ANSWER

The correct answer is hidradenitis suppurativa (HS; choice “c”).

DISCUSSION

HS (also known as acne inversa) is a relatively common condition first described in 1839 by French physician Frederick Velpeau, who thought it was probably a form of acne. Because HS only affects intertriginous areas (groin, axillae, inframammary, intergluteal, and abdominal folds rich in apocrine glands), during the next 130 years, it was presumed that this disease was solely caused by malfunctioning apocrine glands.

Though experts disagree about the true etiology of HS, most agree that it is caused by several environmental and genetic factors leading to plugged or malfunctioning hair follicles and apocrine glands that become inflamed, swollen, painful, and purulent. In severe cases, tracts develop between lesions, resulting in the formation of ropy, linear hypertrophic scarring. Early on and in milder cases, comedones can manifest—often in multiples—along with widely scattered cysts. It appears that a case can be made for a genetic predisposition to develop HS because at least one-third of affected patients report a positive family history.

Females (usually postpubescent) are affected at 3 times the rate of males. Hormones, especially androgens, appear to play a role. This assertion is bolstered not only by the age of onset, but also because HS has been observed to improve after pregnancy and after menopause.

Though not causative, smoking and obesity have a strong statistical correlation with HS as exacerbating factors. Many patients with HS find movement from exercise too painful, which may contribute to obesity.

Because HS has a wide range of clinical presentations, the Hurley Staging scale can help clinicians distinguish the condition’s severity by stages I, II, or III. Stage I manifests with scant signs of disease, including comedones and sparsely separated small cysts. Stage II includes numerous painful cysts with tract formation between lesions. Stage III involves symptoms described in the other stages as well as multiple large, painful, draining cysts; widespread erythema; and extensive hypertrophic scarring.

Regarding the differential, the culture would have identified community-acquired methicillin-resistant Staphylococcus aureus (choice “a”) or flesh-eating bacterial infection (choice “d”), but neither would be as chronic as the patient’s disease. Acne conglobata (choice “b”) manifests with chronic dense acne largely confined to the trunk. Interestingly, acne conglobata, HS, dissecting cellulitis of the scalp, and pilonidal cyst are collectively known as the follicular occlusion tetrad.

TREATMENT

Treatment for HS is limited. Adalimumab is the most recent and promising biologic, though its use comes at a high cost ($60,000/y) and with an adverse effect profile that should give any prescriber pause. Also, the best one could hope for in using adalimumab is about a 30% improvement in the patient.

Before using a biologic, other options should at least be considered. Though not entirely satisfactory, there are oral antibiotics (minocycline, trimethoprim/sulfa, or a combination of rifampin and clindamycin) or intralesional steroids. Incision and drainage of individual lesions and isotretinoin therapy can temporarily relieve pain, but they are not effective as long-term therapies. Large-scale surgical extirpation of the affected tissue can be considered in extreme cases, but there can be recurrences and associated morbidity (eg, chronic lymphedema in the affected arm, extreme scarring, and postoperative pain).

ANSWER

The correct answer is hidradenitis suppurativa (HS; choice “c”).

DISCUSSION

HS (also known as acne inversa) is a relatively common condition first described in 1839 by French physician Frederick Velpeau, who thought it was probably a form of acne. Because HS only affects intertriginous areas (groin, axillae, inframammary, intergluteal, and abdominal folds rich in apocrine glands), during the next 130 years, it was presumed that this disease was solely caused by malfunctioning apocrine glands.

Though experts disagree about the true etiology of HS, most agree that it is caused by several environmental and genetic factors leading to plugged or malfunctioning hair follicles and apocrine glands that become inflamed, swollen, painful, and purulent. In severe cases, tracts develop between lesions, resulting in the formation of ropy, linear hypertrophic scarring. Early on and in milder cases, comedones can manifest—often in multiples—along with widely scattered cysts. It appears that a case can be made for a genetic predisposition to develop HS because at least one-third of affected patients report a positive family history.

Females (usually postpubescent) are affected at 3 times the rate of males. Hormones, especially androgens, appear to play a role. This assertion is bolstered not only by the age of onset, but also because HS has been observed to improve after pregnancy and after menopause.

Though not causative, smoking and obesity have a strong statistical correlation with HS as exacerbating factors. Many patients with HS find movement from exercise too painful, which may contribute to obesity.

Because HS has a wide range of clinical presentations, the Hurley Staging scale can help clinicians distinguish the condition’s severity by stages I, II, or III. Stage I manifests with scant signs of disease, including comedones and sparsely separated small cysts. Stage II includes numerous painful cysts with tract formation between lesions. Stage III involves symptoms described in the other stages as well as multiple large, painful, draining cysts; widespread erythema; and extensive hypertrophic scarring.

Regarding the differential, the culture would have identified community-acquired methicillin-resistant Staphylococcus aureus (choice “a”) or flesh-eating bacterial infection (choice “d”), but neither would be as chronic as the patient’s disease. Acne conglobata (choice “b”) manifests with chronic dense acne largely confined to the trunk. Interestingly, acne conglobata, HS, dissecting cellulitis of the scalp, and pilonidal cyst are collectively known as the follicular occlusion tetrad.

TREATMENT

Treatment for HS is limited. Adalimumab is the most recent and promising biologic, though its use comes at a high cost ($60,000/y) and with an adverse effect profile that should give any prescriber pause. Also, the best one could hope for in using adalimumab is about a 30% improvement in the patient.

Before using a biologic, other options should at least be considered. Though not entirely satisfactory, there are oral antibiotics (minocycline, trimethoprim/sulfa, or a combination of rifampin and clindamycin) or intralesional steroids. Incision and drainage of individual lesions and isotretinoin therapy can temporarily relieve pain, but they are not effective as long-term therapies. Large-scale surgical extirpation of the affected tissue can be considered in extreme cases, but there can be recurrences and associated morbidity (eg, chronic lymphedema in the affected arm, extreme scarring, and postoperative pain).

ANSWER

The correct answer is hidradenitis suppurativa (HS; choice “c”).

DISCUSSION

HS (also known as acne inversa) is a relatively common condition first described in 1839 by French physician Frederick Velpeau, who thought it was probably a form of acne. Because HS only affects intertriginous areas (groin, axillae, inframammary, intergluteal, and abdominal folds rich in apocrine glands), during the next 130 years, it was presumed that this disease was solely caused by malfunctioning apocrine glands.

Though experts disagree about the true etiology of HS, most agree that it is caused by several environmental and genetic factors leading to plugged or malfunctioning hair follicles and apocrine glands that become inflamed, swollen, painful, and purulent. In severe cases, tracts develop between lesions, resulting in the formation of ropy, linear hypertrophic scarring. Early on and in milder cases, comedones can manifest—often in multiples—along with widely scattered cysts. It appears that a case can be made for a genetic predisposition to develop HS because at least one-third of affected patients report a positive family history.

Females (usually postpubescent) are affected at 3 times the rate of males. Hormones, especially androgens, appear to play a role. This assertion is bolstered not only by the age of onset, but also because HS has been observed to improve after pregnancy and after menopause.

Though not causative, smoking and obesity have a strong statistical correlation with HS as exacerbating factors. Many patients with HS find movement from exercise too painful, which may contribute to obesity.

Because HS has a wide range of clinical presentations, the Hurley Staging scale can help clinicians distinguish the condition’s severity by stages I, II, or III. Stage I manifests with scant signs of disease, including comedones and sparsely separated small cysts. Stage II includes numerous painful cysts with tract formation between lesions. Stage III involves symptoms described in the other stages as well as multiple large, painful, draining cysts; widespread erythema; and extensive hypertrophic scarring.

Regarding the differential, the culture would have identified community-acquired methicillin-resistant Staphylococcus aureus (choice “a”) or flesh-eating bacterial infection (choice “d”), but neither would be as chronic as the patient’s disease. Acne conglobata (choice “b”) manifests with chronic dense acne largely confined to the trunk. Interestingly, acne conglobata, HS, dissecting cellulitis of the scalp, and pilonidal cyst are collectively known as the follicular occlusion tetrad.

TREATMENT

Treatment for HS is limited. Adalimumab is the most recent and promising biologic, though its use comes at a high cost ($60,000/y) and with an adverse effect profile that should give any prescriber pause. Also, the best one could hope for in using adalimumab is about a 30% improvement in the patient.

Before using a biologic, other options should at least be considered. Though not entirely satisfactory, there are oral antibiotics (minocycline, trimethoprim/sulfa, or a combination of rifampin and clindamycin) or intralesional steroids. Incision and drainage of individual lesions and isotretinoin therapy can temporarily relieve pain, but they are not effective as long-term therapies. Large-scale surgical extirpation of the affected tissue can be considered in extreme cases, but there can be recurrences and associated morbidity (eg, chronic lymphedema in the affected arm, extreme scarring, and postoperative pain).

Amid all the chaos and problems caused by COVID-19, one might hope that physicians would get a break on their complicated payment-reporting programs.

But that’s not the case: The government recently released the 2021 proposed rule for the Quality Payment Program (QPP), often referred to by its most popular participation track, the Merit-Based Incentive Payment System (MIPS). The program, which launched in 2017, gets annual updates, and this year is no different.

Some good news has made primary care and some other physicians happy.

The government’s proposal includes significant changes to reimbursement for all physicians. Most important, the government is boosting rates for the office/outpatient evaluation and management (E/M) codes, combined with simplifying coding requirements.

Specialties that rely heavily on office-based E/M services are delighted at this change. Those include internists, family physicians, neurologists, pulmonologists, dermatologists, and all other specialties that rely heavily on office encounters.

According to the estimates from the Centers for Medicare & Medicaid Services (CMS), endocrinologists and rheumatologists are the big winners, at 17% and 16% projected increases, respectively. The government has been pushing to make this shift in reimbursement from surgeries and procedures to office visits for years. Although some physicians may celebrate the change, others will not.

The reimbursement plan for professional services depends on budget neutrality, meaning that the budget increases need to be counterbalanced by budget declines. Specialties that rely heavily on procedures and surgeries will suffer losses. These corresponding reductions felt by proceduralists and surgeons will counterbalance the good fortune of physicians who rely on office visits for the bulk of their revenue. Radiologists, for example, are projected by CMS to experience a 11% downturn, and cardiac surgeons face a 9% decline.

These consequences are significant. The 2021 shift may be the single biggest transfer of reimbursement in the history of the scale, which was adopted in the early 1990s.

If the change affected only Medicare reimbursement, perhaps it would be less significant. Because the majority of private payers use the government’s scale – the resource-based relative value scale – the impact will reverberate across physicians’ bottom lines. Given the state of many physicians’ finances, driven by the pandemic, this may send some affected physicians into a downward spiral.

The boost to E/M reimbursement – which represents approximately 20% of the overall Medicare payout to physicians each year – puts downward pressure on the professional services conversion factor as well.

For 2021, it is proposed to be $32.2605, representing a decrease of $3.83 from the 2020 conversion factor of $36.0896. The resultant conversion factor – which serves as a multiplier applied to the relative value unit to come up with the payment – effectively reduces payments to physicians across the board by 10.6%. Thus, even those who enjoy the benefits of the new E/M increases will see the potential reimbursement high point cut down.

Before launching into the changes in store for 2021, it’s good to determine whether you are an eligible clinician: You need to have more than $90,000 in Medicare Part B charges per year, see more than 200 Medicare Part B patients per year, and provide 200 or more covered professional services to Part B patients.

The program is voluntary, but there are steep penalties for eligible clinicians who don’t participate. For the 2021 reporting year, a 9% penalty will be imposed on Medicare reimbursement in 2023 in the event of participation failure. You can verify your participation status here; you’ll need your National Provider Identifier to run the search, but it takes only seconds to determine your eligibility.

A 9% penalty is a pretty big hit to your income. With 9% at stake, eligible clinicians need to actively engage in the program. Although there have been changes, the basic four-category system remains the same for the MIPS track, as follows: quality, cost, improvement activities, and promoting interoperability.

The four category weights, used to evaluate performance, are changing in 2021. Cost category weight goes up by 5 percentage points, to be 20% of the clinician’s score, and the quality category goes down by 5 percentage points to contribute 40% to the weight. Promoting interoperability remains 25% of the score, with improvement activities constituting the final 15%.

Other key changes include the following:

• The CMS’s Web interface for submission for quality measures will be shuttered in 2021. Users of this submission method will have to find and use another way to report their quality measures.
• Quality measures will be scored against pre-COVID benchmarks in lieu of comparisons with the 2020 reporting year; 206 quality measures are proposed for 2021, compared with the current list of 219.
• Telehealth will be incorporated in the cost category by updates to the measure specifications for the episode-based and total per capita cost measures.
• A new health information exchange measure is added to the promoting interoperability category, and “incorporating” replaces “reconciling” in the reporting requirement “Support Electronic Referral Loops by Receiving and Incorporating Health Information.”

To avoid the 9% penalty, eligible clinicians must earn 50 points in 2021, up from 45 in the current year. Achieving “exceptional performance” remains at 85 points. This elevated level of engagement allows access to a pot of money Congress set aside for high performers.

Many physicians feel that too much work is required to earn the “paltry” bonuses; even a perfect score of 100 has only resulted in bonuses of 1.88% and 1.68%, respectively, in the past 2 years. That includes the $500 million allocation that Congress set aside; this extra funding to reward exceptional performance is only available for the first 6 years of the law. Although the 2019 scores have been released to participants, CMS has not yet announced the overall national average, but it’s expected to be minimal.

The combination of meager payouts and a diminishing funding mechanism has physicians questioning participation altogether. My recent conversations with physicians who qualify for the program revealed their intention to participate, but only at a level to achieve the minimum threshold of 45 points this year and 50 in 2021. With so little upside, it’s impossible to make a business case to aim for the stars.

Perhaps the biggest change in 2021, however, is that the program is not making the previously planned switch to MIPS Value Pathways (MVPs). MVPs were designed to align the four performance categories around a specialty, medical condition, or patient population.

CMS introduced MVPs by giving an example of diabetes: “Endocrinologist reports same ‘foundation’ of PI [promoting interoperability] and population health measures as all other clinicians but now has a MIPS Value Pathway with measures and activities that focus on diabetes prevention and treatment.” CMS had expected MVPs to launch in 2021 for all program participants; because of the pandemic, CMS announced an extension for at least 1 year. This comes as a relief to physicians who are just trying to keep the lights on given the financial pressures brought on by the pandemic.

MVPs, however, will be incorporated into the MIPS Alternative Payment Model (APM) participation segment. This will affect many physicians because this is the path that accountable care organizations (ACOs) have taken. If you are part of an ACO and you report through it, you’ll see some more changes than your colleagues in 2021.

The good news is that ACOs that participate in MIPS and the Medicare Shared Savings Program will have to report only once to satisfy the requirements for both programs. The construct for this new APM-based program is called the “APM Performance Pathway.” This pathway incorporates six population health–based measures that cross-cut specialties.

CMS is also proposing that telemedicine reimbursement will become permanent. As of now, telemedicine services will only be paid when a public health emergency has been declared. This ability to reimburse physicians for telemedicine would end when the current public health emergency is over. CMS is proposing to extend reimbursement beyond the pandemic, which will benefit all physicians who perform these remote encounters.

The CMS proposal would also make some other requirements easier to achieve. The use of codes 99495 and 99496 – the transitional care management codes – is expanding by reducing several key accompanying-services restrictions. Before the public health emergency, there were constraints related to scope of practice; the proposal would extend the ability of advanced practice providers to order diagnostic tests, even after the public health emergency ends.

Furthermore, the proposal reduces restrictions related to billing for remote physiologic monitoring services and outlines the possibility of a new, higher-paying virtual visit code.

Although the Quality Payment Program will undergo some changes, they are minor. Be aware of the requirement to hit the 50-point mark to avoid the steep penalties, however. Perhaps greater benefit will be achieved through the government’s continued push to refine the reimbursement system. As a result of budget neutrality, however, these changes will boost some physicians while resulting in losses for others.

The government’s proposed changes are not final, and there is a period during which they are accepting comments on the proposal; the final rule will be announced in November.

If you want to wash your hands of this now, apply for the 2020 performance year hardship for the Quality Payment Program. The application is now open and available through December 31, 2020; completing it will release you of any program requirements in 2020 (and avoid that hefty 9% penalty on your 2022 reimbursement).

This way, you won’t have to concern yourself with any of these rules until next year; the government’s extension of this “get out of jail free” card is a welcome relief for physicians who are frustrated by the regulatory burdens despite the pressure exerted by COVID. Spending 15 minutes to complete this form is well worth your time and may eliminate much of your worry.
 

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

Amid all the chaos and problems caused by COVID-19, one might hope that physicians would get a break on their complicated payment-reporting programs.

But that’s not the case: The government recently released the 2021 proposed rule for the Quality Payment Program (QPP), often referred to by its most popular participation track, the Merit-Based Incentive Payment System (MIPS). The program, which launched in 2017, gets annual updates, and this year is no different.

Some good news has made primary care and some other physicians happy.

The government’s proposal includes significant changes to reimbursement for all physicians. Most important, the government is boosting rates for the office/outpatient evaluation and management (E/M) codes, combined with simplifying coding requirements.

Specialties that rely heavily on office-based E/M services are delighted at this change. Those include internists, family physicians, neurologists, pulmonologists, dermatologists, and all other specialties that rely heavily on office encounters.

