasive and unifocal adenocarcinoma that was grade I, II, or III, and had lymph nodes that were either negative or had micrometastases (pN0 or pN1). The trial randomized these women to either standard, whole-breast radiation with 40 gray, a reduced-dosage regimen that delivered 40 gray to the tumor bed but 36 gray to the rest of the breast, or a partial regimen that delivered 40 gray to the tumor bed and no radiation at all to the rest of the ipsilateral breast. All three regimens were administered as 15 fractions.
After a median follow-up of 71 months, the 674 women randomized to the reduced regimen had a 26% reduction in their absolute local recurrence rate compared with the 674 whole-breast controls. The 670 women randomized to the partial regimen had an absolute reduction of 39%. Both of these relative reductions were statistically significant. These efficacy results also met the study’s prespecified primary endpoint for noninferiority for controlling local recurrences in the ipsilateral breast, Dr. Coles reported.
For the study’s secondary endpoints of various measures of adverse effects to the normal breast tissue, the partial-dosage regimen led to a statistically significant reduction in patient assessment of changed breast appearance (P = .005) and a reduced rate of patient perception of increased breast firmness (P = .001). The adverse-effects endpoints also showed a significant reduction with the partial regimen in physician assessment of breast edema (P = .0053). The overall rate of patients free of any adverse effect in their normal breast tissue after 5 years was 72% in the control patients, 79% in those who received the reduced-dose regimen (P = .042), and 81% in those who received the partial dose (P = .004).
An expert panel is scheduled to review new evidence on breast radiotherapy later in March, and these new data may produce a change in the recommended irradiation protocol, Dr. Coles said.
On Twitter @mitchelzoler
I believe that these 5-year results are sufficient to make the partial-dose radiation regimen our new standard treatment. The advantage is to better spare the normal breast tissue from radiation damage while maintaining similar local control compared with standard radiotherapy that irradiates the entire breast.
In the results reported by Dr. Coles, partial breast irradiation produced excellent local control with more limited toxicity. It should be used for women with an early, small, low-risk breast cancer detected by screening with no or very limited lymph node metastases. I estimate that about a third of women with breast cancer fall into this category. There seems to be no reason to not apply these findings to any woman who meets the enrollment criteria for the study.
One limitation of this study is that it involved a median 5-year follow-up, whereas we usually focus on 10-year follow-up data. However, we know that local-recurrence rates are usually low during years 6-10 following breast irradiation for these types of patients, so I think the 5-year data are sufficient.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Dr. Emiel J.T. Rutgers is a surgical oncologist and clinical director of the Netherlands Cancer Institute in Amsterdam. He had no disclosures. He made these comments during an interview.
I believe that these 5-year results are sufficient to make the partial-dose radiation regimen our new standard treatment. The advantage is to better spare the normal breast tissue from radiation damage while maintaining similar local control compared with standard radiotherapy that irradiates the entire breast.
In the results reported by Dr. Coles, partial breast irradiation produced excellent local control with more limited toxicity. It should be used for women with an early, small, low-risk breast cancer detected by screening with no or very limited lymph node metastases. I estimate that about a third of women with breast cancer fall into this category. There seems to be no reason to not apply these findings to any woman who meets the enrollment criteria for the study.
One limitation of this study is that it involved a median 5-year follow-up, whereas we usually focus on 10-year follow-up data. However, we know that local-recurrence rates are usually low during years 6-10 following breast irradiation for these types of patients, so I think the 5-year data are sufficient.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Dr. Emiel J.T. Rutgers is a surgical oncologist and clinical director of the Netherlands Cancer Institute in Amsterdam. He had no disclosures. He made these comments during an interview.
I believe that these 5-year results are sufficient to make the partial-dose radiation regimen our new standard treatment. The advantage is to better spare the normal breast tissue from radiation damage while maintaining similar local control compared with standard radiotherapy that irradiates the entire breast.
In the results reported by Dr. Coles, partial breast irradiation produced excellent local control with more limited toxicity. It should be used for women with an early, small, low-risk breast cancer detected by screening with no or very limited lymph node metastases. I estimate that about a third of women with breast cancer fall into this category. There seems to be no reason to not apply these findings to any woman who meets the enrollment criteria for the study.
One limitation of this study is that it involved a median 5-year follow-up, whereas we usually focus on 10-year follow-up data. However, we know that local-recurrence rates are usually low during years 6-10 following breast irradiation for these types of patients, so I think the 5-year data are sufficient.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Dr. Emiel J.T. Rutgers is a surgical oncologist and clinical director of the Netherlands Cancer Institute in Amsterdam. He had no disclosures. He made these comments during an interview.
AMSTERDAM – Modifying the standard radiation dosage to women with early-stage breast cancer so that the tumor-bed dosage remained the same but eliminated the dosage delivered to surrounding breast tissue led to similar 5-year efficacy and reduced adverse effects in a multicenter U.K. trial that involved more than 2,000 patients.
“Partial-breast radiotherapy was noninferior to whole-breast radiotherpy for reducing local recurrences and reduced the severity of overall breast appearance and breast hardness,” Dr. Charlotte Coles said at the European Breast Cancer Congress. “I consider this practice changing,” concluded Dr. Coles of Cambridge (England) University Hospitals.
While some experts at the meeting agreed with Dr. Coles’ assessment of the findings, others took a more skeptical view, focusing on the median follow-up of just 5 years.
