Guidelines

Ensuring that older adults who have experienced a hip or vertebral fracture understand they likely have osteoporosis, and offering prompt drug treatment for the condition, are among five fundamental recommendations put together by a coalition of U.S. and international bone health experts and health care organizations to help prevent secondary fractures.

The recommendations were announced at the annual meeting of the American Society for Bone and Mineral Research (ASBMR) in Montreal. The 40-member group that developed the recommendations, called the ASBMR Secondary Fracture Prevention Initiative Coalition, includes the American Association of Clinical Endocrinologists/American College of Endocrinology, the Endocrine Society, the American College of Rheumatology, the American College of Physicians, the American Geriatrics Society, the American Academy of Physical Medicine and Rehabilitation, and the American Academy of Orthopaedic Surgeons.

Additional fundamental recommendations from the Coalition advised ensuring that patients’ primary health care providers are aware of the fracture, regularly assessing the risk of falls, and routinely reevaluating patients who are being treated for osteoporosis. These suggestions were developed in response to growing evidence of a rising trend in osteoporosis patients not being prescribed appropriate medications or not taking them, the ASBMR said.

“The very simple message is if you’ve got somebody who has had a hip fracture or a vertebral fracture, that needs secondary prevention just like somebody who’s had an MI needs to be on a statin and a beta blocker,” said coalition cochair Sundeep Khosla, MD, a past president of the ASBMR and director of the Center for Clinical and Translational Science at the Mayo Clinic, Rochester, Minn. “You can’t ignore the fracture because it’s not immediately life-threatening. Down the road they’re going to have another hip fracture if nothing is done.”

Only 23% of elderly patients who have a hip fracture receive osteoporosis medication to reduce future fracture risk, according to the ASBMR. A 30-year downward trend in the number of hip fractures in the United States has recently plateaued, raising concerns this may have been caused by doctors and patients not following diagnostic and treatment guidelines, the organization noted.

The reasons for the plateau are uncertain, Dr. Khosla said, but could include a reluctance by patients to take bisphosphonates following some reports of relatively rare side effects, such as atypical femoral fractures and osteonecrosis of the jaw. In addition, he said, reimbursement for dual-energy x-ray absorptiometry (DEXA) scans to measure bone mineral density has gone down, which has led to fewer osteoporosis diagnoses. But fracture prevention is important, he said. Of the 300,000 hip fractures in the United States each year, one of every two patients never regains their previous functioning. In addition, one of every four hip fracture patients ends up in a nursing home or dies within a year, according to the ASBMR.

The recommendations and more data about osteoporosis treatment are available on the coalition’s website, www.secondaryfractures.org. An action plan for clinicians should be added to the site sometime this fall, Dr. Khosla said.

There are five fundamental recommendations:

First, communicate three simple messages to patients and their family/caregivers throughout the fracture care and healing process. These include: Their broken bone likely means they have osteoporosis and are at high risk for breaking more bones; breaking bones means they may have to use a walker, cane, or wheelchair or move from their home to a residential facility and will be at higher risk for premature death; and there are actions they can take to reduce their risk.

This is key, said coalition cochair Douglas P. Kiel, MD, a past president of ASBMR, the director of the Musculoskeletal Research Center at the Institute for Aging Research at Hebrew SeniorLife in Boston, and a professor of medicine at Harvard Medical School, also in Boston.

“If you talk to people who have had a broken bone, they view this as an accident and not that they have anything wrong with them,” he said. “The communication should be that if you broke something, it is not a random, chance event. You have osteoporosis, and if you don’t do anything about it, you’re going to be at great risk of a life-threatening, independence-threatening fracture in the future.”

Second, ensure the patient’s primary health care provider is made aware of the occurrence of the fracture. Take action to be sure the communication is made.

Third, regularly assess the risk of falling in women and men age 65 years or older who have had a hip or vertebral fracture. At minimum, take a history of falls within the last year, minimize the use of medications associated with increased risk for falls, evaluate patients for conditions associated with an increased risk for falls, and strongly consider referring patients to physical and/or occupational therapy or a physiatrist for evaluation and interventions to improve impairments in mobility, gait, and balance to reduce the risk for falls.

Fourth, reduce the risk of additional fractures by offering pharmacologic therapy for osteoporosis to women and men age 65 years or older who have had a hip or vertebral fracture. This can begin in the hospital and be included in discharge orders. Do not delay initiation of therapy for bone mineral density (BMD) testing. Consider patients’ oral health before starting therapy with bisphosphonates or denosumab (Prolia).

Most hip fracture patients leave the hospital without osteoporosis medications, Dr. Kiel said. It could be that hospital-based physicians are concerned patients are still unsteady such that they may not want to start patients on a new medication when they’re discharging them. Physicians in rehabilitation units may not prescribe these medications because they feel they have the patients for a short time, so by the time the patient returns to their primary care provider, the patient may have the same mistaken impression the fracture was an accident.

“We’re advocating not to delay treatment for any of these care transitions or because you think they need a BMD test,” Dr. Kiel said. “Just get them treated like they do with heart attacks.”

Finally, follow and reevaluate women and men age 65 years or older who have had a hip or vertebral fracture and are being treated for osteoporosis because it is a life-long chronic condition. This can help reinforce key messages about osteoporosis and associated fractures, identify any barriers to treatment adherence, assess the risk of falls, evaluate the effectiveness of a treatment plan, monitor for adverse effects, and determine whether any changes in treatment should be made, including whether any osteoporosis pharmacotherapy should be changed or discontinued.

Ideally, patients should be managed in the context of a multidisciplinary clinical system that includes case management, such as a fracture liaison service, according to the recommendations.

Besides the fundamental five recommendations, the documents lists another seven that deal with referring patients, prescribing vitamin D, counseling on lifestyle and diet, discussing pharmacotherapy benefits and risks, weighing first-line therapy options, and determining the duration of pharmacotherapy.

Ensuring that older adults who have experienced a hip or vertebral fracture understand they likely have osteoporosis, and offering prompt drug treatment for the condition, are among five fundamental recommendations put together by a coalition of U.S. and international bone health experts and health care organizations to help prevent secondary fractures.

The recommendations were announced at the annual meeting of the American Society for Bone and Mineral Research (ASBMR) in Montreal. The 40-member group that developed the recommendations, called the ASBMR Secondary Fracture Prevention Initiative Coalition, includes the American Association of Clinical Endocrinologists/American College of Endocrinology, the Endocrine Society, the American College of Rheumatology, the American College of Physicians, the American Geriatrics Society, the American Academy of Physical Medicine and Rehabilitation, and the American Academy of Orthopaedic Surgeons.

Additional fundamental recommendations from the Coalition advised ensuring that patients’ primary health care providers are aware of the fracture, regularly assessing the risk of falls, and routinely reevaluating patients who are being treated for osteoporosis. These suggestions were developed in response to growing evidence of a rising trend in osteoporosis patients not being prescribed appropriate medications or not taking them, the ASBMR said.

“The very simple message is if you’ve got somebody who has had a hip fracture or a vertebral fracture, that needs secondary prevention just like somebody who’s had an MI needs to be on a statin and a beta blocker,” said coalition cochair Sundeep Khosla, MD, a past president of the ASBMR and director of the Center for Clinical and Translational Science at the Mayo Clinic, Rochester, Minn. “You can’t ignore the fracture because it’s not immediately life-threatening. Down the road they’re going to have another hip fracture if nothing is done.”

Only 23% of elderly patients who have a hip fracture receive osteoporosis medication to reduce future fracture risk, according to the ASBMR. A 30-year downward trend in the number of hip fractures in the United States has recently plateaued, raising concerns this may have been caused by doctors and patients not following diagnostic and treatment guidelines, the organization noted.

The reasons for the plateau are uncertain, Dr. Khosla said, but could include a reluctance by patients to take bisphosphonates following some reports of relatively rare side effects, such as atypical femoral fractures and osteonecrosis of the jaw. In addition, he said, reimbursement for dual-energy x-ray absorptiometry (DEXA) scans to measure bone mineral density has gone down, which has led to fewer osteoporosis diagnoses. But fracture prevention is important, he said. Of the 300,000 hip fractures in the United States each year, one of every two patients never regains their previous functioning. In addition, one of every four hip fracture patients ends up in a nursing home or dies within a year, according to the ASBMR.

The recommendations and more data about osteoporosis treatment are available on the coalition’s website, www.secondaryfractures.org. An action plan for clinicians should be added to the site sometime this fall, Dr. Khosla said.

There are five fundamental recommendations:

First, communicate three simple messages to patients and their family/caregivers throughout the fracture care and healing process. These include: Their broken bone likely means they have osteoporosis and are at high risk for breaking more bones; breaking bones means they may have to use a walker, cane, or wheelchair or move from their home to a residential facility and will be at higher risk for premature death; and there are actions they can take to reduce their risk.

This is key, said coalition cochair Douglas P. Kiel, MD, a past president of ASBMR, the director of the Musculoskeletal Research Center at the Institute for Aging Research at Hebrew SeniorLife in Boston, and a professor of medicine at Harvard Medical School, also in Boston.

“If you talk to people who have had a broken bone, they view this as an accident and not that they have anything wrong with them,” he said. “The communication should be that if you broke something, it is not a random, chance event. You have osteoporosis, and if you don’t do anything about it, you’re going to be at great risk of a life-threatening, independence-threatening fracture in the future.”

Second, ensure the patient’s primary health care provider is made aware of the occurrence of the fracture. Take action to be sure the communication is made.

Third, regularly assess the risk of falling in women and men age 65 years or older who have had a hip or vertebral fracture. At minimum, take a history of falls within the last year, minimize the use of medications associated with increased risk for falls, evaluate patients for conditions associated with an increased risk for falls, and strongly consider referring patients to physical and/or occupational therapy or a physiatrist for evaluation and interventions to improve impairments in mobility, gait, and balance to reduce the risk for falls.

Fourth, reduce the risk of additional fractures by offering pharmacologic therapy for osteoporosis to women and men age 65 years or older who have had a hip or vertebral fracture. This can begin in the hospital and be included in discharge orders. Do not delay initiation of therapy for bone mineral density (BMD) testing. Consider patients’ oral health before starting therapy with bisphosphonates or denosumab (Prolia).

Most hip fracture patients leave the hospital without osteoporosis medications, Dr. Kiel said. It could be that hospital-based physicians are concerned patients are still unsteady such that they may not want to start patients on a new medication when they’re discharging them. Physicians in rehabilitation units may not prescribe these medications because they feel they have the patients for a short time, so by the time the patient returns to their primary care provider, the patient may have the same mistaken impression the fracture was an accident.

“We’re advocating not to delay treatment for any of these care transitions or because you think they need a BMD test,” Dr. Kiel said. “Just get them treated like they do with heart attacks.”

Finally, follow and reevaluate women and men age 65 years or older who have had a hip or vertebral fracture and are being treated for osteoporosis because it is a life-long chronic condition. This can help reinforce key messages about osteoporosis and associated fractures, identify any barriers to treatment adherence, assess the risk of falls, evaluate the effectiveness of a treatment plan, monitor for adverse effects, and determine whether any changes in treatment should be made, including whether any osteoporosis pharmacotherapy should be changed or discontinued.

Ideally, patients should be managed in the context of a multidisciplinary clinical system that includes case management, such as a fracture liaison service, according to the recommendations.

Besides the fundamental five recommendations, the documents lists another seven that deal with referring patients, prescribing vitamin D, counseling on lifestyle and diet, discussing pharmacotherapy benefits and risks, weighing first-line therapy options, and determining the duration of pharmacotherapy.

Ensuring that older adults who have experienced a hip or vertebral fracture understand they likely have osteoporosis, and offering prompt drug treatment for the condition, are among five fundamental recommendations put together by a coalition of U.S. and international bone health experts and health care organizations to help prevent secondary fractures.

