A combined formulation of calcipotriol and 5-fluorouracil (5-FU) outperformed 5-FU alone in reducing the number of actinic keratoses (AKs), with a shorter treatment course and less inflammation than typically seen with 5-FU alone, researchers reported in a study published online in November.

5-FU is effective, but it produces crusting and significant irritation, and is temporarily disfiguring, creating discomfort and inconvenience that often leads to poor patient compliance with treatment.

Robert Boston

A combined formulation of calcipotriol and 5-fluorouracil (5-FU) outperformed 5-FU alone in reducing the number of actinic keratoses (AKs), with a shorter treatment course and less inflammation than typically seen with 5-FU alone, researchers reported in a study published online in November.

5-FU is effective, but it produces crusting and significant irritation, and is temporarily disfiguring, creating discomfort and inconvenience that often leads to poor patient compliance with treatment.

Robert Boston

A combined formulation of calcipotriol and 5-fluorouracil (5-FU) outperformed 5-FU alone in reducing the number of actinic keratoses (AKs), with a shorter treatment course and less inflammation than typically seen with 5-FU alone, researchers reported in a study published online in November.

5-FU is effective, but it produces crusting and significant irritation, and is temporarily disfiguring, creating discomfort and inconvenience that often leads to poor patient compliance with treatment.

Robert Boston

Acute generalized exanthematous pustulosis (AGEP)

Acute generalized exanthematous pustulosis (AGEP) is a fairly rare condition, with a reported incidence of one to five cases per million people per year. AGEP affects both sexes, but with a slight female predominance. Although the median age of occurrence is 56 years, people of all ages can develop AGEP. In approximately 90% of cases, AGEP is caused by a drug reaction, with the most common culprits being antibiotics, diltiazem, and antimalarials.

Fever, leukocytosis with an elevated neutrophil count ( greater than 7,000/microL), and mild eosinophilia are commonly observed during the acute phase of AGEP. Systemic involvement is fairly uncommon, with a study of 58 cases exhibiting organ involvement in 17% of patients. When systemic involvement was observed, hepatic, pulmonary, and renal dysfunction were most common. Hepatic dysfunction can result in elevated transaminase levels in some patients. Similarly, reduced creatinine clearance may be observed because of renal involvement.

The management of AGEP involves removal of the offending agent. Antiseptic solutions and moist dressings may be used during the pustular phase to prevent infection. Emollients can aid in restoring skin barrier function during the desquamation phase. Antibiotics are not necessary prophylactically and should be avoided unless infection occurs. Pruritus and inflammation may be treated with topical corticosteroids in prolonged cases. Systemic corticosteroids are generally unwarranted as AGEP is a self-limited condition that is known to spontaneously resolve with the removal of the causative drug.

This case and photo were submitted by Natasha Cowan, BS, University of California, San Diego, and Brooke Resh Sateesh MD, San Diego Family Dermatology.

Acute generalized exanthematous pustulosis (AGEP)

Acute generalized exanthematous pustulosis (AGEP) is a fairly rare condition, with a reported incidence of one to five cases per million people per year. AGEP affects both sexes, but with a slight female predominance. Although the median age of occurrence is 56 years, people of all ages can develop AGEP. In approximately 90% of cases, AGEP is caused by a drug reaction, with the most common culprits being antibiotics, diltiazem, and antimalarials.

Fever, leukocytosis with an elevated neutrophil count ( greater than 7,000/microL), and mild eosinophilia are commonly observed during the acute phase of AGEP. Systemic involvement is fairly uncommon, with a study of 58 cases exhibiting organ involvement in 17% of patients. When systemic involvement was observed, hepatic, pulmonary, and renal dysfunction were most common. Hepatic dysfunction can result in elevated transaminase levels in some patients. Similarly, reduced creatinine clearance may be observed because of renal involvement.

The management of AGEP involves removal of the offending agent. Antiseptic solutions and moist dressings may be used during the pustular phase to prevent infection. Emollients can aid in restoring skin barrier function during the desquamation phase. Antibiotics are not necessary prophylactically and should be avoided unless infection occurs. Pruritus and inflammation may be treated with topical corticosteroids in prolonged cases. Systemic corticosteroids are generally unwarranted as AGEP is a self-limited condition that is known to spontaneously resolve with the removal of the causative drug.

This case and photo were submitted by Natasha Cowan, BS, University of California, San Diego, and Brooke Resh Sateesh MD, San Diego Family Dermatology.

Acute generalized exanthematous pustulosis (AGEP)

Acute generalized exanthematous pustulosis (AGEP) is a fairly rare condition, with a reported incidence of one to five cases per million people per year. AGEP affects both sexes, but with a slight female predominance. Although the median age of occurrence is 56 years, people of all ages can develop AGEP. In approximately 90% of cases, AGEP is caused by a drug reaction, with the most common culprits being antibiotics, diltiazem, and antimalarials.

Fever, leukocytosis with an elevated neutrophil count ( greater than 7,000/microL), and mild eosinophilia are commonly observed during the acute phase of AGEP. Systemic involvement is fairly uncommon, with a study of 58 cases exhibiting organ involvement in 17% of patients. When systemic involvement was observed, hepatic, pulmonary, and renal dysfunction were most common. Hepatic dysfunction can result in elevated transaminase levels in some patients. Similarly, reduced creatinine clearance may be observed because of renal involvement.

The management of AGEP involves removal of the offending agent. Antiseptic solutions and moist dressings may be used during the pustular phase to prevent infection. Emollients can aid in restoring skin barrier function during the desquamation phase. Antibiotics are not necessary prophylactically and should be avoided unless infection occurs. Pruritus and inflammation may be treated with topical corticosteroids in prolonged cases. Systemic corticosteroids are generally unwarranted as AGEP is a self-limited condition that is known to spontaneously resolve with the removal of the causative drug.

This case and photo were submitted by Natasha Cowan, BS, University of California, San Diego, and Brooke Resh Sateesh MD, San Diego Family Dermatology.

Landmark guidelines addressing the psychosocial needs of persons with diabetes are being met with praise overall, but some question whether endocrinologists and others are up to the task of providing the extensive mental health services called for in the document.

Although the American Diabetes Association has often addressed the specific psychosocial concerns of persons with diabetes, the ADA’s first-ever position statement on the subject reflects a state-of-the-art approach to delivering integrated mental health and specialty services to this patient population. That alone makes the document a milestone in diabetes care, according to Yehuda Handelsman, MD, , medical director of the Metabolic Institute of America in Tarzana, Calif., and chair of the American College of Endocrinology 2011 Comprehensive Diabetes Guidelines. “It raises the importance of the psychological being in diabetes. This has been mentioned before in guidelines, but it has never been the focus. In that respect, this [document] is very important,” Dr. Handelsman said in an interview.

The guidelines detail the most common psychological factors facing persons with diabetes throughout the life span, including diabetes distress, depression, anxiety, eating disorders, and diabetes-related cognitive dysfunction later in life. There is also a section addressing considerations such as mental and emotional preparation before and after bariatric surgery. Clinicians are urged to practice preventive care by assessing patients’ mental states regularly. A list of age-appropriate resources for screens and other measurement tools is included in the guidelines.

Despite the guidelines’ thoroughness, Dr. Handelsman said he is not optimistic they will change much in the way of practice. “The people who wrote this are psychologists and other mental health professionals. This is what they do. When we endocrinologists see patients, we don’t have these [skills]. It’s not so easy to incorporate these suggestions into daily practice,” Dr. Handelsman, said.

Adding mental health screening and referrals likely works well for all models of chronic illness care, according to Victor L. Roberts, MD, MBA, a clinical endocrinologist in Winter Park, Fla.
However, “I don’t see how a primary care doctor will have the time to [follow all the guidelines] and determine what is going on with the patient’s mental health,” observed Dr. Roberts, who works with many central Florida primary care clinics.

“But they can tell if someone is mildly or moderately depressed, and they can refer the patient for evaluation just like you would refer them for an EKG, a blood test, or a consultation to an endocrinologist,” he added. “Look at depression as a comorbidity.”

Not treating depression and anxiety as medical conditions means patient outcomes are almost guaranteed to be poor, he said.

“If someone is depressed, they are not listening. They’re worried, they’re not paying attention, their ability to incorporate new information is impaired,” Dr. Roberts added. That leads to less facility for self care and can contribute to a bidirectional conundrum of depression and worsening health, particularly in diabetes.