“There is still some question about the long-term results for local recurrence rates,” said Dr. Robert Mansel, professor of surgical oncology at Cardiff (Wales) University. In addition, “the rationale for doing this is to reduce side effects to the whole breast, but the results showed little difference in side effects” between women who received the standard radiation dosage and those who received a reduced dosage, “so the rationale for doing this is not quite there,” said Dr. Mansel, the session’s designated discussant.
The Intensity Modulated Partial Breast Radiotherapy for Women with Early Breast Cancer (IMPORT LOW) trial enrolled 2,018 patients with early breast cancer at 30 U.K. centers during 2007-2010. Patients underwent breast conservation surgery and were at least 50 years old, had a tumor of 3 cm or less, had an invasive and unifocal adenocarcinoma that was grade I, II, or III, and had lymph nodes that were either negative or had micrometastases (pN0 or pN1). The trial randomized these women to either standard, whole-breast radiation with 40 gray, a reduced-dosage regimen that delivered 40 gray to the tumor bed but 36 gray to the rest of the breast, or a partial regimen that delivered 40 gray to the tumor bed and no radiation at all to the rest of the ipsilateral breast. All three regimens were administered as 15 fractions.
After a median follow-up of 71 months, the 674 women randomized to the reduced regimen had a 26% reduction in their absolute local recurrence rate compared with the 674 whole-breast controls. The 670 women randomized to the partial regimen had an absolute reduction of 39%. Both of these relative reductions were statistically significant. These efficacy results also met the study’s prespecified primary endpoint for noninferiority for controlling local recurrences in the ipsilateral breast, Dr. Coles reported.
For the study’s secondary endpoints of various measures of adverse effects to the normal breast tissue, the partial-dosage regimen led to a statistically significant reduction in patient assessment of changed breast appearance (P = .005) and a reduced rate of patient perception of increased breast firmness (P = .001). The adverse-effects endpoints also showed a significant reduction with the partial regimen in physician assessment of breast edema (P = .0053). The overall rate of patients free of any adverse effect in their normal breast tissue after 5 years was 72% in the control patients, 79% in those who received the reduced-dose regimen (P = .042), and 81% in those who received the partial dose (P = .004).
An expert panel is scheduled to review new evidence on breast radiotherapy later in March, and these new data may produce a change in the recommended irradiation protocol, Dr. Coles said.
On Twitter @mitchelzoler
AMSTERDAM – Modifying the standard radiation dosage to women with early-stage breast cancer so that the tumor-bed dosage remained the same but eliminated the dosage delivered to surrounding breast tissue led to similar 5-year efficacy and reduced adverse effects in a multicenter U.K. trial that involved more than 2,000 patients.
“Partial-breast radiotherapy was noninferior to whole-breast radiotherpy for reducing local recurrences and reduced the severity of overall breast appearance and breast hardness,” Dr. Charlotte Coles said at the European Breast Cancer Congress. “I consider this practice changing,” concluded Dr. Coles of Cambridge (England) University Hospitals.
While some experts at the meeting agreed with Dr. Coles’ assessment of the findings, others took a more skeptical view, focusing on the median follow-up of just 5 years.
“There is still some question about the long-term results for local recurrence rates,” said Dr. Robert Mansel, professor of surgical oncology at Cardiff (Wales) University. In addition, “the rationale for doing this is to reduce side effects to the whole breast, but the results showed little difference in side effects” between women who received the standard radiation dosage and those who received a reduced dosage, “so the rationale for doing this is not quite there,” said Dr. Mansel, the session’s designated discussant.
The Intensity Modulated Partial Breast Radiotherapy for Women with Early Breast Cancer (IMPORT LOW) trial enrolled 2,018 patients with early breast cancer at 30 U.K. centers during 2007-2010. Patients underwent breast conservation surgery and were at least 50 years old, had a tumor of 3 cm or less, had an invasive and unifocal adenocarcinoma that was grade I, II, or III, and had lymph nodes that were either negative or had micrometastases (pN0 or pN1). The trial randomized these women to either standard, whole-breast radiation with 40 gray, a reduced-dosage regimen that delivered 40 gray to the tumor bed but 36 gray to the rest of the breast, or a partial regimen that delivered 40 gray to the tumor bed and no radiation at all to the rest of the ipsilateral breast. All three regimens were administered as 15 fractions.
After a median follow-up of 71 months, the 674 women randomized to the reduced regimen had a 26% reduction in their absolute local recurrence rate compared with the 674 whole-breast controls. The 670 women randomized to the partial regimen had an absolute reduction of 39%. Both of these relative reductions were statistically significant. These efficacy results also met the study’s prespecified primary endpoint for noninferiority for controlling local recurrences in the ipsilateral breast, Dr. Coles reported.
For the study’s secondary endpoints of various measures of adverse effects to the normal breast tissue, the partial-dosage regimen led to a statistically significant reduction in patient assessment of changed breast appearance (P = .005) and a reduced rate of patient perception of increased breast firmness (P = .001). The adverse-effects endpoints also showed a significant reduction with the partial regimen in physician assessment of breast edema (P = .0053). The overall rate of patients free of any adverse effect in their normal breast tissue after 5 years was 72% in the control patients, 79% in those who received the reduced-dose regimen (P = .042), and 81% in those who received the partial dose (P = .004).
An expert panel is scheduled to review new evidence on breast radiotherapy later in March, and these new data may produce a change in the recommended irradiation protocol, Dr. Coles said.
On Twitter @mitchelzoler
AT EBCC 10
Key clinical point: Maintaining the standard breast cancer radiation dosage to the tumor bed while eliminating the dosage to the rest of the breast maintained efficacy and improved posttreatment breast appearance.