The recommendations were announced at the annual meeting of the American Society for Bone and Mineral Research (ASBMR) in Montreal. The 40-member group that developed the recommendations, called the ASBMR Secondary Fracture Prevention Initiative Coalition, includes the American Association of Clinical Endocrinologists/American College of Endocrinology, the Endocrine Society, the American College of Rheumatology, the American College of Physicians, the American Geriatrics Society, the American Academy of Physical Medicine and Rehabilitation, and the American Academy of Orthopaedic Surgeons.

Additional fundamental recommendations from the Coalition advised ensuring that patients’ primary health care providers are aware of the fracture, regularly assessing the risk of falls, and routinely reevaluating patients who are being treated for osteoporosis. These suggestions were developed in response to growing evidence of a rising trend in osteoporosis patients not being prescribed appropriate medications or not taking them, the ASBMR said.

“The very simple message is if you’ve got somebody who has had a hip fracture or a vertebral fracture, that needs secondary prevention just like somebody who’s had an MI needs to be on a statin and a beta blocker,” said coalition cochair Sundeep Khosla, MD, a past president of the ASBMR and director of the Center for Clinical and Translational Science at the Mayo Clinic, Rochester, Minn. “You can’t ignore the fracture because it’s not immediately life-threatening. Down the road they’re going to have another hip fracture if nothing is done.”

Only 23% of elderly patients who have a hip fracture receive osteoporosis medication to reduce future fracture risk, according to the ASBMR. A 30-year downward trend in the number of hip fractures in the United States has recently plateaued, raising concerns this may have been caused by doctors and patients not following diagnostic and treatment guidelines, the organization noted.

The reasons for the plateau are uncertain, Dr. Khosla said, but could include a reluctance by patients to take bisphosphonates following some reports of relatively rare side effects, such as atypical femoral fractures and osteonecrosis of the jaw. In addition, he said, reimbursement for dual-energy x-ray absorptiometry (DEXA) scans to measure bone mineral density has gone down, which has led to fewer osteoporosis diagnoses. But fracture prevention is important, he said. Of the 300,000 hip fractures in the United States each year, one of every two patients never regains their previous functioning. In addition, one of every four hip fracture patients ends up in a nursing home or dies within a year, according to the ASBMR.

The recommendations and more data about osteoporosis treatment are available on the coalition’s website, www.secondaryfractures.org. An action plan for clinicians should be added to the site sometime this fall, Dr. Khosla said.

There are five fundamental recommendations:

First, communicate three simple messages to patients and their family/caregivers throughout the fracture care and healing process. These include: Their broken bone likely means they have osteoporosis and are at high risk for breaking more bones; breaking bones means they may have to use a walker, cane, or wheelchair or move from their home to a residential facility and will be at higher risk for premature death; and there are actions they can take to reduce their risk.

This is key, said coalition cochair Douglas P. Kiel, MD, a past president of ASBMR, the director of the Musculoskeletal Research Center at the Institute for Aging Research at Hebrew SeniorLife in Boston, and a professor of medicine at Harvard Medical School, also in Boston.

“If you talk to people who have had a broken bone, they view this as an accident and not that they have anything wrong with them,” he said. “The communication should be that if you broke something, it is not a random, chance event. You have osteoporosis, and if you don’t do anything about it, you’re going to be at great risk of a life-threatening, independence-threatening fracture in the future.”

Second, ensure the patient’s primary health care provider is made aware of the occurrence of the fracture. Take action to be sure the communication is made.

Third, regularly assess the risk of falling in women and men age 65 years or older who have had a hip or vertebral fracture. At minimum, take a history of falls within the last year, minimize the use of medications associated with increased risk for falls, evaluate patients for conditions associated with an increased risk for falls, and strongly consider referring patients to physical and/or occupational therapy or a physiatrist for evaluation and interventions to improve impairments in mobility, gait, and balance to reduce the risk for falls.

Fourth, reduce the risk of additional fractures by offering pharmacologic therapy for osteoporosis to women and men age 65 years or older who have had a hip or vertebral fracture. This can begin in the hospital and be included in discharge orders. Do not delay initiation of therapy for bone mineral density (BMD) testing. Consider patients’ oral health before starting therapy with bisphosphonates or denosumab (Prolia).

Most hip fracture patients leave the hospital without osteoporosis medications, Dr. Kiel said. It could be that hospital-based physicians are concerned patients are still unsteady such that they may not want to start patients on a new medication when they’re discharging them. Physicians in rehabilitation units may not prescribe these medications because they feel they have the patients for a short time, so by the time the patient returns to their primary care provider, the patient may have the same mistaken impression the fracture was an accident.

“We’re advocating not to delay treatment for any of these care transitions or because you think they need a BMD test,” Dr. Kiel said. “Just get them treated like they do with heart attacks.”

Finally, follow and reevaluate women and men age 65 years or older who have had a hip or vertebral fracture and are being treated for osteoporosis because it is a life-long chronic condition. This can help reinforce key messages about osteoporosis and associated fractures, identify any barriers to treatment adherence, assess the risk of falls, evaluate the effectiveness of a treatment plan, monitor for adverse effects, and determine whether any changes in treatment should be made, including whether any osteoporosis pharmacotherapy should be changed or discontinued.

Ideally, patients should be managed in the context of a multidisciplinary clinical system that includes case management, such as a fracture liaison service, according to the recommendations.

Besides the fundamental five recommendations, the documents lists another seven that deal with referring patients, prescribing vitamin D, counseling on lifestyle and diet, discussing pharmacotherapy benefits and risks, weighing first-line therapy options, and determining the duration of pharmacotherapy.

The anti-interleukin-6 antibody siltuximab is central to first-line treatment of idiopathic multicentric Castleman disease (MCD), although adjuvant chemotherapy can be critical in severe cases, according to the first-ever consensus treatment guidelines based on symptom severity.

Courtesy Penn Medicine

Early intervention with combination chemotherapy may prevent a fatal outcome in patients with severe idiopathic MCD, according to the guidelines, which are based on input from 42 experts from 10 countries.

The guidelines should help clinicians select therapy, evaluate response, and thereby improve outcomes for this difficult-to-treat disease, according to guideline co-author David C. Fajgenbaum, MD, who is himself an idiopathic MCD patient. Frits van Rhee, MD, PhD, is the first author of the guidelines.*

“Right now we recommend siltuximab first line for everyone,” Dr. Fajgenbaum said in an interview, “but if we continue to dig deeper, it may be that there are clinical cases within idiopathic MCD that we think are even better candidates than others, and there may be alternative therapies for other patients.”

Experts reviewed published literature and a series of 344 clinical cases to develop the guidelines, which are published in the journal Blood.

Treating idiopathic MCD is challenging because of the rarity and heterogeneity of the disease, among other factors, said Dr. Fajgenbaum, of the division of translational medicine and human genetics at the University of Pennsylvania, Philadelphia.

Some 6,000-7,000 cases of Castleman disease are diagnosed yearly, and of those, only about 1,000 cases are idiopathic MCD, according to Dr. Fajgenbaum.

“Even within idiopathic MCD, there is some heterogeneity,” he said. “Some patients present in the intensive care unit with life-threatening multiple organ failure and will die within weeks of presentation, whereas others will have a slower presentation and certainly not nearly as aggressive presentation.”

Although the exact etiology of idiopathic MCD is unknown, human interleukin (IL)-6 is the most common pathological driver, experts said in the guidelines.

Siltuximab and tocilizumab are two IL-6–directed therapies used to treat multicentric Castleman disease, with siltuximab targeting IL-6 itself and tocilizumab targeting the IL-6 receptor. Siltuximab is recommended as the first choice because of rigorous data supporting its use, including randomized clinical trial data, while tocilizumab is recommended if siltuximab is not available.

However, clinicians need to carefully monitor laboratory results and clinical features for patients on these drugs because about 50% of idiopathic MCD patients don’t have a satisfactory response to first-line anti–IL-6 treatments, Dr. Fajgenbaum said.

“Once you get to second-line therapies, that’s really where the level of evidence is lower,” he said.

Second-line therapy should include rituximab, and immunomodulatory/immunosuppressive agents or steroids may be added, according to the guidelines.

Third line therapy is “less well defined,” according to the guidelines, and experts generally recommended immunomodulatory/immunosuppressive agents such as cyclosporine A, sirolimus, thalidomide, and lenalidomide.

Cytotoxic chemotherapy has a high response rate but also a high rate of relapse and significant toxicities, according to the data analysis conducted as part of the guideline development process. Based on that, the experts said to avoid it unless the patient progresses to severe idiopathic MCD.

“Patients who are literally dying in the intensive care unit, given the right combination chemotherapy, can improve within days to weeks and can even leave the hospital,” Dr. Fajgenbaum said. “It’s not necessarily going to be the answer long term, but it can be life saving in the short term. So we recommended a really quite aggressive approach for these patients.”

To bolster the evidence base, investigators in the Castleman Disease Collaborative Network (CDCN) set up an international registry to collect treatment and outcome data for 500 patients. After the first year and a half, 150 patients were enrolled, and the investigators have identified more than 30 drugs that have been used off label to treat idiopathic MCD, according to Dr. Fajgenbaum.

“Some of the drugs are demonstrating efficacy in small numbers,” he said. “With the goal of 500 patients total, we can certainly hope to see some trends.”

Dr. Fajgenbaum was diagnosed with idiopathic MCD as a medical student.

“That certainly served as a very strong personal motivator for me to get involved in the disease,” he said. “But as I’ve gotten more and more involved, I’ve obviously met a lot of other patients, and that really is a huge motivator for all members of the CDCN. We want more options for more patients more quickly so we can help as many people as possible.”

Dr. Fajgenbaum reported research funding from Janssen. Coauthors reported disclosures related to Janssen, Bristol-Myers Squibb, Genentech, Merck, Celgene, Incyte, Pfizer, Sequenom, and Foundation Medicine, among others.

SOURCE: van Rhee F et al. Blood. 2018 Sep 4. doi: 10.1182/blood-2018-07-862334.

This story was updated 10/01/2018.

The anti-interleukin-6 antibody siltuximab is central to first-line treatment of idiopathic multicentric Castleman disease (MCD), although adjuvant chemotherapy can be critical in severe cases, according to the first-ever consensus treatment guidelines based on symptom severity.

Courtesy Penn Medicine

Early intervention with combination chemotherapy may prevent a fatal outcome in patients with severe idiopathic MCD, according to the guidelines, which are based on input from 42 experts from 10 countries.

The guidelines should help clinicians select therapy, evaluate response, and thereby improve outcomes for this difficult-to-treat disease, according to guideline co-author David C. Fajgenbaum, MD, who is himself an idiopathic MCD patient. Frits van Rhee, MD, PhD, is the first author of the guidelines.*

“Right now we recommend siltuximab first line for everyone,” Dr. Fajgenbaum said in an interview, “but if we continue to dig deeper, it may be that there are clinical cases within idiopathic MCD that we think are even better candidates than others, and there may be alternative therapies for other patients.”

Experts reviewed published literature and a series of 344 clinical cases to develop the guidelines, which are published in the journal Blood.

Treating idiopathic MCD is challenging because of the rarity and heterogeneity of the disease, among other factors, said Dr. Fajgenbaum, of the division of translational medicine and human genetics at the University of Pennsylvania, Philadelphia.

Some 6,000-7,000 cases of Castleman disease are diagnosed yearly, and of those, only about 1,000 cases are idiopathic MCD, according to Dr. Fajgenbaum.

“Even within idiopathic MCD, there is some heterogeneity,” he said. “Some patients present in the intensive care unit with life-threatening multiple organ failure and will die within weeks of presentation, whereas others will have a slower presentation and certainly not nearly as aggressive presentation.”

Although the exact etiology of idiopathic MCD is unknown, human interleukin (IL)-6 is the most common pathological driver, experts said in the guidelines.

Siltuximab and tocilizumab are two IL-6–directed therapies used to treat multicentric Castleman disease, with siltuximab targeting IL-6 itself and tocilizumab targeting the IL-6 receptor. Siltuximab is recommended as the first choice because of rigorous data supporting its use, including randomized clinical trial data, while tocilizumab is recommended if siltuximab is not available.