An embrace of value-based care as envisioned by the guidelines’ authors is irrelevant, however, if qualified mental health specialists – particularly those trained specifically in the psychosocial needs of people with diabetes – are nowhere to be found. “I [practice] in the middle of Los Angeles, and I can tell you that in a 30-mile radius, there is not a psychologist anywhere that I can refer a diabetes patient to,” Dr. Handelsman said.

To that end, the ADA has developed a partnership with the American Psychological Association to educate psychologists about the kinds of mental health challenges specific to patients with diabetes. The curriculum will be introduced later this year during the ADA’s scientific sessions meeting. At present, none of the classes are accredited, but Dr. Young-Hyman said her “pie-in-the-sky dream” would be to expand the program and continuing medical education units.

“We see the capacity issues and want to address them,” Dr. Young-Hyman said. That alone may not be enough to change practice in the specialty setting where integrated care, as provided by Dr. Hellman’s clinic, currently is the exception, according to Dr. Handelsman.

Although he said it was likely that guidelines issued by ACE will be expanded to incorporate the ADA’s recommendations, he challenged the ADA to advocate directly to endocrinology societies to educate them on the practical application of their recommendations.

“Take the guidelines and make us use them,” he said in the interview. Otherwise, because most clinical endocrinologists are not trained to address psychosocial concerns, unless a specialist already has an interest in mental health, Dr. Handelsman said that specialist largely will ignore this document. “Some in the field will read it ... but we will not take it to the streets.”

Despite his “guarded optimism,” neither does Dr. Roberts see how practice for primary care physicians will change much – at least, not in the near future, given what he called the already “bone crushing” constraints on their time.

Yet, he warned that not dealing with mental health issues means not delivering complete care.
“Depression is a complication of diabetes, in my expert opinion,” Dr. Roberts cautioned.

“Primary care physicians need to not sidestep this. They need to make it clear to their patients that dealing with depression is part and parcel of dealing with their chronic disease. The position statement can at least be a clarion call to consider mental health a medical condition that we can address in a matter-of-fact way.”

The American Diabetes Association’s recommendations for psychosocial care in diabetes are as follows:

• Integrate psychosocial care with collaborative, patient-centered medical care, and provide psychosocial care to all people with diabetes, with the goals of optimizing health outcomes and health-related quality of life. (Evidence level A.)

• Consider assessing symptoms of diabetes distress, depression, anxiety, and disordered eating and of cognitive capacities using patient-appropriate standardized/validated tools at the initial visit, at periodic intervals, and when there is a change in disease, treatment, or life circumstance. Include caregivers and family members in this assessment. (Evidence level B.)

• Consider monitoring patient performance of self-management behaviors as well as psychosocial factors impacting the person’s self-management. (Evidence level E.)

• Consider assessing life circumstances that can affect physical and psychological health outcomes and their incorporation into intervention strategies. (Evidence level E.)

• Address psychosocial problems upon identification. If an intervention cannot be initiated during the visit when the problem is identified, a follow-up visit or referral to a qualified behavioral health care provider may be scheduled during that visit. (Evidence level E.)

Dr. Handelsman chaired the American College of Endocrinology 2011 Comprehensive Diabetes Guidelines committee and is the immediate past president of ACE. Dr. Hellman is an editorial board member of Diabetes Care. Dr. Young-Hyman had no relevant disclosures.

[email protected]

On Twitter @whitneymcknight

Landmark guidelines addressing the psychosocial needs of persons with diabetes are being met with praise overall, but some question whether endocrinologists and others are up to the task of providing the extensive mental health services called for in the document.

Although the American Diabetes Association has often addressed the specific psychosocial concerns of persons with diabetes, the ADA’s first-ever position statement on the subject reflects a state-of-the-art approach to delivering integrated mental health and specialty services to this patient population. That alone makes the document a milestone in diabetes care, according to Yehuda Handelsman, MD, , medical director of the Metabolic Institute of America in Tarzana, Calif., and chair of the American College of Endocrinology 2011 Comprehensive Diabetes Guidelines. “It raises the importance of the psychological being in diabetes. This has been mentioned before in guidelines, but it has never been the focus. In that respect, this [document] is very important,” Dr. Handelsman said in an interview.

The guidelines detail the most common psychological factors facing persons with diabetes throughout the life span, including diabetes distress, depression, anxiety, eating disorders, and diabetes-related cognitive dysfunction later in life. There is also a section addressing considerations such as mental and emotional preparation before and after bariatric surgery. Clinicians are urged to practice preventive care by assessing patients’ mental states regularly. A list of age-appropriate resources for screens and other measurement tools is included in the guidelines.

Despite the guidelines’ thoroughness, Dr. Handelsman said he is not optimistic they will change much in the way of practice. “The people who wrote this are psychologists and other mental health professionals. This is what they do. When we endocrinologists see patients, we don’t have these [skills]. It’s not so easy to incorporate these suggestions into daily practice,” Dr. Handelsman, said.

Adding mental health screening and referrals likely works well for all models of chronic illness care, according to Victor L. Roberts, MD, MBA, a clinical endocrinologist in Winter Park, Fla.
However, “I don’t see how a primary care doctor will have the time to [follow all the guidelines] and determine what is going on with the patient’s mental health,” observed Dr. Roberts, who works with many central Florida primary care clinics.

“But they can tell if someone is mildly or moderately depressed, and they can refer the patient for evaluation just like you would refer them for an EKG, a blood test, or a consultation to an endocrinologist,” he added. “Look at depression as a comorbidity.”

Not treating depression and anxiety as medical conditions means patient outcomes are almost guaranteed to be poor, he said.

“If someone is depressed, they are not listening. They’re worried, they’re not paying attention, their ability to incorporate new information is impaired,” Dr. Roberts added. That leads to less facility for self care and can contribute to a bidirectional conundrum of depression and worsening health, particularly in diabetes.

An embrace of value-based care as envisioned by the guidelines’ authors is irrelevant, however, if qualified mental health specialists – particularly those trained specifically in the psychosocial needs of people with diabetes – are nowhere to be found. “I [practice] in the middle of Los Angeles, and I can tell you that in a 30-mile radius, there is not a psychologist anywhere that I can refer a diabetes patient to,” Dr. Handelsman said.

To that end, the ADA has developed a partnership with the American Psychological Association to educate psychologists about the kinds of mental health challenges specific to patients with diabetes. The curriculum will be introduced later this year during the ADA’s scientific sessions meeting. At present, none of the classes are accredited, but Dr. Young-Hyman said her “pie-in-the-sky dream” would be to expand the program and continuing medical education units.

“We see the capacity issues and want to address them,” Dr. Young-Hyman said. That alone may not be enough to change practice in the specialty setting where integrated care, as provided by Dr. Hellman’s clinic, currently is the exception, according to Dr. Handelsman.

Although he said it was likely that guidelines issued by ACE will be expanded to incorporate the ADA’s recommendations, he challenged the ADA to advocate directly to endocrinology societies to educate them on the practical application of their recommendations.

“Take the guidelines and make us use them,” he said in the interview. Otherwise, because most clinical endocrinologists are not trained to address psychosocial concerns, unless a specialist already has an interest in mental health, Dr. Handelsman said that specialist largely will ignore this document. “Some in the field will read it ... but we will not take it to the streets.”

Despite his “guarded optimism,” neither does Dr. Roberts see how practice for primary care physicians will change much – at least, not in the near future, given what he called the already “bone crushing” constraints on their time.

Yet, he warned that not dealing with mental health issues means not delivering complete care.
“Depression is a complication of diabetes, in my expert opinion,” Dr. Roberts cautioned.

“Primary care physicians need to not sidestep this. They need to make it clear to their patients that dealing with depression is part and parcel of dealing with their chronic disease. The position statement can at least be a clarion call to consider mental health a medical condition that we can address in a matter-of-fact way.”

The American Diabetes Association’s recommendations for psychosocial care in diabetes are as follows:

• Integrate psychosocial care with collaborative, patient-centered medical care, and provide psychosocial care to all people with diabetes, with the goals of optimizing health outcomes and health-related quality of life. (Evidence level A.)

• Consider assessing symptoms of diabetes distress, depression, anxiety, and disordered eating and of cognitive capacities using patient-appropriate standardized/validated tools at the initial visit, at periodic intervals, and when there is a change in disease, treatment, or life circumstance. Include caregivers and family members in this assessment. (Evidence level B.)

• Consider monitoring patient performance of self-management behaviors as well as psychosocial factors impacting the person’s self-management. (Evidence level E.)

• Consider assessing life circumstances that can affect physical and psychological health outcomes and their incorporation into intervention strategies. (Evidence level E.)