Major finding: Women not receiving radiation to their normal breast tissue had a 39% reduction in local recurrences, compared with controls.
Data source: The IMPORT LOW study, which randomized 2,018 women with early breast cancer at 30 U.K. centers for a median of 5 years.
Disclosures: IMPORT LOW received no commercial support. Dr. Coles and Dr. Mansel has no disclosures.
VIDEO: Ischemic-stroke thrombectomy use widens and refines
LOS ANGELES – The use of endovascular thrombectomy in the United States to treat appropriate patients with acute ischemic stroke mushroomed during the past year, following several early-2015 reports that collectively documented the dramatic clinical benefit of the treatment.
As endovascular thrombectomy use grows, stroke centers are also refining and reshaping delivery of the treatment in concert with administration of intravenous tissue plasminogen activator (TPA; alteplase; Activase), which remains a key partner in producing best outcomes for acute ischemic-stroke patients with a proximal occlusion of a large cerebral artery. Collapsing delivery of the two treatments into a more seamless and streamlined process shaves critical minutes to treatment delivery, an approach called parallel processing. Recent findings have also emboldened stroke specialists to seriously consider simplifying the brain imaging that stroke patients receive prior to these treatments, a step that could further cut time to intervention while also making thrombectomy even more widely available.
Use of thrombectomy surges
The biggest endovascular thrombectomy news of the past year is how it has taken off for treating selected patients with acute ischemic stroke. “The rollout over the past year has been explosive. Everything pretty much shut down after the negative trial results in 2013, but now more hospitals are offering thrombectomy,” said Dr. Thomas A. Kent, professor of neurology and director of stroke research and education at Baylor College of Medicine in Houston, in an interview at the International Stroke Conference sponsored by the American Heart Association.
The best documentation of this surge came in a poster presented at the conference by researchers at the University of California, San Francisco. They analyzed data on treatment of 357,973 patients with acute ischemic stroke who were hospitalized at any one of 161 U.S. academic medical centers during October 2009-July 2015 and included in the University Healthsystem Consortium database. They tracked the percentage of patients treated endovascularly during each calendar quarter of the study period.
During 2009-2013, use of endovascular treatment rose steadily but gradually, from 1.5% of stroke patients in 2009 to 3.1% during the fourth quarter of 2012. Then, following three reports of no benefit from endovascular treatment presented at the International Stroke Conference in February 2013 – the IMS III, MR RESCUE, and SYNTHESIS trials – the endovascular rate dropped immediately and quickly bottomed out at a level of 2.6% that remained steady through the third quarter of 2014. But when the positive endovascular results from the MR CLEAN study became public in the final week of 2014, endovascular use began to quickly rise again, and then began to skyrocket during the first quarter of 2015 with three additional positive trial results reported during the Stroke Conference in February 2015. By the end of the second quarter of 2015, usage stood at 4.7%, representing a projected year-over-year increase of about 150% for all of 2015, compared with 2014, reported Dr. Anthony S. Kim, a vascular neurologist and medical director of the Stroke Center at the University of California, San Francisco, and his associates.
To put these percentages in perspective, experts estimate that roughly 10%-15% of all stroke patients qualify for thrombectomy intervention.
Their data also showed that the percentage of hospitals included in the database that performed endovascular therapies for stroke rose steadily from about 40% of centers in 2009 to nearly 60% by mid-2015.
“Endovascular therapy with newer-generation devices is increasingly part of standard treatment for acute ischemic stroke,” they said in their poster. In addition, they cited a “new urgency to evaluate regional access to embolectomy [another name for thrombectomy] nationally and to identify system-based solutions to improve access in underserved areas.”
Several stroke experts interviewed at the conference added their own anecdotal view of thrombectomy’s rapidly expanding use for appropriate acute ischemic stroke patients during 2015, and the need for continued effort to broaden its U.S. availability.
“The number of thrombectomies fell off after the negative 2013 trials and stayed flat until a year ago, but then jumped up. It has been very dramatic,” said Dr. Wade S. Smith, professor of neurology and director of the neurovascular service at the University of California, San Francisco.
“Thrombectomy use tremendously increased since February 2015,” said Dr. Mark J. Alberts, professor of neurology and medical director of the neurology service at the University of Texas Southwestern Medical Center in Dallas, in a video interview during the conference. But despite this growth, “the major challenge [today] is geography;” that is, reaching patients in suburban and rural areas who are not as close to the primarily urban medical centers that currently offer the procedure.
“We now have about 100 certified comprehensive stroke centers in the U.S.,” and by definition comprehensive stroke centers have the capability of treating patients with endovascular thrombectomy, noted Dr. Jeffrey Saver, professor of neurology and director of the stroke unit at the University of California, Los Angeles.
“Certification of these centers did not begin until about 2-3 years ago. But we probably need 300-400 of these centers” to provide thrombectomy to most U.S. stroke patients, he said. “A lot of additional hospitals are close to certification. I anticipate that over the next 1-2 years we will be in the neighborhood of having the number of centers we need,” Dr. Saver said in an interview.
Making thrombectomy better
In addition to expanding availability, the specifics of how endovascular thrombectomy gets delivered is evolving. A major trend is movement toward a “parallel processing” model, in which patients with an acute clinical presentation of a stroke amenable for endovascular treatment simultaneously undergo CT angiography to confirm and localize the large-artery clot causing their stroke, receive intravenous TPA, and undergo preparation for the endovascular access needed to remove the clot.