However, clinicians need to carefully monitor laboratory results and clinical features for patients on these drugs because about 50% of idiopathic MCD patients don’t have a satisfactory response to first-line anti–IL-6 treatments, Dr. Fajgenbaum said.

“Once you get to second-line therapies, that’s really where the level of evidence is lower,” he said.

Second-line therapy should include rituximab, and immunomodulatory/immunosuppressive agents or steroids may be added, according to the guidelines.

Third line therapy is “less well defined,” according to the guidelines, and experts generally recommended immunomodulatory/immunosuppressive agents such as cyclosporine A, sirolimus, thalidomide, and lenalidomide.

Cytotoxic chemotherapy has a high response rate but also a high rate of relapse and significant toxicities, according to the data analysis conducted as part of the guideline development process. Based on that, the experts said to avoid it unless the patient progresses to severe idiopathic MCD.

“Patients who are literally dying in the intensive care unit, given the right combination chemotherapy, can improve within days to weeks and can even leave the hospital,” Dr. Fajgenbaum said. “It’s not necessarily going to be the answer long term, but it can be life saving in the short term. So we recommended a really quite aggressive approach for these patients.”

To bolster the evidence base, investigators in the Castleman Disease Collaborative Network (CDCN) set up an international registry to collect treatment and outcome data for 500 patients. After the first year and a half, 150 patients were enrolled, and the investigators have identified more than 30 drugs that have been used off label to treat idiopathic MCD, according to Dr. Fajgenbaum.

“Some of the drugs are demonstrating efficacy in small numbers,” he said. “With the goal of 500 patients total, we can certainly hope to see some trends.”

Dr. Fajgenbaum was diagnosed with idiopathic MCD as a medical student.

“That certainly served as a very strong personal motivator for me to get involved in the disease,” he said. “But as I’ve gotten more and more involved, I’ve obviously met a lot of other patients, and that really is a huge motivator for all members of the CDCN. We want more options for more patients more quickly so we can help as many people as possible.”

Dr. Fajgenbaum reported research funding from Janssen. Coauthors reported disclosures related to Janssen, Bristol-Myers Squibb, Genentech, Merck, Celgene, Incyte, Pfizer, Sequenom, and Foundation Medicine, among others.

SOURCE: van Rhee F et al. Blood. 2018 Sep 4. doi: 10.1182/blood-2018-07-862334.

This story was updated 10/01/2018.

The anti-interleukin-6 antibody siltuximab is central to first-line treatment of idiopathic multicentric Castleman disease (MCD), although adjuvant chemotherapy can be critical in severe cases, according to the first-ever consensus treatment guidelines based on symptom severity.

Courtesy Penn Medicine

Early intervention with combination chemotherapy may prevent a fatal outcome in patients with severe idiopathic MCD, according to the guidelines, which are based on input from 42 experts from 10 countries.

The guidelines should help clinicians select therapy, evaluate response, and thereby improve outcomes for this difficult-to-treat disease, according to guideline co-author David C. Fajgenbaum, MD, who is himself an idiopathic MCD patient. Frits van Rhee, MD, PhD, is the first author of the guidelines.*

“Right now we recommend siltuximab first line for everyone,” Dr. Fajgenbaum said in an interview, “but if we continue to dig deeper, it may be that there are clinical cases within idiopathic MCD that we think are even better candidates than others, and there may be alternative therapies for other patients.”

Experts reviewed published literature and a series of 344 clinical cases to develop the guidelines, which are published in the journal Blood.

Treating idiopathic MCD is challenging because of the rarity and heterogeneity of the disease, among other factors, said Dr. Fajgenbaum, of the division of translational medicine and human genetics at the University of Pennsylvania, Philadelphia.

Some 6,000-7,000 cases of Castleman disease are diagnosed yearly, and of those, only about 1,000 cases are idiopathic MCD, according to Dr. Fajgenbaum.

“Even within idiopathic MCD, there is some heterogeneity,” he said. “Some patients present in the intensive care unit with life-threatening multiple organ failure and will die within weeks of presentation, whereas others will have a slower presentation and certainly not nearly as aggressive presentation.”

Although the exact etiology of idiopathic MCD is unknown, human interleukin (IL)-6 is the most common pathological driver, experts said in the guidelines.

Siltuximab and tocilizumab are two IL-6–directed therapies used to treat multicentric Castleman disease, with siltuximab targeting IL-6 itself and tocilizumab targeting the IL-6 receptor. Siltuximab is recommended as the first choice because of rigorous data supporting its use, including randomized clinical trial data, while tocilizumab is recommended if siltuximab is not available.

However, clinicians need to carefully monitor laboratory results and clinical features for patients on these drugs because about 50% of idiopathic MCD patients don’t have a satisfactory response to first-line anti–IL-6 treatments, Dr. Fajgenbaum said.

“Once you get to second-line therapies, that’s really where the level of evidence is lower,” he said.

Second-line therapy should include rituximab, and immunomodulatory/immunosuppressive agents or steroids may be added, according to the guidelines.

Third line therapy is “less well defined,” according to the guidelines, and experts generally recommended immunomodulatory/immunosuppressive agents such as cyclosporine A, sirolimus, thalidomide, and lenalidomide.

Cytotoxic chemotherapy has a high response rate but also a high rate of relapse and significant toxicities, according to the data analysis conducted as part of the guideline development process. Based on that, the experts said to avoid it unless the patient progresses to severe idiopathic MCD.

“Patients who are literally dying in the intensive care unit, given the right combination chemotherapy, can improve within days to weeks and can even leave the hospital,” Dr. Fajgenbaum said. “It’s not necessarily going to be the answer long term, but it can be life saving in the short term. So we recommended a really quite aggressive approach for these patients.”

To bolster the evidence base, investigators in the Castleman Disease Collaborative Network (CDCN) set up an international registry to collect treatment and outcome data for 500 patients. After the first year and a half, 150 patients were enrolled, and the investigators have identified more than 30 drugs that have been used off label to treat idiopathic MCD, according to Dr. Fajgenbaum.

“Some of the drugs are demonstrating efficacy in small numbers,” he said. “With the goal of 500 patients total, we can certainly hope to see some trends.”

Dr. Fajgenbaum was diagnosed with idiopathic MCD as a medical student.

“That certainly served as a very strong personal motivator for me to get involved in the disease,” he said. “But as I’ve gotten more and more involved, I’ve obviously met a lot of other patients, and that really is a huge motivator for all members of the CDCN. We want more options for more patients more quickly so we can help as many people as possible.”

Dr. Fajgenbaum reported research funding from Janssen. Coauthors reported disclosures related to Janssen, Bristol-Myers Squibb, Genentech, Merck, Celgene, Incyte, Pfizer, Sequenom, and Foundation Medicine, among others.

SOURCE: van Rhee F et al. Blood. 2018 Sep 4. doi: 10.1182/blood-2018-07-862334.

This story was updated 10/01/2018.

A well-woman visit with an ob.gyn. should include preventive services and counseling, according to an updated committee opinion from the American College of Obstetricians and Gynecologists’ Committee on Gynecologic Practice.

Alexander Raths/Fotolia.com

“A well-woman visit provides an excellent opportunity to counsel patients about maintaining a healthy lifestyle and minimizing health risks,” according to the opinion, published in Obstetrics & Gynecology. The updated opinion coincides with the release of the new Well-Woman Chart from the Women’s Preventive Services Initiative.

Previous research suggests that many women prefer an ob.gyn. or other women’s health care specialist not only for reproductive health care but also for services such as cervical cancer screening, contraception, and treatment for sexually transmitted infections, the committee members wrote. Although surveys of ob.gyns. show that most provide some level of overall health and primary care, the screening and other clinical preventive services were not consistent.

The committee opinion consequently recommends that the “periodic well-woman care visit should include screening, evaluation and counseling, and immunizations based on age and risk factors.” However, the committee acknowledged that the interval for specific services varies among patients, as does the scope of services provided in different settings.

“Taking a comprehensive history (specifically obtaining detailed information on symptoms and past medical and gynecologic history) will inform if certain components of the physical examination, including breast or pelvic examination, are indicated at that visit and will inform shared decision making for these examinations,” committee members wrote. Topics that should be addressed during lifespan include sexual health (which may include contraception, prepregnancy counseling, sexually transmitted infections, and infertility), vulvovaginal symptoms, and bone health.

Not all components of a physical may be required at a well-woman visit, but ob.gyns. can play a key role by encouraging and facilitating healthy behaviors, counseling on preventive health strategies, and engaging women in shared decision-making. Screening for smoking, poor diet, and lack of physical activity are important. Ob.gyns. also can be part of the team-based care for women that may include physician assistants, nurse practitioners, and other medical professionals.

The most notable change from the previous opinion is that it coincides with the Women’s Preventive Services Initiative’s release of a Well-Woman Chart, which is designed to help ob.gyns. navigate the implementation of ACOG’s well-woman guidance, Christopher Zahn, MD, vice president of practice activities for ACOG, said in an interview.

“In tandem, these documents support ob.gyns. and other women’s health care providers’ efforts to make well-woman visits more personalized care that prioritizes shared decision-making over a woman’s lifetime,” he said. The opinion statement also includes the Women’s Preventive Services Initiative as a source of information for recommendations on well-woman care, and includes new guidance on the elements of a physical exam, including the pelvic exam.

“Ob.gyns. care for women over their lifetime, and increasingly this includes a lot of preventive care. The committee opinion details ACOG’s overall approach to well-women care and the role of the ob.gyn. as a provider of preventive services,” said Dr. Zahn. “The accompanying well-woman chart, targeted to providers, summarizes needed preventive services ensuring that time can be spent effectively and productively during each well-woman visit. By centering shared decision making and care tailored to each woman’s health care needs at every life stage, the well-woman visit is a fundamental part of the patient-provider relationship.”

Dr. Zahn noted that ongoing, high-quality research is essential to determine what strategies are most effective for women’s preventive care needs at every life stage. “Further research is also needed to identify screening strategies for women in certain higher risk groups and to reduce disparities in outcomes in certain populations of women. From cancer screening to new contraceptive methods, to managing symptoms of menopause, the more research we have to support our recommendations for these services, the more effectively we can care for women and help to keep them healthy for many, many years,” he emphasized.

The committee recommended additional resources for ob.gyns. and other health care providers, as well as for patients. The resources are available online at www.acog.org/More-Info/WellWoman.

The new opinion statement, which replaces the previous opinion issued in 2012, was developed by the ACOG Committee on Gynecologic Practice in collaboration with committee member Catherine Witkop, MD, MPH, of the Uniformed Health Sciences University in Bethesda, Md. The committee members had no relevant financial conflicts to disclose.
 

A well-woman visit with an ob.gyn. should include preventive services and counseling, according to an updated committee opinion from the American College of Obstetricians and Gynecologists’ Committee on Gynecologic Practice.

Alexander Raths/Fotolia.com

“A well-woman visit provides an excellent opportunity to counsel patients about maintaining a healthy lifestyle and minimizing health risks,” according to the opinion, published in Obstetrics & Gynecology. The updated opinion coincides with the release of the new Well-Woman Chart from the Women’s Preventive Services Initiative.

Previous research suggests that many women prefer an ob.gyn. or other women’s health care specialist not only for reproductive health care but also for services such as cervical cancer screening, contraception, and treatment for sexually transmitted infections, the committee members wrote. Although surveys of ob.gyns. show that most provide some level of overall health and primary care, the screening and other clinical preventive services were not consistent.

The committee opinion consequently recommends that the “periodic well-woman care visit should include screening, evaluation and counseling, and immunizations based on age and risk factors.” However, the committee acknowledged that the interval for specific services varies among patients, as does the scope of services provided in different settings.

“Taking a comprehensive history (specifically obtaining detailed information on symptoms and past medical and gynecologic history) will inform if certain components of the physical examination, including breast or pelvic examination, are indicated at that visit and will inform shared decision making for these examinations,” committee members wrote. Topics that should be addressed during lifespan include sexual health (which may include contraception, prepregnancy counseling, sexually transmitted infections, and infertility), vulvovaginal symptoms, and bone health.