According to the estimates from the Centers for Medicare & Medicaid Services (CMS), endocrinologists and rheumatologists are the big winners, at 17% and 16% projected increases, respectively. The government has been pushing to make this shift in reimbursement from surgeries and procedures to office visits for years. Although some physicians may celebrate the change, others will not.

The reimbursement plan for professional services depends on budget neutrality, meaning that the budget increases need to be counterbalanced by budget declines. Specialties that rely heavily on procedures and surgeries will suffer losses. These corresponding reductions felt by proceduralists and surgeons will counterbalance the good fortune of physicians who rely on office visits for the bulk of their revenue. Radiologists, for example, are projected by CMS to experience a 11% downturn, and cardiac surgeons face a 9% decline.

These consequences are significant. The 2021 shift may be the single biggest transfer of reimbursement in the history of the scale, which was adopted in the early 1990s.

If the change affected only Medicare reimbursement, perhaps it would be less significant. Because the majority of private payers use the government’s scale – the resource-based relative value scale – the impact will reverberate across physicians’ bottom lines. Given the state of many physicians’ finances, driven by the pandemic, this may send some affected physicians into a downward spiral.

The boost to E/M reimbursement – which represents approximately 20% of the overall Medicare payout to physicians each year – puts downward pressure on the professional services conversion factor as well.

For 2021, it is proposed to be $32.2605, representing a decrease of $3.83 from the 2020 conversion factor of $36.0896. The resultant conversion factor – which serves as a multiplier applied to the relative value unit to come up with the payment – effectively reduces payments to physicians across the board by 10.6%. Thus, even those who enjoy the benefits of the new E/M increases will see the potential reimbursement high point cut down.

Before launching into the changes in store for 2021, it’s good to determine whether you are an eligible clinician: You need to have more than $90,000 in Medicare Part B charges per year, see more than 200 Medicare Part B patients per year, and provide 200 or more covered professional services to Part B patients.

The program is voluntary, but there are steep penalties for eligible clinicians who don’t participate. For the 2021 reporting year, a 9% penalty will be imposed on Medicare reimbursement in 2023 in the event of participation failure. You can verify your participation status here; you’ll need your National Provider Identifier to run the search, but it takes only seconds to determine your eligibility.

A 9% penalty is a pretty big hit to your income. With 9% at stake, eligible clinicians need to actively engage in the program. Although there have been changes, the basic four-category system remains the same for the MIPS track, as follows: quality, cost, improvement activities, and promoting interoperability.

The four category weights, used to evaluate performance, are changing in 2021. Cost category weight goes up by 5 percentage points, to be 20% of the clinician’s score, and the quality category goes down by 5 percentage points to contribute 40% to the weight. Promoting interoperability remains 25% of the score, with improvement activities constituting the final 15%.

Other key changes include the following:

• The CMS’s Web interface for submission for quality measures will be shuttered in 2021. Users of this submission method will have to find and use another way to report their quality measures.
• Quality measures will be scored against pre-COVID benchmarks in lieu of comparisons with the 2020 reporting year; 206 quality measures are proposed for 2021, compared with the current list of 219.
• Telehealth will be incorporated in the cost category by updates to the measure specifications for the episode-based and total per capita cost measures.
• A new health information exchange measure is added to the promoting interoperability category, and “incorporating” replaces “reconciling” in the reporting requirement “Support Electronic Referral Loops by Receiving and Incorporating Health Information.”

To avoid the 9% penalty, eligible clinicians must earn 50 points in 2021, up from 45 in the current year. Achieving “exceptional performance” remains at 85 points. This elevated level of engagement allows access to a pot of money Congress set aside for high performers.

Many physicians feel that too much work is required to earn the “paltry” bonuses; even a perfect score of 100 has only resulted in bonuses of 1.88% and 1.68%, respectively, in the past 2 years. That includes the $500 million allocation that Congress set aside; this extra funding to reward exceptional performance is only available for the first 6 years of the law. Although the 2019 scores have been released to participants, CMS has not yet announced the overall national average, but it’s expected to be minimal.

The combination of meager payouts and a diminishing funding mechanism has physicians questioning participation altogether. My recent conversations with physicians who qualify for the program revealed their intention to participate, but only at a level to achieve the minimum threshold of 45 points this year and 50 in 2021. With so little upside, it’s impossible to make a business case to aim for the stars.

Perhaps the biggest change in 2021, however, is that the program is not making the previously planned switch to MIPS Value Pathways (MVPs). MVPs were designed to align the four performance categories around a specialty, medical condition, or patient population.

CMS introduced MVPs by giving an example of diabetes: “Endocrinologist reports same ‘foundation’ of PI [promoting interoperability] and population health measures as all other clinicians but now has a MIPS Value Pathway with measures and activities that focus on diabetes prevention and treatment.” CMS had expected MVPs to launch in 2021 for all program participants; because of the pandemic, CMS announced an extension for at least 1 year. This comes as a relief to physicians who are just trying to keep the lights on given the financial pressures brought on by the pandemic.

MVPs, however, will be incorporated into the MIPS Alternative Payment Model (APM) participation segment. This will affect many physicians because this is the path that accountable care organizations (ACOs) have taken. If you are part of an ACO and you report through it, you’ll see some more changes than your colleagues in 2021.

The good news is that ACOs that participate in MIPS and the Medicare Shared Savings Program will have to report only once to satisfy the requirements for both programs. The construct for this new APM-based program is called the “APM Performance Pathway.” This pathway incorporates six population health–based measures that cross-cut specialties.

CMS is also proposing that telemedicine reimbursement will become permanent. As of now, telemedicine services will only be paid when a public health emergency has been declared. This ability to reimburse physicians for telemedicine would end when the current public health emergency is over. CMS is proposing to extend reimbursement beyond the pandemic, which will benefit all physicians who perform these remote encounters.

The CMS proposal would also make some other requirements easier to achieve. The use of codes 99495 and 99496 – the transitional care management codes – is expanding by reducing several key accompanying-services restrictions. Before the public health emergency, there were constraints related to scope of practice; the proposal would extend the ability of advanced practice providers to order diagnostic tests, even after the public health emergency ends.

Furthermore, the proposal reduces restrictions related to billing for remote physiologic monitoring services and outlines the possibility of a new, higher-paying virtual visit code.

Although the Quality Payment Program will undergo some changes, they are minor. Be aware of the requirement to hit the 50-point mark to avoid the steep penalties, however. Perhaps greater benefit will be achieved through the government’s continued push to refine the reimbursement system. As a result of budget neutrality, however, these changes will boost some physicians while resulting in losses for others.

The government’s proposed changes are not final, and there is a period during which they are accepting comments on the proposal; the final rule will be announced in November.

If you want to wash your hands of this now, apply for the 2020 performance year hardship for the Quality Payment Program. The application is now open and available through December 31, 2020; completing it will release you of any program requirements in 2020 (and avoid that hefty 9% penalty on your 2022 reimbursement).

This way, you won’t have to concern yourself with any of these rules until next year; the government’s extension of this “get out of jail free” card is a welcome relief for physicians who are frustrated by the regulatory burdens despite the pressure exerted by COVID. Spending 15 minutes to complete this form is well worth your time and may eliminate much of your worry.
 

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

Amid all the chaos and problems caused by COVID-19, one might hope that physicians would get a break on their complicated payment-reporting programs.

But that’s not the case: The government recently released the 2021 proposed rule for the Quality Payment Program (QPP), often referred to by its most popular participation track, the Merit-Based Incentive Payment System (MIPS). The program, which launched in 2017, gets annual updates, and this year is no different.

Some good news has made primary care and some other physicians happy.

The government’s proposal includes significant changes to reimbursement for all physicians. Most important, the government is boosting rates for the office/outpatient evaluation and management (E/M) codes, combined with simplifying coding requirements.

Specialties that rely heavily on office-based E/M services are delighted at this change. Those include internists, family physicians, neurologists, pulmonologists, dermatologists, and all other specialties that rely heavily on office encounters.

According to the estimates from the Centers for Medicare & Medicaid Services (CMS), endocrinologists and rheumatologists are the big winners, at 17% and 16% projected increases, respectively. The government has been pushing to make this shift in reimbursement from surgeries and procedures to office visits for years. Although some physicians may celebrate the change, others will not.

The reimbursement plan for professional services depends on budget neutrality, meaning that the budget increases need to be counterbalanced by budget declines. Specialties that rely heavily on procedures and surgeries will suffer losses. These corresponding reductions felt by proceduralists and surgeons will counterbalance the good fortune of physicians who rely on office visits for the bulk of their revenue. Radiologists, for example, are projected by CMS to experience a 11% downturn, and cardiac surgeons face a 9% decline.

These consequences are significant. The 2021 shift may be the single biggest transfer of reimbursement in the history of the scale, which was adopted in the early 1990s.

If the change affected only Medicare reimbursement, perhaps it would be less significant. Because the majority of private payers use the government’s scale – the resource-based relative value scale – the impact will reverberate across physicians’ bottom lines. Given the state of many physicians’ finances, driven by the pandemic, this may send some affected physicians into a downward spiral.

The boost to E/M reimbursement – which represents approximately 20% of the overall Medicare payout to physicians each year – puts downward pressure on the professional services conversion factor as well.

For 2021, it is proposed to be $32.2605, representing a decrease of $3.83 from the 2020 conversion factor of $36.0896. The resultant conversion factor – which serves as a multiplier applied to the relative value unit to come up with the payment – effectively reduces payments to physicians across the board by 10.6%. Thus, even those who enjoy the benefits of the new E/M increases will see the potential reimbursement high point cut down.

Before launching into the changes in store for 2021, it’s good to determine whether you are an eligible clinician: You need to have more than $90,000 in Medicare Part B charges per year, see more than 200 Medicare Part B patients per year, and provide 200 or more covered professional services to Part B patients.

The program is voluntary, but there are steep penalties for eligible clinicians who don’t participate. For the 2021 reporting year, a 9% penalty will be imposed on Medicare reimbursement in 2023 in the event of participation failure. You can verify your participation status here; you’ll need your National Provider Identifier to run the search, but it takes only seconds to determine your eligibility.

A 9% penalty is a pretty big hit to your income. With 9% at stake, eligible clinicians need to actively engage in the program. Although there have been changes, the basic four-category system remains the same for the MIPS track, as follows: quality, cost, improvement activities, and promoting interoperability.

The four category weights, used to evaluate performance, are changing in 2021. Cost category weight goes up by 5 percentage points, to be 20% of the clinician’s score, and the quality category goes down by 5 percentage points to contribute 40% to the weight. Promoting interoperability remains 25% of the score, with improvement activities constituting the final 15%.

Other key changes include the following:

• The CMS’s Web interface for submission for quality measures will be shuttered in 2021. Users of this submission method will have to find and use another way to report their quality measures.
• Quality measures will be scored against pre-COVID benchmarks in lieu of comparisons with the 2020 reporting year; 206 quality measures are proposed for 2021, compared with the current list of 219.
• Telehealth will be incorporated in the cost category by updates to the measure specifications for the episode-based and total per capita cost measures.
• A new health information exchange measure is added to the promoting interoperability category, and “incorporating” replaces “reconciling” in the reporting requirement “Support Electronic Referral Loops by Receiving and Incorporating Health Information.”

To avoid the 9% penalty, eligible clinicians must earn 50 points in 2021, up from 45 in the current year. Achieving “exceptional performance” remains at 85 points. This elevated level of engagement allows access to a pot of money Congress set aside for high performers.

Many physicians feel that too much work is required to earn the “paltry” bonuses; even a perfect score of 100 has only resulted in bonuses of 1.88% and 1.68%, respectively, in the past 2 years. That includes the $500 million allocation that Congress set aside; this extra funding to reward exceptional performance is only available for the first 6 years of the law. Although the 2019 scores have been released to participants, CMS has not yet announced the overall national average, but it’s expected to be minimal.

The combination of meager payouts and a diminishing funding mechanism has physicians questioning participation altogether. My recent conversations with physicians who qualify for the program revealed their intention to participate, but only at a level to achieve the minimum threshold of 45 points this year and 50 in 2021. With so little upside, it’s impossible to make a business case to aim for the stars.

Perhaps the biggest change in 2021, however, is that the program is not making the previously planned switch to MIPS Value Pathways (MVPs). MVPs were designed to align the four performance categories around a specialty, medical condition, or patient population.

CMS introduced MVPs by giving an example of diabetes: “Endocrinologist reports same ‘foundation’ of PI [promoting interoperability] and population health measures as all other clinicians but now has a MIPS Value Pathway with measures and activities that focus on diabetes prevention and treatment.” CMS had expected MVPs to launch in 2021 for all program participants; because of the pandemic, CMS announced an extension for at least 1 year. This comes as a relief to physicians who are just trying to keep the lights on given the financial pressures brought on by the pandemic.

MVPs, however, will be incorporated into the MIPS Alternative Payment Model (APM) participation segment. This will affect many physicians because this is the path that accountable care organizations (ACOs) have taken. If you are part of an ACO and you report through it, you’ll see some more changes than your colleagues in 2021.

The good news is that ACOs that participate in MIPS and the Medicare Shared Savings Program will have to report only once to satisfy the requirements for both programs. The construct for this new APM-based program is called the “APM Performance Pathway.” This pathway incorporates six population health–based measures that cross-cut specialties.

CMS is also proposing that telemedicine reimbursement will become permanent. As of now, telemedicine services will only be paid when a public health emergency has been declared. This ability to reimburse physicians for telemedicine would end when the current public health emergency is over. CMS is proposing to extend reimbursement beyond the pandemic, which will benefit all physicians who perform these remote encounters.

The CMS proposal would also make some other requirements easier to achieve. The use of codes 99495 and 99496 – the transitional care management codes – is expanding by reducing several key accompanying-services restrictions. Before the public health emergency, there were constraints related to scope of practice; the proposal would extend the ability of advanced practice providers to order diagnostic tests, even after the public health emergency ends.

Furthermore, the proposal reduces restrictions related to billing for remote physiologic monitoring services and outlines the possibility of a new, higher-paying virtual visit code.

Although the Quality Payment Program will undergo some changes, they are minor. Be aware of the requirement to hit the 50-point mark to avoid the steep penalties, however. Perhaps greater benefit will be achieved through the government’s continued push to refine the reimbursement system. As a result of budget neutrality, however, these changes will boost some physicians while resulting in losses for others.

The government’s proposed changes are not final, and there is a period during which they are accepting comments on the proposal; the final rule will be announced in November.

If you want to wash your hands of this now, apply for the 2020 performance year hardship for the Quality Payment Program. The application is now open and available through December 31, 2020; completing it will release you of any program requirements in 2020 (and avoid that hefty 9% penalty on your 2022 reimbursement).

This way, you won’t have to concern yourself with any of these rules until next year; the government’s extension of this “get out of jail free” card is a welcome relief for physicians who are frustrated by the regulatory burdens despite the pressure exerted by COVID. Spending 15 minutes to complete this form is well worth your time and may eliminate much of your worry.
 

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

In patients with completely resected non–small cell lung cancer and proven N2 disease, postoperative radiotherapy (PORT) provided no significant improvement in disease-free survival (DFS) at 3 years, according to a phase 3 trial.

Investigator Cécile Le Péchoux, MD, a radiation oncologist from Institut Gustave Roussy in Paris, presented the results of the Lung ART trial at the European Society for Medical Oncology Virtual Congress 2020.

The results resolve what ESMO commentator Rafal Dziadziuszko, MD, PhD, of Medical University of Gdansk (Poland), called “perhaps the longest ongoing debate in thoracic oncology,” on whether or not to irradiate patients with mediastinal lymph node involvement after surgery.

Dr. Dziadziuszko noted that some past studies have suggested PORT may provide improved local control and a survival benefit, but other studies have shown no survival benefit and evidence of harm with PORT.

“So here is an academic study with the answer,” Dr. Dziadziuszko said.
 

Study details

The intention-to-treat population of Lung ART included 252 patients randomized to receive 5.5 weeks of PORT (54 Gy) and 249 patients randomized to the control arm without PORT.

The patients’ median age was 61 years, 66% were men, and adenocarcinoma was the predominant histology (76% of patients in the control arm and 70% in the PORT arm). All patients had received adjuvant or neoadjuvant chemotherapy.

The median follow-up was 4.8 years. The 3-year DFS rate was 47.1% in the PORT arm and 43.8% in the control arm (hazard ratio, 0.85; 95% confidence interval, 0.67-1.07, P = .16). The median DFS was 30.5 months with PORT and 22.8 months in the control group. As for DFS components, the rate for death as a first event was 14.6% in the PORT arm and 5.3% among controls.

The mediastinal relapse rate was higher among controls, at 46.1% versus 25.0% with PORT.

The 3-year overall survival rate was 66.5% among patients in the PORT arm and 68.5% in the control arm.

At least one grade 3-4 toxicity was reported in 23.7% of the PORT group and in 15.0% of controls. The grade 3-4 cardiopulmonary toxicity rate of 10.8% in the PORT arm and 4.9% in the control arm needs to be further explored, Dr. Le Péchoux said.
 

Applying the results to practice

In response to a question as to which patients might benefit from PORT, Dr. Le Péchoux pointed out that, among patients who have nodes in the inferior part of the mediastinum closer to the heart, PORT might be more toxic.