A pooled analysis of the recent, positive endovascular thrombectomy trials that was presented at the conference showed how quick you need to be to obtain a benefit from the procedures. “This gives us a starting point to further improve the target metrics for imaging and puncture times,” Dr. Saver said. “We want to shorten door-to-needle times for TPA and door-to-puncture times for thrombectomy, and the processes that need to be addressed for rapid delivery of both of these are very similar. We need for patients to only make a pit stop in the ED; we need to have the catheterization team ready to go in the thrombectomy suite within 30 minutes; and we need to emphasize speed in access to the target clot rather than time-consuming diagnostic angiography.”
“We now face the issue of how to best integrate TPA treatment and clot removal.” Dr. Kent said. “People are still trying to work that out. With parallel processing there is some overuse of resources: Some patients recover with TPA alone and don’t need thrombectomy. We are getting closer to the cardiology model of MI treatment. It’s now clear that there needs to be a simple, safe, effective way to do both TPA treatment and thrombectomy. We need to model ourselves on the cardiology experience.”
“If you can deal with the TPA decision in the same room without moving patients from room to room, from a scanner to a catheterization suite, you can really shorten the time to treatment,” Dr. Smith explained. “This is identical to the model that cardiologists have developed. We should now consider taking stroke patients directly to the angiography room in addition to administering TPA. We still need cross-sectional imaging, but the quality of the image from an angiography suite is probably sufficient to make a TPA decision. So you can start TPA while you are getting arterial access. The idea is simultaneous approaches to the patient instead of serial.”
“The whole system moves at the same time to eliminate wasted time,” Dr. Alberts summed up.
One of the big questions that has come up in this effort to speed up treatment and carve the quickest route to endovascular thrombectomy is whether TPA remains necessary. The skeptics’ position is, why waste time administering TPA if you’re also going to take out the offending clot?
The answer, at least for now, is that all signs indicate that giving TPA helps and is worth delivering.
“The 2015 thrombectomy trials had big differences among them in the dosage of TPA administered, and in the percentage of patients who received TPA. When 100% of patients received TPA they had the best outcomes,” Dr. Kent said. “There was a clear synergistic relationship between thrombectomy and TPA. There has been a trend to think about sending patients straight to thrombectomy and skipping TPA, but my colleagues and I think that we need to hold off on doing that. For now, if a patient is eligible to receive TPA they should get it and then quickly move to endovascular therapy. We are not yet ready to know it’s okay to go straight to endovascular treatment. In SWIFT-PRIME, it was pretty clear that the good outcomes were attributable to both [thrombectomy plus TPA]. Treating patients with TPA helps soften the clot to make it easier to remove, and improves flow through collateral arteries.”
“Our data in Memphis show that patients do better with thrombectomy plus intravenous TPA than on TPA alone,” agreed Dr. Lucas Elijovich, a neurologist at the University of Tennessee Health Science Center in Memphis, in an interview.
Simpler imaging also saves time
Although it’s not yet proven, another new wrinkle in working up acute ischemic-stroke patients for TPA and thrombectomy treatment is the idea that simpler and more widely available CT imaging, especially CT angiography of cerebral arteries, may suffice for confirming and localizing the culprit clot.
This concept received a significant boost at the International Stroke Conference in data reported from the Pragmatic Ischaemic Stroke Thrombectomy Evaluation (PISTE) trial, yet another study that compared treatment with TPA alone with TPA plus endovascular thrombectomy, this time in 65 randomized patients treated at any of 11 U.K. centers. PISTE had a low enrollment level because the trial stopped prematurely, in July 2015, following the news that several fully completed trials had collectively established the superiority of endovascular thrombectomy plus TPA, thereby making it unethical to continue yet another randomized study.
This premature stoppage prevented PISTE from itself producing a statistically significant difference for its primary efficacy endpoint in favor of the combined treatment, although the results did show a nominal advantage to using thrombectomy plus TPA over TPA alone that was fully consistent with the other studies, Dr. Keith W. Muir reported at the conference.
But what made the PISTE results especially notable was that the trial achieved this consistent outcome with a “simpler” imaging protocol for patients during their workup that used only CT angiography, avoiding the cerebral CT perfusion imaging or MRI used in several of the other TPA-plus-thrombectomy versus TPA-only trials, noted Dr. Muir, professor of neuroscience and head of the stroke imaging group at the University of Glasgow.
“PISTE raises the question of how much imaging is necessary,” Dr. Kent commented.
“The PISTE results are exciting. A lot of us believe that all we need to know is that there is a blockage in a target vessel,” Dr. Smith said. “If we have that information, then we can identify a population of patients who will benefit from [thrombectomy]. CT angiography is simple and can easily fit into work flows.”
“PISTE used a very simple imaging system that makes thrombectomy even more applicable and generalizable to less resourced health systems,” Dr. Saver said. “Although the results from PISTE were not internally statistically significant because the trial ended early, the results were consistent with the external studies of thrombectomy, so it provides further evidence for benefit from thrombectomy.” And because the consistent results were achieved with simpler imaging it suggests simpler imaging may be all that’s needed.
“That’s a major question to wrestle with,” Dr. Saver suggested. “We need addition trials with a head-to-head comparison of simpler and more sophisticated imaging so we can tailor treatment to patients who would benefit from simpler and faster imaging.”