Not all components of a physical may be required at a well-woman visit, but ob.gyns. can play a key role by encouraging and facilitating healthy behaviors, counseling on preventive health strategies, and engaging women in shared decision-making. Screening for smoking, poor diet, and lack of physical activity are important. Ob.gyns. also can be part of the team-based care for women that may include physician assistants, nurse practitioners, and other medical professionals.

The most notable change from the previous opinion is that it coincides with the Women’s Preventive Services Initiative’s release of a Well-Woman Chart, which is designed to help ob.gyns. navigate the implementation of ACOG’s well-woman guidance, Christopher Zahn, MD, vice president of practice activities for ACOG, said in an interview.

“In tandem, these documents support ob.gyns. and other women’s health care providers’ efforts to make well-woman visits more personalized care that prioritizes shared decision-making over a woman’s lifetime,” he said. The opinion statement also includes the Women’s Preventive Services Initiative as a source of information for recommendations on well-woman care, and includes new guidance on the elements of a physical exam, including the pelvic exam.

“Ob.gyns. care for women over their lifetime, and increasingly this includes a lot of preventive care. The committee opinion details ACOG’s overall approach to well-women care and the role of the ob.gyn. as a provider of preventive services,” said Dr. Zahn. “The accompanying well-woman chart, targeted to providers, summarizes needed preventive services ensuring that time can be spent effectively and productively during each well-woman visit. By centering shared decision making and care tailored to each woman’s health care needs at every life stage, the well-woman visit is a fundamental part of the patient-provider relationship.”

Dr. Zahn noted that ongoing, high-quality research is essential to determine what strategies are most effective for women’s preventive care needs at every life stage. “Further research is also needed to identify screening strategies for women in certain higher risk groups and to reduce disparities in outcomes in certain populations of women. From cancer screening to new contraceptive methods, to managing symptoms of menopause, the more research we have to support our recommendations for these services, the more effectively we can care for women and help to keep them healthy for many, many years,” he emphasized.

The committee recommended additional resources for ob.gyns. and other health care providers, as well as for patients. The resources are available online at www.acog.org/More-Info/WellWoman.

The new opinion statement, which replaces the previous opinion issued in 2012, was developed by the ACOG Committee on Gynecologic Practice in collaboration with committee member Catherine Witkop, MD, MPH, of the Uniformed Health Sciences University in Bethesda, Md. The committee members had no relevant financial conflicts to disclose.
 

A well-woman visit with an ob.gyn. should include preventive services and counseling, according to an updated committee opinion from the American College of Obstetricians and Gynecologists’ Committee on Gynecologic Practice.

Alexander Raths/Fotolia.com

“A well-woman visit provides an excellent opportunity to counsel patients about maintaining a healthy lifestyle and minimizing health risks,” according to the opinion, published in Obstetrics & Gynecology. The updated opinion coincides with the release of the new Well-Woman Chart from the Women’s Preventive Services Initiative.

Previous research suggests that many women prefer an ob.gyn. or other women’s health care specialist not only for reproductive health care but also for services such as cervical cancer screening, contraception, and treatment for sexually transmitted infections, the committee members wrote. Although surveys of ob.gyns. show that most provide some level of overall health and primary care, the screening and other clinical preventive services were not consistent.

The committee opinion consequently recommends that the “periodic well-woman care visit should include screening, evaluation and counseling, and immunizations based on age and risk factors.” However, the committee acknowledged that the interval for specific services varies among patients, as does the scope of services provided in different settings.

“Taking a comprehensive history (specifically obtaining detailed information on symptoms and past medical and gynecologic history) will inform if certain components of the physical examination, including breast or pelvic examination, are indicated at that visit and will inform shared decision making for these examinations,” committee members wrote. Topics that should be addressed during lifespan include sexual health (which may include contraception, prepregnancy counseling, sexually transmitted infections, and infertility), vulvovaginal symptoms, and bone health.

Not all components of a physical may be required at a well-woman visit, but ob.gyns. can play a key role by encouraging and facilitating healthy behaviors, counseling on preventive health strategies, and engaging women in shared decision-making. Screening for smoking, poor diet, and lack of physical activity are important. Ob.gyns. also can be part of the team-based care for women that may include physician assistants, nurse practitioners, and other medical professionals.

The most notable change from the previous opinion is that it coincides with the Women’s Preventive Services Initiative’s release of a Well-Woman Chart, which is designed to help ob.gyns. navigate the implementation of ACOG’s well-woman guidance, Christopher Zahn, MD, vice president of practice activities for ACOG, said in an interview.

“In tandem, these documents support ob.gyns. and other women’s health care providers’ efforts to make well-woman visits more personalized care that prioritizes shared decision-making over a woman’s lifetime,” he said. The opinion statement also includes the Women’s Preventive Services Initiative as a source of information for recommendations on well-woman care, and includes new guidance on the elements of a physical exam, including the pelvic exam.

“Ob.gyns. care for women over their lifetime, and increasingly this includes a lot of preventive care. The committee opinion details ACOG’s overall approach to well-women care and the role of the ob.gyn. as a provider of preventive services,” said Dr. Zahn. “The accompanying well-woman chart, targeted to providers, summarizes needed preventive services ensuring that time can be spent effectively and productively during each well-woman visit. By centering shared decision making and care tailored to each woman’s health care needs at every life stage, the well-woman visit is a fundamental part of the patient-provider relationship.”

Dr. Zahn noted that ongoing, high-quality research is essential to determine what strategies are most effective for women’s preventive care needs at every life stage. “Further research is also needed to identify screening strategies for women in certain higher risk groups and to reduce disparities in outcomes in certain populations of women. From cancer screening to new contraceptive methods, to managing symptoms of menopause, the more research we have to support our recommendations for these services, the more effectively we can care for women and help to keep them healthy for many, many years,” he emphasized.

The committee recommended additional resources for ob.gyns. and other health care providers, as well as for patients. The resources are available online at www.acog.org/More-Info/WellWoman.

The new opinion statement, which replaces the previous opinion issued in 2012, was developed by the ACOG Committee on Gynecologic Practice in collaboration with committee member Catherine Witkop, MD, MPH, of the Uniformed Health Sciences University in Bethesda, Md. The committee members had no relevant financial conflicts to disclose.
 

The American Academy of Pediatric has issued a policy statement regarding teen drivers because, although becoming a driver is a rite of passage for many, there are unique risks associated with teen drivers – and important ways to address them.

Vladimir Piskunov/iStockphoto

“In 2015, among 15- to 20-year-old individuals, 1,886 young drivers died in MVCs [motor vehicle crashes], which is an increase of 9% from 2014,” the statement explains. “Another 195,000 young drivers were in MVCs, which is up 14% from 2014.”

Risk factors associated with crashes in teenage drivers include their inexperience, the presence of other teens in the car, high-speed and risky driving, distraction, lack of sleep, nighttime driving, and alcohol, marijuana, and medication use. Mobile phones and other electronic devices pose a major threat to driver safety because they contribute opportunities for three different kinds of distraction – visual, manual, and cognitive. Drug and alcohol use poses another threat; for example, tetrahydrocannabinol, found in marijuana, is associated with a 1.25 higher risk of crash, according Elizabeth M. Alderman, MD, and her associates on the Committee on Adolescence and the Council on Injury, Violence, and Poison Prevention who crafted the policy statement.

The policy statement also outlined several interventions to help mitigate these risks. Graduated driver licensing, which has been adopted in all 50 states, has helped reduce teen crashes by promoting skills development and reducing exposure to risky-driving situations. Parents can help model safer-driving practices and set expectations, as well as monitor and affect their teens’ driving behaviors during the supervised-driving phase. Driver education programs, on the other hand, counterintuitively have little effect on teen driving safety, which the authors suggested is because “the knowledge required to pass licensing exams is seldom related to an evidence-based understanding of the behaviors and skills associated with novice driver crash risk.” There also have been technological advances that can help improve driving safety among teenage drivers, such as automatic braking and lane-maintenance alerts.

“Policies, programs, and technologies exist to mitigate these risks but, in most cases, depend on active participation by the teenager and parents,” the authors concluded. “Pediatricians, communities, and governments need to take action to better educate teen drivers and their parents around these risks and strategies to reduce them.”

The full policy statement includes specific recommendations for anticipatory guidance, professional practice, community advocacy, and legislative advocacy. It also includes many resources and links to further information.

[email protected]

SOURCE: Alderman EM et al. Pediatrics. 2018 Oct;142(4):e20182163.

The American Academy of Pediatric has issued a policy statement regarding teen drivers because, although becoming a driver is a rite of passage for many, there are unique risks associated with teen drivers – and important ways to address them.

Vladimir Piskunov/iStockphoto

“In 2015, among 15- to 20-year-old individuals, 1,886 young drivers died in MVCs [motor vehicle crashes], which is an increase of 9% from 2014,” the statement explains. “Another 195,000 young drivers were in MVCs, which is up 14% from 2014.”

Risk factors associated with crashes in teenage drivers include their inexperience, the presence of other teens in the car, high-speed and risky driving, distraction, lack of sleep, nighttime driving, and alcohol, marijuana, and medication use. Mobile phones and other electronic devices pose a major threat to driver safety because they contribute opportunities for three different kinds of distraction – visual, manual, and cognitive. Drug and alcohol use poses another threat; for example, tetrahydrocannabinol, found in marijuana, is associated with a 1.25 higher risk of crash, according Elizabeth M. Alderman, MD, and her associates on the Committee on Adolescence and the Council on Injury, Violence, and Poison Prevention who crafted the policy statement.

The policy statement also outlined several interventions to help mitigate these risks. Graduated driver licensing, which has been adopted in all 50 states, has helped reduce teen crashes by promoting skills development and reducing exposure to risky-driving situations. Parents can help model safer-driving practices and set expectations, as well as monitor and affect their teens’ driving behaviors during the supervised-driving phase. Driver education programs, on the other hand, counterintuitively have little effect on teen driving safety, which the authors suggested is because “the knowledge required to pass licensing exams is seldom related to an evidence-based understanding of the behaviors and skills associated with novice driver crash risk.” There also have been technological advances that can help improve driving safety among teenage drivers, such as automatic braking and lane-maintenance alerts.

“Policies, programs, and technologies exist to mitigate these risks but, in most cases, depend on active participation by the teenager and parents,” the authors concluded. “Pediatricians, communities, and governments need to take action to better educate teen drivers and their parents around these risks and strategies to reduce them.”

The full policy statement includes specific recommendations for anticipatory guidance, professional practice, community advocacy, and legislative advocacy. It also includes many resources and links to further information.

[email protected]

SOURCE: Alderman EM et al. Pediatrics. 2018 Oct;142(4):e20182163.

The American Academy of Pediatric has issued a policy statement regarding teen drivers because, although becoming a driver is a rite of passage for many, there are unique risks associated with teen drivers – and important ways to address them.

Vladimir Piskunov/iStockphoto

“In 2015, among 15- to 20-year-old individuals, 1,886 young drivers died in MVCs [motor vehicle crashes], which is an increase of 9% from 2014,” the statement explains. “Another 195,000 young drivers were in MVCs, which is up 14% from 2014.”

Risk factors associated with crashes in teenage drivers include their inexperience, the presence of other teens in the car, high-speed and risky driving, distraction, lack of sleep, nighttime driving, and alcohol, marijuana, and medication use. Mobile phones and other electronic devices pose a major threat to driver safety because they contribute opportunities for three different kinds of distraction – visual, manual, and cognitive. Drug and alcohol use poses another threat; for example, tetrahydrocannabinol, found in marijuana, is associated with a 1.25 higher risk of crash, according Elizabeth M. Alderman, MD, and her associates on the Committee on Adolescence and the Council on Injury, Violence, and Poison Prevention who crafted the policy statement.