• Address psychosocial problems upon identification. If an intervention cannot be initiated during the visit when the problem is identified, a follow-up visit or referral to a qualified behavioral health care provider may be scheduled during that visit. (Evidence level E.)

Dr. Handelsman chaired the American College of Endocrinology 2011 Comprehensive Diabetes Guidelines committee and is the immediate past president of ACE. Dr. Hellman is an editorial board member of Diabetes Care. Dr. Young-Hyman had no relevant disclosures.

[email protected]

On Twitter @whitneymcknight

Landmark guidelines addressing the psychosocial needs of persons with diabetes are being met with praise overall, but some question whether endocrinologists and others are up to the task of providing the extensive mental health services called for in the document.

Although the American Diabetes Association has often addressed the specific psychosocial concerns of persons with diabetes, the ADA’s first-ever position statement on the subject reflects a state-of-the-art approach to delivering integrated mental health and specialty services to this patient population. That alone makes the document a milestone in diabetes care, according to Yehuda Handelsman, MD, , medical director of the Metabolic Institute of America in Tarzana, Calif., and chair of the American College of Endocrinology 2011 Comprehensive Diabetes Guidelines. “It raises the importance of the psychological being in diabetes. This has been mentioned before in guidelines, but it has never been the focus. In that respect, this [document] is very important,” Dr. Handelsman said in an interview.

The guidelines detail the most common psychological factors facing persons with diabetes throughout the life span, including diabetes distress, depression, anxiety, eating disorders, and diabetes-related cognitive dysfunction later in life. There is also a section addressing considerations such as mental and emotional preparation before and after bariatric surgery. Clinicians are urged to practice preventive care by assessing patients’ mental states regularly. A list of age-appropriate resources for screens and other measurement tools is included in the guidelines.

Despite the guidelines’ thoroughness, Dr. Handelsman said he is not optimistic they will change much in the way of practice. “The people who wrote this are psychologists and other mental health professionals. This is what they do. When we endocrinologists see patients, we don’t have these [skills]. It’s not so easy to incorporate these suggestions into daily practice,” Dr. Handelsman, said.

Adding mental health screening and referrals likely works well for all models of chronic illness care, according to Victor L. Roberts, MD, MBA, a clinical endocrinologist in Winter Park, Fla.
However, “I don’t see how a primary care doctor will have the time to [follow all the guidelines] and determine what is going on with the patient’s mental health,” observed Dr. Roberts, who works with many central Florida primary care clinics.

“But they can tell if someone is mildly or moderately depressed, and they can refer the patient for evaluation just like you would refer them for an EKG, a blood test, or a consultation to an endocrinologist,” he added. “Look at depression as a comorbidity.”

Not treating depression and anxiety as medical conditions means patient outcomes are almost guaranteed to be poor, he said.

“If someone is depressed, they are not listening. They’re worried, they’re not paying attention, their ability to incorporate new information is impaired,” Dr. Roberts added. That leads to less facility for self care and can contribute to a bidirectional conundrum of depression and worsening health, particularly in diabetes.

An embrace of value-based care as envisioned by the guidelines’ authors is irrelevant, however, if qualified mental health specialists – particularly those trained specifically in the psychosocial needs of people with diabetes – are nowhere to be found. “I [practice] in the middle of Los Angeles, and I can tell you that in a 30-mile radius, there is not a psychologist anywhere that I can refer a diabetes patient to,” Dr. Handelsman said.

To that end, the ADA has developed a partnership with the American Psychological Association to educate psychologists about the kinds of mental health challenges specific to patients with diabetes. The curriculum will be introduced later this year during the ADA’s scientific sessions meeting. At present, none of the classes are accredited, but Dr. Young-Hyman said her “pie-in-the-sky dream” would be to expand the program and continuing medical education units.

“We see the capacity issues and want to address them,” Dr. Young-Hyman said. That alone may not be enough to change practice in the specialty setting where integrated care, as provided by Dr. Hellman’s clinic, currently is the exception, according to Dr. Handelsman.

Although he said it was likely that guidelines issued by ACE will be expanded to incorporate the ADA’s recommendations, he challenged the ADA to advocate directly to endocrinology societies to educate them on the practical application of their recommendations.

“Take the guidelines and make us use them,” he said in the interview. Otherwise, because most clinical endocrinologists are not trained to address psychosocial concerns, unless a specialist already has an interest in mental health, Dr. Handelsman said that specialist largely will ignore this document. “Some in the field will read it ... but we will not take it to the streets.”

Despite his “guarded optimism,” neither does Dr. Roberts see how practice for primary care physicians will change much – at least, not in the near future, given what he called the already “bone crushing” constraints on their time.

Yet, he warned that not dealing with mental health issues means not delivering complete care.
“Depression is a complication of diabetes, in my expert opinion,” Dr. Roberts cautioned.

“Primary care physicians need to not sidestep this. They need to make it clear to their patients that dealing with depression is part and parcel of dealing with their chronic disease. The position statement can at least be a clarion call to consider mental health a medical condition that we can address in a matter-of-fact way.”

The American Diabetes Association’s recommendations for psychosocial care in diabetes are as follows:

• Integrate psychosocial care with collaborative, patient-centered medical care, and provide psychosocial care to all people with diabetes, with the goals of optimizing health outcomes and health-related quality of life. (Evidence level A.)

• Consider assessing symptoms of diabetes distress, depression, anxiety, and disordered eating and of cognitive capacities using patient-appropriate standardized/validated tools at the initial visit, at periodic intervals, and when there is a change in disease, treatment, or life circumstance. Include caregivers and family members in this assessment. (Evidence level B.)

• Consider monitoring patient performance of self-management behaviors as well as psychosocial factors impacting the person’s self-management. (Evidence level E.)

• Consider assessing life circumstances that can affect physical and psychological health outcomes and their incorporation into intervention strategies. (Evidence level E.)

• Address psychosocial problems upon identification. If an intervention cannot be initiated during the visit when the problem is identified, a follow-up visit or referral to a qualified behavioral health care provider may be scheduled during that visit. (Evidence level E.)

Dr. Handelsman chaired the American College of Endocrinology 2011 Comprehensive Diabetes Guidelines committee and is the immediate past president of ACE. Dr. Hellman is an editorial board member of Diabetes Care. Dr. Young-Hyman had no relevant disclosures.

[email protected]

On Twitter @whitneymcknight

[WpProQuiz 16]

[WpProQuiz 16]

[WpProQuiz 16]

NEW ORLEANS – Despite increasing use of transcatheter aortic valve replacement for patients with severe aortic stenosis at intermediate risk for surgery, the procedure is meeting selected resistance because of ongoing concerns about the procedure’s limitations.

As more data emerge from randomized trials and registries, cardiologists and cardiothoracic surgeons see the choice between transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) for patients at intermediate surgical risk as something to individualize based on factors that include age, the type of TAVR access possible (transfemoral or an alternative route), and of course, patient preference. An added variable is the constant stream of new data that keeps TAVR in flux, with improved and smaller valves and delivery systems coming onto the market that eclipse the experience and lessons learned from older TAVR systems.

In intermediate-risk patients, usually defined as those with a Society of Thoracic Surgeons (STS) mortality risk score of 4%-8%, “I think you can go either way,” said Frank W. Sellke, MD, at the American Heart Association scientific sessions.

“If a patient is 90 years old and can’t expect to live more than a couple of years, you use TAVR; but if the patient is 55 years old and can expect to live 30 years, I would recommend SAVR,” said Dr. Sellke, professor and chief of cardiothoracic surgery at Brown University in Providence, R.I.

He rattled off four things about TAVR that keep it from being for everyone: periprocedural vascular complications, higher rates of paravalvular leak than with surgery, leaflet thrombosis (a phenomenon with unclear clinical consequences), and undocumented long-term durability.

Dr. Sellke made these comments while discussing the report at the meeting on registry data collected from nearly 6,000 intermediate-risk patients who underwent TAVR or SAVR in Germany during January 2011 through December 2013 and assembled in the German Aortic Valve Registry. During that 3-year period, German TAVR patients could receive either the SAPIEN XT valve or the CoreValve, two TAVR systems that now have been superseded in both Europe and the United States by next-generation systems, SAPIEN 3 and Evolut R.

Limitations of a transthoracic approach

Another factor limiting TAVR is the endovascular approach. The best TAVR results by far have come from using a transfemoral approach for endovascular valve placement, but experts estimate that today at least 10% of patients considered for TAVR have a vascular anatomy that makes the transfemoral TAVR impossible. In the past, when such patients underwent TAVR, it was via either a transapical or transaortic approach (collectively called transthoracic), although additional endovascular entry sites are now being tested.