“For the moment, we did not see anything that would give us a clue,” Dr. Le Péchoux said. “We have a lot to investigate.”

Further analyses looking at patterns of failure, predictive factors of efficacy and toxicity, quality of radiotherapy, and quality of surgery are planned, she added.

Dr. Le Péchoux concluded: “Conformal PORT cannot be recommended as standard of care in all completely resected stage IIIAN2 [non–small cell lung cancer] patients.”

Dr. Dziadziuszko commented further: “For my practice, this is a clear message that routine PORT should not be used in these patients. We are looking for more effective systemic therapies.”

He added that “over 50% 5-year survival in these patients is a great result, and is made possible by modern staging and modern surgery.”

The Lung ART study was sponsored by Gustave Roussy and supported by the French National Cancer Institute, French Health Ministry, and a Cancer Research UK grant. Dr. Le Péchoux and Dr. Dziadziuszko reported no conflicts of interest related to the presentation.

SOURCE: Le Péchoux C et al. ESMO 2020, Abstract LBA3_PR.

In patients with completely resected non–small cell lung cancer and proven N2 disease, postoperative radiotherapy (PORT) provided no significant improvement in disease-free survival (DFS) at 3 years, according to a phase 3 trial.

Investigator Cécile Le Péchoux, MD, a radiation oncologist from Institut Gustave Roussy in Paris, presented the results of the Lung ART trial at the European Society for Medical Oncology Virtual Congress 2020.

The results resolve what ESMO commentator Rafal Dziadziuszko, MD, PhD, of Medical University of Gdansk (Poland), called “perhaps the longest ongoing debate in thoracic oncology,” on whether or not to irradiate patients with mediastinal lymph node involvement after surgery.

Dr. Dziadziuszko noted that some past studies have suggested PORT may provide improved local control and a survival benefit, but other studies have shown no survival benefit and evidence of harm with PORT.

“So here is an academic study with the answer,” Dr. Dziadziuszko said.
 

Study details

The intention-to-treat population of Lung ART included 252 patients randomized to receive 5.5 weeks of PORT (54 Gy) and 249 patients randomized to the control arm without PORT.

The patients’ median age was 61 years, 66% were men, and adenocarcinoma was the predominant histology (76% of patients in the control arm and 70% in the PORT arm). All patients had received adjuvant or neoadjuvant chemotherapy.

The median follow-up was 4.8 years. The 3-year DFS rate was 47.1% in the PORT arm and 43.8% in the control arm (hazard ratio, 0.85; 95% confidence interval, 0.67-1.07, P = .16). The median DFS was 30.5 months with PORT and 22.8 months in the control group. As for DFS components, the rate for death as a first event was 14.6% in the PORT arm and 5.3% among controls.

The mediastinal relapse rate was higher among controls, at 46.1% versus 25.0% with PORT.

The 3-year overall survival rate was 66.5% among patients in the PORT arm and 68.5% in the control arm.

At least one grade 3-4 toxicity was reported in 23.7% of the PORT group and in 15.0% of controls. The grade 3-4 cardiopulmonary toxicity rate of 10.8% in the PORT arm and 4.9% in the control arm needs to be further explored, Dr. Le Péchoux said.
 

Applying the results to practice

In response to a question as to which patients might benefit from PORT, Dr. Le Péchoux pointed out that, among patients who have nodes in the inferior part of the mediastinum closer to the heart, PORT might be more toxic.

“For the moment, we did not see anything that would give us a clue,” Dr. Le Péchoux said. “We have a lot to investigate.”

Further analyses looking at patterns of failure, predictive factors of efficacy and toxicity, quality of radiotherapy, and quality of surgery are planned, she added.

Dr. Le Péchoux concluded: “Conformal PORT cannot be recommended as standard of care in all completely resected stage IIIAN2 [non–small cell lung cancer] patients.”

Dr. Dziadziuszko commented further: “For my practice, this is a clear message that routine PORT should not be used in these patients. We are looking for more effective systemic therapies.”

He added that “over 50% 5-year survival in these patients is a great result, and is made possible by modern staging and modern surgery.”

The Lung ART study was sponsored by Gustave Roussy and supported by the French National Cancer Institute, French Health Ministry, and a Cancer Research UK grant. Dr. Le Péchoux and Dr. Dziadziuszko reported no conflicts of interest related to the presentation.

SOURCE: Le Péchoux C et al. ESMO 2020, Abstract LBA3_PR.

In patients with completely resected non–small cell lung cancer and proven N2 disease, postoperative radiotherapy (PORT) provided no significant improvement in disease-free survival (DFS) at 3 years, according to a phase 3 trial.

Investigator Cécile Le Péchoux, MD, a radiation oncologist from Institut Gustave Roussy in Paris, presented the results of the Lung ART trial at the European Society for Medical Oncology Virtual Congress 2020.

The results resolve what ESMO commentator Rafal Dziadziuszko, MD, PhD, of Medical University of Gdansk (Poland), called “perhaps the longest ongoing debate in thoracic oncology,” on whether or not to irradiate patients with mediastinal lymph node involvement after surgery.

Dr. Dziadziuszko noted that some past studies have suggested PORT may provide improved local control and a survival benefit, but other studies have shown no survival benefit and evidence of harm with PORT.

“So here is an academic study with the answer,” Dr. Dziadziuszko said.
 

Study details

The intention-to-treat population of Lung ART included 252 patients randomized to receive 5.5 weeks of PORT (54 Gy) and 249 patients randomized to the control arm without PORT.

The patients’ median age was 61 years, 66% were men, and adenocarcinoma was the predominant histology (76% of patients in the control arm and 70% in the PORT arm). All patients had received adjuvant or neoadjuvant chemotherapy.

The median follow-up was 4.8 years. The 3-year DFS rate was 47.1% in the PORT arm and 43.8% in the control arm (hazard ratio, 0.85; 95% confidence interval, 0.67-1.07, P = .16). The median DFS was 30.5 months with PORT and 22.8 months in the control group. As for DFS components, the rate for death as a first event was 14.6% in the PORT arm and 5.3% among controls.

The mediastinal relapse rate was higher among controls, at 46.1% versus 25.0% with PORT.

The 3-year overall survival rate was 66.5% among patients in the PORT arm and 68.5% in the control arm.

At least one grade 3-4 toxicity was reported in 23.7% of the PORT group and in 15.0% of controls. The grade 3-4 cardiopulmonary toxicity rate of 10.8% in the PORT arm and 4.9% in the control arm needs to be further explored, Dr. Le Péchoux said.
 

Applying the results to practice

In response to a question as to which patients might benefit from PORT, Dr. Le Péchoux pointed out that, among patients who have nodes in the inferior part of the mediastinum closer to the heart, PORT might be more toxic.

“For the moment, we did not see anything that would give us a clue,” Dr. Le Péchoux said. “We have a lot to investigate.”

Further analyses looking at patterns of failure, predictive factors of efficacy and toxicity, quality of radiotherapy, and quality of surgery are planned, she added.

Dr. Le Péchoux concluded: “Conformal PORT cannot be recommended as standard of care in all completely resected stage IIIAN2 [non–small cell lung cancer] patients.”

Dr. Dziadziuszko commented further: “For my practice, this is a clear message that routine PORT should not be used in these patients. We are looking for more effective systemic therapies.”

He added that “over 50% 5-year survival in these patients is a great result, and is made possible by modern staging and modern surgery.”

The Lung ART study was sponsored by Gustave Roussy and supported by the French National Cancer Institute, French Health Ministry, and a Cancer Research UK grant. Dr. Le Péchoux and Dr. Dziadziuszko reported no conflicts of interest related to the presentation.

SOURCE: Le Péchoux C et al. ESMO 2020, Abstract LBA3_PR.

An international survey provides new insights into how COVID-19 has affected, and may continue to affect, the field of oncology.

The survey showed that “COVID-19 has had a major impact on the organization of patient care, on the well-being of caregivers, on continued medical education, and on clinical trial activities in oncology,” stated Guy Jerusalem, MD, PhD, of Centre Hospitalier Universitaire de Liège (Belgium).

Dr. Jerusalem presented these findings at the European Society for Medical Oncology Virtual Congress 2020.

The survey was distributed by 20 oncologists from 10 of the countries most affected by COVID-19. Responses were obtained from 109 oncologists representing centers in 18 countries. The responses were recorded between June 17 and July 14, 2020.

The survey consisted of 95 items intended to evaluate the impact of COVID-19 on the organization of oncologic care. Questions encompassed the capacity and service offered at each center, the magnitude of COVID-19–based care interruptions and the reasons for them, the ensuing challenges faced, interventions implemented, and the estimated harms to patients during the pandemic.

The 109 oncologists surveyed had a median of 20 years of oncology experience. A majority of respondents were men (61.5%), and the median age was 48.5 years.

The respondents had worked predominantly (62.4%) at academic hospitals, with 29.6% at community hospitals. Most respondents worked at general hospitals with an oncology unit (66.1%) rather than a specialized separate cancer center (32.1%).

The most common specialty was breast cancer (60.6%), followed by gastrointestinal cancer (10.1%), urogenital cancer (9.2%), and lung cancer (8.3%).
 

Impact on treatment

The treatment modalities affected by the pandemic – through cancellations or delays in more than 10% of patients – included surgery (in 34% of centers), chemotherapy (22%), radiotherapy (13.7%), checkpoint inhibitor therapy (9.1%), monoclonal antibodies (9%), and oral targeted therapy (3.7%).

Among oncologists treating breast cancer, cancellations/delays in more than 10% of patients were reported for everolimus (18%), CDK4/6 inhibitors (8.9%), and endocrine therapy (2.2%).

Overall, 34.8% of respondents reported increased use of granulocyte colony–stimulating factor, and 6.4% reported increased use of erythropoietin.

On the other hand, 11.1% of respondents reported a decrease in the use of double immunotherapy, and 21.9% reported decreased use of corticosteroids.

Not only can the immunosuppressive effects of steroid use increase infection risks, Dr. Jerusalem noted, fever suppression can lead to a delayed diagnosis of COVID-19.

“To circumvent potential higher infection risks or greater disease severity, we use lower doses of steroids, but this is not based on studies,” he said.

“Previous exposure to steroids or being on steroids at the time of COVID-19 infection is a detrimental factor for complications and mortality,” commented ESMO President Solange Peters, MD, PhD, of Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.

Frontline Medical News

Dr. Peters noted that the observation was based on lung cancer registry findings. Furthermore, because data from smaller outbreaks of other coronavirus infections suggested worse prognosis and increased mortality, steroid use was already feared in the very early days of the COVID-19 pandemic.

Lastly, earlier cessation of palliative treatment was observed in 32.1% of centers, and 64.2% of respondents agreed that undertreatment because of COVID-19 is a major concern.

Dr. Jerusalem noted that the survey data do not explain the early cessation of palliative treatment. “I suspect that many patients died at home rather than alone in institutions because it was the only way they could die with their families around them.”
 

Telehealth, meetings, and trials

The survey also revealed rationales for the use of teleconsultation, including follow-up (94.5%), oral therapy (92.7%), immunotherapy (57.8%), and chemotherapy (55%).

Most respondents reported more frequent use of virtual meetings for continuing medical education (94%), oncologic team meetings (92%), and tumor boards (82%).

While about 82% of respondents said they were likely to continue the use of telemedicine, 45% said virtual conferences are not an acceptable alternative to live international conferences such as ESMO, Dr. Jerusalem said.

Finally, nearly three-quarters of respondents (72.5%) said all clinical trial activities are or will soon be activated, or never stopped, at their centers. On the other hand, 27.5% of respondents reported that their centers had major protocol violations or deviations, and 37% of respondents said they expect significant reductions in clinical trial activities this year.

Dr. Jerusalem concluded that COVID-19 is having a major, long-term impact on the organization of patient care, caregivers, continued medical education, and clinical trial activities in oncology.

He cautioned that “the risk of a delayed diagnosis of new cancers and economic consequences of COVID-19 on access to health care and cancer treatments have to be carefully evaluated.”

This research was funded by Fondation Léon Fredericq. Dr. Jerusalem disclosed relationships with Novartis, Roche, Lilly, Pfizer, Amgen, Bristol-Myers Squibb, AstraZeneca, Daiichi Sankyo, AbbVie, MedImmune, and Merck. Dr. Peters disclosed relationships with AbbVie, Amgen, AstraZeneca, and many other companies.

SOURCE: Jerusalem G et al. ESMO 2020, Abstract LBA76.

An international survey provides new insights into how COVID-19 has affected, and may continue to affect, the field of oncology.

The survey showed that “COVID-19 has had a major impact on the organization of patient care, on the well-being of caregivers, on continued medical education, and on clinical trial activities in oncology,” stated Guy Jerusalem, MD, PhD, of Centre Hospitalier Universitaire de Liège (Belgium).

Dr. Jerusalem presented these findings at the European Society for Medical Oncology Virtual Congress 2020.

The survey was distributed by 20 oncologists from 10 of the countries most affected by COVID-19. Responses were obtained from 109 oncologists representing centers in 18 countries. The responses were recorded between June 17 and July 14, 2020.

The survey consisted of 95 items intended to evaluate the impact of COVID-19 on the organization of oncologic care. Questions encompassed the capacity and service offered at each center, the magnitude of COVID-19–based care interruptions and the reasons for them, the ensuing challenges faced, interventions implemented, and the estimated harms to patients during the pandemic.

The 109 oncologists surveyed had a median of 20 years of oncology experience. A majority of respondents were men (61.5%), and the median age was 48.5 years.

The respondents had worked predominantly (62.4%) at academic hospitals, with 29.6% at community hospitals. Most respondents worked at general hospitals with an oncology unit (66.1%) rather than a specialized separate cancer center (32.1%).

The most common specialty was breast cancer (60.6%), followed by gastrointestinal cancer (10.1%), urogenital cancer (9.2%), and lung cancer (8.3%).
 

Impact on treatment

The treatment modalities affected by the pandemic – through cancellations or delays in more than 10% of patients – included surgery (in 34% of centers), chemotherapy (22%), radiotherapy (13.7%), checkpoint inhibitor therapy (9.1%), monoclonal antibodies (9%), and oral targeted therapy (3.7%).

Among oncologists treating breast cancer, cancellations/delays in more than 10% of patients were reported for everolimus (18%), CDK4/6 inhibitors (8.9%), and endocrine therapy (2.2%).

Overall, 34.8% of respondents reported increased use of granulocyte colony–stimulating factor, and 6.4% reported increased use of erythropoietin.

On the other hand, 11.1% of respondents reported a decrease in the use of double immunotherapy, and 21.9% reported decreased use of corticosteroids.

Not only can the immunosuppressive effects of steroid use increase infection risks, Dr. Jerusalem noted, fever suppression can lead to a delayed diagnosis of COVID-19.

“To circumvent potential higher infection risks or greater disease severity, we use lower doses of steroids, but this is not based on studies,” he said.

“Previous exposure to steroids or being on steroids at the time of COVID-19 infection is a detrimental factor for complications and mortality,” commented ESMO President Solange Peters, MD, PhD, of Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.

Frontline Medical News

Dr. Peters noted that the observation was based on lung cancer registry findings. Furthermore, because data from smaller outbreaks of other coronavirus infections suggested worse prognosis and increased mortality, steroid use was already feared in the very early days of the COVID-19 pandemic.

Lastly, earlier cessation of palliative treatment was observed in 32.1% of centers, and 64.2% of respondents agreed that undertreatment because of COVID-19 is a major concern.

Dr. Jerusalem noted that the survey data do not explain the early cessation of palliative treatment. “I suspect that many patients died at home rather than alone in institutions because it was the only way they could die with their families around them.”
 

Telehealth, meetings, and trials

The survey also revealed rationales for the use of teleconsultation, including follow-up (94.5%), oral therapy (92.7%), immunotherapy (57.8%), and chemotherapy (55%).

Most respondents reported more frequent use of virtual meetings for continuing medical education (94%), oncologic team meetings (92%), and tumor boards (82%).

While about 82% of respondents said they were likely to continue the use of telemedicine, 45% said virtual conferences are not an acceptable alternative to live international conferences such as ESMO, Dr. Jerusalem said.

Finally, nearly three-quarters of respondents (72.5%) said all clinical trial activities are or will soon be activated, or never stopped, at their centers. On the other hand, 27.5% of respondents reported that their centers had major protocol violations or deviations, and 37% of respondents said they expect significant reductions in clinical trial activities this year.

Dr. Jerusalem concluded that COVID-19 is having a major, long-term impact on the organization of patient care, caregivers, continued medical education, and clinical trial activities in oncology.

He cautioned that “the risk of a delayed diagnosis of new cancers and economic consequences of COVID-19 on access to health care and cancer treatments have to be carefully evaluated.”

This research was funded by Fondation Léon Fredericq. Dr. Jerusalem disclosed relationships with Novartis, Roche, Lilly, Pfizer, Amgen, Bristol-Myers Squibb, AstraZeneca, Daiichi Sankyo, AbbVie, MedImmune, and Merck. Dr. Peters disclosed relationships with AbbVie, Amgen, AstraZeneca, and many other companies.

SOURCE: Jerusalem G et al. ESMO 2020, Abstract LBA76.

An international survey provides new insights into how COVID-19 has affected, and may continue to affect, the field of oncology.