The policy statement also outlined several interventions to help mitigate these risks. Graduated driver licensing, which has been adopted in all 50 states, has helped reduce teen crashes by promoting skills development and reducing exposure to risky-driving situations. Parents can help model safer-driving practices and set expectations, as well as monitor and affect their teens’ driving behaviors during the supervised-driving phase. Driver education programs, on the other hand, counterintuitively have little effect on teen driving safety, which the authors suggested is because “the knowledge required to pass licensing exams is seldom related to an evidence-based understanding of the behaviors and skills associated with novice driver crash risk.” There also have been technological advances that can help improve driving safety among teenage drivers, such as automatic braking and lane-maintenance alerts.

“Policies, programs, and technologies exist to mitigate these risks but, in most cases, depend on active participation by the teenager and parents,” the authors concluded. “Pediatricians, communities, and governments need to take action to better educate teen drivers and their parents around these risks and strategies to reduce them.”

The full policy statement includes specific recommendations for anticipatory guidance, professional practice, community advocacy, and legislative advocacy. It also includes many resources and links to further information.

[email protected]

SOURCE: Alderman EM et al. Pediatrics. 2018 Oct;142(4):e20182163.

ORLANDO – Uveal melanoma has little in common with it’s cutaneous namesake, and its distinct characteristics necessitated the development of specific guidelines for diagnosis and management, which were released earlier this year by the National Comprehensive Cancer Network (NCCN).

Unlike cutaneous melanoma, uveal melanoma is usually treated with radiotherapy rather than surgery, and primary treatment is based on tumor size, according to Christopher A. Barker, MD, a radiation oncologist and director of clinical investigations in the department of radiation at Memorial Sloan Kettering Cancer Center, New York.

Further, molecular testing aids in prognosis in uveal melanoma but not in predicting treatment response as it can in cutaneous disease, and recurrences of uveal melanoma are typically distant – usually occurring in the liver – rather than in the skin or lymph nodes as with cutaneous melanoma.

These and other diagnosis- and treatment-related issues are outlined in the new guidelines, which are the first developed by the NCCN for uveal melanoma.

Guidelines exist in several countries, including Australia, the United Kingdom, Canada, and the United States (published by The American Brachytherapy Society), but until now none have provided pathway-based strategies for the management of all stages of this rare disease that affects about 1 in 200,000 Americans, typically Caucasians in their 50s, 60s, or 70s, Dr. Barker, a member of the NCCN Melanoma guidelines panel and the uveal melanoma subcommittee, said at the NCCN’s annual meeting where he presented the guidelines.

The median age of diagnosis is 60 years, he noted.

The NCCN guidelines specifically address melanoma arising in the choroid and ciliary body of the uvea. The choroid is the predominant site of uveal melanoma origin, and tumors arising there may involve the ciliary body as well, although the latter is a rare site of melanoma origin. The iris is also a rare site of origin, and tumors arising there are typically indolent in nature and thus are not part of the new guidelines, he explained.

Risk factors include choroidal nevi, ocular melanocytosis, and familial uveal melanoma associated with germline BAP1 mutation, neurofibromatosis, or dysplastic nevus syndrome; cutaneous melanoma is not a risk factor, he said.

The guidelines address clinical presentation, diagnostic work-up, and staging; primary treatments; and metastatic risks and follow-up imaging.

Presentation, diagnosis, and staging

About two-thirds of patients with uveal melanoma present because of changes in their vision, and about a third present with no new symptoms and are diagnosed during routine evaluation, Dr. Barker said.

“History and physical exam, and specifically attention to any prior malignancies, is important,” he said. “A comprehensive eye examination is absolutely vital to the evaluation and staging of patients with uveal melanoma.”

Numerous additional testing options, including autofluorescence of the ocular fundus, retinal fluorescein angiography of the ocular fundus, and transillumination, among others, are listed in the guidelines, which note that MRI is sometimes needed to confirm diagnosis.

Biopsies, however, are generally only performed to confirm diagnosis if needed or for prognostic analysis for risk stratification.

Staging is determined mainly by tumor size, which is known to be associated with outcomes in patients with uveal melanoma, and is based on criteria from both the Collaborative Ocular Melanoma Study (COMS) staging system and the American Joint Committee on Cancer (AJCC) staging manual, Dr. Barker said.

The COMS system was developed based on separate studies of small, medium, and large tumors and helped define primary tumor management and establish existing standards of care. The AJCC system was developed subsequently and focuses more on tumor features that may improve clinical predictions.

Primary treatments

Options for primary treatment for small tumors (largest diameter 5-16 mm and thickness less than 2.5 mm) include plaque brachytherapy, partical beam radiation, and laser ablation in highly select patients. For medium tumors (18mm or less at largest diameter and thickness of 2.5-10 mm), they include plaque brachytherapy, particle beam radiation, and enucleation, according to the guidelines.

Large tumors can be treated with radiotherapy (preferably particle beam radiation, Dr. Barker said) or enucleation. Large tumors are those greater than 18mm with any thickness, those with thickness greater than 10mm with any diameter, and those with thickness greater than 8mm with optic nerve involvement.

In patients for whom surgical removal is selected, “ there are a few unusual situations where additional local adjuvant therapy might be considered,” Dr. Barker said, explaining, for example, that the presence of microscopically positive or close margins after enucleation without evidence of gross residual disease in the orbit may be observed or may warrant map biopsy and/or particle beam or photon beam radiotherapy to the orbit.

For visible extraocular tumors or suspicion of gross disease in the orbit, biopsy of the extraocular tissue is recommended when possible, along with either intraoperative cryotherapy, orbital exenteration, or particle beam or photon beam radiotherapy to the orbit, he added.

Metastatic risks and follow-up imaging

Recent studies, including Cancer Genome Atlas Research Network studies, have elucidated the genomics of both uveal and cutaneous melanomas, and they show “a completely different mutation spectrum” for uveal melanoma, Dr. Barker said.

These genomic studies demonstrate that cutaneous melanoma involves mutations that predict response to certain treatments, while those found in uveal melanoma do not, but they are, however, associated with the probability of metastasis, he said.

For example, various studies have shown that BRAF mutation in cutaneous melanoma predicts response to RAF or MEK inhibition and that the overall number of mutations in cutaneous melanoma may predict response to immunotherapy.

In uveal melanoma, alterations in ElFAX1, SF3B1, or BAP1 have been shown to indicate low, intermediate, and high risk of metastasis, respectively.

Other factors associated with the risk of metastasis after primary tumor treatment in uveal melanoma include clinical factors (tumor size, ciliary body involvement, and extraocular extension); histopathologic factors (spindle or epithelioid cell type); and cytogenetics (status of chromosomes 3, 6, and 8), he said.

An AJCC Ophthalmic Oncology Task Force study published in 2015, for example, showed that the 5-year metastasis-free survival was 97% for AJCC stage T1 disease, 85% for stage T2, 77% for stage T3, and 61% for stage T4. T-stage modifiers, which are based on particular tumor characteristics, such as ciliary body involvement (CBI) and extraocular extension (EXE), were also associated with the risk of distant metastasis: 5-year metastasis-free survival was 90%, 72%, 54% and 33% for AJCC T_a (no CBI or EXE), T_b (CBI only), T_c (EXE only), and T_d tumors (CBI and EXE), respectively.

Follow-up imaging after primary tumor treatment should be based on the most likely site of metastatic recurrence, which is the liver in 90% of uveal melanoma metastases.

“For this reason, surveillance of high-risk patients with uveal melanoma should include specific imaging of the liver,” Dr. Barker said, who noted that the NCCN risk stratification–based surveillance guidelines categorize patients as either low, medium, or high risk for metastasis based on the various characteristics that can affect risk.

“These risk groups help clinicians identify how often imaging should be performed in their surveillance strategy,” he said, adding that those who are high risk based on BAP1 mutation, PRAME mutation, CBI, or EXE, for example, should undergo imaging to evaluate signs or symptoms every 3-6 months for 5 years, every 6-12 months for 10 years, and then as clinically indicated thereafter.

The guideline calls for less stringent imaging for low- and medium-risk patients.

“Now, what happens when distant metastases are identified? Unfortunately there is no single systemic therapy that has proven to be most effective for uveal melanoma,” he said. “For this reason, the NCCN guideline encourages clinical trial participation whenever possible for patients who develop distant metastasis.”

This is because drugs effective for cutaneous melanoma are far less effective for uveal melanoma, but do elicit response in some patients and can be considered, he explained.

[email protected]

ORLANDO – Uveal melanoma has little in common with it’s cutaneous namesake, and its distinct characteristics necessitated the development of specific guidelines for diagnosis and management, which were released earlier this year by the National Comprehensive Cancer Network (NCCN).

Unlike cutaneous melanoma, uveal melanoma is usually treated with radiotherapy rather than surgery, and primary treatment is based on tumor size, according to Christopher A. Barker, MD, a radiation oncologist and director of clinical investigations in the department of radiation at Memorial Sloan Kettering Cancer Center, New York.

Further, molecular testing aids in prognosis in uveal melanoma but not in predicting treatment response as it can in cutaneous disease, and recurrences of uveal melanoma are typically distant – usually occurring in the liver – rather than in the skin or lymph nodes as with cutaneous melanoma.

These and other diagnosis- and treatment-related issues are outlined in the new guidelines, which are the first developed by the NCCN for uveal melanoma.

Guidelines exist in several countries, including Australia, the United Kingdom, Canada, and the United States (published by The American Brachytherapy Society), but until now none have provided pathway-based strategies for the management of all stages of this rare disease that affects about 1 in 200,000 Americans, typically Caucasians in their 50s, 60s, or 70s, Dr. Barker, a member of the NCCN Melanoma guidelines panel and the uveal melanoma subcommittee, said at the NCCN’s annual meeting where he presented the guidelines.

The median age of diagnosis is 60 years, he noted.

The NCCN guidelines specifically address melanoma arising in the choroid and ciliary body of the uvea. The choroid is the predominant site of uveal melanoma origin, and tumors arising there may involve the ciliary body as well, although the latter is a rare site of melanoma origin. The iris is also a rare site of origin, and tumors arising there are typically indolent in nature and thus are not part of the new guidelines, he explained.

Risk factors include choroidal nevi, ocular melanocytosis, and familial uveal melanoma associated with germline BAP1 mutation, neurofibromatosis, or dysplastic nevus syndrome; cutaneous melanoma is not a risk factor, he said.

The guidelines address clinical presentation, diagnostic work-up, and staging; primary treatments; and metastatic risks and follow-up imaging.

Presentation, diagnosis, and staging

About two-thirds of patients with uveal melanoma present because of changes in their vision, and about a third present with no new symptoms and are diagnosed during routine evaluation, Dr. Barker said.

“History and physical exam, and specifically attention to any prior malignancies, is important,” he said. “A comprehensive eye examination is absolutely vital to the evaluation and staging of patients with uveal melanoma.”

Numerous additional testing options, including autofluorescence of the ocular fundus, retinal fluorescein angiography of the ocular fundus, and transillumination, among others, are listed in the guidelines, which note that MRI is sometimes needed to confirm diagnosis.

Biopsies, however, are generally only performed to confirm diagnosis if needed or for prognostic analysis for risk stratification.

Staging is determined mainly by tumor size, which is known to be associated with outcomes in patients with uveal melanoma, and is based on criteria from both the Collaborative Ocular Melanoma Study (COMS) staging system and the American Joint Committee on Cancer (AJCC) staging manual, Dr. Barker said.

The COMS system was developed based on separate studies of small, medium, and large tumors and helped define primary tumor management and establish existing standards of care. The AJCC system was developed subsequently and focuses more on tumor features that may improve clinical predictions.

Primary treatments

Options for primary treatment for small tumors (largest diameter 5-16 mm and thickness less than 2.5 mm) include plaque brachytherapy, partical beam radiation, and laser ablation in highly select patients. For medium tumors (18mm or less at largest diameter and thickness of 2.5-10 mm), they include plaque brachytherapy, particle beam radiation, and enucleation, according to the guidelines.

Large tumors can be treated with radiotherapy (preferably particle beam radiation, Dr. Barker said) or enucleation. Large tumors are those greater than 18mm with any thickness, those with thickness greater than 10mm with any diameter, and those with thickness greater than 8mm with optic nerve involvement.