The limitations of transthoracic TAVR were underscored by results from a prespecified quality-of-life analysis done as part of the PARTNER 2 trial that compared the SAPIEN XT system with SAVR in intermediate-risk patients (N Engl J Med. 2016 April 27;374[17]:1609-20).

Mitchel L. Zoler/Frontline Medical News

Mitchel L. Zoler/Frontline Medical News

Concerns about durability

The durability of TAVR valves is another concern that has recently been influencing patients as they decide between TAVR and SAVR, said Dr. Smith. “A lot of patients don’t want TAVR because of their concerns about its durability.” These patients usually cite evidence reported in May 2016 at the annual congress of the European Association of Percutaneous Cardiovascular Interventions in Paris by Danny Dvir, MD, on longer-term follow-up of 378 patients who underwent TAVR at either of two pioneering centers. A retrospective review suggested a valve degeneration rate of about 50% after 8 years, Dr. Dvir reported.

This report “has gotten a lot of penetration over the Internet, and a lot of patients don’t like the uncertainty” about TAVR durability that this report produced. “A lot of the time now, patients come in with a fixed idea of whether they want TAVR or SAVR,” Dr. Smith said.

Dr. Smith essentially agreed with Dr. Sellke on the current role for TAVR relative to SAVR in lower-risk patients.

“If the patient is clearly intermediate risk, with an STS mortality risk of more than 6% and is at least 80 years old, then they’ll have TAVR 99% of the time. But if it’s a 75 year old with an STS score of 3.2% and otherwise healthy, the best choice is not as clear.”

Another cardiothoracic surgeon with lots of TAVR experience, Michael J. Reardon, MD, has much more enthusiasm for TAVR. “In my practice, I use TAVR exclusively in patients at least 80 years old. I don‘t care how healthy they look,” said Dr. Reardon, professor of cardiovascular surgery at Houston Methodist. He acknowledged that broader use of TAVR for intermediate-risk patients is getting push back from other cardiothoracic surgeons.

Dr. Sellke is one such surgeon, and he called uncertain TAVR valve durability the deciding factor. “We need longer-term data on [TAVR] valve longevity before we routinely put them into intermediate- or low-risk patients,” he said during a panel discussion at the meeting.

Dr. Reardon highlighted that newer TAVR systems have been reducing problems such as paravalvular leaks and the need for pacemakers following placement of self-expanding TAVR valves. Despite these technical improvements, the final frontier for TAVR for lower-risk patients is valve durability, Dr. Reardon said in an interview.

“I’m convinced the durability is there, and that any 80-year-old patient who is anatomically suited for transfemoral TAVR should get it no matter now healthy they look. If their likely survival is 15 years or less, then they are reasonable candidates for TAVR.”

Dr. Sellke had no relevant disclosures. PARTNER 2 was funded by Edwards, the company that markets Sapient TAVR systems. Dr. Cohen had no relevant disclosures. Dr. Smith has been an investigator in the PARTNER studies. Dr. Reardon has been a consultant to Medtronic, the company that markets the CoreValve and Evolut R TAVR systems.

[email protected]

On Twitter @mitchelzoler

NEW ORLEANS – Despite increasing use of transcatheter aortic valve replacement for patients with severe aortic stenosis at intermediate risk for surgery, the procedure is meeting selected resistance because of ongoing concerns about the procedure’s limitations.

As more data emerge from randomized trials and registries, cardiologists and cardiothoracic surgeons see the choice between transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) for patients at intermediate surgical risk as something to individualize based on factors that include age, the type of TAVR access possible (transfemoral or an alternative route), and of course, patient preference. An added variable is the constant stream of new data that keeps TAVR in flux, with improved and smaller valves and delivery systems coming onto the market that eclipse the experience and lessons learned from older TAVR systems.

In intermediate-risk patients, usually defined as those with a Society of Thoracic Surgeons (STS) mortality risk score of 4%-8%, “I think you can go either way,” said Frank W. Sellke, MD, at the American Heart Association scientific sessions.

“If a patient is 90 years old and can’t expect to live more than a couple of years, you use TAVR; but if the patient is 55 years old and can expect to live 30 years, I would recommend SAVR,” said Dr. Sellke, professor and chief of cardiothoracic surgery at Brown University in Providence, R.I.

He rattled off four things about TAVR that keep it from being for everyone: periprocedural vascular complications, higher rates of paravalvular leak than with surgery, leaflet thrombosis (a phenomenon with unclear clinical consequences), and undocumented long-term durability.

Dr. Sellke made these comments while discussing the report at the meeting on registry data collected from nearly 6,000 intermediate-risk patients who underwent TAVR or SAVR in Germany during January 2011 through December 2013 and assembled in the German Aortic Valve Registry. During that 3-year period, German TAVR patients could receive either the SAPIEN XT valve or the CoreValve, two TAVR systems that now have been superseded in both Europe and the United States by next-generation systems, SAPIEN 3 and Evolut R.

Limitations of a transthoracic approach

Another factor limiting TAVR is the endovascular approach. The best TAVR results by far have come from using a transfemoral approach for endovascular valve placement, but experts estimate that today at least 10% of patients considered for TAVR have a vascular anatomy that makes the transfemoral TAVR impossible. In the past, when such patients underwent TAVR, it was via either a transapical or transaortic approach (collectively called transthoracic), although additional endovascular entry sites are now being tested.

The limitations of transthoracic TAVR were underscored by results from a prespecified quality-of-life analysis done as part of the PARTNER 2 trial that compared the SAPIEN XT system with SAVR in intermediate-risk patients (N Engl J Med. 2016 April 27;374[17]:1609-20).

Mitchel L. Zoler/Frontline Medical News

Mitchel L. Zoler/Frontline Medical News

Concerns about durability

The durability of TAVR valves is another concern that has recently been influencing patients as they decide between TAVR and SAVR, said Dr. Smith. “A lot of patients don’t want TAVR because of their concerns about its durability.” These patients usually cite evidence reported in May 2016 at the annual congress of the European Association of Percutaneous Cardiovascular Interventions in Paris by Danny Dvir, MD, on longer-term follow-up of 378 patients who underwent TAVR at either of two pioneering centers. A retrospective review suggested a valve degeneration rate of about 50% after 8 years, Dr. Dvir reported.

This report “has gotten a lot of penetration over the Internet, and a lot of patients don’t like the uncertainty” about TAVR durability that this report produced. “A lot of the time now, patients come in with a fixed idea of whether they want TAVR or SAVR,” Dr. Smith said.

Dr. Smith essentially agreed with Dr. Sellke on the current role for TAVR relative to SAVR in lower-risk patients.

“If the patient is clearly intermediate risk, with an STS mortality risk of more than 6% and is at least 80 years old, then they’ll have TAVR 99% of the time. But if it’s a 75 year old with an STS score of 3.2% and otherwise healthy, the best choice is not as clear.”

Another cardiothoracic surgeon with lots of TAVR experience, Michael J. Reardon, MD, has much more enthusiasm for TAVR. “In my practice, I use TAVR exclusively in patients at least 80 years old. I don‘t care how healthy they look,” said Dr. Reardon, professor of cardiovascular surgery at Houston Methodist. He acknowledged that broader use of TAVR for intermediate-risk patients is getting push back from other cardiothoracic surgeons.

Dr. Sellke is one such surgeon, and he called uncertain TAVR valve durability the deciding factor. “We need longer-term data on [TAVR] valve longevity before we routinely put them into intermediate- or low-risk patients,” he said during a panel discussion at the meeting.

Dr. Reardon highlighted that newer TAVR systems have been reducing problems such as paravalvular leaks and the need for pacemakers following placement of self-expanding TAVR valves. Despite these technical improvements, the final frontier for TAVR for lower-risk patients is valve durability, Dr. Reardon said in an interview.

“I’m convinced the durability is there, and that any 80-year-old patient who is anatomically suited for transfemoral TAVR should get it no matter now healthy they look. If their likely survival is 15 years or less, then they are reasonable candidates for TAVR.”

Dr. Sellke had no relevant disclosures. PARTNER 2 was funded by Edwards, the company that markets Sapient TAVR systems. Dr. Cohen had no relevant disclosures. Dr. Smith has been an investigator in the PARTNER studies. Dr. Reardon has been a consultant to Medtronic, the company that markets the CoreValve and Evolut R TAVR systems.

[email protected]

On Twitter @mitchelzoler

NEW ORLEANS – Despite increasing use of transcatheter aortic valve replacement for patients with severe aortic stenosis at intermediate risk for surgery, the procedure is meeting selected resistance because of ongoing concerns about the procedure’s limitations.