The survey showed that “COVID-19 has had a major impact on the organization of patient care, on the well-being of caregivers, on continued medical education, and on clinical trial activities in oncology,” stated Guy Jerusalem, MD, PhD, of Centre Hospitalier Universitaire de Liège (Belgium).

Dr. Jerusalem presented these findings at the European Society for Medical Oncology Virtual Congress 2020.

The survey was distributed by 20 oncologists from 10 of the countries most affected by COVID-19. Responses were obtained from 109 oncologists representing centers in 18 countries. The responses were recorded between June 17 and July 14, 2020.

The survey consisted of 95 items intended to evaluate the impact of COVID-19 on the organization of oncologic care. Questions encompassed the capacity and service offered at each center, the magnitude of COVID-19–based care interruptions and the reasons for them, the ensuing challenges faced, interventions implemented, and the estimated harms to patients during the pandemic.

The 109 oncologists surveyed had a median of 20 years of oncology experience. A majority of respondents were men (61.5%), and the median age was 48.5 years.

The respondents had worked predominantly (62.4%) at academic hospitals, with 29.6% at community hospitals. Most respondents worked at general hospitals with an oncology unit (66.1%) rather than a specialized separate cancer center (32.1%).

The most common specialty was breast cancer (60.6%), followed by gastrointestinal cancer (10.1%), urogenital cancer (9.2%), and lung cancer (8.3%).
 

Impact on treatment

The treatment modalities affected by the pandemic – through cancellations or delays in more than 10% of patients – included surgery (in 34% of centers), chemotherapy (22%), radiotherapy (13.7%), checkpoint inhibitor therapy (9.1%), monoclonal antibodies (9%), and oral targeted therapy (3.7%).

Among oncologists treating breast cancer, cancellations/delays in more than 10% of patients were reported for everolimus (18%), CDK4/6 inhibitors (8.9%), and endocrine therapy (2.2%).

Overall, 34.8% of respondents reported increased use of granulocyte colony–stimulating factor, and 6.4% reported increased use of erythropoietin.

On the other hand, 11.1% of respondents reported a decrease in the use of double immunotherapy, and 21.9% reported decreased use of corticosteroids.

Not only can the immunosuppressive effects of steroid use increase infection risks, Dr. Jerusalem noted, fever suppression can lead to a delayed diagnosis of COVID-19.

“To circumvent potential higher infection risks or greater disease severity, we use lower doses of steroids, but this is not based on studies,” he said.

“Previous exposure to steroids or being on steroids at the time of COVID-19 infection is a detrimental factor for complications and mortality,” commented ESMO President Solange Peters, MD, PhD, of Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.

Frontline Medical News

Dr. Peters noted that the observation was based on lung cancer registry findings. Furthermore, because data from smaller outbreaks of other coronavirus infections suggested worse prognosis and increased mortality, steroid use was already feared in the very early days of the COVID-19 pandemic.

Lastly, earlier cessation of palliative treatment was observed in 32.1% of centers, and 64.2% of respondents agreed that undertreatment because of COVID-19 is a major concern.

Dr. Jerusalem noted that the survey data do not explain the early cessation of palliative treatment. “I suspect that many patients died at home rather than alone in institutions because it was the only way they could die with their families around them.”
 

Telehealth, meetings, and trials

The survey also revealed rationales for the use of teleconsultation, including follow-up (94.5%), oral therapy (92.7%), immunotherapy (57.8%), and chemotherapy (55%).

Most respondents reported more frequent use of virtual meetings for continuing medical education (94%), oncologic team meetings (92%), and tumor boards (82%).

While about 82% of respondents said they were likely to continue the use of telemedicine, 45% said virtual conferences are not an acceptable alternative to live international conferences such as ESMO, Dr. Jerusalem said.

Finally, nearly three-quarters of respondents (72.5%) said all clinical trial activities are or will soon be activated, or never stopped, at their centers. On the other hand, 27.5% of respondents reported that their centers had major protocol violations or deviations, and 37% of respondents said they expect significant reductions in clinical trial activities this year.

Dr. Jerusalem concluded that COVID-19 is having a major, long-term impact on the organization of patient care, caregivers, continued medical education, and clinical trial activities in oncology.

He cautioned that “the risk of a delayed diagnosis of new cancers and economic consequences of COVID-19 on access to health care and cancer treatments have to be carefully evaluated.”

This research was funded by Fondation Léon Fredericq. Dr. Jerusalem disclosed relationships with Novartis, Roche, Lilly, Pfizer, Amgen, Bristol-Myers Squibb, AstraZeneca, Daiichi Sankyo, AbbVie, MedImmune, and Merck. Dr. Peters disclosed relationships with AbbVie, Amgen, AstraZeneca, and many other companies.

SOURCE: Jerusalem G et al. ESMO 2020, Abstract LBA76.

Adding metformin to standard care for advanced prostate cancer appeared to lengthen time to castration-resistant disease in a small, randomized trial.

“According to our data, metformin potentially prolongs the time to progression … when combined with androgen deprivation therapy,” said investigator Reham ALGhandour, MD, PhD, an assistant lecturer of medical oncology at Mansoura (Egypt) University.

Dr. ALGhandour presented the data at the European Society for Medical Oncology Virtual Congress 2020.

Prior observational studies have indicated that metformin may benefit patients with prostate cancer. A meta-analysis of cohort studies suggested metformin can significantly improve overall, cancer-specific, and recurrence-free survival in prostate cancer patients.

To explore this further, Dr. ALGhandour and colleagues conducted a randomized trial. They enrolled 124 men with high-risk locally advanced or metastatic hormone-sensitive prostate cancer.

The investigators randomized 62 patients to testosterone suppression with or without antiandrogen, and 62 others to a standard regimen plus metformin at 850 mg twice daily.

All patients had an Easter Cooperative Oncology Group performance score of 0-2, were set to receive androgen deprivation therapy long term, and had no prior metformin use. Docetaxel was permitted for metastatic patients, and external beam radiation therapy was used for localized and regional disease.
 

Results: ‘Dramatic’ but not ‘definitive’

At a median follow-up of 18 months, there was a significant difference in time to castration-resistant prostate cancer. The median time to progression was 29 months with metformin and 20 months with standard therapy alone (P = .01).

Subgroup analyses showed a benefit with metformin in men with N1 disease (P = .001) and men with localized disease/low tumor burden (P = .008).

There was no significant difference in overall survival between the treatment arms (P = .1). The median overall survival was not reached in either arm.

About 4% of metformin patients had grade 2 diarrhea, but adverse events were otherwise comparable between the arms and mostly related to androgen deprivation.

“The authors have got some pretty dramatic findings,” said Noel Clarke, MBBS, a consultant urologist at Salford Royal Hospital and The Christie, Manchester, England, who was a discussant for the study.

Dr. Clarke said the data are “hypothesis generating,” but, because of small numbers, the study “really falls well short of anything that is definitive.”

“We’ll have to wait for bigger studies,” Dr. Clarke said, adding that one arm of the STAMPEDE trial has recruited 2,200 prostate cancer patients to standard of care plus metformin.

“We will report on this trial presently,” he said. “Hopefully, this will add to the body of literature which will determine whether or not metformin is useful with standard of care in this disease.”

Dr. Clarke said the possible benefits of metformin are probably related to energetics in prostate cancer.

“AMPK [AMP-activated protein kinase] is the energy superhighway regulator,” he explained. “[I]t slows down the effects of cell proliferation and energy usage, and it promotes the use of energy storage mechanisms.

“Metformin, because it acts on AMPK to up-regulate it … enhances the effect of AMPK, shutting down the catabolic elements and impeding other elements of prostate cancer migration. So AMPK inhibits epithelial to mesenchymal transition, which is well known as a metastatic mechanism.”

There was no outside funding for this study, and the investigators didn’t report any disclosures. Dr. Clarke disclosed relationships with Janssen, Astellas, Sanofi, and AstraZeneca.

[email protected]

SOURCE: ALGhandour R et al. ESMO 2020, Abstract 617MO.

Adding metformin to standard care for advanced prostate cancer appeared to lengthen time to castration-resistant disease in a small, randomized trial.

“According to our data, metformin potentially prolongs the time to progression … when combined with androgen deprivation therapy,” said investigator Reham ALGhandour, MD, PhD, an assistant lecturer of medical oncology at Mansoura (Egypt) University.

Dr. ALGhandour presented the data at the European Society for Medical Oncology Virtual Congress 2020.

Prior observational studies have indicated that metformin may benefit patients with prostate cancer. A meta-analysis of cohort studies suggested metformin can significantly improve overall, cancer-specific, and recurrence-free survival in prostate cancer patients.

To explore this further, Dr. ALGhandour and colleagues conducted a randomized trial. They enrolled 124 men with high-risk locally advanced or metastatic hormone-sensitive prostate cancer.

The investigators randomized 62 patients to testosterone suppression with or without antiandrogen, and 62 others to a standard regimen plus metformin at 850 mg twice daily.

All patients had an Easter Cooperative Oncology Group performance score of 0-2, were set to receive androgen deprivation therapy long term, and had no prior metformin use. Docetaxel was permitted for metastatic patients, and external beam radiation therapy was used for localized and regional disease.
 

Results: ‘Dramatic’ but not ‘definitive’

At a median follow-up of 18 months, there was a significant difference in time to castration-resistant prostate cancer. The median time to progression was 29 months with metformin and 20 months with standard therapy alone (P = .01).

Subgroup analyses showed a benefit with metformin in men with N1 disease (P = .001) and men with localized disease/low tumor burden (P = .008).

There was no significant difference in overall survival between the treatment arms (P = .1). The median overall survival was not reached in either arm.

About 4% of metformin patients had grade 2 diarrhea, but adverse events were otherwise comparable between the arms and mostly related to androgen deprivation.

“The authors have got some pretty dramatic findings,” said Noel Clarke, MBBS, a consultant urologist at Salford Royal Hospital and The Christie, Manchester, England, who was a discussant for the study.

Dr. Clarke said the data are “hypothesis generating,” but, because of small numbers, the study “really falls well short of anything that is definitive.”

“We’ll have to wait for bigger studies,” Dr. Clarke said, adding that one arm of the STAMPEDE trial has recruited 2,200 prostate cancer patients to standard of care plus metformin.

“We will report on this trial presently,” he said. “Hopefully, this will add to the body of literature which will determine whether or not metformin is useful with standard of care in this disease.”

Dr. Clarke said the possible benefits of metformin are probably related to energetics in prostate cancer.

“AMPK [AMP-activated protein kinase] is the energy superhighway regulator,” he explained. “[I]t slows down the effects of cell proliferation and energy usage, and it promotes the use of energy storage mechanisms.

“Metformin, because it acts on AMPK to up-regulate it … enhances the effect of AMPK, shutting down the catabolic elements and impeding other elements of prostate cancer migration. So AMPK inhibits epithelial to mesenchymal transition, which is well known as a metastatic mechanism.”

There was no outside funding for this study, and the investigators didn’t report any disclosures. Dr. Clarke disclosed relationships with Janssen, Astellas, Sanofi, and AstraZeneca.

[email protected]

SOURCE: ALGhandour R et al. ESMO 2020, Abstract 617MO.

Adding metformin to standard care for advanced prostate cancer appeared to lengthen time to castration-resistant disease in a small, randomized trial.

“According to our data, metformin potentially prolongs the time to progression … when combined with androgen deprivation therapy,” said investigator Reham ALGhandour, MD, PhD, an assistant lecturer of medical oncology at Mansoura (Egypt) University.

Dr. ALGhandour presented the data at the European Society for Medical Oncology Virtual Congress 2020.

Prior observational studies have indicated that metformin may benefit patients with prostate cancer. A meta-analysis of cohort studies suggested metformin can significantly improve overall, cancer-specific, and recurrence-free survival in prostate cancer patients.

To explore this further, Dr. ALGhandour and colleagues conducted a randomized trial. They enrolled 124 men with high-risk locally advanced or metastatic hormone-sensitive prostate cancer.

The investigators randomized 62 patients to testosterone suppression with or without antiandrogen, and 62 others to a standard regimen plus metformin at 850 mg twice daily.

All patients had an Easter Cooperative Oncology Group performance score of 0-2, were set to receive androgen deprivation therapy long term, and had no prior metformin use. Docetaxel was permitted for metastatic patients, and external beam radiation therapy was used for localized and regional disease.
 

Results: ‘Dramatic’ but not ‘definitive’

At a median follow-up of 18 months, there was a significant difference in time to castration-resistant prostate cancer. The median time to progression was 29 months with metformin and 20 months with standard therapy alone (P = .01).

Subgroup analyses showed a benefit with metformin in men with N1 disease (P = .001) and men with localized disease/low tumor burden (P = .008).

There was no significant difference in overall survival between the treatment arms (P = .1). The median overall survival was not reached in either arm.

About 4% of metformin patients had grade 2 diarrhea, but adverse events were otherwise comparable between the arms and mostly related to androgen deprivation.

“The authors have got some pretty dramatic findings,” said Noel Clarke, MBBS, a consultant urologist at Salford Royal Hospital and The Christie, Manchester, England, who was a discussant for the study.

Dr. Clarke said the data are “hypothesis generating,” but, because of small numbers, the study “really falls well short of anything that is definitive.”

“We’ll have to wait for bigger studies,” Dr. Clarke said, adding that one arm of the STAMPEDE trial has recruited 2,200 prostate cancer patients to standard of care plus metformin.

“We will report on this trial presently,” he said. “Hopefully, this will add to the body of literature which will determine whether or not metformin is useful with standard of care in this disease.”

Dr. Clarke said the possible benefits of metformin are probably related to energetics in prostate cancer.

“AMPK [AMP-activated protein kinase] is the energy superhighway regulator,” he explained. “[I]t slows down the effects of cell proliferation and energy usage, and it promotes the use of energy storage mechanisms.

“Metformin, because it acts on AMPK to up-regulate it … enhances the effect of AMPK, shutting down the catabolic elements and impeding other elements of prostate cancer migration. So AMPK inhibits epithelial to mesenchymal transition, which is well known as a metastatic mechanism.”

There was no outside funding for this study, and the investigators didn’t report any disclosures. Dr. Clarke disclosed relationships with Janssen, Astellas, Sanofi, and AstraZeneca.

[email protected]

SOURCE: ALGhandour R et al. ESMO 2020, Abstract 617MO.

• Even in a virtual environment, the Society of Gynecologic Surgeons delivers without a “glitch”
• Transvaginal reconstructive surgery for POP: Innovative approach to graft augmentation in the post-mesh era
• How to build your identity as a physician online

Patrick Culligan, MD

Co-Director, Urogynecology
Valley Hospital System
Ridgewood, New Jersey
Professor, Gynecology & Urology
Weill Cornell Medical College
New York, New York

Jessica Sosa-Stanley, MD

Fellow, Minimally Invasive Gynecologic Surgery
St. Luke’s University Health Network
The Institute for Female Pelvic Medicine
Bethlehem, Pennsylvania

Vincent R. Lucente, MD, MBA

Section Chief, Urogynecology
Chief, Gynecology
Medical Director, Pelvic Health Center
St. Luke’s University Health Network
Partner & Chief Medical Officer
The Institute for Female Pelvic Medicine &
Reconstructive Surgery
Clinical Professor, Obstetrics and Gynecology
Temple University College of Medicine
Bethlehem, Pennsylvania

Michael J. Kennelly, MD

Medical Director, Charlotte Continence Center
Carolinas Medical Center
Director of Urology
Carolinas Rehabilitation Hospital
Co-Director, Women’s Center for Pelvic Health
Clinical Professor, Department of Surgery, Division
of Urology
University of North Carolina, Chapel Hill

Sachin B. Shenoy, MD

Resident
New York-Presbyterian Brooklyn Methodist Hospital
Brooklyn, New York

Brad Bowman, MD

Chief Medical Officer
Healthgrades
Atlanta, Georgia

Peter M. Lotze, MD

Urogynecologist
Women’s Pelvic Restorative Center
Houston, Texas

Heather Schueppert

Chief Marketing Officer
Unified Women’s Healthcare
Boca Raton, Florida

• Even in a virtual environment, the Society of Gynecologic Surgeons delivers without a “glitch”
• Transvaginal reconstructive surgery for POP: Innovative approach to graft augmentation in the post-mesh era
• How to build your identity as a physician online

Patrick Culligan, MD

Co-Director, Urogynecology
Valley Hospital System
Ridgewood, New Jersey
Professor, Gynecology & Urology
Weill Cornell Medical College
New York, New York

Jessica Sosa-Stanley, MD

Fellow, Minimally Invasive Gynecologic Surgery
St. Luke’s University Health Network
The Institute for Female Pelvic Medicine
Bethlehem, Pennsylvania

Vincent R. Lucente, MD, MBA

Section Chief, Urogynecology
Chief, Gynecology
Medical Director, Pelvic Health Center
St. Luke’s University Health Network
Partner & Chief Medical Officer
The Institute for Female Pelvic Medicine &
Reconstructive Surgery
Clinical Professor, Obstetrics and Gynecology
Temple University College of Medicine
Bethlehem, Pennsylvania

Michael J. Kennelly, MD

Medical Director, Charlotte Continence Center
Carolinas Medical Center
Director of Urology
Carolinas Rehabilitation Hospital
Co-Director, Women’s Center for Pelvic Health
Clinical Professor, Department of Surgery, Division
of Urology
University of North Carolina, Chapel Hill

Sachin B. Shenoy, MD

Resident
New York-Presbyterian Brooklyn Methodist Hospital
Brooklyn, New York

Brad Bowman, MD

Chief Medical Officer
Healthgrades
Atlanta, Georgia

Peter M. Lotze, MD

Urogynecologist
Women’s Pelvic Restorative Center
Houston, Texas

Heather Schueppert

Chief Marketing Officer
Unified Women’s Healthcare
Boca Raton, Florida

• Even in a virtual environment, the Society of Gynecologic Surgeons delivers without a “glitch”
• Transvaginal reconstructive surgery for POP: Innovative approach to graft augmentation in the post-mesh era
• How to build your identity as a physician online

Patrick Culligan, MD

Co-Director, Urogynecology
Valley Hospital System
Ridgewood, New Jersey
Professor, Gynecology & Urology
Weill Cornell Medical College
New York, New York

Jessica Sosa-Stanley, MD

Fellow, Minimally Invasive Gynecologic Surgery
St. Luke’s University Health Network
The Institute for Female Pelvic Medicine
Bethlehem, Pennsylvania

Vincent R. Lucente, MD, MBA

Section Chief, Urogynecology
Chief, Gynecology
Medical Director, Pelvic Health Center
St. Luke’s University Health Network
Partner & Chief Medical Officer
The Institute for Female Pelvic Medicine &
Reconstructive Surgery
Clinical Professor, Obstetrics and Gynecology
Temple University College of Medicine
Bethlehem, Pennsylvania

Michael J. Kennelly, MD

Medical Director, Charlotte Continence Center
Carolinas Medical Center
Director of Urology
Carolinas Rehabilitation Hospital
Co-Director, Women’s Center for Pelvic Health
Clinical Professor, Department of Surgery, Division
of Urology
University of North Carolina, Chapel Hill

Sachin B. Shenoy, MD

Resident
New York-Presbyterian Brooklyn Methodist Hospital
Brooklyn, New York

Brad Bowman, MD

Chief Medical Officer
Healthgrades
Atlanta, Georgia

Peter M. Lotze, MD

Urogynecologist
Women’s Pelvic Restorative Center
Houston, Texas

Heather Schueppert

Chief Marketing Officer
Unified Women’s Healthcare
Boca Raton, Florida

Individuals with major depressive disorder (MDD) have an increased heart rate – a finding that may have the potential to identify individuals at risk for the disorder and predict treatment response, early research suggests.

enot-poloskun/Getty Images

Using the rapid-action of the novel antidepressant ketamine and the latest wearable 24-hour electrocardiogram (ECG) technology, investigators found that heart rate could distinguish MDD patients from healthy individuals.