In patients for whom surgical removal is selected, “ there are a few unusual situations where additional local adjuvant therapy might be considered,” Dr. Barker said, explaining, for example, that the presence of microscopically positive or close margins after enucleation without evidence of gross residual disease in the orbit may be observed or may warrant map biopsy and/or particle beam or photon beam radiotherapy to the orbit.

For visible extraocular tumors or suspicion of gross disease in the orbit, biopsy of the extraocular tissue is recommended when possible, along with either intraoperative cryotherapy, orbital exenteration, or particle beam or photon beam radiotherapy to the orbit, he added.

Metastatic risks and follow-up imaging

Recent studies, including Cancer Genome Atlas Research Network studies, have elucidated the genomics of both uveal and cutaneous melanomas, and they show “a completely different mutation spectrum” for uveal melanoma, Dr. Barker said.

These genomic studies demonstrate that cutaneous melanoma involves mutations that predict response to certain treatments, while those found in uveal melanoma do not, but they are, however, associated with the probability of metastasis, he said.

For example, various studies have shown that BRAF mutation in cutaneous melanoma predicts response to RAF or MEK inhibition and that the overall number of mutations in cutaneous melanoma may predict response to immunotherapy.

In uveal melanoma, alterations in ElFAX1, SF3B1, or BAP1 have been shown to indicate low, intermediate, and high risk of metastasis, respectively.

Other factors associated with the risk of metastasis after primary tumor treatment in uveal melanoma include clinical factors (tumor size, ciliary body involvement, and extraocular extension); histopathologic factors (spindle or epithelioid cell type); and cytogenetics (status of chromosomes 3, 6, and 8), he said.

An AJCC Ophthalmic Oncology Task Force study published in 2015, for example, showed that the 5-year metastasis-free survival was 97% for AJCC stage T1 disease, 85% for stage T2, 77% for stage T3, and 61% for stage T4. T-stage modifiers, which are based on particular tumor characteristics, such as ciliary body involvement (CBI) and extraocular extension (EXE), were also associated with the risk of distant metastasis: 5-year metastasis-free survival was 90%, 72%, 54% and 33% for AJCC T_a (no CBI or EXE), T_b (CBI only), T_c (EXE only), and T_d tumors (CBI and EXE), respectively.

Follow-up imaging after primary tumor treatment should be based on the most likely site of metastatic recurrence, which is the liver in 90% of uveal melanoma metastases.

“For this reason, surveillance of high-risk patients with uveal melanoma should include specific imaging of the liver,” Dr. Barker said, who noted that the NCCN risk stratification–based surveillance guidelines categorize patients as either low, medium, or high risk for metastasis based on the various characteristics that can affect risk.

“These risk groups help clinicians identify how often imaging should be performed in their surveillance strategy,” he said, adding that those who are high risk based on BAP1 mutation, PRAME mutation, CBI, or EXE, for example, should undergo imaging to evaluate signs or symptoms every 3-6 months for 5 years, every 6-12 months for 10 years, and then as clinically indicated thereafter.

The guideline calls for less stringent imaging for low- and medium-risk patients.

“Now, what happens when distant metastases are identified? Unfortunately there is no single systemic therapy that has proven to be most effective for uveal melanoma,” he said. “For this reason, the NCCN guideline encourages clinical trial participation whenever possible for patients who develop distant metastasis.”

This is because drugs effective for cutaneous melanoma are far less effective for uveal melanoma, but do elicit response in some patients and can be considered, he explained.

[email protected]

ORLANDO – Uveal melanoma has little in common with it’s cutaneous namesake, and its distinct characteristics necessitated the development of specific guidelines for diagnosis and management, which were released earlier this year by the National Comprehensive Cancer Network (NCCN).

Unlike cutaneous melanoma, uveal melanoma is usually treated with radiotherapy rather than surgery, and primary treatment is based on tumor size, according to Christopher A. Barker, MD, a radiation oncologist and director of clinical investigations in the department of radiation at Memorial Sloan Kettering Cancer Center, New York.

Further, molecular testing aids in prognosis in uveal melanoma but not in predicting treatment response as it can in cutaneous disease, and recurrences of uveal melanoma are typically distant – usually occurring in the liver – rather than in the skin or lymph nodes as with cutaneous melanoma.

These and other diagnosis- and treatment-related issues are outlined in the new guidelines, which are the first developed by the NCCN for uveal melanoma.

Guidelines exist in several countries, including Australia, the United Kingdom, Canada, and the United States (published by The American Brachytherapy Society), but until now none have provided pathway-based strategies for the management of all stages of this rare disease that affects about 1 in 200,000 Americans, typically Caucasians in their 50s, 60s, or 70s, Dr. Barker, a member of the NCCN Melanoma guidelines panel and the uveal melanoma subcommittee, said at the NCCN’s annual meeting where he presented the guidelines.

The median age of diagnosis is 60 years, he noted.

The NCCN guidelines specifically address melanoma arising in the choroid and ciliary body of the uvea. The choroid is the predominant site of uveal melanoma origin, and tumors arising there may involve the ciliary body as well, although the latter is a rare site of melanoma origin. The iris is also a rare site of origin, and tumors arising there are typically indolent in nature and thus are not part of the new guidelines, he explained.

Risk factors include choroidal nevi, ocular melanocytosis, and familial uveal melanoma associated with germline BAP1 mutation, neurofibromatosis, or dysplastic nevus syndrome; cutaneous melanoma is not a risk factor, he said.

The guidelines address clinical presentation, diagnostic work-up, and staging; primary treatments; and metastatic risks and follow-up imaging.

Presentation, diagnosis, and staging

About two-thirds of patients with uveal melanoma present because of changes in their vision, and about a third present with no new symptoms and are diagnosed during routine evaluation, Dr. Barker said.

“History and physical exam, and specifically attention to any prior malignancies, is important,” he said. “A comprehensive eye examination is absolutely vital to the evaluation and staging of patients with uveal melanoma.”

Numerous additional testing options, including autofluorescence of the ocular fundus, retinal fluorescein angiography of the ocular fundus, and transillumination, among others, are listed in the guidelines, which note that MRI is sometimes needed to confirm diagnosis.

Biopsies, however, are generally only performed to confirm diagnosis if needed or for prognostic analysis for risk stratification.

Staging is determined mainly by tumor size, which is known to be associated with outcomes in patients with uveal melanoma, and is based on criteria from both the Collaborative Ocular Melanoma Study (COMS) staging system and the American Joint Committee on Cancer (AJCC) staging manual, Dr. Barker said.

The COMS system was developed based on separate studies of small, medium, and large tumors and helped define primary tumor management and establish existing standards of care. The AJCC system was developed subsequently and focuses more on tumor features that may improve clinical predictions.

Primary treatments

Options for primary treatment for small tumors (largest diameter 5-16 mm and thickness less than 2.5 mm) include plaque brachytherapy, partical beam radiation, and laser ablation in highly select patients. For medium tumors (18mm or less at largest diameter and thickness of 2.5-10 mm), they include plaque brachytherapy, particle beam radiation, and enucleation, according to the guidelines.

Large tumors can be treated with radiotherapy (preferably particle beam radiation, Dr. Barker said) or enucleation. Large tumors are those greater than 18mm with any thickness, those with thickness greater than 10mm with any diameter, and those with thickness greater than 8mm with optic nerve involvement.

In patients for whom surgical removal is selected, “ there are a few unusual situations where additional local adjuvant therapy might be considered,” Dr. Barker said, explaining, for example, that the presence of microscopically positive or close margins after enucleation without evidence of gross residual disease in the orbit may be observed or may warrant map biopsy and/or particle beam or photon beam radiotherapy to the orbit.

For visible extraocular tumors or suspicion of gross disease in the orbit, biopsy of the extraocular tissue is recommended when possible, along with either intraoperative cryotherapy, orbital exenteration, or particle beam or photon beam radiotherapy to the orbit, he added.

Metastatic risks and follow-up imaging

Recent studies, including Cancer Genome Atlas Research Network studies, have elucidated the genomics of both uveal and cutaneous melanomas, and they show “a completely different mutation spectrum” for uveal melanoma, Dr. Barker said.

These genomic studies demonstrate that cutaneous melanoma involves mutations that predict response to certain treatments, while those found in uveal melanoma do not, but they are, however, associated with the probability of metastasis, he said.

For example, various studies have shown that BRAF mutation in cutaneous melanoma predicts response to RAF or MEK inhibition and that the overall number of mutations in cutaneous melanoma may predict response to immunotherapy.

In uveal melanoma, alterations in ElFAX1, SF3B1, or BAP1 have been shown to indicate low, intermediate, and high risk of metastasis, respectively.

Other factors associated with the risk of metastasis after primary tumor treatment in uveal melanoma include clinical factors (tumor size, ciliary body involvement, and extraocular extension); histopathologic factors (spindle or epithelioid cell type); and cytogenetics (status of chromosomes 3, 6, and 8), he said.

An AJCC Ophthalmic Oncology Task Force study published in 2015, for example, showed that the 5-year metastasis-free survival was 97% for AJCC stage T1 disease, 85% for stage T2, 77% for stage T3, and 61% for stage T4. T-stage modifiers, which are based on particular tumor characteristics, such as ciliary body involvement (CBI) and extraocular extension (EXE), were also associated with the risk of distant metastasis: 5-year metastasis-free survival was 90%, 72%, 54% and 33% for AJCC T_a (no CBI or EXE), T_b (CBI only), T_c (EXE only), and T_d tumors (CBI and EXE), respectively.

Follow-up imaging after primary tumor treatment should be based on the most likely site of metastatic recurrence, which is the liver in 90% of uveal melanoma metastases.

“For this reason, surveillance of high-risk patients with uveal melanoma should include specific imaging of the liver,” Dr. Barker said, who noted that the NCCN risk stratification–based surveillance guidelines categorize patients as either low, medium, or high risk for metastasis based on the various characteristics that can affect risk.

“These risk groups help clinicians identify how often imaging should be performed in their surveillance strategy,” he said, adding that those who are high risk based on BAP1 mutation, PRAME mutation, CBI, or EXE, for example, should undergo imaging to evaluate signs or symptoms every 3-6 months for 5 years, every 6-12 months for 10 years, and then as clinically indicated thereafter.

The guideline calls for less stringent imaging for low- and medium-risk patients.

“Now, what happens when distant metastases are identified? Unfortunately there is no single systemic therapy that has proven to be most effective for uveal melanoma,” he said. “For this reason, the NCCN guideline encourages clinical trial participation whenever possible for patients who develop distant metastasis.”

This is because drugs effective for cutaneous melanoma are far less effective for uveal melanoma, but do elicit response in some patients and can be considered, he explained.

[email protected]

The U.S. Preventive Services Task Force advises clinicians to refer or offer intensive behavioral weight-loss interventions to obese adults, according to an updated recommendation statement published in JAMA.

Top Photo Group/ThinkStock

Obesity affects more than one-third of U.S. adults, according to federal statistics. It carries increased risk for comorbidities including heart disease, diabetes, and various cancers, as well as increased risk of death among adults younger than 65 years, noted lead author Susan J. Curry, PhD, of the University of Iowa, Iowa City, and members of the Task Force.

The B recommendation applies to obese adults; obesity was defined as a body mass index of 30 kg/m² or higher. The evidence review focused on interventions for weight loss and weight maintenance that could be provided in primary care or referred from primary care, such as nutrition counseling, exercise strategies, and goal setting.

The Task Force found adequate evidence that behavior-based weight-loss interventions improved weight, reduced incidence of type 2 diabetes, and helped maintain weight loss after interventions ended.

The Task Force found small to no evidence of harm associated with any of the behavioral weight-loss interventions, which included group sessions, personal sessions, print-based interventions, and technology-based interventions (such as text messages). Although interventions that combined drug therapy with behavioral intervention resulted in greater weight loss over 12-18 months, compared with behavioral interventions alone, the attrition rates were high and data on weight-loss maintenance after discontinuation of the drugs were limited, the Task Force noted.