As more data emerge from randomized trials and registries, cardiologists and cardiothoracic surgeons see the choice between transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) for patients at intermediate surgical risk as something to individualize based on factors that include age, the type of TAVR access possible (transfemoral or an alternative route), and of course, patient preference. An added variable is the constant stream of new data that keeps TAVR in flux, with improved and smaller valves and delivery systems coming onto the market that eclipse the experience and lessons learned from older TAVR systems.

In intermediate-risk patients, usually defined as those with a Society of Thoracic Surgeons (STS) mortality risk score of 4%-8%, “I think you can go either way,” said Frank W. Sellke, MD, at the American Heart Association scientific sessions.

“If a patient is 90 years old and can’t expect to live more than a couple of years, you use TAVR; but if the patient is 55 years old and can expect to live 30 years, I would recommend SAVR,” said Dr. Sellke, professor and chief of cardiothoracic surgery at Brown University in Providence, R.I.

He rattled off four things about TAVR that keep it from being for everyone: periprocedural vascular complications, higher rates of paravalvular leak than with surgery, leaflet thrombosis (a phenomenon with unclear clinical consequences), and undocumented long-term durability.

Dr. Sellke made these comments while discussing the report at the meeting on registry data collected from nearly 6,000 intermediate-risk patients who underwent TAVR or SAVR in Germany during January 2011 through December 2013 and assembled in the German Aortic Valve Registry. During that 3-year period, German TAVR patients could receive either the SAPIEN XT valve or the CoreValve, two TAVR systems that now have been superseded in both Europe and the United States by next-generation systems, SAPIEN 3 and Evolut R.

Limitations of a transthoracic approach

Another factor limiting TAVR is the endovascular approach. The best TAVR results by far have come from using a transfemoral approach for endovascular valve placement, but experts estimate that today at least 10% of patients considered for TAVR have a vascular anatomy that makes the transfemoral TAVR impossible. In the past, when such patients underwent TAVR, it was via either a transapical or transaortic approach (collectively called transthoracic), although additional endovascular entry sites are now being tested.

The limitations of transthoracic TAVR were underscored by results from a prespecified quality-of-life analysis done as part of the PARTNER 2 trial that compared the SAPIEN XT system with SAVR in intermediate-risk patients (N Engl J Med. 2016 April 27;374[17]:1609-20).

Mitchel L. Zoler/Frontline Medical News

Mitchel L. Zoler/Frontline Medical News

Concerns about durability

The durability of TAVR valves is another concern that has recently been influencing patients as they decide between TAVR and SAVR, said Dr. Smith. “A lot of patients don’t want TAVR because of their concerns about its durability.” These patients usually cite evidence reported in May 2016 at the annual congress of the European Association of Percutaneous Cardiovascular Interventions in Paris by Danny Dvir, MD, on longer-term follow-up of 378 patients who underwent TAVR at either of two pioneering centers. A retrospective review suggested a valve degeneration rate of about 50% after 8 years, Dr. Dvir reported.

This report “has gotten a lot of penetration over the Internet, and a lot of patients don’t like the uncertainty” about TAVR durability that this report produced. “A lot of the time now, patients come in with a fixed idea of whether they want TAVR or SAVR,” Dr. Smith said.

Dr. Smith essentially agreed with Dr. Sellke on the current role for TAVR relative to SAVR in lower-risk patients.

“If the patient is clearly intermediate risk, with an STS mortality risk of more than 6% and is at least 80 years old, then they’ll have TAVR 99% of the time. But if it’s a 75 year old with an STS score of 3.2% and otherwise healthy, the best choice is not as clear.”

Another cardiothoracic surgeon with lots of TAVR experience, Michael J. Reardon, MD, has much more enthusiasm for TAVR. “In my practice, I use TAVR exclusively in patients at least 80 years old. I don‘t care how healthy they look,” said Dr. Reardon, professor of cardiovascular surgery at Houston Methodist. He acknowledged that broader use of TAVR for intermediate-risk patients is getting push back from other cardiothoracic surgeons.

Dr. Sellke is one such surgeon, and he called uncertain TAVR valve durability the deciding factor. “We need longer-term data on [TAVR] valve longevity before we routinely put them into intermediate- or low-risk patients,” he said during a panel discussion at the meeting.

Dr. Reardon highlighted that newer TAVR systems have been reducing problems such as paravalvular leaks and the need for pacemakers following placement of self-expanding TAVR valves. Despite these technical improvements, the final frontier for TAVR for lower-risk patients is valve durability, Dr. Reardon said in an interview.

“I’m convinced the durability is there, and that any 80-year-old patient who is anatomically suited for transfemoral TAVR should get it no matter now healthy they look. If their likely survival is 15 years or less, then they are reasonable candidates for TAVR.”

Dr. Sellke had no relevant disclosures. PARTNER 2 was funded by Edwards, the company that markets Sapient TAVR systems. Dr. Cohen had no relevant disclosures. Dr. Smith has been an investigator in the PARTNER studies. Dr. Reardon has been a consultant to Medtronic, the company that markets the CoreValve and Evolut R TAVR systems.

[email protected]

On Twitter @mitchelzoler

A mass spectrometry test was able to rapidly measure lung maturity in premature infants at risk for respiratory distress syndrome (RDS), according to Henrik Verder, MD, of Holbaek (Denmark) University Hospital, and his associates.

Samples of gastric aspirates were taken from 136 infants with gestation periods of 24-31 weeks, and analyzed with mass spectrometry. Of this group, 61 developed RDS, and 7 died before the end of the study period. With a lecithin/sphingomyelin (L/S) cut-off ratio of 2.2, sensitivity of the mass spectrometry test was 92%, specificity was 73%, positive predictive value was 74%, and negative predictive was value of 92%. Sensitivity was high for all gestational age groups, the investigators noted.

Oropharyngeal secretions were sampled from an additional group of 59 infants and analyzed using spectrometry, with an L/S cut-off value of 3.7; however sensitivity and specificity were lower than for gastric aspirates.

“This test could help identify which infants will benefit from very early surfactant treatment, with the potential to significantly improve clinical outcomes resulting in less severe RDS, less need of mechanical ventilation and oxygen and less severe bronchopulmonary dysplasia,” the investigators concluded.

Find the study in Acta Paediatrica (2016. doi: 10.1111/apa.13683)

[email protected]

A mass spectrometry test was able to rapidly measure lung maturity in premature infants at risk for respiratory distress syndrome (RDS), according to Henrik Verder, MD, of Holbaek (Denmark) University Hospital, and his associates.

Samples of gastric aspirates were taken from 136 infants with gestation periods of 24-31 weeks, and analyzed with mass spectrometry. Of this group, 61 developed RDS, and 7 died before the end of the study period. With a lecithin/sphingomyelin (L/S) cut-off ratio of 2.2, sensitivity of the mass spectrometry test was 92%, specificity was 73%, positive predictive value was 74%, and negative predictive was value of 92%. Sensitivity was high for all gestational age groups, the investigators noted.

Oropharyngeal secretions were sampled from an additional group of 59 infants and analyzed using spectrometry, with an L/S cut-off value of 3.7; however sensitivity and specificity were lower than for gastric aspirates.

“This test could help identify which infants will benefit from very early surfactant treatment, with the potential to significantly improve clinical outcomes resulting in less severe RDS, less need of mechanical ventilation and oxygen and less severe bronchopulmonary dysplasia,” the investigators concluded.

Find the study in Acta Paediatrica (2016. doi: 10.1111/apa.13683)

[email protected]

A mass spectrometry test was able to rapidly measure lung maturity in premature infants at risk for respiratory distress syndrome (RDS), according to Henrik Verder, MD, of Holbaek (Denmark) University Hospital, and his associates.

Samples of gastric aspirates were taken from 136 infants with gestation periods of 24-31 weeks, and analyzed with mass spectrometry. Of this group, 61 developed RDS, and 7 died before the end of the study period. With a lecithin/sphingomyelin (L/S) cut-off ratio of 2.2, sensitivity of the mass spectrometry test was 92%, specificity was 73%, positive predictive value was 74%, and negative predictive was value of 92%. Sensitivity was high for all gestational age groups, the investigators noted.

Oropharyngeal secretions were sampled from an additional group of 59 infants and analyzed using spectrometry, with an L/S cut-off value of 3.7; however sensitivity and specificity were lower than for gastric aspirates.

“This test could help identify which infants will benefit from very early surfactant treatment, with the potential to significantly improve clinical outcomes resulting in less severe RDS, less need of mechanical ventilation and oxygen and less severe bronchopulmonary dysplasia,” the investigators concluded.