They also found that patients with MDD with the highest resting heart rate had a greater treatment response. In fact, on average, depressed patients had a heart rate that was roughly 10-15 beats per minute higher than healthy controls.

The innovative design of the proof-of-concept study “allowed us to see that average resting heart rate may change quite suddenly to reflect the change in mood,” lead investigator Carmen Schiweck, PhD, Goethe University, Frankfurt am Main, Germany, said in an interview.

These results could have “exciting implications for treatment selection,” and the researchers plan to assess the potential for heart rate to act as an early warning system for depression, they noted.

The findings were presented at the 33rd European College of Neuropsychopharmacology (ECNP) Congress, which was held online this year because of the COVID-19 pandemic.

Identifying trait markers

There have been recent attempts to assess heart rate or heart rate variability (HRV) in patients with MDD to identify trait markers, which are present regardless of the disease phase, or state markers, which are present only during a depressive phase.

However, heart rate and HRV are “highly variable” over a 24-hour cycle, a fact that has been ignored by recent classification efforts, the researchers noted. Moreover, most commonly used antidepressants have a long onset of action, which makes studying their impact on the heart rate challenging.

The researchers’ goal was to determine whether heart rate and HRV could be used as trait markers to distinguish MDD patients from healthy individuals and, through the use of ketamine, whether they can also act as state markers for depression.

For the study, 16 treatment-resistant patients with MDD and 16 age- and sex-matched healthy controls wore a portable ECG device for 4 consecutive days and 3 nights. Heart rate and HRV data were subsequently averaged to obtain a 24-hour ECG.

Participants then received a single infusion of intravenous ketamine for 40 minutes. After waiting for 1 hour, the patients resumed ECG recording for an additional 4 days, with changes in mood assessed using the Hamilton Rating Scale for Depression (HAM-D).

Results showed that, compared with the control group, patients with MDD had a significantly higher 24-hour heart rate (P < .001) and a significantly lower HRV, as measured by the root mean square of successive differences (P < .001).

The investigators also found a reduction in heart rate amplitude, which indicates “significant blunting of circadian rhythm variation throughout the day and less recovery at night.”
 

Ninety percent accuracy

Harmonic and binary regression showed that heart rate was able to identify those with MDD versus those in the control group, particularly using nighttime readings, with 90.6% accuracy. The data correctly identified 14 (87.5%) patients and 15 (93.8%) members of the control group.

Following treatment, heart rate decreased significantly among the MDD group (P < .001), but there was no significant change in HRV (P = .295).

There was a significant positive association between baseline heart rate and response to treatment on the HAM-D (r = .55; P = .046), which suggested better outcomes in patients with a higher heart rate.

Interestingly, while heart rate was positively correlated with depression severity before treatment (r = .59; P = .03), this relationship disappeared following treatment (r = –0.04; P = .90), suggesting heart rate changes were not linked to depression states.

While heart rate levels may be useful as a trait marker and, potentially, for predicting response to antidepressant treatment, they did not show potential as a state marker, the investigators noted.

They suggested that, while the results need to be confirmed in longitudinal studies, approval of a ketamine nasal spray “may open up new avenues to conceive treatment paradigms, as explored in this study.”

However, “this is a small proof-of-concept study,” the investigators acknowledged. They also point out that only six of the patients with MDD had a reduction in HAM-D scores of at least 30% in response to treatment.

Future research plans

Dr. Schiweck said in an interview that her team was able to identify differences in heart rate and HRV in MDD patients that were not observed in other studies because portable at-home devices allowed them to monitor heart rate continuously over days.

The use of ketamine may also have been advantageous because the Netherlands Study of Depression and Anxiety (NESDA), which was published in 2010, clearly showed that “traditional antidepressants,” in particular tricyclic antidepressants, have a strong influence on heart rate and HRV, Dr. Schiweck said.

The team next wants to replicate their study in patients who take nonketamine antidepressants and then remit, because most of the recent studies “just assess patients who are remitted and patients who are currently depressed, but it’s a cross-sectional study design,” said Schiweck.

“If we can follow up the same patients over time then we might really know if it is possible to use heart rate as a state marker for depression,” she added. “That’s what we tried to do with ketamine, but our study was very, very small.”

She noted that the investigators would also like to assess individuals who are “very stressed” and may show some depressive symptoms but don’t yet have a diagnosis of depression.

Mind-body link

Commenting on the findings, Brenda W.J.H. Penninx, MD, PhD, professor of psychiatric epidemiology at the VU University Medical Center in Amsterdam, said the concept of higher heart rate and lower HRV in depression “is indicative of more sympathetic drive and less parasympathetic drive of the autonomic nervous system.”

“That fits with the overall thought that depression is a state with more continuous exposure to stress overactivation of the body, which can be reflected in the [hypothalamic-pituitary-adrenal] axis, leading to higher levels of cortisol stress hormone. But it can also be reflected in the parasympathetic and sympathetic activation of the autonomic nervous system,” she said.

Dr. Penninx, who was also the principal investigator of the NESDA study, was not involved with the current research.

She noted that the NESDA study showed that, when patients with depressive disorder are compared with a healthy controls group, they have a higher heart rate and lower HRV. “But if we then divide people into medicated and nonmedicated people ... then we see that these deviations are only seen in people using medication,” she added.

“Our findings indicate that at least the use of antidepressants is having quite a large impact on autonomic nervous system dysregulation,” Dr. Penninx said. The difference with the current study, she pointed out, is that “it examines the problem over a completely different time scale.”

Although this offers advantages, the current study did not have the large patient numbers that were included in the NESDA study and “they were not clearly able to distinguish the effect of disease from medication,” noted Dr. Penninx.

In addition, this is not an easy area to investigate because there are multiple factors that can mitigate results, including the psychiatric state of the patient, use of medications for both mental illness and cardiometabolic disease, and a patient’s age and gender.

Still, the study clearly illustrates the importance of the interplay between mental health and somatic health and that there is “a very clear indication that we don’t need to separate those,” Dr. Penninx said.

The study was funded by a TGO-IWT Grant from Belgium. The study authors and Dr. Penninx have disclosed no relevant financial relationships.
 

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

Individuals with major depressive disorder (MDD) have an increased heart rate – a finding that may have the potential to identify individuals at risk for the disorder and predict treatment response, early research suggests.

enot-poloskun/Getty Images

Using the rapid-action of the novel antidepressant ketamine and the latest wearable 24-hour electrocardiogram (ECG) technology, investigators found that heart rate could distinguish MDD patients from healthy individuals.

They also found that patients with MDD with the highest resting heart rate had a greater treatment response. In fact, on average, depressed patients had a heart rate that was roughly 10-15 beats per minute higher than healthy controls.

The innovative design of the proof-of-concept study “allowed us to see that average resting heart rate may change quite suddenly to reflect the change in mood,” lead investigator Carmen Schiweck, PhD, Goethe University, Frankfurt am Main, Germany, said in an interview.

These results could have “exciting implications for treatment selection,” and the researchers plan to assess the potential for heart rate to act as an early warning system for depression, they noted.

The findings were presented at the 33rd European College of Neuropsychopharmacology (ECNP) Congress, which was held online this year because of the COVID-19 pandemic.

Identifying trait markers

There have been recent attempts to assess heart rate or heart rate variability (HRV) in patients with MDD to identify trait markers, which are present regardless of the disease phase, or state markers, which are present only during a depressive phase.

However, heart rate and HRV are “highly variable” over a 24-hour cycle, a fact that has been ignored by recent classification efforts, the researchers noted. Moreover, most commonly used antidepressants have a long onset of action, which makes studying their impact on the heart rate challenging.

The researchers’ goal was to determine whether heart rate and HRV could be used as trait markers to distinguish MDD patients from healthy individuals and, through the use of ketamine, whether they can also act as state markers for depression.

For the study, 16 treatment-resistant patients with MDD and 16 age- and sex-matched healthy controls wore a portable ECG device for 4 consecutive days and 3 nights. Heart rate and HRV data were subsequently averaged to obtain a 24-hour ECG.

Participants then received a single infusion of intravenous ketamine for 40 minutes. After waiting for 1 hour, the patients resumed ECG recording for an additional 4 days, with changes in mood assessed using the Hamilton Rating Scale for Depression (HAM-D).

Results showed that, compared with the control group, patients with MDD had a significantly higher 24-hour heart rate (P < .001) and a significantly lower HRV, as measured by the root mean square of successive differences (P < .001).

The investigators also found a reduction in heart rate amplitude, which indicates “significant blunting of circadian rhythm variation throughout the day and less recovery at night.”
 

Ninety percent accuracy

Harmonic and binary regression showed that heart rate was able to identify those with MDD versus those in the control group, particularly using nighttime readings, with 90.6% accuracy. The data correctly identified 14 (87.5%) patients and 15 (93.8%) members of the control group.

Following treatment, heart rate decreased significantly among the MDD group (P < .001), but there was no significant change in HRV (P = .295).

There was a significant positive association between baseline heart rate and response to treatment on the HAM-D (r = .55; P = .046), which suggested better outcomes in patients with a higher heart rate.

Interestingly, while heart rate was positively correlated with depression severity before treatment (r = .59; P = .03), this relationship disappeared following treatment (r = –0.04; P = .90), suggesting heart rate changes were not linked to depression states.

While heart rate levels may be useful as a trait marker and, potentially, for predicting response to antidepressant treatment, they did not show potential as a state marker, the investigators noted.

They suggested that, while the results need to be confirmed in longitudinal studies, approval of a ketamine nasal spray “may open up new avenues to conceive treatment paradigms, as explored in this study.”

However, “this is a small proof-of-concept study,” the investigators acknowledged. They also point out that only six of the patients with MDD had a reduction in HAM-D scores of at least 30% in response to treatment.

Future research plans

Dr. Schiweck said in an interview that her team was able to identify differences in heart rate and HRV in MDD patients that were not observed in other studies because portable at-home devices allowed them to monitor heart rate continuously over days.

The use of ketamine may also have been advantageous because the Netherlands Study of Depression and Anxiety (NESDA), which was published in 2010, clearly showed that “traditional antidepressants,” in particular tricyclic antidepressants, have a strong influence on heart rate and HRV, Dr. Schiweck said.

The team next wants to replicate their study in patients who take nonketamine antidepressants and then remit, because most of the recent studies “just assess patients who are remitted and patients who are currently depressed, but it’s a cross-sectional study design,” said Schiweck.

“If we can follow up the same patients over time then we might really know if it is possible to use heart rate as a state marker for depression,” she added. “That’s what we tried to do with ketamine, but our study was very, very small.”

She noted that the investigators would also like to assess individuals who are “very stressed” and may show some depressive symptoms but don’t yet have a diagnosis of depression.

Mind-body link

Commenting on the findings, Brenda W.J.H. Penninx, MD, PhD, professor of psychiatric epidemiology at the VU University Medical Center in Amsterdam, said the concept of higher heart rate and lower HRV in depression “is indicative of more sympathetic drive and less parasympathetic drive of the autonomic nervous system.”

“That fits with the overall thought that depression is a state with more continuous exposure to stress overactivation of the body, which can be reflected in the [hypothalamic-pituitary-adrenal] axis, leading to higher levels of cortisol stress hormone. But it can also be reflected in the parasympathetic and sympathetic activation of the autonomic nervous system,” she said.

Dr. Penninx, who was also the principal investigator of the NESDA study, was not involved with the current research.

She noted that the NESDA study showed that, when patients with depressive disorder are compared with a healthy controls group, they have a higher heart rate and lower HRV. “But if we then divide people into medicated and nonmedicated people ... then we see that these deviations are only seen in people using medication,” she added.

“Our findings indicate that at least the use of antidepressants is having quite a large impact on autonomic nervous system dysregulation,” Dr. Penninx said. The difference with the current study, she pointed out, is that “it examines the problem over a completely different time scale.”

Although this offers advantages, the current study did not have the large patient numbers that were included in the NESDA study and “they were not clearly able to distinguish the effect of disease from medication,” noted Dr. Penninx.

In addition, this is not an easy area to investigate because there are multiple factors that can mitigate results, including the psychiatric state of the patient, use of medications for both mental illness and cardiometabolic disease, and a patient’s age and gender.

Still, the study clearly illustrates the importance of the interplay between mental health and somatic health and that there is “a very clear indication that we don’t need to separate those,” Dr. Penninx said.

The study was funded by a TGO-IWT Grant from Belgium. The study authors and Dr. Penninx have disclosed no relevant financial relationships.
 

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

Individuals with major depressive disorder (MDD) have an increased heart rate – a finding that may have the potential to identify individuals at risk for the disorder and predict treatment response, early research suggests.

enot-poloskun/Getty Images

Using the rapid-action of the novel antidepressant ketamine and the latest wearable 24-hour electrocardiogram (ECG) technology, investigators found that heart rate could distinguish MDD patients from healthy individuals.

They also found that patients with MDD with the highest resting heart rate had a greater treatment response. In fact, on average, depressed patients had a heart rate that was roughly 10-15 beats per minute higher than healthy controls.

The innovative design of the proof-of-concept study “allowed us to see that average resting heart rate may change quite suddenly to reflect the change in mood,” lead investigator Carmen Schiweck, PhD, Goethe University, Frankfurt am Main, Germany, said in an interview.

These results could have “exciting implications for treatment selection,” and the researchers plan to assess the potential for heart rate to act as an early warning system for depression, they noted.

The findings were presented at the 33rd European College of Neuropsychopharmacology (ECNP) Congress, which was held online this year because of the COVID-19 pandemic.

Identifying trait markers

There have been recent attempts to assess heart rate or heart rate variability (HRV) in patients with MDD to identify trait markers, which are present regardless of the disease phase, or state markers, which are present only during a depressive phase.

However, heart rate and HRV are “highly variable” over a 24-hour cycle, a fact that has been ignored by recent classification efforts, the researchers noted. Moreover, most commonly used antidepressants have a long onset of action, which makes studying their impact on the heart rate challenging.

The researchers’ goal was to determine whether heart rate and HRV could be used as trait markers to distinguish MDD patients from healthy individuals and, through the use of ketamine, whether they can also act as state markers for depression.

For the study, 16 treatment-resistant patients with MDD and 16 age- and sex-matched healthy controls wore a portable ECG device for 4 consecutive days and 3 nights. Heart rate and HRV data were subsequently averaged to obtain a 24-hour ECG.

Participants then received a single infusion of intravenous ketamine for 40 minutes. After waiting for 1 hour, the patients resumed ECG recording for an additional 4 days, with changes in mood assessed using the Hamilton Rating Scale for Depression (HAM-D).

Results showed that, compared with the control group, patients with MDD had a significantly higher 24-hour heart rate (P < .001) and a significantly lower HRV, as measured by the root mean square of successive differences (P < .001).

The investigators also found a reduction in heart rate amplitude, which indicates “significant blunting of circadian rhythm variation throughout the day and less recovery at night.”
 