Dr. Kent had no disclosures. Dr. Kim has received research funding from SanBio and Biogen. Dr. Smith served on the data safety and monitoring board for a trial funded by Stryker. Dr. Alberts has been a consultant to Genentech. Dr. Saver has been a consultant to Stryker, Neuravi, Cognition Medical, Boehringer Ingelheim, and Medtronic. Dr. Elijovich has been a consultant to Stryker and Codman and received research support from Siemens. Dr. Muir has received research support from ReNeuron and unrestricted grants from Codman and Covidien.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
LOS ANGELES – The use of endovascular thrombectomy in the United States to treat appropriate patients with acute ischemic stroke mushroomed during the past year, following several early-2015 reports that collectively documented the dramatic clinical benefit of the treatment.
As endovascular thrombectomy use grows, stroke centers are also refining and reshaping delivery of the treatment in concert with administration of intravenous tissue plasminogen activator (TPA; alteplase; Activase), which remains a key partner in producing best outcomes for acute ischemic-stroke patients with a proximal occlusion of a large cerebral artery. Collapsing delivery of the two treatments into a more seamless and streamlined process shaves critical minutes to treatment delivery, an approach called parallel processing. Recent findings have also emboldened stroke specialists to seriously consider simplifying the brain imaging that stroke patients receive prior to these treatments, a step that could further cut time to intervention while also making thrombectomy even more widely available.
Use of thrombectomy surges
The biggest endovascular thrombectomy news of the past year is how it has taken off for treating selected patients with acute ischemic stroke. “The rollout over the past year has been explosive. Everything pretty much shut down after the negative trial results in 2013, but now more hospitals are offering thrombectomy,” said Dr. Thomas A. Kent, professor of neurology and director of stroke research and education at Baylor College of Medicine in Houston, in an interview at the International Stroke Conference sponsored by the American Heart Association.
The best documentation of this surge came in a poster presented at the conference by researchers at the University of California, San Francisco. They analyzed data on treatment of 357,973 patients with acute ischemic stroke who were hospitalized at any one of 161 U.S. academic medical centers during October 2009-July 2015 and included in the University Healthsystem Consortium database. They tracked the percentage of patients treated endovascularly during each calendar quarter of the study period.
During 2009-2013, use of endovascular treatment rose steadily but gradually, from 1.5% of stroke patients in 2009 to 3.1% during the fourth quarter of 2012. Then, following three reports of no benefit from endovascular treatment presented at the International Stroke Conference in February 2013 – the IMS III, MR RESCUE, and SYNTHESIS trials – the endovascular rate dropped immediately and quickly bottomed out at a level of 2.6% that remained steady through the third quarter of 2014. But when the positive endovascular results from the MR CLEAN study became public in the final week of 2014, endovascular use began to quickly rise again, and then began to skyrocket during the first quarter of 2015 with three additional positive trial results reported during the Stroke Conference in February 2015. By the end of the second quarter of 2015, usage stood at 4.7%, representing a projected year-over-year increase of about 150% for all of 2015, compared with 2014, reported Dr. Anthony S. Kim, a vascular neurologist and medical director of the Stroke Center at the University of California, San Francisco, and his associates.
To put these percentages in perspective, experts estimate that roughly 10%-15% of all stroke patients qualify for thrombectomy intervention.
Their data also showed that the percentage of hospitals included in the database that performed endovascular therapies for stroke rose steadily from about 40% of centers in 2009 to nearly 60% by mid-2015.
“Endovascular therapy with newer-generation devices is increasingly part of standard treatment for acute ischemic stroke,” they said in their poster. In addition, they cited a “new urgency to evaluate regional access to embolectomy [another name for thrombectomy] nationally and to identify system-based solutions to improve access in underserved areas.”
Several stroke experts interviewed at the conference added their own anecdotal view of thrombectomy’s rapidly expanding use for appropriate acute ischemic stroke patients during 2015, and the need for continued effort to broaden its U.S. availability.
“The number of thrombectomies fell off after the negative 2013 trials and stayed flat until a year ago, but then jumped up. It has been very dramatic,” said Dr. Wade S. Smith, professor of neurology and director of the neurovascular service at the University of California, San Francisco.
“Thrombectomy use tremendously increased since February 2015,” said Dr. Mark J. Alberts, professor of neurology and medical director of the neurology service at the University of Texas Southwestern Medical Center in Dallas, in a video interview during the conference. But despite this growth, “the major challenge [today] is geography;” that is, reaching patients in suburban and rural areas who are not as close to the primarily urban medical centers that currently offer the procedure.
“We now have about 100 certified comprehensive stroke centers in the U.S.,” and by definition comprehensive stroke centers have the capability of treating patients with endovascular thrombectomy, noted Dr. Jeffrey Saver, professor of neurology and director of the stroke unit at the University of California, Los Angeles.
“Certification of these centers did not begin until about 2-3 years ago. But we probably need 300-400 of these centers” to provide thrombectomy to most U.S. stroke patients, he said. “A lot of additional hospitals are close to certification. I anticipate that over the next 1-2 years we will be in the neighborhood of having the number of centers we need,” Dr. Saver said in an interview.
Making thrombectomy better
In addition to expanding availability, the specifics of how endovascular thrombectomy gets delivered is evolving. A major trend is movement toward a “parallel processing” model, in which patients with an acute clinical presentation of a stroke amenable for endovascular treatment simultaneously undergo CT angiography to confirm and localize the large-artery clot causing their stroke, receive intravenous TPA, and undergo preparation for the endovascular access needed to remove the clot.