Find the study in Acta Paediatrica (2016. doi: 10.1111/apa.13683)

[email protected]

The struggle to defeat Ebola virus disease continues globally, although it may not always make the headlines. To catch up on what you may have missed, here are some notable news items and journal articles published over the past few weeks that are worth a second look.

A study in Cell found that specific amino acid substitutions in the Ebola virus glycoprotein have increased tropism for human cells, while reducing tropism for bat cells, and such increased infectivity may have contributed to the wide geographic distribution of some viral lineages.

CDC/Daniel J. DeNoon

[email protected]

On Twitter @richpizzi

The struggle to defeat Ebola virus disease continues globally, although it may not always make the headlines. To catch up on what you may have missed, here are some notable news items and journal articles published over the past few weeks that are worth a second look.

A study in Cell found that specific amino acid substitutions in the Ebola virus glycoprotein have increased tropism for human cells, while reducing tropism for bat cells, and such increased infectivity may have contributed to the wide geographic distribution of some viral lineages.

CDC/Daniel J. DeNoon

[email protected]

On Twitter @richpizzi

The struggle to defeat Ebola virus disease continues globally, although it may not always make the headlines. To catch up on what you may have missed, here are some notable news items and journal articles published over the past few weeks that are worth a second look.

A study in Cell found that specific amino acid substitutions in the Ebola virus glycoprotein have increased tropism for human cells, while reducing tropism for bat cells, and such increased infectivity may have contributed to the wide geographic distribution of some viral lineages.

CDC/Daniel J. DeNoon

[email protected]

On Twitter @richpizzi

SAN ANTONIO – When does adjuvant therapy with an aromatase inhibitor become too much of a good thing? Or to put it another way, what’s the optimal duration of extended aromatase inhibitor therapy? That’s the question that three clinical trials have tried – but largely failed – to answer.

For example, the randomized, double-blinded NSABP B-42 trial, comparing extended therapy with letrozole (Femara) in postmenopausal women with hormone receptor–positive (HR+) breast cancer who have completed previous adjuvant therapy with an aromatase inhibitor (AI) showed no difference in disease-free survival (DFS) after 7 years of follow-up between women treated with extended letrozole or placebo.

DATA data

In the DATA study, also presented here, investigators from the Netherlands compared 6 years of anastrozole (Arimidex) to 3 years of anastrozole following 2 or 3 years of adjuvant tamoxifen for postmenopausal women with estrogen receptor–positive (ER+), and/or progesterone receptor–positive (PR+) breast cancer.

They found that “adapted” DFS (DFS starting 3 years after randomization) and adapted overall survival (OS) were similar between the two groups.

“The findings of the DATA study do not support extended adjuvant AI use after 5 years of sequential endocrine therapy for all postmenopausal hormone receptor–positive breast cancer patients,” said Vivianne Tjan-Heijnen, MD, of Maastricht University Medical Center in the Netherlands.

Less than ideal

In the optimistically named IDEAL trial, a separate team of investigators, also from the Netherlands, looked at the relative merits of continuing adjuvant therapy with letrozole for 2.5 or 5 years following 5 years of adjuvant therapy with tamoxifen, an AI, or a combination in postmenopausal women with HR+ breast cancer.

They found no differences in either DFS or OS between patients treated for 5 years or those treated for only half that long.

“We conclude that there is no benefit of extending AI-based therapy longer than two-and-a-half years,” said Erik Blok, MD, of Leiden University Medical Center in the Netherlands.

Give what to whom for how long?

Results of the trials raise more questions than they answer, said Michael Gnant, MD, of the Medical University of Vienna, the invited discussant.

“Essentially, these three trials did not reach the necessary statistical significance levels to demonstrate a clear benefit for the respective AI extension,” he said.

“Can other agents we use in luminal breast cancer help? Frankly, I don’t think so. Based on their tolerability profile, and in part also on financial toxicity, I don’t think that the promising agents we explore in many situations for the treatment of hormone receptor–positive breast cancer will realistically be used in the extended adjuvant setting,” he said.

What’s needed, he said, are new strategies for targeting the chronic part of luminal breast cancer recurrence risk. Using endocrine therapies in this setting will likely be ineffective. Instead, agents that could directly target dormant cancer stem cells would “eliminate the source of late metastases for good.”

The best evidence to date clearly points to individualized treatment plans for patients, Dr. Gnant said.

For example, for a patient who has had 2-5 years of tamoxifen, an AI for 2.5-5 additional years can help to prevent recurrences, provided that the patient has risk factors for recurrence and excellent bone health.

“Based on the trial results, it is more complex for a patient who comes off initial or sequential AI. There are factors favoring the extension of AI treatment, and other factors to speak against such extension. I suggest to start with patient features at this time,” he said.

Currently, the main factor driving the choice of extended AI therapy will be how well the patient has tolerated AIs in the first years of therapy and whether she is at increased risk for fractures, suggesting younger age as a factor favoring extended AI use.

Patients with higher clinicopathologic risk factors such as node positivity or more luminal type tumors, as well as higher risk according to genomic studies, might also benefit from extended AI therapy, he said.

Biomarkers needed

“What the data from these and other trials tell us is that endocrine therapy is not for everyone. We need biomarkers that can tell us who should be getting extended endocrine therapy, be it 10 years or even a longer duration of time, versus a subgroup that might do very well with 5 five years of AI,” Aditya Bardia, MBBS, MPH, of the breast cancer division at Massachusetts General Hospital Cancer Center in Boston, said in an interview.

There are several such biomarkers under investigation, but they need validation and testing in large scale clinical trials before they find their way into day-to-practice, he said.

Dr. Bardia was not involved in the studies.

NSABP B-42 was sponsored by PrECOG with financial support from Novartis. Dr. Mamounas reported having no conflicts of interest. The DATA trial was sponsored by the Dutch Breast Cancer Research Group and Novartis. Dr. Tjan-Heijnen reported nothing to disclose. IDEAL was supported by the Dutch Breast Cancer Research Group and Novartis. Dr. Blok reported nothing to disclose.

SAN ANTONIO – When does adjuvant therapy with an aromatase inhibitor become too much of a good thing? Or to put it another way, what’s the optimal duration of extended aromatase inhibitor therapy? That’s the question that three clinical trials have tried – but largely failed – to answer.

For example, the randomized, double-blinded NSABP B-42 trial, comparing extended therapy with letrozole (Femara) in postmenopausal women with hormone receptor–positive (HR+) breast cancer who have completed previous adjuvant therapy with an aromatase inhibitor (AI) showed no difference in disease-free survival (DFS) after 7 years of follow-up between women treated with extended letrozole or placebo.

DATA data

In the DATA study, also presented here, investigators from the Netherlands compared 6 years of anastrozole (Arimidex) to 3 years of anastrozole following 2 or 3 years of adjuvant tamoxifen for postmenopausal women with estrogen receptor–positive (ER+), and/or progesterone receptor–positive (PR+) breast cancer.

They found that “adapted” DFS (DFS starting 3 years after randomization) and adapted overall survival (OS) were similar between the two groups.

“The findings of the DATA study do not support extended adjuvant AI use after 5 years of sequential endocrine therapy for all postmenopausal hormone receptor–positive breast cancer patients,” said Vivianne Tjan-Heijnen, MD, of Maastricht University Medical Center in the Netherlands.

Less than ideal

In the optimistically named IDEAL trial, a separate team of investigators, also from the Netherlands, looked at the relative merits of continuing adjuvant therapy with letrozole for 2.5 or 5 years following 5 years of adjuvant therapy with tamoxifen, an AI, or a combination in postmenopausal women with HR+ breast cancer.

They found no differences in either DFS or OS between patients treated for 5 years or those treated for only half that long.

“We conclude that there is no benefit of extending AI-based therapy longer than two-and-a-half years,” said Erik Blok, MD, of Leiden University Medical Center in the Netherlands.

Give what to whom for how long?

Results of the trials raise more questions than they answer, said Michael Gnant, MD, of the Medical University of Vienna, the invited discussant.

“Essentially, these three trials did not reach the necessary statistical significance levels to demonstrate a clear benefit for the respective AI extension,” he said.

“Can other agents we use in luminal breast cancer help? Frankly, I don’t think so. Based on their tolerability profile, and in part also on financial toxicity, I don’t think that the promising agents we explore in many situations for the treatment of hormone receptor–positive breast cancer will realistically be used in the extended adjuvant setting,” he said.