Ninety percent accuracy

Harmonic and binary regression showed that heart rate was able to identify those with MDD versus those in the control group, particularly using nighttime readings, with 90.6% accuracy. The data correctly identified 14 (87.5%) patients and 15 (93.8%) members of the control group.

Following treatment, heart rate decreased significantly among the MDD group (P < .001), but there was no significant change in HRV (P = .295).

There was a significant positive association between baseline heart rate and response to treatment on the HAM-D (r = .55; P = .046), which suggested better outcomes in patients with a higher heart rate.

Interestingly, while heart rate was positively correlated with depression severity before treatment (r = .59; P = .03), this relationship disappeared following treatment (r = –0.04; P = .90), suggesting heart rate changes were not linked to depression states.

While heart rate levels may be useful as a trait marker and, potentially, for predicting response to antidepressant treatment, they did not show potential as a state marker, the investigators noted.

They suggested that, while the results need to be confirmed in longitudinal studies, approval of a ketamine nasal spray “may open up new avenues to conceive treatment paradigms, as explored in this study.”

However, “this is a small proof-of-concept study,” the investigators acknowledged. They also point out that only six of the patients with MDD had a reduction in HAM-D scores of at least 30% in response to treatment.

Future research plans

Dr. Schiweck said in an interview that her team was able to identify differences in heart rate and HRV in MDD patients that were not observed in other studies because portable at-home devices allowed them to monitor heart rate continuously over days.

The use of ketamine may also have been advantageous because the Netherlands Study of Depression and Anxiety (NESDA), which was published in 2010, clearly showed that “traditional antidepressants,” in particular tricyclic antidepressants, have a strong influence on heart rate and HRV, Dr. Schiweck said.

The team next wants to replicate their study in patients who take nonketamine antidepressants and then remit, because most of the recent studies “just assess patients who are remitted and patients who are currently depressed, but it’s a cross-sectional study design,” said Schiweck.

“If we can follow up the same patients over time then we might really know if it is possible to use heart rate as a state marker for depression,” she added. “That’s what we tried to do with ketamine, but our study was very, very small.”

She noted that the investigators would also like to assess individuals who are “very stressed” and may show some depressive symptoms but don’t yet have a diagnosis of depression.

Mind-body link

Commenting on the findings, Brenda W.J.H. Penninx, MD, PhD, professor of psychiatric epidemiology at the VU University Medical Center in Amsterdam, said the concept of higher heart rate and lower HRV in depression “is indicative of more sympathetic drive and less parasympathetic drive of the autonomic nervous system.”

“That fits with the overall thought that depression is a state with more continuous exposure to stress overactivation of the body, which can be reflected in the [hypothalamic-pituitary-adrenal] axis, leading to higher levels of cortisol stress hormone. But it can also be reflected in the parasympathetic and sympathetic activation of the autonomic nervous system,” she said.

Dr. Penninx, who was also the principal investigator of the NESDA study, was not involved with the current research.

She noted that the NESDA study showed that, when patients with depressive disorder are compared with a healthy controls group, they have a higher heart rate and lower HRV. “But if we then divide people into medicated and nonmedicated people ... then we see that these deviations are only seen in people using medication,” she added.

“Our findings indicate that at least the use of antidepressants is having quite a large impact on autonomic nervous system dysregulation,” Dr. Penninx said. The difference with the current study, she pointed out, is that “it examines the problem over a completely different time scale.”

Although this offers advantages, the current study did not have the large patient numbers that were included in the NESDA study and “they were not clearly able to distinguish the effect of disease from medication,” noted Dr. Penninx.

In addition, this is not an easy area to investigate because there are multiple factors that can mitigate results, including the psychiatric state of the patient, use of medications for both mental illness and cardiometabolic disease, and a patient’s age and gender.

Still, the study clearly illustrates the importance of the interplay between mental health and somatic health and that there is “a very clear indication that we don’t need to separate those,” Dr. Penninx said.

The study was funded by a TGO-IWT Grant from Belgium. The study authors and Dr. Penninx have disclosed no relevant financial relationships.
 

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

Maintenance is a important component of therapy for acute lymphoblastic leukemia, but it’s still a relatively new concept in the treat of patients with acute myeloid leukemia (AML).

The topic of AML maintenance “has become quite hot actually, recently, after languishing for years behind ALL, a disease where maintenance is absolutely critical to overall survival; we haven’t had that much to talk about it in AML until recently,” said Gail J. Roboz, MD, from Weill Cornell Medicine and The New York Presbyterian Hospital, both in New York.

Dr. Roboz discussed her approach to AML maintenance during the virtual American Society of Hematology Meeting on Hematologic Malignancies.

The current AML treatment paradigm starts with remission induction via intensive or less-intensive therapies, followed by consolidation with chemotherapy or with autologous or allogeneic stem cell transplantation (SCT), with maintenance considered as a possibility for some patients.

“Strictly speaking, maintenance is the idea of keeping someone in remission, but we’ve gotten used to it that maintenance is postremission therapy that is different from what you had in your induction,” she noted. “That said, the exact nature of maintenance, while it most traditionally refers to an ongoing lower-intensity therapy, is a little bit complicated these days of what exactly constitutes maintenance.”

Current AML treatments generally fail to completely eliminate leukemic cells, so nearly all patients have remissions with minimal residual disease (MRD).

“You have a heterogeneous mix of leukemia stem cells, progenitors, blast cells, and you are in remission but there are still leftovers, and those leftovers result in disease relapse, and the goal of postremission therapy to basically target and hopefully eradicate the leftovers,” Dr. Roboz said.

Focusing on the postremission period is vital because most patients with AML will die within 1 year after disease relapse.
 

Many options, none great

National Comprehensive Cancer Network AML guidelines recommend a variety of approaches to postremission therapy for patients younger than 60 years with AML, including, depending on risk, either histone deacetylase inhibitors, gemtuzumab ozogamicin (Mylotarg), chemotherapy, and/or SCT, but none of these options, strictly speaking, is called maintenance, she noted.

For patients 60 years and older, “there’s also a likelihood of proceeding with hypomethylating [HMA]-based therapy in such a way that, if they’re responding to initial treatment, they get ongoing therapy with whatever HMA or hypomethylating-based regimen they’re responding to. So is that called maintenance? Is that called ongoing therapy? Continuing therapy? It’s a subject of some controversy,” she added.

For patients younger than 60, hematopoietic SCT has been the ultimate form of maintenance, and increasingly allogeneic SCT is being employed in the United States for patients older than 60 years, including those 70 years and older.

“That has been a good thing, because we’ve been able to offer more patients potentially curative therapy, but the problem is that allo transplant is not a free lunch either, and there are significant risks of nonrelapse mortality, especially for patients going into the transplant with other comorbidities,” Dr. Roboz said.

The majority of older patients may not be cured with transplant because of the use of reduced-intensity conditioning regimens with the result of extended disease-free survival but eventual relapse from residual disease.

“The question is, if you’re an older patient and you can’t get an ablative transplant and you do have residual disease, what’s the likelihood of actually being cured at 2 years, and do you really want to go through the headaches of having a transplant?” she said.
 

Nontransplant options

In the RATIFY trial, patients 60 years and younger with newly diagnosed AML with activating FLT3-mutations were randomized to induction chemotherapy with daunorubicin and cytarabine, consolidation with an histone deacetylase inhibitor, and then maintenance for up to 12 cycles with either midostaurin or placebo.

Although the trial met its primary endpoint of an improvement in overall survival with midostaurin (4-year overall survival, 51.4% vs. 44.3% with placebo), there is still uncertainty as to whether the observed survival benefit was caused by midostaurin or by something else, Dr. Roboz said.

“That said, it certainly has become common to use FLT3 inhibitors as postremission strategy for patients, with consolidation, with allo transplant, after allo transplant – wherever you can get the inhibitor in there,” she said.

The isocitrate dehydrogenase inhibitors ivosidenib (for IDH1) and enasidenib (IDH2) have also been tried in a postremission maintenance-like setting, but have thus far not been demonstrated in clinical trials to be effective in this setting, she added.

Gemtuzumab ozogamicin, an anti-CD33 antibody conjugated to calicheamicin, was approved in 2000 for adults 60 years and older with CD33+ AML in first remission, and in 2017 for adults with newly diagnosed CD33+ AML, as well as adults and children 2 years and older with relapsed or refractory CD33+ AML, but there are no data to show whether this antibody-drug conjugate could have benefit in a maintenance setting.

As previously reported, the combination of the BCL-2 inhibitor venetoclax (Venclexta) with azacitidine was associated with a significant improvement in overall survival, compared with azacitidine alone, in the VIALE-A trial.

“The question now is, in these studies most of the time patients are given a combination of aza and venetoclax that actually continues until they progress; is that called maintenance if you’re getting ongoing cycles? Not sure what to call it, but this is quite myelosuppressive, and there are many, many postremission modifications in dose and schedule that could take up a whole separate lecture,” Dr. Roboz commented.

She added, however, that the combination is effective across nearly all subgroups, and may be more generally applicable for maintenance-style therapy in older patients with AML.
 

Survival benefit

Dr. Roboz was a coinvestigator for the QUAZAR AML-001 trial (NCT01757535), results of which were reported at the 2019 ASH annual meeting. It was the first trial to show that a maintenance therapy with CC-486, an oral formulation of azacitidine, can improve overall survival in patients with AML in remission.

Among 472 patients with poor-risk AML in first complete remission who were not eligible for transplantation, median relapse-free survival was 10.2 months with CC-486 vs. 4.8 months with placebo plus best supportive care, and median overall survival with CC-486 was 24.7 months vs. 14.8 months, an absolute difference of 9.9 months.

This oral formulation of azacitidine was approved by U.S. Food and Drug Administration on Sept. 1, 2020 for use in adult patients with AML in complete remission or complete remission with incomplete blood count recovery following intensive induction chemotherapy and are not able to complete intensive curative therapy. It is sold under the trade name Onureg.

“This is likely to become now the standard of care for AML patients, for the group that was shown to benefit in the clinical trial,” Dr. Roboz said.

The drug was effective at prolonging relapse-free survival regardless of sex, age, remission status (complete remission or complete remission with incomplete blood count recovery) at randomization, cytogenetic risk category, or MRD status.

“We were very gratified to see that there was no reduction in health-related quality of life, which meant that the agent was tolerable, it could be continued for multiple cycles, and there are actually patients, including one of mine, who are many years out with ongoing therapy,” she said.

No funding source for the presentation was reported. Dr. Roboz disclosed consultancy/advisory board activity for multiple pharmaceutical companies; data safety and monitoring committee activity for MEI Pharma, Helsinn, and Takeda; and research funding from Cellectis.

Maintenance is a important component of therapy for acute lymphoblastic leukemia, but it’s still a relatively new concept in the treat of patients with acute myeloid leukemia (AML).

The topic of AML maintenance “has become quite hot actually, recently, after languishing for years behind ALL, a disease where maintenance is absolutely critical to overall survival; we haven’t had that much to talk about it in AML until recently,” said Gail J. Roboz, MD, from Weill Cornell Medicine and The New York Presbyterian Hospital, both in New York.

Dr. Roboz discussed her approach to AML maintenance during the virtual American Society of Hematology Meeting on Hematologic Malignancies.

The current AML treatment paradigm starts with remission induction via intensive or less-intensive therapies, followed by consolidation with chemotherapy or with autologous or allogeneic stem cell transplantation (SCT), with maintenance considered as a possibility for some patients.

“Strictly speaking, maintenance is the idea of keeping someone in remission, but we’ve gotten used to it that maintenance is postremission therapy that is different from what you had in your induction,” she noted. “That said, the exact nature of maintenance, while it most traditionally refers to an ongoing lower-intensity therapy, is a little bit complicated these days of what exactly constitutes maintenance.”

Current AML treatments generally fail to completely eliminate leukemic cells, so nearly all patients have remissions with minimal residual disease (MRD).

“You have a heterogeneous mix of leukemia stem cells, progenitors, blast cells, and you are in remission but there are still leftovers, and those leftovers result in disease relapse, and the goal of postremission therapy to basically target and hopefully eradicate the leftovers,” Dr. Roboz said.

Focusing on the postremission period is vital because most patients with AML will die within 1 year after disease relapse.
 

Many options, none great

National Comprehensive Cancer Network AML guidelines recommend a variety of approaches to postremission therapy for patients younger than 60 years with AML, including, depending on risk, either histone deacetylase inhibitors, gemtuzumab ozogamicin (Mylotarg), chemotherapy, and/or SCT, but none of these options, strictly speaking, is called maintenance, she noted.

For patients 60 years and older, “there’s also a likelihood of proceeding with hypomethylating [HMA]-based therapy in such a way that, if they’re responding to initial treatment, they get ongoing therapy with whatever HMA or hypomethylating-based regimen they’re responding to. So is that called maintenance? Is that called ongoing therapy? Continuing therapy? It’s a subject of some controversy,” she added.

For patients younger than 60, hematopoietic SCT has been the ultimate form of maintenance, and increasingly allogeneic SCT is being employed in the United States for patients older than 60 years, including those 70 years and older.

“That has been a good thing, because we’ve been able to offer more patients potentially curative therapy, but the problem is that allo transplant is not a free lunch either, and there are significant risks of nonrelapse mortality, especially for patients going into the transplant with other comorbidities,” Dr. Roboz said.

The majority of older patients may not be cured with transplant because of the use of reduced-intensity conditioning regimens with the result of extended disease-free survival but eventual relapse from residual disease.

“The question is, if you’re an older patient and you can’t get an ablative transplant and you do have residual disease, what’s the likelihood of actually being cured at 2 years, and do you really want to go through the headaches of having a transplant?” she said.
 

Nontransplant options

In the RATIFY trial, patients 60 years and younger with newly diagnosed AML with activating FLT3-mutations were randomized to induction chemotherapy with daunorubicin and cytarabine, consolidation with an histone deacetylase inhibitor, and then maintenance for up to 12 cycles with either midostaurin or placebo.

Although the trial met its primary endpoint of an improvement in overall survival with midostaurin (4-year overall survival, 51.4% vs. 44.3% with placebo), there is still uncertainty as to whether the observed survival benefit was caused by midostaurin or by something else, Dr. Roboz said.

“That said, it certainly has become common to use FLT3 inhibitors as postremission strategy for patients, with consolidation, with allo transplant, after allo transplant – wherever you can get the inhibitor in there,” she said.

The isocitrate dehydrogenase inhibitors ivosidenib (for IDH1) and enasidenib (IDH2) have also been tried in a postremission maintenance-like setting, but have thus far not been demonstrated in clinical trials to be effective in this setting, she added.

Gemtuzumab ozogamicin, an anti-CD33 antibody conjugated to calicheamicin, was approved in 2000 for adults 60 years and older with CD33+ AML in first remission, and in 2017 for adults with newly diagnosed CD33+ AML, as well as adults and children 2 years and older with relapsed or refractory CD33+ AML, but there are no data to show whether this antibody-drug conjugate could have benefit in a maintenance setting.

As previously reported, the combination of the BCL-2 inhibitor venetoclax (Venclexta) with azacitidine was associated with a significant improvement in overall survival, compared with azacitidine alone, in the VIALE-A trial.

“The question now is, in these studies most of the time patients are given a combination of aza and venetoclax that actually continues until they progress; is that called maintenance if you’re getting ongoing cycles? Not sure what to call it, but this is quite myelosuppressive, and there are many, many postremission modifications in dose and schedule that could take up a whole separate lecture,” Dr. Roboz commented.

She added, however, that the combination is effective across nearly all subgroups, and may be more generally applicable for maintenance-style therapy in older patients with AML.
 

Survival benefit

Dr. Roboz was a coinvestigator for the QUAZAR AML-001 trial (NCT01757535), results of which were reported at the 2019 ASH annual meeting. It was the first trial to show that a maintenance therapy with CC-486, an oral formulation of azacitidine, can improve overall survival in patients with AML in remission.

Among 472 patients with poor-risk AML in first complete remission who were not eligible for transplantation, median relapse-free survival was 10.2 months with CC-486 vs. 4.8 months with placebo plus best supportive care, and median overall survival with CC-486 was 24.7 months vs. 14.8 months, an absolute difference of 9.9 months.

This oral formulation of azacitidine was approved by U.S. Food and Drug Administration on Sept. 1, 2020 for use in adult patients with AML in complete remission or complete remission with incomplete blood count recovery following intensive induction chemotherapy and are not able to complete intensive curative therapy. It is sold under the trade name Onureg.

“This is likely to become now the standard of care for AML patients, for the group that was shown to benefit in the clinical trial,” Dr. Roboz said.

The drug was effective at prolonging relapse-free survival regardless of sex, age, remission status (complete remission or complete remission with incomplete blood count recovery) at randomization, cytogenetic risk category, or MRD status.

“We were very gratified to see that there was no reduction in health-related quality of life, which meant that the agent was tolerable, it could be continued for multiple cycles, and there are actually patients, including one of mine, who are many years out with ongoing therapy,” she said.

No funding source for the presentation was reported. Dr. Roboz disclosed consultancy/advisory board activity for multiple pharmaceutical companies; data safety and monitoring committee activity for MEI Pharma, Helsinn, and Takeda; and research funding from Cellectis.

Maintenance is a important component of therapy for acute lymphoblastic leukemia, but it’s still a relatively new concept in the treat of patients with acute myeloid leukemia (AML).