A pooled analysis of the recent, positive endovascular thrombectomy trials that was presented at the conference showed how quick you need to be to obtain a benefit from the procedures. “This gives us a starting point to further improve the target metrics for imaging and puncture times,” Dr. Saver said. “We want to shorten door-to-needle times for TPA and door-to-puncture times for thrombectomy, and the processes that need to be addressed for rapid delivery of both of these are very similar. We need for patients to only make a pit stop in the ED; we need to have the catheterization team ready to go in the thrombectomy suite within 30 minutes; and we need to emphasize speed in access to the target clot rather than time-consuming diagnostic angiography.”
“We now face the issue of how to best integrate TPA treatment and clot removal.” Dr. Kent said. “People are still trying to work that out. With parallel processing there is some overuse of resources: Some patients recover with TPA alone and don’t need thrombectomy. We are getting closer to the cardiology model of MI treatment. It’s now clear that there needs to be a simple, safe, effective way to do both TPA treatment and thrombectomy. We need to model ourselves on the cardiology experience.”
“If you can deal with the TPA decision in the same room without moving patients from room to room, from a scanner to a catheterization suite, you can really shorten the time to treatment,” Dr. Smith explained. “This is identical to the model that cardiologists have developed. We should now consider taking stroke patients directly to the angiography room in addition to administering TPA. We still need cross-sectional imaging, but the quality of the image from an angiography suite is probably sufficient to make a TPA decision. So you can start TPA while you are getting arterial access. The idea is simultaneous approaches to the patient instead of serial.”
“The whole system moves at the same time to eliminate wasted time,” Dr. Alberts summed up.
One of the big questions that has come up in this effort to speed up treatment and carve the quickest route to endovascular thrombectomy is whether TPA remains necessary. The skeptics’ position is, why waste time administering TPA if you’re also going to take out the offending clot?
The answer, at least for now, is that all signs indicate that giving TPA helps and is worth delivering.
“The 2015 thrombectomy trials had big differences among them in the dosage of TPA administered, and in the percentage of patients who received TPA. When 100% of patients received TPA they had the best outcomes,” Dr. Kent said. “There was a clear synergistic relationship between thrombectomy and TPA. There has been a trend to think about sending patients straight to thrombectomy and skipping TPA, but my colleagues and I think that we need to hold off on doing that. For now, if a patient is eligible to receive TPA they should get it and then quickly move to endovascular therapy. We are not yet ready to know it’s okay to go straight to endovascular treatment. In SWIFT-PRIME, it was pretty clear that the good outcomes were attributable to both [thrombectomy plus TPA]. Treating patients with TPA helps soften the clot to make it easier to remove, and improves flow through collateral arteries.”
“Our data in Memphis show that patients do better with thrombectomy plus intravenous TPA than on TPA alone,” agreed Dr. Lucas Elijovich, a neurologist at the University of Tennessee Health Science Center in Memphis, in an interview.
Simpler imaging also saves time
Although it’s not yet proven, another new wrinkle in working up acute ischemic-stroke patients for TPA and thrombectomy treatment is the idea that simpler and more widely available CT imaging, especially CT angiography of cerebral arteries, may suffice for confirming and localizing the culprit clot.
This concept received a significant boost at the International Stroke Conference in data reported from the Pragmatic Ischaemic Stroke Thrombectomy Evaluation (PISTE) trial, yet another study that compared treatment with TPA alone with TPA plus endovascular thrombectomy, this time in 65 randomized patients treated at any of 11 U.K. centers. PISTE had a low enrollment level because the trial stopped prematurely, in July 2015, following the news that several fully completed trials had collectively established the superiority of endovascular thrombectomy plus TPA, thereby making it unethical to continue yet another randomized study.
This premature stoppage prevented PISTE from itself producing a statistically significant difference for its primary efficacy endpoint in favor of the combined treatment, although the results did show a nominal advantage to using thrombectomy plus TPA over TPA alone that was fully consistent with the other studies, Dr. Keith W. Muir reported at the conference.
But what made the PISTE results especially notable was that the trial achieved this consistent outcome with a “simpler” imaging protocol for patients during their workup that used only CT angiography, avoiding the cerebral CT perfusion imaging or MRI used in several of the other TPA-plus-thrombectomy versus TPA-only trials, noted Dr. Muir, professor of neuroscience and head of the stroke imaging group at the University of Glasgow.
“PISTE raises the question of how much imaging is necessary,” Dr. Kent commented.
“The PISTE results are exciting. A lot of us believe that all we need to know is that there is a blockage in a target vessel,” Dr. Smith said. “If we have that information, then we can identify a population of patients who will benefit from [thrombectomy]. CT angiography is simple and can easily fit into work flows.”
“PISTE used a very simple imaging system that makes thrombectomy even more applicable and generalizable to less resourced health systems,” Dr. Saver said. “Although the results from PISTE were not internally statistically significant because the trial ended early, the results were consistent with the external studies of thrombectomy, so it provides further evidence for benefit from thrombectomy.” And because the consistent results were achieved with simpler imaging it suggests simpler imaging may be all that’s needed.
“That’s a major question to wrestle with,” Dr. Saver suggested. “We need addition trials with a head-to-head comparison of simpler and more sophisticated imaging so we can tailor treatment to patients who would benefit from simpler and faster imaging.”
Dr. Kent had no disclosures. Dr. Kim has received research funding from SanBio and Biogen. Dr. Smith served on the data safety and monitoring board for a trial funded by Stryker. Dr. Alberts has been a consultant to Genentech. Dr. Saver has been a consultant to Stryker, Neuravi, Cognition Medical, Boehringer Ingelheim, and Medtronic. Dr. Elijovich has been a consultant to Stryker and Codman and received research support from Siemens. Dr. Muir has received research support from ReNeuron and unrestricted grants from Codman and Covidien.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
LOS ANGELES – The use of endovascular thrombectomy in the United States to treat appropriate patients with acute ischemic stroke mushroomed during the past year, following several early-2015 reports that collectively documented the dramatic clinical benefit of the treatment.