What’s needed, he said, are new strategies for targeting the chronic part of luminal breast cancer recurrence risk. Using endocrine therapies in this setting will likely be ineffective. Instead, agents that could directly target dormant cancer stem cells would “eliminate the source of late metastases for good.”

The best evidence to date clearly points to individualized treatment plans for patients, Dr. Gnant said.

For example, for a patient who has had 2-5 years of tamoxifen, an AI for 2.5-5 additional years can help to prevent recurrences, provided that the patient has risk factors for recurrence and excellent bone health.

“Based on the trial results, it is more complex for a patient who comes off initial or sequential AI. There are factors favoring the extension of AI treatment, and other factors to speak against such extension. I suggest to start with patient features at this time,” he said.

Currently, the main factor driving the choice of extended AI therapy will be how well the patient has tolerated AIs in the first years of therapy and whether she is at increased risk for fractures, suggesting younger age as a factor favoring extended AI use.

Patients with higher clinicopathologic risk factors such as node positivity or more luminal type tumors, as well as higher risk according to genomic studies, might also benefit from extended AI therapy, he said.

Biomarkers needed

“What the data from these and other trials tell us is that endocrine therapy is not for everyone. We need biomarkers that can tell us who should be getting extended endocrine therapy, be it 10 years or even a longer duration of time, versus a subgroup that might do very well with 5 five years of AI,” Aditya Bardia, MBBS, MPH, of the breast cancer division at Massachusetts General Hospital Cancer Center in Boston, said in an interview.

There are several such biomarkers under investigation, but they need validation and testing in large scale clinical trials before they find their way into day-to-practice, he said.

Dr. Bardia was not involved in the studies.

NSABP B-42 was sponsored by PrECOG with financial support from Novartis. Dr. Mamounas reported having no conflicts of interest. The DATA trial was sponsored by the Dutch Breast Cancer Research Group and Novartis. Dr. Tjan-Heijnen reported nothing to disclose. IDEAL was supported by the Dutch Breast Cancer Research Group and Novartis. Dr. Blok reported nothing to disclose.

SAN ANTONIO – When does adjuvant therapy with an aromatase inhibitor become too much of a good thing? Or to put it another way, what’s the optimal duration of extended aromatase inhibitor therapy? That’s the question that three clinical trials have tried – but largely failed – to answer.

For example, the randomized, double-blinded NSABP B-42 trial, comparing extended therapy with letrozole (Femara) in postmenopausal women with hormone receptor–positive (HR+) breast cancer who have completed previous adjuvant therapy with an aromatase inhibitor (AI) showed no difference in disease-free survival (DFS) after 7 years of follow-up between women treated with extended letrozole or placebo.

DATA data

In the DATA study, also presented here, investigators from the Netherlands compared 6 years of anastrozole (Arimidex) to 3 years of anastrozole following 2 or 3 years of adjuvant tamoxifen for postmenopausal women with estrogen receptor–positive (ER+), and/or progesterone receptor–positive (PR+) breast cancer.

They found that “adapted” DFS (DFS starting 3 years after randomization) and adapted overall survival (OS) were similar between the two groups.

“The findings of the DATA study do not support extended adjuvant AI use after 5 years of sequential endocrine therapy for all postmenopausal hormone receptor–positive breast cancer patients,” said Vivianne Tjan-Heijnen, MD, of Maastricht University Medical Center in the Netherlands.

Less than ideal

In the optimistically named IDEAL trial, a separate team of investigators, also from the Netherlands, looked at the relative merits of continuing adjuvant therapy with letrozole for 2.5 or 5 years following 5 years of adjuvant therapy with tamoxifen, an AI, or a combination in postmenopausal women with HR+ breast cancer.

They found no differences in either DFS or OS between patients treated for 5 years or those treated for only half that long.

“We conclude that there is no benefit of extending AI-based therapy longer than two-and-a-half years,” said Erik Blok, MD, of Leiden University Medical Center in the Netherlands.

Give what to whom for how long?

Results of the trials raise more questions than they answer, said Michael Gnant, MD, of the Medical University of Vienna, the invited discussant.

“Essentially, these three trials did not reach the necessary statistical significance levels to demonstrate a clear benefit for the respective AI extension,” he said.

“Can other agents we use in luminal breast cancer help? Frankly, I don’t think so. Based on their tolerability profile, and in part also on financial toxicity, I don’t think that the promising agents we explore in many situations for the treatment of hormone receptor–positive breast cancer will realistically be used in the extended adjuvant setting,” he said.

What’s needed, he said, are new strategies for targeting the chronic part of luminal breast cancer recurrence risk. Using endocrine therapies in this setting will likely be ineffective. Instead, agents that could directly target dormant cancer stem cells would “eliminate the source of late metastases for good.”

The best evidence to date clearly points to individualized treatment plans for patients, Dr. Gnant said.

For example, for a patient who has had 2-5 years of tamoxifen, an AI for 2.5-5 additional years can help to prevent recurrences, provided that the patient has risk factors for recurrence and excellent bone health.

“Based on the trial results, it is more complex for a patient who comes off initial or sequential AI. There are factors favoring the extension of AI treatment, and other factors to speak against such extension. I suggest to start with patient features at this time,” he said.

Currently, the main factor driving the choice of extended AI therapy will be how well the patient has tolerated AIs in the first years of therapy and whether she is at increased risk for fractures, suggesting younger age as a factor favoring extended AI use.

Patients with higher clinicopathologic risk factors such as node positivity or more luminal type tumors, as well as higher risk according to genomic studies, might also benefit from extended AI therapy, he said.

Biomarkers needed

“What the data from these and other trials tell us is that endocrine therapy is not for everyone. We need biomarkers that can tell us who should be getting extended endocrine therapy, be it 10 years or even a longer duration of time, versus a subgroup that might do very well with 5 five years of AI,” Aditya Bardia, MBBS, MPH, of the breast cancer division at Massachusetts General Hospital Cancer Center in Boston, said in an interview.

There are several such biomarkers under investigation, but they need validation and testing in large scale clinical trials before they find their way into day-to-practice, he said.

Dr. Bardia was not involved in the studies.

NSABP B-42 was sponsored by PrECOG with financial support from Novartis. Dr. Mamounas reported having no conflicts of interest. The DATA trial was sponsored by the Dutch Breast Cancer Research Group and Novartis. Dr. Tjan-Heijnen reported nothing to disclose. IDEAL was supported by the Dutch Breast Cancer Research Group and Novartis. Dr. Blok reported nothing to disclose.

If you work on the front lines of medical care treating patients with hepatitis, you may not have time to review all the hepatitis research that enters the medical literature every month. Here’s a quick look at some notable news items and journal articles published over the past month, covering a variety of the major hepatitis viruses.

The introduction of universal mass vaccination against hepatitis A in countries with intermediate endemicity for HAV infection led to a considerable decrease in the incidence of HAV in vaccinated and in nonvaccinated age groups alike.

©Zerbor/Thinkstock

A recent study identified a novel hepatitis B virus subgenotype D10 circulating in Ethiopia, underlining the high genetic variability of HBV strains in Africa.

A study in the Journal of Viral Hepatitis found that baseline hepatitis B core antibody predicts treatment response in chronic hepatitis B patients receiving long-term entecavir.

A novel quantitative microarray antibody capture assay was able to identify extremely high hepatitis delta virus prevalence amongst hepatitis B virus–infected Mongolians.

The albumin-bilirubin (ALBI) score was effective in predicting the long-term prognosis for patients with hepatitis B virus–related cirrhosis and was more accurate than Child-Pugh and Model for End-Stage Liver Disease (MELD) scores.

A study in Hepatology found that proanthocyanidin (PAC) and its analogs present a new class of anti–hepatitis B virus agents that directly target the preS1 region of the HBV large surface protein and could contribute to the development of a potent, well-tolerated, and broadly active inhibitor of HBV infection.

A hepatitis C virus core antigen (HCV-Ag) assay proved to be useful in monitoring treatment of HCV-infected patients with sustained viral response and in patients who experienced treatment failures, according to a study in Diagnostic Microbiology and Infectious Disease.

The introduction of a managed care network for patients infected with hepatitis C virus increased access to care and reduced all-cause mortality, according to a recent study.

A study in South Korea found that hepatitis B infection was associated with an increased incidence of thrombocytopenia in healthy adults without cirrhosis.

A proof-of-concept study demonstrated that peritransplant immunoprophylaxis combined with a single oral direct-acting antiviral in the immediate post-transplant period can prevent HCV recurrence.

A study in the Journal of Viral Hepatitis established the baseline mortality and hepatocellular carcinoma progression rates in decompensated cirrhosis patients against which the impact of new antiviral therapies could be measured.