The topic of AML maintenance “has become quite hot actually, recently, after languishing for years behind ALL, a disease where maintenance is absolutely critical to overall survival; we haven’t had that much to talk about it in AML until recently,” said Gail J. Roboz, MD, from Weill Cornell Medicine and The New York Presbyterian Hospital, both in New York.

Dr. Roboz discussed her approach to AML maintenance during the virtual American Society of Hematology Meeting on Hematologic Malignancies.

The current AML treatment paradigm starts with remission induction via intensive or less-intensive therapies, followed by consolidation with chemotherapy or with autologous or allogeneic stem cell transplantation (SCT), with maintenance considered as a possibility for some patients.

“Strictly speaking, maintenance is the idea of keeping someone in remission, but we’ve gotten used to it that maintenance is postremission therapy that is different from what you had in your induction,” she noted. “That said, the exact nature of maintenance, while it most traditionally refers to an ongoing lower-intensity therapy, is a little bit complicated these days of what exactly constitutes maintenance.”

Current AML treatments generally fail to completely eliminate leukemic cells, so nearly all patients have remissions with minimal residual disease (MRD).

“You have a heterogeneous mix of leukemia stem cells, progenitors, blast cells, and you are in remission but there are still leftovers, and those leftovers result in disease relapse, and the goal of postremission therapy to basically target and hopefully eradicate the leftovers,” Dr. Roboz said.

Focusing on the postremission period is vital because most patients with AML will die within 1 year after disease relapse.
 

Many options, none great

National Comprehensive Cancer Network AML guidelines recommend a variety of approaches to postremission therapy for patients younger than 60 years with AML, including, depending on risk, either histone deacetylase inhibitors, gemtuzumab ozogamicin (Mylotarg), chemotherapy, and/or SCT, but none of these options, strictly speaking, is called maintenance, she noted.

For patients 60 years and older, “there’s also a likelihood of proceeding with hypomethylating [HMA]-based therapy in such a way that, if they’re responding to initial treatment, they get ongoing therapy with whatever HMA or hypomethylating-based regimen they’re responding to. So is that called maintenance? Is that called ongoing therapy? Continuing therapy? It’s a subject of some controversy,” she added.

For patients younger than 60, hematopoietic SCT has been the ultimate form of maintenance, and increasingly allogeneic SCT is being employed in the United States for patients older than 60 years, including those 70 years and older.

“That has been a good thing, because we’ve been able to offer more patients potentially curative therapy, but the problem is that allo transplant is not a free lunch either, and there are significant risks of nonrelapse mortality, especially for patients going into the transplant with other comorbidities,” Dr. Roboz said.

The majority of older patients may not be cured with transplant because of the use of reduced-intensity conditioning regimens with the result of extended disease-free survival but eventual relapse from residual disease.

“The question is, if you’re an older patient and you can’t get an ablative transplant and you do have residual disease, what’s the likelihood of actually being cured at 2 years, and do you really want to go through the headaches of having a transplant?” she said.
 

Nontransplant options

In the RATIFY trial, patients 60 years and younger with newly diagnosed AML with activating FLT3-mutations were randomized to induction chemotherapy with daunorubicin and cytarabine, consolidation with an histone deacetylase inhibitor, and then maintenance for up to 12 cycles with either midostaurin or placebo.

Although the trial met its primary endpoint of an improvement in overall survival with midostaurin (4-year overall survival, 51.4% vs. 44.3% with placebo), there is still uncertainty as to whether the observed survival benefit was caused by midostaurin or by something else, Dr. Roboz said.

“That said, it certainly has become common to use FLT3 inhibitors as postremission strategy for patients, with consolidation, with allo transplant, after allo transplant – wherever you can get the inhibitor in there,” she said.

The isocitrate dehydrogenase inhibitors ivosidenib (for IDH1) and enasidenib (IDH2) have also been tried in a postremission maintenance-like setting, but have thus far not been demonstrated in clinical trials to be effective in this setting, she added.

Gemtuzumab ozogamicin, an anti-CD33 antibody conjugated to calicheamicin, was approved in 2000 for adults 60 years and older with CD33+ AML in first remission, and in 2017 for adults with newly diagnosed CD33+ AML, as well as adults and children 2 years and older with relapsed or refractory CD33+ AML, but there are no data to show whether this antibody-drug conjugate could have benefit in a maintenance setting.

As previously reported, the combination of the BCL-2 inhibitor venetoclax (Venclexta) with azacitidine was associated with a significant improvement in overall survival, compared with azacitidine alone, in the VIALE-A trial.

“The question now is, in these studies most of the time patients are given a combination of aza and venetoclax that actually continues until they progress; is that called maintenance if you’re getting ongoing cycles? Not sure what to call it, but this is quite myelosuppressive, and there are many, many postremission modifications in dose and schedule that could take up a whole separate lecture,” Dr. Roboz commented.

She added, however, that the combination is effective across nearly all subgroups, and may be more generally applicable for maintenance-style therapy in older patients with AML.
 

Survival benefit

Dr. Roboz was a coinvestigator for the QUAZAR AML-001 trial (NCT01757535), results of which were reported at the 2019 ASH annual meeting. It was the first trial to show that a maintenance therapy with CC-486, an oral formulation of azacitidine, can improve overall survival in patients with AML in remission.

Among 472 patients with poor-risk AML in first complete remission who were not eligible for transplantation, median relapse-free survival was 10.2 months with CC-486 vs. 4.8 months with placebo plus best supportive care, and median overall survival with CC-486 was 24.7 months vs. 14.8 months, an absolute difference of 9.9 months.

This oral formulation of azacitidine was approved by U.S. Food and Drug Administration on Sept. 1, 2020 for use in adult patients with AML in complete remission or complete remission with incomplete blood count recovery following intensive induction chemotherapy and are not able to complete intensive curative therapy. It is sold under the trade name Onureg.

“This is likely to become now the standard of care for AML patients, for the group that was shown to benefit in the clinical trial,” Dr. Roboz said.

The drug was effective at prolonging relapse-free survival regardless of sex, age, remission status (complete remission or complete remission with incomplete blood count recovery) at randomization, cytogenetic risk category, or MRD status.

“We were very gratified to see that there was no reduction in health-related quality of life, which meant that the agent was tolerable, it could be continued for multiple cycles, and there are actually patients, including one of mine, who are many years out with ongoing therapy,” she said.

No funding source for the presentation was reported. Dr. Roboz disclosed consultancy/advisory board activity for multiple pharmaceutical companies; data safety and monitoring committee activity for MEI Pharma, Helsinn, and Takeda; and research funding from Cellectis.

“A treat-to-target approach is useful in the management of osteoporosis” was the motion proposed in a debate during the recent virtual American Society of Bone and Mineral Research (ASBMR) 2020 annual meeting, and when the votes came in, Michael McClung, MD, who argued against the motion, carried the day.

Agreement with the motion dropped from 63%-46% after McClung, of the Oregon Osteoporosis Center, Portland, put his views forward in opposition to those of Celia L. Gregson, PhD, University of Bristol (England), who argued for the motion on behalf of the European Calcified Tissue Society (ECTS).

Disagreement with the statement rose from 37% predebate to 54% in the postdebate audience polls.

“The debate is part education and part entertainment,” said Dr. McClung, who represented the ASBMR. “I could just as easily have made a strong argument for the motion,” he emphasized in an interview.

On the other hand, “had I been in the audience, as a member of ASBMR relying on data and evidence to make clinical decisions, I would have voted against the motion. As appealing as the strategy sounds, we don’t yet have the hard evidence to support its use nor is there a consensus about what an appropriate target should be, he noted.

Similarly, the debate comoderator and incoming ASBMR President, Suzanne M. Jan de Beur, MD, from Johns Hopkins University, Baltimore, said that a treat-to-target strategy for osteoporosis is an attractive idea, but there is no consensus on how to apply it nor evidence that it improves clinical outcomes.
 

Treat to target to guide osteoporosis therapy is like going “backwards”

In treat to target, the target – such as bone mineral density (BMD) (the most common one) – is identified before treatment is started, Dr. McClung explained (and as stated in a review article in the New England Journal of Medicine he coauthored on the topic). 

“While treat to target has appealing concepts, using risk factors to guide therapy is almost backwards,” he said. “We can’t change bone density very much.”

Treat to target is “not quite ready for prime time,” he concluded in his rebuttal.

Invited to speculate on which of Dr. McClung’s arguments swayed the audience, Dr. Gregson conceded that with a treat-to-target strategy “there is too much focus on getting one target for the whole global population with osteoporosis.”

“This is an oversimplification of a complex disease, and it misses the main message that the target should be decided with the patient not for the patient, which means one can’t just have one rule for everyone. There has to be scope to have different targets for different people so that we can deliver individualized care.”

Also, she noted, “generally people don’t vote to change familiar systems.”
 

Arguments for treat to target

Dr. Gregson began her argument, however, by stating that treat to target “is now a feasible and useful approach in osteoporosis care.”

The main reasons for adopting this treatment strategy are as follows:

• It provides a proactive approach with a clear goal.
• It includes periodic treatment reassessment, which allows for prompt revisions to treatment.
• It can use targets to guide treatment timing and patient monitoring.
• It includes shared decision-making, the preferred method of patient care.
• It could improve treatment adherence through patient “buy-in” of the target.
• It can use targets to address the risk of rare side effects.
• It allows for sequential treatments, especially for patients at highest risk of fracture.
• It can include more patient-centered outcomes such as reduced , restored range of movement, and ability to live independently.

“Patients are not interested in their T-score. They are interested in pain,” said Dr. Gregson.

“Reduced fracture risk is a very important goal,” she emphasized. Patients “with osteoporosis and a high fracture risk have the most to gain from a treat-to-target approach.”

“Improved access to anabolic osteoporosis treatments mean achieving those goals or targets are now more achievable than ever,” she concluded.

Arguments against treat to target

“Do we truly have an appropriate, meaningful target for osteoporosis?” Dr. McClung began in his counterargument, which cast a seed of doubt in the minds of the audience.

Targets such as no fractures, fracture risk (FRAX score), bone turnover markers, and bone strength have limitations.

Moreover, “do we have treatment strategies to move patients to the chosen target?” he continued. “What is the evidence that a treat-to-target strategy provides better outcomes than our current treatment paradigm?”

After pointing out a lack of evidence that treat to target leads to better outcomes in osteoporosis, he did allow that “recent data about the relationship between treatment-related BMD values and current fracture risk are appreciated and welcomed.”

“However, a treat-to-target strategy will only be successful if the targets are individualized for each patient, those targets are attainable for most patients, and we have evidence that adopting this strategy improves clinical outcomes,” he summarized.

He then quoted his late wife Betsy Love McClung, RN, MN, who had said, “We don’t treat osteoporosis; we treat patients with osteoporosis.”

Dr. McClung wrapped up by stressing: “We should not treat T-scores or any other specific target. We should individualize our therapy based upon the patient’s risk of fracture and other clinical factors.”

As members of the ECTS and ASBMR, and “proud of our reputation of our societies as being scientifically based and driven,” Dr. McClung concluded, “recognizing that a treat-to-target strategy has appeal, we should certainly encourage more research and be attentive to those results.

“But we must hold off on the adoption of the strategy until we have evidence convincing us of its clinical value.”
 

When to use a treat-to-target strategy

However, “there are some specific situations where I use something like a treat-to-target strategy,” Dr. McClung conceded. “That is, I make decisions and recommendations to the patients about one drug rather than another because I want to maximize the improvement in their bone density.”

For example, “We have known for 15 years that denosumab results in greater increases in bone density than do bisphosphonates,” he continued.

“So I have used that information to make treatment decisions long before the term ‘treat to target’ entered the vocabulary of osteoporosis experts. I simply wanted to induce the largest possible gains in bone density – but I didn’t have a ‘target’ in mind.”

But for most patients, treatment decisions are made based on other factors, such as their fracture risk, he added. BMD is an important risk factor for fracture, but not as important as having had a recent fracture or being old and frail.

“Unfortunately, in most of today’s health systems, decisions about treatment are made on the basis of cost,” he continued. “More often than not, the health plan rules rather than optimal medical practice are the main guides to treatment decisions.”   

According to Dr. Gregson, “in some instances, treat to target would be very helpful. I don’t think it will suit everyone, but I think we should have it in our portfolio of management approaches, and we should as an osteoporosis community be trained in its use.”
 

“Attractive idea, but ...”

Invited to weigh in, Dr. Jan de Beur noted that A1c, blood pressure, and LDL cholesterol targets are used to improve clinical outcomes in patients with diabetes, hypertension, and hyperlipidemia, respectively.

However, “treat to target for the treatment of low BMD is controversial because it is an attractive idea but without consensus on what the target should be and without evidence that treat to target improves clinical outcomes,” she reiterated.

“The potential benefits of treat to target are proactive, clear goals to achieve, shared decision-making with the patient, the possibility for improved adherence, justification for sequence treatments, and balancing risk of rare side effects.”

On the other hand, “barriers to operationalizing the treat-to-target concept is that there is lack of consensus on the target to be achieved [as any specific target may minimize other important risk factors],” she noted.

There is also a “lack of evidence that demonstrates improved clinical outcomes over choosing therapy based on fracture risk, and lack of ability to achieve the target with available therapies in those with very-low bone density,” she concluded.

Dr. McClung has reported receiving consulting fees from Amgen and Myovant and speaker honoraria from Amgen. Dr. Gregson and Dr. Jan de Beur have reported no relevant financial relationships.
 

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

“A treat-to-target approach is useful in the management of osteoporosis” was the motion proposed in a debate during the recent virtual American Society of Bone and Mineral Research (ASBMR) 2020 annual meeting, and when the votes came in, Michael McClung, MD, who argued against the motion, carried the day.

Agreement with the motion dropped from 63%-46% after McClung, of the Oregon Osteoporosis Center, Portland, put his views forward in opposition to those of Celia L. Gregson, PhD, University of Bristol (England), who argued for the motion on behalf of the European Calcified Tissue Society (ECTS).

Disagreement with the statement rose from 37% predebate to 54% in the postdebate audience polls.

“The debate is part education and part entertainment,” said Dr. McClung, who represented the ASBMR. “I could just as easily have made a strong argument for the motion,” he emphasized in an interview.

On the other hand, “had I been in the audience, as a member of ASBMR relying on data and evidence to make clinical decisions, I would have voted against the motion. As appealing as the strategy sounds, we don’t yet have the hard evidence to support its use nor is there a consensus about what an appropriate target should be, he noted.

Similarly, the debate comoderator and incoming ASBMR President, Suzanne M. Jan de Beur, MD, from Johns Hopkins University, Baltimore, said that a treat-to-target strategy for osteoporosis is an attractive idea, but there is no consensus on how to apply it nor evidence that it improves clinical outcomes.
 

Treat to target to guide osteoporosis therapy is like going “backwards”

In treat to target, the target – such as bone mineral density (BMD) (the most common one) – is identified before treatment is started, Dr. McClung explained (and as stated in a review article in the New England Journal of Medicine he coauthored on the topic). 

“While treat to target has appealing concepts, using risk factors to guide therapy is almost backwards,” he said. “We can’t change bone density very much.”

Treat to target is “not quite ready for prime time,” he concluded in his rebuttal.

Invited to speculate on which of Dr. McClung’s arguments swayed the audience, Dr. Gregson conceded that with a treat-to-target strategy “there is too much focus on getting one target for the whole global population with osteoporosis.”

“This is an oversimplification of a complex disease, and it misses the main message that the target should be decided with the patient not for the patient, which means one can’t just have one rule for everyone. There has to be scope to have different targets for different people so that we can deliver individualized care.”

Also, she noted, “generally people don’t vote to change familiar systems.”
 

Arguments for treat to target

Dr. Gregson began her argument, however, by stating that treat to target “is now a feasible and useful approach in osteoporosis care.”

The main reasons for adopting this treatment strategy are as follows:

• It provides a proactive approach with a clear goal.
• It includes periodic treatment reassessment, which allows for prompt revisions to treatment.
• It can use targets to guide treatment timing and patient monitoring.
• It includes shared decision-making, the preferred method of patient care.
• It could improve treatment adherence through patient “buy-in” of the target.
• It can use targets to address the risk of rare side effects.
• It allows for sequential treatments, especially for patients at highest risk of fracture.
• It can include more patient-centered outcomes such as reduced , restored range of movement, and ability to live independently.

“Patients are not interested in their T-score. They are interested in pain,” said Dr. Gregson.

“Reduced fracture risk is a very important goal,” she emphasized. Patients “with osteoporosis and a high fracture risk have the most to gain from a treat-to-target approach.”

“Improved access to anabolic osteoporosis treatments mean achieving those goals or targets are now more achievable than ever,” she concluded.

Arguments against treat to target

“Do we truly have an appropriate, meaningful target for osteoporosis?” Dr. McClung began in his counterargument, which cast a seed of doubt in the minds of the audience.

Targets such as no fractures, fracture risk (FRAX score), bone turnover markers, and bone strength have limitations.

Moreover, “do we have treatment strategies to move patients to the chosen target?” he continued. “What is the evidence that a treat-to-target strategy provides better outcomes than our current treatment paradigm?”

After pointing out a lack of evidence that treat to target leads to better outcomes in osteoporosis, he did allow that “recent data about the relationship between treatment-related BMD values and current fracture risk are appreciated and welcomed.”