As endovascular thrombectomy use grows, stroke centers are also refining and reshaping delivery of the treatment in concert with administration of intravenous tissue plasminogen activator (TPA; alteplase; Activase), which remains a key partner in producing best outcomes for acute ischemic-stroke patients with a proximal occlusion of a large cerebral artery. Collapsing delivery of the two treatments into a more seamless and streamlined process shaves critical minutes to treatment delivery, an approach called parallel processing. Recent findings have also emboldened stroke specialists to seriously consider simplifying the brain imaging that stroke patients receive prior to these treatments, a step that could further cut time to intervention while also making thrombectomy even more widely available.
Use of thrombectomy surges
The biggest endovascular thrombectomy news of the past year is how it has taken off for treating selected patients with acute ischemic stroke. “The rollout over the past year has been explosive. Everything pretty much shut down after the negative trial results in 2013, but now more hospitals are offering thrombectomy,” said Dr. Thomas A. Kent, professor of neurology and director of stroke research and education at Baylor College of Medicine in Houston, in an interview at the International Stroke Conference sponsored by the American Heart Association.
The best documentation of this surge came in a poster presented at the conference by researchers at the University of California, San Francisco. They analyzed data on treatment of 357,973 patients with acute ischemic stroke who were hospitalized at any one of 161 U.S. academic medical centers during October 2009-July 2015 and included in the University Healthsystem Consortium database. They tracked the percentage of patients treated endovascularly during each calendar quarter of the study period.
During 2009-2013, use of endovascular treatment rose steadily but gradually, from 1.5% of stroke patients in 2009 to 3.1% during the fourth quarter of 2012. Then, following three reports of no benefit from endovascular treatment presented at the International Stroke Conference in February 2013 – the IMS III, MR RESCUE, and SYNTHESIS trials – the endovascular rate dropped immediately and quickly bottomed out at a level of 2.6% that remained steady through the third quarter of 2014. But when the positive endovascular results from the MR CLEAN study became public in the final week of 2014, endovascular use began to quickly rise again, and then began to skyrocket during the first quarter of 2015 with three additional positive trial results reported during the Stroke Conference in February 2015. By the end of the second quarter of 2015, usage stood at 4.7%, representing a projected year-over-year increase of about 150% for all of 2015, compared with 2014, reported Dr. Anthony S. Kim, a vascular neurologist and medical director of the Stroke Center at the University of California, San Francisco, and his associates.
To put these percentages in perspective, experts estimate that roughly 10%-15% of all stroke patients qualify for thrombectomy intervention.
Their data also showed that the percentage of hospitals included in the database that performed endovascular therapies for stroke rose steadily from about 40% of centers in 2009 to nearly 60% by mid-2015.
“Endovascular therapy with newer-generation devices is increasingly part of standard treatment for acute ischemic stroke,” they said in their poster. In addition, they cited a “new urgency to evaluate regional access to embolectomy [another name for thrombectomy] nationally and to identify system-based solutions to improve access in underserved areas.”
Several stroke experts interviewed at the conference added their own anecdotal view of thrombectomy’s rapidly expanding use for appropriate acute ischemic stroke patients during 2015, and the need for continued effort to broaden its U.S. availability.
“The number of thrombectomies fell off after the negative 2013 trials and stayed flat until a year ago, but then jumped up. It has been very dramatic,” said Dr. Wade S. Smith, professor of neurology and director of the neurovascular service at the University of California, San Francisco.
“Thrombectomy use tremendously increased since February 2015,” said Dr. Mark J. Alberts, professor of neurology and medical director of the neurology service at the University of Texas Southwestern Medical Center in Dallas, in a video interview during the conference. But despite this growth, “the major challenge [today] is geography;” that is, reaching patients in suburban and rural areas who are not as close to the primarily urban medical centers that currently offer the procedure.
“We now have about 100 certified comprehensive stroke centers in the U.S.,” and by definition comprehensive stroke centers have the capability of treating patients with endovascular thrombectomy, noted Dr. Jeffrey Saver, professor of neurology and director of the stroke unit at the University of California, Los Angeles.
“Certification of these centers did not begin until about 2-3 years ago. But we probably need 300-400 of these centers” to provide thrombectomy to most U.S. stroke patients, he said. “A lot of additional hospitals are close to certification. I anticipate that over the next 1-2 years we will be in the neighborhood of having the number of centers we need,” Dr. Saver said in an interview.
Making thrombectomy better
In addition to expanding availability, the specifics of how endovascular thrombectomy gets delivered is evolving. A major trend is movement toward a “parallel processing” model, in which patients with an acute clinical presentation of a stroke amenable for endovascular treatment simultaneously undergo CT angiography to confirm and localize the large-artery clot causing their stroke, receive intravenous TPA, and undergo preparation for the endovascular access needed to remove the clot.
A pooled analysis of the recent, positive endovascular thrombectomy trials that was presented at the conference showed how quick you need to be to obtain a benefit from the procedures. “This gives us a starting point to further improve the target metrics for imaging and puncture times,” Dr. Saver said. “We want to shorten door-to-needle times for TPA and door-to-puncture times for thrombectomy, and the processes that need to be addressed for rapid delivery of both of these are very similar. We need for patients to only make a pit stop in the ED; we need to have the catheterization team ready to go in the thrombectomy suite within 30 minutes; and we need to emphasize speed in access to the target clot rather than time-consuming diagnostic angiography.”