“As a result, the USPSTF encourages clinicians to promote behavioral interventions as the primary focus of effective interventions for weight loss in adults,” they wrote.

The Task Force acknowledged the need for future research in subgroups and to explore whether factors such as genetics and untreated conditions are barriers to behavior-based weight loss interventions.

In the evidence review published in JAMA, Erin S. LeBlanc, MD, of Kaiser Permanente in Portland, Ore., and her colleagues reviewed data from 122 randomized, controlled trials including more than 62,000 persons and 2 observational studies including more than 209,000 persons.

The researchers found behavioral interventions were associated with greater weight loss and less risk of developing diabetes, compared with control interventions.

Intensive behavioral interventions included counseling patients about healthy eating, encouraging physical activity, setting weight and health goals, and assisting with weight monitoring. The interventions ranged from text messaging to in-person sessions for individuals or groups. The average absolute weight loss in the trials included in the review ranged from –0.5 kg to –9.3 kg (–1.1 lb to –20.5 lb) for intervention patients and from +1.4 kg to –5.6 kg (+3.1 lb to –12.3 lb) in controls.

Limitations of the review included a lack of data on population subgroups and a lack of long-term data on weight and health outcomes, the researchers noted. However, the results support the value of behavior-based therapy for obesity treatment.

The final recommendation is consistent with the 2018 draft recommendation and updates the 2012 final recommendation on obesity management.

The researchers and Task Force members had no relevant financial conflicts to disclose.

SOURCE: U.S. Preventive Services Task Force. JAMA. 2018;320(11):1163-71. doi: 10.1001/jama.2018.13022.

The U.S. Preventive Services Task Force advises clinicians to refer or offer intensive behavioral weight-loss interventions to obese adults, according to an updated recommendation statement published in JAMA.

Top Photo Group/ThinkStock

Obesity affects more than one-third of U.S. adults, according to federal statistics. It carries increased risk for comorbidities including heart disease, diabetes, and various cancers, as well as increased risk of death among adults younger than 65 years, noted lead author Susan J. Curry, PhD, of the University of Iowa, Iowa City, and members of the Task Force.

The B recommendation applies to obese adults; obesity was defined as a body mass index of 30 kg/m² or higher. The evidence review focused on interventions for weight loss and weight maintenance that could be provided in primary care or referred from primary care, such as nutrition counseling, exercise strategies, and goal setting.

The Task Force found adequate evidence that behavior-based weight-loss interventions improved weight, reduced incidence of type 2 diabetes, and helped maintain weight loss after interventions ended.

The Task Force found small to no evidence of harm associated with any of the behavioral weight-loss interventions, which included group sessions, personal sessions, print-based interventions, and technology-based interventions (such as text messages). Although interventions that combined drug therapy with behavioral intervention resulted in greater weight loss over 12-18 months, compared with behavioral interventions alone, the attrition rates were high and data on weight-loss maintenance after discontinuation of the drugs were limited, the Task Force noted.

“As a result, the USPSTF encourages clinicians to promote behavioral interventions as the primary focus of effective interventions for weight loss in adults,” they wrote.

The Task Force acknowledged the need for future research in subgroups and to explore whether factors such as genetics and untreated conditions are barriers to behavior-based weight loss interventions.

In the evidence review published in JAMA, Erin S. LeBlanc, MD, of Kaiser Permanente in Portland, Ore., and her colleagues reviewed data from 122 randomized, controlled trials including more than 62,000 persons and 2 observational studies including more than 209,000 persons.

The researchers found behavioral interventions were associated with greater weight loss and less risk of developing diabetes, compared with control interventions.

Intensive behavioral interventions included counseling patients about healthy eating, encouraging physical activity, setting weight and health goals, and assisting with weight monitoring. The interventions ranged from text messaging to in-person sessions for individuals or groups. The average absolute weight loss in the trials included in the review ranged from –0.5 kg to –9.3 kg (–1.1 lb to –20.5 lb) for intervention patients and from +1.4 kg to –5.6 kg (+3.1 lb to –12.3 lb) in controls.

Limitations of the review included a lack of data on population subgroups and a lack of long-term data on weight and health outcomes, the researchers noted. However, the results support the value of behavior-based therapy for obesity treatment.

The final recommendation is consistent with the 2018 draft recommendation and updates the 2012 final recommendation on obesity management.

The researchers and Task Force members had no relevant financial conflicts to disclose.

SOURCE: U.S. Preventive Services Task Force. JAMA. 2018;320(11):1163-71. doi: 10.1001/jama.2018.13022.

The U.S. Preventive Services Task Force advises clinicians to refer or offer intensive behavioral weight-loss interventions to obese adults, according to an updated recommendation statement published in JAMA.

Top Photo Group/ThinkStock

Obesity affects more than one-third of U.S. adults, according to federal statistics. It carries increased risk for comorbidities including heart disease, diabetes, and various cancers, as well as increased risk of death among adults younger than 65 years, noted lead author Susan J. Curry, PhD, of the University of Iowa, Iowa City, and members of the Task Force.

The B recommendation applies to obese adults; obesity was defined as a body mass index of 30 kg/m² or higher. The evidence review focused on interventions for weight loss and weight maintenance that could be provided in primary care or referred from primary care, such as nutrition counseling, exercise strategies, and goal setting.

The Task Force found adequate evidence that behavior-based weight-loss interventions improved weight, reduced incidence of type 2 diabetes, and helped maintain weight loss after interventions ended.

The Task Force found small to no evidence of harm associated with any of the behavioral weight-loss interventions, which included group sessions, personal sessions, print-based interventions, and technology-based interventions (such as text messages). Although interventions that combined drug therapy with behavioral intervention resulted in greater weight loss over 12-18 months, compared with behavioral interventions alone, the attrition rates were high and data on weight-loss maintenance after discontinuation of the drugs were limited, the Task Force noted.

“As a result, the USPSTF encourages clinicians to promote behavioral interventions as the primary focus of effective interventions for weight loss in adults,” they wrote.

The Task Force acknowledged the need for future research in subgroups and to explore whether factors such as genetics and untreated conditions are barriers to behavior-based weight loss interventions.

In the evidence review published in JAMA, Erin S. LeBlanc, MD, of Kaiser Permanente in Portland, Ore., and her colleagues reviewed data from 122 randomized, controlled trials including more than 62,000 persons and 2 observational studies including more than 209,000 persons.

The researchers found behavioral interventions were associated with greater weight loss and less risk of developing diabetes, compared with control interventions.

Intensive behavioral interventions included counseling patients about healthy eating, encouraging physical activity, setting weight and health goals, and assisting with weight monitoring. The interventions ranged from text messaging to in-person sessions for individuals or groups. The average absolute weight loss in the trials included in the review ranged from –0.5 kg to –9.3 kg (–1.1 lb to –20.5 lb) for intervention patients and from +1.4 kg to –5.6 kg (+3.1 lb to –12.3 lb) in controls.

Limitations of the review included a lack of data on population subgroups and a lack of long-term data on weight and health outcomes, the researchers noted. However, the results support the value of behavior-based therapy for obesity treatment.

The final recommendation is consistent with the 2018 draft recommendation and updates the 2012 final recommendation on obesity management.

The researchers and Task Force members had no relevant financial conflicts to disclose.

SOURCE: U.S. Preventive Services Task Force. JAMA. 2018;320(11):1163-71. doi: 10.1001/jama.2018.13022.

The American Society of Clinical Oncology (ASCO) has released a policy statement addressing financial barriers that may prevent cancer patients from participating in clinical trials.

The four main recommendations in ASCO’s policy statement are:

• Payers should create clear, consistent, streamlined, and transparent policies regarding clinical trial coverage.
• Patients should receive easy-to-understand information about potential out-of-pocket costs.
• “Ethically appropriate” financial compensation for out-of-pocket costs should be allowed.
• Researchers should be incentivized to investigate and “better characterize” costs incurred by cancer patients in clinical trials as well as identify ways to “mitigate the risk of trial-associated financial hardship.”

ASCO’s full policy statement, “Addressing Financial Barriers to Patient Participation in Clinical Trials,” is available on the Journal of Clinical Oncology website.

SOURCE: Winkfield KM et al. J Clin Oncol. 2018 Sep 13:JCO1801132. doi: 10.1200/JCO.18.01132.

The American Society of Clinical Oncology (ASCO) has released a policy statement addressing financial barriers that may prevent cancer patients from participating in clinical trials.

The four main recommendations in ASCO’s policy statement are:

• Payers should create clear, consistent, streamlined, and transparent policies regarding clinical trial coverage.
• Patients should receive easy-to-understand information about potential out-of-pocket costs.
• “Ethically appropriate” financial compensation for out-of-pocket costs should be allowed.
• Researchers should be incentivized to investigate and “better characterize” costs incurred by cancer patients in clinical trials as well as identify ways to “mitigate the risk of trial-associated financial hardship.”

ASCO’s full policy statement, “Addressing Financial Barriers to Patient Participation in Clinical Trials,” is available on the Journal of Clinical Oncology website.

SOURCE: Winkfield KM et al. J Clin Oncol. 2018 Sep 13:JCO1801132. doi: 10.1200/JCO.18.01132.

The American Society of Clinical Oncology (ASCO) has released a policy statement addressing financial barriers that may prevent cancer patients from participating in clinical trials.

The four main recommendations in ASCO’s policy statement are:

• Payers should create clear, consistent, streamlined, and transparent policies regarding clinical trial coverage.
• Patients should receive easy-to-understand information about potential out-of-pocket costs.
• “Ethically appropriate” financial compensation for out-of-pocket costs should be allowed.
• Researchers should be incentivized to investigate and “better characterize” costs incurred by cancer patients in clinical trials as well as identify ways to “mitigate the risk of trial-associated financial hardship.”

ASCO’s full policy statement, “Addressing Financial Barriers to Patient Participation in Clinical Trials,” is available on the Journal of Clinical Oncology website.

SOURCE: Winkfield KM et al. J Clin Oncol. 2018 Sep 13:JCO1801132. doi: 10.1200/JCO.18.01132.

Proton therapy can help mitigate toxicity in adults with mediastinal lymphomas, but only when this modality offers a clear advantage over intensity-modulated radiotherapy, according to new guidelines from the International Lymphoma Radiation Oncology Group.

Proton therapy reduces radiation dose to organs at risk in certain clinical presentations, such as when the mediastinal target is on both sides of the heart. The advantages are not always clear in other situations, such as when the target spans the right side of the heart, or when the target is above the heart with no axillary involvement, according to guideline authors Bouthaina Dabaja, MD, professor and section chief of hematology in the department of radiation oncology at the University of Texas MD Anderson Cancer Center, Houston, and her colleagues.

“The limited availability of proton therapy calls for case selection based on a clear understanding of which cases will derive most benefit from proton therapy as compared to advanced photon techniques,” Dr. Dabaja and her coauthors said in the guidelines, which were published in the journal Blood (doi: 10.1182/blood-2018-03-837633).

Along with intensity-modulated radiotherapy and 3-dimensional conformal radiotherapy, proton therapy presents “another opportunity” for more conformal dose distribution and better sparing of organs at risk, according to the consensus recommendations. Proton therapy can greatly benefit certain patients with mediastinal disease. These include young female patients to reduce breast dose and risk of a secondary breast cancer, patients at high risk of radiation-related toxicity due to previous treatment, and patients with disease spanning below the origin of the left main stem coronary artery that is anterior to, posterior to, or on the left side of the heart.

“The relation of disease to organs at risk determines the situations in which proton therapy is most beneficial,” the experts said in the guidelines. However, the consideration of proton therapy needs to factor the complexities of proton therapy planning, the need to manage uncertainties, and the “evolving nature of the technology,” which includes the development of pencil beam scanning.

While passive scattering proton therapy (PSPT) is the least complex delivery technique, it is challenging because beams can conform only to one side of the target; by contrast, the experts said, active mode pencil beam scanning proton therapy (PBSPT) potentially provides better conformity and sparing of organs at risk.