Genetic distance-based network analyses can be used to identify characteristics associated with hepatitis C virus transmission, informing targeted prevention and treatment strategies, according to a recent study.

According to a new study, primary T-cell immunodeficiency is associated with a lower spontaneous clearance of hepatitis C virus, while female sex and coinfection with hepatitis B virus are associated with a higher spontaneous clearance.

A study in the Journal of Viral Hepatitis found that the induction of humoral and cellular immune response to hepatitis B virus vaccine can be upregulated by CpG oligonucleotides complexed with Dectin-1 ligand.

[email protected]
On Twitter @richpizzi

If you work on the front lines of medical care treating patients with hepatitis, you may not have time to review all the hepatitis research that enters the medical literature every month. Here’s a quick look at some notable news items and journal articles published over the past month, covering a variety of the major hepatitis viruses.

The introduction of universal mass vaccination against hepatitis A in countries with intermediate endemicity for HAV infection led to a considerable decrease in the incidence of HAV in vaccinated and in nonvaccinated age groups alike.

©Zerbor/Thinkstock

A recent study identified a novel hepatitis B virus subgenotype D10 circulating in Ethiopia, underlining the high genetic variability of HBV strains in Africa.

A study in the Journal of Viral Hepatitis found that baseline hepatitis B core antibody predicts treatment response in chronic hepatitis B patients receiving long-term entecavir.

A novel quantitative microarray antibody capture assay was able to identify extremely high hepatitis delta virus prevalence amongst hepatitis B virus–infected Mongolians.

The albumin-bilirubin (ALBI) score was effective in predicting the long-term prognosis for patients with hepatitis B virus–related cirrhosis and was more accurate than Child-Pugh and Model for End-Stage Liver Disease (MELD) scores.

A study in Hepatology found that proanthocyanidin (PAC) and its analogs present a new class of anti–hepatitis B virus agents that directly target the preS1 region of the HBV large surface protein and could contribute to the development of a potent, well-tolerated, and broadly active inhibitor of HBV infection.

A hepatitis C virus core antigen (HCV-Ag) assay proved to be useful in monitoring treatment of HCV-infected patients with sustained viral response and in patients who experienced treatment failures, according to a study in Diagnostic Microbiology and Infectious Disease.

The introduction of a managed care network for patients infected with hepatitis C virus increased access to care and reduced all-cause mortality, according to a recent study.

A study in South Korea found that hepatitis B infection was associated with an increased incidence of thrombocytopenia in healthy adults without cirrhosis.

A proof-of-concept study demonstrated that peritransplant immunoprophylaxis combined with a single oral direct-acting antiviral in the immediate post-transplant period can prevent HCV recurrence.

A study in the Journal of Viral Hepatitis established the baseline mortality and hepatocellular carcinoma progression rates in decompensated cirrhosis patients against which the impact of new antiviral therapies could be measured.

Genetic distance-based network analyses can be used to identify characteristics associated with hepatitis C virus transmission, informing targeted prevention and treatment strategies, according to a recent study.

According to a new study, primary T-cell immunodeficiency is associated with a lower spontaneous clearance of hepatitis C virus, while female sex and coinfection with hepatitis B virus are associated with a higher spontaneous clearance.

A study in the Journal of Viral Hepatitis found that the induction of humoral and cellular immune response to hepatitis B virus vaccine can be upregulated by CpG oligonucleotides complexed with Dectin-1 ligand.

[email protected]
On Twitter @richpizzi

If you work on the front lines of medical care treating patients with hepatitis, you may not have time to review all the hepatitis research that enters the medical literature every month. Here’s a quick look at some notable news items and journal articles published over the past month, covering a variety of the major hepatitis viruses.

The introduction of universal mass vaccination against hepatitis A in countries with intermediate endemicity for HAV infection led to a considerable decrease in the incidence of HAV in vaccinated and in nonvaccinated age groups alike.

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A recent study identified a novel hepatitis B virus subgenotype D10 circulating in Ethiopia, underlining the high genetic variability of HBV strains in Africa.

A study in the Journal of Viral Hepatitis found that baseline hepatitis B core antibody predicts treatment response in chronic hepatitis B patients receiving long-term entecavir.

A novel quantitative microarray antibody capture assay was able to identify extremely high hepatitis delta virus prevalence amongst hepatitis B virus–infected Mongolians.

The albumin-bilirubin (ALBI) score was effective in predicting the long-term prognosis for patients with hepatitis B virus–related cirrhosis and was more accurate than Child-Pugh and Model for End-Stage Liver Disease (MELD) scores.

A study in Hepatology found that proanthocyanidin (PAC) and its analogs present a new class of anti–hepatitis B virus agents that directly target the preS1 region of the HBV large surface protein and could contribute to the development of a potent, well-tolerated, and broadly active inhibitor of HBV infection.

A hepatitis C virus core antigen (HCV-Ag) assay proved to be useful in monitoring treatment of HCV-infected patients with sustained viral response and in patients who experienced treatment failures, according to a study in Diagnostic Microbiology and Infectious Disease.

The introduction of a managed care network for patients infected with hepatitis C virus increased access to care and reduced all-cause mortality, according to a recent study.

A study in South Korea found that hepatitis B infection was associated with an increased incidence of thrombocytopenia in healthy adults without cirrhosis.

A proof-of-concept study demonstrated that peritransplant immunoprophylaxis combined with a single oral direct-acting antiviral in the immediate post-transplant period can prevent HCV recurrence.

A study in the Journal of Viral Hepatitis established the baseline mortality and hepatocellular carcinoma progression rates in decompensated cirrhosis patients against which the impact of new antiviral therapies could be measured.

Genetic distance-based network analyses can be used to identify characteristics associated with hepatitis C virus transmission, informing targeted prevention and treatment strategies, according to a recent study.

According to a new study, primary T-cell immunodeficiency is associated with a lower spontaneous clearance of hepatitis C virus, while female sex and coinfection with hepatitis B virus are associated with a higher spontaneous clearance.

A study in the Journal of Viral Hepatitis found that the induction of humoral and cellular immune response to hepatitis B virus vaccine can be upregulated by CpG oligonucleotides complexed with Dectin-1 ligand.

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VIENNA – In a heavily pretreated population of patients with non–small-cell lung cancer (NSCLC), the investigational checkpoint inhibitor durvalumab was associated with good objective response rates (ORR) and ‘impressive’ overall survival (OS) in a phase II study, Marina Garassino, MD, reported at the World Conference on Lung Cancer.

The primary endpoint of ORR in the open-label, single-arm ATLANTIC trial was achieved by 7% of patients with low (less than 25% of tumor cells) expression of the programmed death ligand 1 (PD-L1) that durvalumab targets (n = 93), by 16.4% of patients with PD-L1 expression of 25% or higher (n = 146), and by 30.9% in patients with PD-L1 expression of 90% or more (n = 68).

Sara Freeman/Frontline Medical News

Sara Freeman/Frontline Medical News

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VIENNA – In a heavily pretreated population of patients with non–small-cell lung cancer (NSCLC), the investigational checkpoint inhibitor durvalumab was associated with good objective response rates (ORR) and ‘impressive’ overall survival (OS) in a phase II study, Marina Garassino, MD, reported at the World Conference on Lung Cancer.

The primary endpoint of ORR in the open-label, single-arm ATLANTIC trial was achieved by 7% of patients with low (less than 25% of tumor cells) expression of the programmed death ligand 1 (PD-L1) that durvalumab targets (n = 93), by 16.4% of patients with PD-L1 expression of 25% or higher (n = 146), and by 30.9% in patients with PD-L1 expression of 90% or more (n = 68).

Sara Freeman/Frontline Medical News

Sara Freeman/Frontline Medical News

[email protected]

VIENNA – In a heavily pretreated population of patients with non–small-cell lung cancer (NSCLC), the investigational checkpoint inhibitor durvalumab was associated with good objective response rates (ORR) and ‘impressive’ overall survival (OS) in a phase II study, Marina Garassino, MD, reported at the World Conference on Lung Cancer.

The primary endpoint of ORR in the open-label, single-arm ATLANTIC trial was achieved by 7% of patients with low (less than 25% of tumor cells) expression of the programmed death ligand 1 (PD-L1) that durvalumab targets (n = 93), by 16.4% of patients with PD-L1 expression of 25% or higher (n = 146), and by 30.9% in patients with PD-L1 expression of 90% or more (n = 68).

Sara Freeman/Frontline Medical News

Sara Freeman/Frontline Medical News

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