“We now face the issue of how to best integrate TPA treatment and clot removal.” Dr. Kent said. “People are still trying to work that out. With parallel processing there is some overuse of resources: Some patients recover with TPA alone and don’t need thrombectomy. We are getting closer to the cardiology model of MI treatment. It’s now clear that there needs to be a simple, safe, effective way to do both TPA treatment and thrombectomy. We need to model ourselves on the cardiology experience.”
“If you can deal with the TPA decision in the same room without moving patients from room to room, from a scanner to a catheterization suite, you can really shorten the time to treatment,” Dr. Smith explained. “This is identical to the model that cardiologists have developed. We should now consider taking stroke patients directly to the angiography room in addition to administering TPA. We still need cross-sectional imaging, but the quality of the image from an angiography suite is probably sufficient to make a TPA decision. So you can start TPA while you are getting arterial access. The idea is simultaneous approaches to the patient instead of serial.”
“The whole system moves at the same time to eliminate wasted time,” Dr. Alberts summed up.
One of the big questions that has come up in this effort to speed up treatment and carve the quickest route to endovascular thrombectomy is whether TPA remains necessary. The skeptics’ position is, why waste time administering TPA if you’re also going to take out the offending clot?
The answer, at least for now, is that all signs indicate that giving TPA helps and is worth delivering.
“The 2015 thrombectomy trials had big differences among them in the dosage of TPA administered, and in the percentage of patients who received TPA. When 100% of patients received TPA they had the best outcomes,” Dr. Kent said. “There was a clear synergistic relationship between thrombectomy and TPA. There has been a trend to think about sending patients straight to thrombectomy and skipping TPA, but my colleagues and I think that we need to hold off on doing that. For now, if a patient is eligible to receive TPA they should get it and then quickly move to endovascular therapy. We are not yet ready to know it’s okay to go straight to endovascular treatment. In SWIFT-PRIME, it was pretty clear that the good outcomes were attributable to both [thrombectomy plus TPA]. Treating patients with TPA helps soften the clot to make it easier to remove, and improves flow through collateral arteries.”
“Our data in Memphis show that patients do better with thrombectomy plus intravenous TPA than on TPA alone,” agreed Dr. Lucas Elijovich, a neurologist at the University of Tennessee Health Science Center in Memphis, in an interview.
Simpler imaging also saves time
Although it’s not yet proven, another new wrinkle in working up acute ischemic-stroke patients for TPA and thrombectomy treatment is the idea that simpler and more widely available CT imaging, especially CT angiography of cerebral arteries, may suffice for confirming and localizing the culprit clot.
This concept received a significant boost at the International Stroke Conference in data reported from the Pragmatic Ischaemic Stroke Thrombectomy Evaluation (PISTE) trial, yet another study that compared treatment with TPA alone with TPA plus endovascular thrombectomy, this time in 65 randomized patients treated at any of 11 U.K. centers. PISTE had a low enrollment level because the trial stopped prematurely, in July 2015, following the news that several fully completed trials had collectively established the superiority of endovascular thrombectomy plus TPA, thereby making it unethical to continue yet another randomized study.
This premature stoppage prevented PISTE from itself producing a statistically significant difference for its primary efficacy endpoint in favor of the combined treatment, although the results did show a nominal advantage to using thrombectomy plus TPA over TPA alone that was fully consistent with the other studies, Dr. Keith W. Muir reported at the conference.
But what made the PISTE results especially notable was that the trial achieved this consistent outcome with a “simpler” imaging protocol for patients during their workup that used only CT angiography, avoiding the cerebral CT perfusion imaging or MRI used in several of the other TPA-plus-thrombectomy versus TPA-only trials, noted Dr. Muir, professor of neuroscience and head of the stroke imaging group at the University of Glasgow.
“PISTE raises the question of how much imaging is necessary,” Dr. Kent commented.
“The PISTE results are exciting. A lot of us believe that all we need to know is that there is a blockage in a target vessel,” Dr. Smith said. “If we have that information, then we can identify a population of patients who will benefit from [thrombectomy]. CT angiography is simple and can easily fit into work flows.”
“PISTE used a very simple imaging system that makes thrombectomy even more applicable and generalizable to less resourced health systems,” Dr. Saver said. “Although the results from PISTE were not internally statistically significant because the trial ended early, the results were consistent with the external studies of thrombectomy, so it provides further evidence for benefit from thrombectomy.” And because the consistent results were achieved with simpler imaging it suggests simpler imaging may be all that’s needed.
“That’s a major question to wrestle with,” Dr. Saver suggested. “We need addition trials with a head-to-head comparison of simpler and more sophisticated imaging so we can tailor treatment to patients who would benefit from simpler and faster imaging.”
Dr. Kent had no disclosures. Dr. Kim has received research funding from SanBio and Biogen. Dr. Smith served on the data safety and monitoring board for a trial funded by Stryker. Dr. Alberts has been a consultant to Genentech. Dr. Saver has been a consultant to Stryker, Neuravi, Cognition Medical, Boehringer Ingelheim, and Medtronic. Dr. Elijovich has been a consultant to Stryker and Codman and received research support from Siemens. Dr. Muir has received research support from ReNeuron and unrestricted grants from Codman and Covidien.
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EXPERT ANALYSIS FROM THE INTERNATIONAL STROKE CONFERENCE