“Because treatment involves delivery of individual controlled spots, inhomogenous doses can be created deliberately,” the guideline authors said in their report.

However, motion management is “of prime importance” with PBSPT, which is more sensitive to density changes in the beam path as compared to PSPT, they added. Toward that end, physicians should pay close attention to evaluating intrafractional movement, which is frequently tied to the breathing cycle.

The guidelines list a total of 11 authors representing The University of Texas MD Anderson Cancer Center; University of Florida, Jacksonville; University of Pennsylvania, Philadelphia; University of Louisiana, Baton Rouge; Proton Therapy Center Czech, Prague; Motol University Hospital, Czech Republic; St. Thomas and Guy Hospital, London; Institut Curie, Paris; and Rigshospitalet, Copenhagen.

Dr. Dabaja and her guideline coauthors reported no funding or conflicts of interest.

Proton therapy can help mitigate toxicity in adults with mediastinal lymphomas, but only when this modality offers a clear advantage over intensity-modulated radiotherapy, according to new guidelines from the International Lymphoma Radiation Oncology Group.

Proton therapy reduces radiation dose to organs at risk in certain clinical presentations, such as when the mediastinal target is on both sides of the heart. The advantages are not always clear in other situations, such as when the target spans the right side of the heart, or when the target is above the heart with no axillary involvement, according to guideline authors Bouthaina Dabaja, MD, professor and section chief of hematology in the department of radiation oncology at the University of Texas MD Anderson Cancer Center, Houston, and her colleagues.

“The limited availability of proton therapy calls for case selection based on a clear understanding of which cases will derive most benefit from proton therapy as compared to advanced photon techniques,” Dr. Dabaja and her coauthors said in the guidelines, which were published in the journal Blood (doi: 10.1182/blood-2018-03-837633).

Along with intensity-modulated radiotherapy and 3-dimensional conformal radiotherapy, proton therapy presents “another opportunity” for more conformal dose distribution and better sparing of organs at risk, according to the consensus recommendations. Proton therapy can greatly benefit certain patients with mediastinal disease. These include young female patients to reduce breast dose and risk of a secondary breast cancer, patients at high risk of radiation-related toxicity due to previous treatment, and patients with disease spanning below the origin of the left main stem coronary artery that is anterior to, posterior to, or on the left side of the heart.

“The relation of disease to organs at risk determines the situations in which proton therapy is most beneficial,” the experts said in the guidelines. However, the consideration of proton therapy needs to factor the complexities of proton therapy planning, the need to manage uncertainties, and the “evolving nature of the technology,” which includes the development of pencil beam scanning.

While passive scattering proton therapy (PSPT) is the least complex delivery technique, it is challenging because beams can conform only to one side of the target; by contrast, the experts said, active mode pencil beam scanning proton therapy (PBSPT) potentially provides better conformity and sparing of organs at risk.

“Because treatment involves delivery of individual controlled spots, inhomogenous doses can be created deliberately,” the guideline authors said in their report.

However, motion management is “of prime importance” with PBSPT, which is more sensitive to density changes in the beam path as compared to PSPT, they added. Toward that end, physicians should pay close attention to evaluating intrafractional movement, which is frequently tied to the breathing cycle.

The guidelines list a total of 11 authors representing The University of Texas MD Anderson Cancer Center; University of Florida, Jacksonville; University of Pennsylvania, Philadelphia; University of Louisiana, Baton Rouge; Proton Therapy Center Czech, Prague; Motol University Hospital, Czech Republic; St. Thomas and Guy Hospital, London; Institut Curie, Paris; and Rigshospitalet, Copenhagen.

Dr. Dabaja and her guideline coauthors reported no funding or conflicts of interest.

Proton therapy can help mitigate toxicity in adults with mediastinal lymphomas, but only when this modality offers a clear advantage over intensity-modulated radiotherapy, according to new guidelines from the International Lymphoma Radiation Oncology Group.

Proton therapy reduces radiation dose to organs at risk in certain clinical presentations, such as when the mediastinal target is on both sides of the heart. The advantages are not always clear in other situations, such as when the target spans the right side of the heart, or when the target is above the heart with no axillary involvement, according to guideline authors Bouthaina Dabaja, MD, professor and section chief of hematology in the department of radiation oncology at the University of Texas MD Anderson Cancer Center, Houston, and her colleagues.

“The limited availability of proton therapy calls for case selection based on a clear understanding of which cases will derive most benefit from proton therapy as compared to advanced photon techniques,” Dr. Dabaja and her coauthors said in the guidelines, which were published in the journal Blood (doi: 10.1182/blood-2018-03-837633).

Along with intensity-modulated radiotherapy and 3-dimensional conformal radiotherapy, proton therapy presents “another opportunity” for more conformal dose distribution and better sparing of organs at risk, according to the consensus recommendations. Proton therapy can greatly benefit certain patients with mediastinal disease. These include young female patients to reduce breast dose and risk of a secondary breast cancer, patients at high risk of radiation-related toxicity due to previous treatment, and patients with disease spanning below the origin of the left main stem coronary artery that is anterior to, posterior to, or on the left side of the heart.

“The relation of disease to organs at risk determines the situations in which proton therapy is most beneficial,” the experts said in the guidelines. However, the consideration of proton therapy needs to factor the complexities of proton therapy planning, the need to manage uncertainties, and the “evolving nature of the technology,” which includes the development of pencil beam scanning.

While passive scattering proton therapy (PSPT) is the least complex delivery technique, it is challenging because beams can conform only to one side of the target; by contrast, the experts said, active mode pencil beam scanning proton therapy (PBSPT) potentially provides better conformity and sparing of organs at risk.

“Because treatment involves delivery of individual controlled spots, inhomogenous doses can be created deliberately,” the guideline authors said in their report.

However, motion management is “of prime importance” with PBSPT, which is more sensitive to density changes in the beam path as compared to PSPT, they added. Toward that end, physicians should pay close attention to evaluating intrafractional movement, which is frequently tied to the breathing cycle.

The guidelines list a total of 11 authors representing The University of Texas MD Anderson Cancer Center; University of Florida, Jacksonville; University of Pennsylvania, Philadelphia; University of Louisiana, Baton Rouge; Proton Therapy Center Czech, Prague; Motol University Hospital, Czech Republic; St. Thomas and Guy Hospital, London; Institut Curie, Paris; and Rigshospitalet, Copenhagen.

Dr. Dabaja and her guideline coauthors reported no funding or conflicts of interest.

MUNICH – The “overwhelming impression” that Paul K. Whelton, MD, has of the newly revised hypertension diagnosis and management guidelines of the European Society of Cardiology is their similarity to hypertension guidelines released by the American College of Cardiology and American Heart Association in November 2017.

“We both recommend the same treatment target, of less than 130/80 mm Hg,” noted Dr. Whelton, professor at Tulane University in New Orleans, although the European guidelines (Euro J Cardiology. 2018 Sep 1; 39[33]:3021-104) put more qualifications on this target and specify treating to no lower than 130 mm Hg systolic pressure in patients who are at least 65 years old as well as in patients with chronic kidney disease at any age. In a video interview, Dr. Whelton also cited areas of disagreement, such as how patients with an untreated blood pressure of 130-139 mm Hg are classified (high normal in the European guidelines, stage 1 hypertension in the U.S. guidelines), and whether initial drug monotherapy is a reasonable treatment strategy (U.S. says yes, Europe says no).

Dr. Whelton noted that recent modeling studies have documented the potential public health benefits from following the diagnosis and management approaches set forth in the 2017 U.S. guidelines (J Am Coll Cardiol. 2018 May;71[19]:e127-e248). For example, an analysis based on data collected by the U.S. National Health and Nutrition Examination Survey during 2013-2016 showed that following the 2017 guidelines for diagnosing and treating hypertension would have resulted in prevention of more than twice the number of cardiovascular disease events nationally as compared with application of the prior, 2014 U.S. hypertension guideline (JAMA. 2014 Feb 5;311[5]:507-20): 610,000 events prevented, compared with 270,000 events prevented. The same study showed that the 2017 guidelines would have nearly doubled the number of all-cause deaths prevented, with 334,000 deaths prevented, compared with 177,000 prevented by applying the 2014 guidelines (JAMA Cardiology. 2018 July;3[7]:572-81).

Dr. Whelton had no commercial disclosures.

[email protected]

MUNICH – The “overwhelming impression” that Paul K. Whelton, MD, has of the newly revised hypertension diagnosis and management guidelines of the European Society of Cardiology is their similarity to hypertension guidelines released by the American College of Cardiology and American Heart Association in November 2017.

“We both recommend the same treatment target, of less than 130/80 mm Hg,” noted Dr. Whelton, professor at Tulane University in New Orleans, although the European guidelines (Euro J Cardiology. 2018 Sep 1; 39[33]:3021-104) put more qualifications on this target and specify treating to no lower than 130 mm Hg systolic pressure in patients who are at least 65 years old as well as in patients with chronic kidney disease at any age. In a video interview, Dr. Whelton also cited areas of disagreement, such as how patients with an untreated blood pressure of 130-139 mm Hg are classified (high normal in the European guidelines, stage 1 hypertension in the U.S. guidelines), and whether initial drug monotherapy is a reasonable treatment strategy (U.S. says yes, Europe says no).

Dr. Whelton noted that recent modeling studies have documented the potential public health benefits from following the diagnosis and management approaches set forth in the 2017 U.S. guidelines (J Am Coll Cardiol. 2018 May;71[19]:e127-e248). For example, an analysis based on data collected by the U.S. National Health and Nutrition Examination Survey during 2013-2016 showed that following the 2017 guidelines for diagnosing and treating hypertension would have resulted in prevention of more than twice the number of cardiovascular disease events nationally as compared with application of the prior, 2014 U.S. hypertension guideline (JAMA. 2014 Feb 5;311[5]:507-20): 610,000 events prevented, compared with 270,000 events prevented. The same study showed that the 2017 guidelines would have nearly doubled the number of all-cause deaths prevented, with 334,000 deaths prevented, compared with 177,000 prevented by applying the 2014 guidelines (JAMA Cardiology. 2018 July;3[7]:572-81).

Dr. Whelton had no commercial disclosures.

[email protected]

MUNICH – The “overwhelming impression” that Paul K. Whelton, MD, has of the newly revised hypertension diagnosis and management guidelines of the European Society of Cardiology is their similarity to hypertension guidelines released by the American College of Cardiology and American Heart Association in November 2017.

“We both recommend the same treatment target, of less than 130/80 mm Hg,” noted Dr. Whelton, professor at Tulane University in New Orleans, although the European guidelines (Euro J Cardiology. 2018 Sep 1; 39[33]:3021-104) put more qualifications on this target and specify treating to no lower than 130 mm Hg systolic pressure in patients who are at least 65 years old as well as in patients with chronic kidney disease at any age. In a video interview, Dr. Whelton also cited areas of disagreement, such as how patients with an untreated blood pressure of 130-139 mm Hg are classified (high normal in the European guidelines, stage 1 hypertension in the U.S. guidelines), and whether initial drug monotherapy is a reasonable treatment strategy (U.S. says yes, Europe says no).

Dr. Whelton noted that recent modeling studies have documented the potential public health benefits from following the diagnosis and management approaches set forth in the 2017 U.S. guidelines (J Am Coll Cardiol. 2018 May;71[19]:e127-e248). For example, an analysis based on data collected by the U.S. National Health and Nutrition Examination Survey during 2013-2016 showed that following the 2017 guidelines for diagnosing and treating hypertension would have resulted in prevention of more than twice the number of cardiovascular disease events nationally as compared with application of the prior, 2014 U.S. hypertension guideline (JAMA. 2014 Feb 5;311[5]:507-20): 610,000 events prevented, compared with 270,000 events prevented. The same study showed that the 2017 guidelines would have nearly doubled the number of all-cause deaths prevented, with 334,000 deaths prevented, compared with 177,000 prevented by applying the 2014 guidelines (JAMA Cardiology. 2018 July;3[7]:572-81).

Dr. Whelton had no commercial disclosures.

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