“However, a treat-to-target strategy will only be successful if the targets are individualized for each patient, those targets are attainable for most patients, and we have evidence that adopting this strategy improves clinical outcomes,” he summarized.

He then quoted his late wife Betsy Love McClung, RN, MN, who had said, “We don’t treat osteoporosis; we treat patients with osteoporosis.”

Dr. McClung wrapped up by stressing: “We should not treat T-scores or any other specific target. We should individualize our therapy based upon the patient’s risk of fracture and other clinical factors.”

As members of the ECTS and ASBMR, and “proud of our reputation of our societies as being scientifically based and driven,” Dr. McClung concluded, “recognizing that a treat-to-target strategy has appeal, we should certainly encourage more research and be attentive to those results.

“But we must hold off on the adoption of the strategy until we have evidence convincing us of its clinical value.”
 

When to use a treat-to-target strategy

However, “there are some specific situations where I use something like a treat-to-target strategy,” Dr. McClung conceded. “That is, I make decisions and recommendations to the patients about one drug rather than another because I want to maximize the improvement in their bone density.”

For example, “We have known for 15 years that denosumab results in greater increases in bone density than do bisphosphonates,” he continued.

“So I have used that information to make treatment decisions long before the term ‘treat to target’ entered the vocabulary of osteoporosis experts. I simply wanted to induce the largest possible gains in bone density – but I didn’t have a ‘target’ in mind.”

But for most patients, treatment decisions are made based on other factors, such as their fracture risk, he added. BMD is an important risk factor for fracture, but not as important as having had a recent fracture or being old and frail.

“Unfortunately, in most of today’s health systems, decisions about treatment are made on the basis of cost,” he continued. “More often than not, the health plan rules rather than optimal medical practice are the main guides to treatment decisions.”   

According to Dr. Gregson, “in some instances, treat to target would be very helpful. I don’t think it will suit everyone, but I think we should have it in our portfolio of management approaches, and we should as an osteoporosis community be trained in its use.”
 

“Attractive idea, but ...”

Invited to weigh in, Dr. Jan de Beur noted that A1c, blood pressure, and LDL cholesterol targets are used to improve clinical outcomes in patients with diabetes, hypertension, and hyperlipidemia, respectively.

However, “treat to target for the treatment of low BMD is controversial because it is an attractive idea but without consensus on what the target should be and without evidence that treat to target improves clinical outcomes,” she reiterated.

“The potential benefits of treat to target are proactive, clear goals to achieve, shared decision-making with the patient, the possibility for improved adherence, justification for sequence treatments, and balancing risk of rare side effects.”

On the other hand, “barriers to operationalizing the treat-to-target concept is that there is lack of consensus on the target to be achieved [as any specific target may minimize other important risk factors],” she noted.

There is also a “lack of evidence that demonstrates improved clinical outcomes over choosing therapy based on fracture risk, and lack of ability to achieve the target with available therapies in those with very-low bone density,” she concluded.

Dr. McClung has reported receiving consulting fees from Amgen and Myovant and speaker honoraria from Amgen. Dr. Gregson and Dr. Jan de Beur have reported no relevant financial relationships.
 

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

“A treat-to-target approach is useful in the management of osteoporosis” was the motion proposed in a debate during the recent virtual American Society of Bone and Mineral Research (ASBMR) 2020 annual meeting, and when the votes came in, Michael McClung, MD, who argued against the motion, carried the day.

Agreement with the motion dropped from 63%-46% after McClung, of the Oregon Osteoporosis Center, Portland, put his views forward in opposition to those of Celia L. Gregson, PhD, University of Bristol (England), who argued for the motion on behalf of the European Calcified Tissue Society (ECTS).

Disagreement with the statement rose from 37% predebate to 54% in the postdebate audience polls.

“The debate is part education and part entertainment,” said Dr. McClung, who represented the ASBMR. “I could just as easily have made a strong argument for the motion,” he emphasized in an interview.

On the other hand, “had I been in the audience, as a member of ASBMR relying on data and evidence to make clinical decisions, I would have voted against the motion. As appealing as the strategy sounds, we don’t yet have the hard evidence to support its use nor is there a consensus about what an appropriate target should be, he noted.

Similarly, the debate comoderator and incoming ASBMR President, Suzanne M. Jan de Beur, MD, from Johns Hopkins University, Baltimore, said that a treat-to-target strategy for osteoporosis is an attractive idea, but there is no consensus on how to apply it nor evidence that it improves clinical outcomes.
 

Treat to target to guide osteoporosis therapy is like going “backwards”

In treat to target, the target – such as bone mineral density (BMD) (the most common one) – is identified before treatment is started, Dr. McClung explained (and as stated in a review article in the New England Journal of Medicine he coauthored on the topic). 

“While treat to target has appealing concepts, using risk factors to guide therapy is almost backwards,” he said. “We can’t change bone density very much.”

Treat to target is “not quite ready for prime time,” he concluded in his rebuttal.

Invited to speculate on which of Dr. McClung’s arguments swayed the audience, Dr. Gregson conceded that with a treat-to-target strategy “there is too much focus on getting one target for the whole global population with osteoporosis.”

“This is an oversimplification of a complex disease, and it misses the main message that the target should be decided with the patient not for the patient, which means one can’t just have one rule for everyone. There has to be scope to have different targets for different people so that we can deliver individualized care.”

Also, she noted, “generally people don’t vote to change familiar systems.”
 

Arguments for treat to target

Dr. Gregson began her argument, however, by stating that treat to target “is now a feasible and useful approach in osteoporosis care.”

The main reasons for adopting this treatment strategy are as follows:

• It provides a proactive approach with a clear goal.
• It includes periodic treatment reassessment, which allows for prompt revisions to treatment.
• It can use targets to guide treatment timing and patient monitoring.
• It includes shared decision-making, the preferred method of patient care.
• It could improve treatment adherence through patient “buy-in” of the target.
• It can use targets to address the risk of rare side effects.
• It allows for sequential treatments, especially for patients at highest risk of fracture.
• It can include more patient-centered outcomes such as reduced , restored range of movement, and ability to live independently.

“Patients are not interested in their T-score. They are interested in pain,” said Dr. Gregson.

“Reduced fracture risk is a very important goal,” she emphasized. Patients “with osteoporosis and a high fracture risk have the most to gain from a treat-to-target approach.”

“Improved access to anabolic osteoporosis treatments mean achieving those goals or targets are now more achievable than ever,” she concluded.

Arguments against treat to target

“Do we truly have an appropriate, meaningful target for osteoporosis?” Dr. McClung began in his counterargument, which cast a seed of doubt in the minds of the audience.

Targets such as no fractures, fracture risk (FRAX score), bone turnover markers, and bone strength have limitations.

Moreover, “do we have treatment strategies to move patients to the chosen target?” he continued. “What is the evidence that a treat-to-target strategy provides better outcomes than our current treatment paradigm?”

After pointing out a lack of evidence that treat to target leads to better outcomes in osteoporosis, he did allow that “recent data about the relationship between treatment-related BMD values and current fracture risk are appreciated and welcomed.”

“However, a treat-to-target strategy will only be successful if the targets are individualized for each patient, those targets are attainable for most patients, and we have evidence that adopting this strategy improves clinical outcomes,” he summarized.

He then quoted his late wife Betsy Love McClung, RN, MN, who had said, “We don’t treat osteoporosis; we treat patients with osteoporosis.”

Dr. McClung wrapped up by stressing: “We should not treat T-scores or any other specific target. We should individualize our therapy based upon the patient’s risk of fracture and other clinical factors.”

As members of the ECTS and ASBMR, and “proud of our reputation of our societies as being scientifically based and driven,” Dr. McClung concluded, “recognizing that a treat-to-target strategy has appeal, we should certainly encourage more research and be attentive to those results.

“But we must hold off on the adoption of the strategy until we have evidence convincing us of its clinical value.”
 

When to use a treat-to-target strategy

However, “there are some specific situations where I use something like a treat-to-target strategy,” Dr. McClung conceded. “That is, I make decisions and recommendations to the patients about one drug rather than another because I want to maximize the improvement in their bone density.”

For example, “We have known for 15 years that denosumab results in greater increases in bone density than do bisphosphonates,” he continued.

“So I have used that information to make treatment decisions long before the term ‘treat to target’ entered the vocabulary of osteoporosis experts. I simply wanted to induce the largest possible gains in bone density – but I didn’t have a ‘target’ in mind.”

But for most patients, treatment decisions are made based on other factors, such as their fracture risk, he added. BMD is an important risk factor for fracture, but not as important as having had a recent fracture or being old and frail.

“Unfortunately, in most of today’s health systems, decisions about treatment are made on the basis of cost,” he continued. “More often than not, the health plan rules rather than optimal medical practice are the main guides to treatment decisions.”   

According to Dr. Gregson, “in some instances, treat to target would be very helpful. I don’t think it will suit everyone, but I think we should have it in our portfolio of management approaches, and we should as an osteoporosis community be trained in its use.”
 

“Attractive idea, but ...”

Invited to weigh in, Dr. Jan de Beur noted that A1c, blood pressure, and LDL cholesterol targets are used to improve clinical outcomes in patients with diabetes, hypertension, and hyperlipidemia, respectively.

However, “treat to target for the treatment of low BMD is controversial because it is an attractive idea but without consensus on what the target should be and without evidence that treat to target improves clinical outcomes,” she reiterated.

“The potential benefits of treat to target are proactive, clear goals to achieve, shared decision-making with the patient, the possibility for improved adherence, justification for sequence treatments, and balancing risk of rare side effects.”

On the other hand, “barriers to operationalizing the treat-to-target concept is that there is lack of consensus on the target to be achieved [as any specific target may minimize other important risk factors],” she noted.

There is also a “lack of evidence that demonstrates improved clinical outcomes over choosing therapy based on fracture risk, and lack of ability to achieve the target with available therapies in those with very-low bone density,” she concluded.

Dr. McClung has reported receiving consulting fees from Amgen and Myovant and speaker honoraria from Amgen. Dr. Gregson and Dr. Jan de Beur have reported no relevant financial relationships.
 

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

When researchers arrived in Seeley Lake, Mont., a town tucked in the northern Rockies, 3 years ago, they could still smell the smoke a day after it cleared from devastating wildfires. Their plan was to chart how long it took for people to recover from living for 7 weeks surrounded by relentless smoke.

They still don’t know, because most residents haven’t recovered. In fact, they’ve gotten worse.

Forest fires had funneled hazardous air into Seeley Lake, a town of fewer than 2,000 people, for 49 days. The air quality was so bad that on some days the monitoring stations couldn’t measure the extent of the pollution. The intensity of the smoke and the length of time residents had been trapped in it were unprecedented, prompting county officials to issue their first evacuation orders because of smoke, not fire risk.

Many people stayed. That made Seeley Lake an ideal place to track the long-term health of people inundated by wildfire pollution.

So far, researchers have found that people’s lung capacity declined in the first 2 years after the smoke cleared. Chris Migliaccio, PhD, an immunologist with the University of Montana, Missoula, and associates found the percentage of residents whose lung function sank below normal thresholds more than doubled in the first year after the fire and remained low a year after that.

“There’s something wrong there,” Dr. Migliaccio said.

While it’s long been known that smoke can be dangerous when in the thick of it – triggering asthma attacks, cardiac arrests, hospitalizations and more – the Seeley Lake research confirmed what public health experts feared: Wildfire haze can have consequences long after it’s gone.

That doesn’t bode well for the 78 million people in the western United States now confronting historic wildfires.

Toxic air from fires has blanketed California and the Pacific Northwest for weeks now, causing some of the world’s worst air quality. California fires have burned roughly 2.3 million acres so far this year, and the wildfire season isn’t over yet. Oregon estimates 500,000 people in the state have been under a notice to either prepare to evacuate or leave. Smoke from the West Coast blazes has drifted as far away as Europe.

Extreme wildfires are predicted to become a regular occurrence because of climate change. And, as more people increasingly settle in fire-prone places, the risks increase. That’s shifted wildfires from being a perennial reality for rural mountain towns to becoming an annual threat for areas across the West.

Perry Hystad, PhD, an associate professor at Oregon State University, Corvallis, said the Seeley Lake research offers unique insights into wildfire smoke’s impact, which until recently had largely been unexplored. He said similar studies are likely to follow because of this fire season.

“This is the question that everybody is asking,” Dr. Hystad said. “‘I’ve been sitting in smoke for 2 weeks, how concerned should I be?’”

Dr. Migliaccio wants to know whether the lung damage he saw in Seeley Lake is reversible – or even treatable. (Think of an inhaler for asthma or other medication that prevents swollen airways.)

But those discoveries will have to wait. The team hasn’t been able to return to Seeley Lake this year because of the coronavirus pandemic.

Dr. Migliaccio said more research is needed on whether wildfire smoke damages organs besides the lungs, and whether routine exposure makes people more susceptible to diseases.

The combination of the fire season and the pandemic has spurred other questions as well, like whether heavy smoke exposure could lead to more COVID-19 deaths. A recent study showed a spike in influenza cases following major fire seasons.

“Now you have the combination of flu season and COVID and the wildfires,” Dr. Migliaccio said. “How are all these things going to interact come late fall or winter?”
 

A case study

Seeley Lake has long known smoke. It sits in a narrow valley between vast stretches of thick forests.

On a recent September day, Boyd Gossard stood on his back porch and pointed toward the mountains that were ablaze in 2017.

Mr. Gossard, 80, expects to have some summer days veiled in haze. But that year, he said, he could hardly see his neighbor’s house a few hundred feet away.

“I’ve seen a lot of smoke in my career,” said Mr. Gossard, who worked in timber management and served as a wildland firefighter. “But having to just live in it like this was very different. It got to you after a while.”

When Missoula County health officials urged people to leave town and flee the hazardous smoke, many residents stayed close to home. Some said their jobs wouldn’t let them leave. Others didn’t have a place to go – or the money to get there.

Health officials warned those who stayed to avoid exercising and breathing too hard, to remain inside, and to follow steps to make their homes as smoke free as possible. The health department also worked to get air filters to those who needed them most.

But when flames got too close, some people had to sleep outside in campsites on the other side of town.
 

Understanding the science of smoke

One of the known dangers of smoke is particulate matter. Smaller than the width of a human hair, it can bypass a body’s defenses, lodging deep into lungs. Lu Hu, PhD, an atmospheric chemist with the University of Montana, said air quality reports are based on how much of that pollution is in the air.

“It’s like lead; there’s no safe level, but still we have a safety measure for what’s allowable,” Dr. Hu said. “Some things kill you fast and some things kill you slowly.”

While air quality measurements can gauge the overall amount of pollution, they can’t assess which specific toxins people are inhaling. Dr. Hu is collaborating with other scientists to better predict how smoke travels and what pollutants people actually breathe.

He said smoke’s chemistry changes based on how far it travels and what’s burning, among other factors.

Over the past few years, teams of researchers drove trucks along fire lines to collect smoke samples. Other scientists boarded cargo planes and flew into smoke plumes to take samples right from a fire’s source. Still others stationed at a mountain lookout captured smoke drifting in from nearby fires. And ground-level machines at a Missoula site logged data over 2 summers.

Bob Yokelson, PhD, a longtime smoke researcher with the University of Montana, said scientists are getting closer to understanding its contents. And, he said, “it’s not all bad news.”

Temperature and sunlight can change some pollutants over time. Some dangerous particles seem to disappear. But others, such as ozone, can increase as smoke ages.

Dr. Yokelson said scientists are still a long way from determining a safe level of exposure to the hundred-odd pollutants in smoke.

“We can complete the circle by measuring not only what’s in smoke, but measuring what’s happening to the people who breathe it,” Dr. Yokelson said. “That’s where the future of health research on smoke is going to go.”
 

Coping with nowhere to flee

In the meantime, those studying wildland smoke hope what they’ve learned so far can better prepare people to live in the haze when evacuation isn’t an option.

Joan Wollan, 82, was one of the Seeley Lake study participants. She stayed put during the 2017 fire because her house at the time sat on a border of the evacuation zone. The air made her eyes burn and her husband cough. She ordered air filters to create cleaner air inside her home, which helped.

On a recent day, the air in Mrs. Wollan’s new neighborhood in Missoula turned that familiar gray-orange as traces of fires from elsewhere appeared. Local health officials warned that western Montana could get hit by some of the worst air quality the state had seen since those 2017 fires.

If it got bad enough, Mrs. Wollan said, she’d get the filters out of storage or look for a way to get to cleaner air – “if there is someplace in Montana that isn’t smoky.”

KHN (Kaiser Health News) is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

When researchers arrived in Seeley Lake, Mont., a town tucked in the northern Rockies, 3 years ago, they could still smell the smoke a day after it cleared from devastating wildfires. Their plan was to chart how long it took for people to recover from living for 7 weeks surrounded by relentless smoke.

They still don’t know, because most residents haven’t recovered. In fact, they’ve gotten worse.

Forest fires had funneled hazardous air into Seeley Lake, a town of fewer than 2,000 people, for 49 days. The air quality was so bad that on some days the monitoring stations couldn’t measure the extent of the pollution. The intensity of the smoke and the length of time residents had been trapped in it were unprecedented, prompting county officials to issue their first evacuation orders because of smoke, not fire risk.

Many people stayed. That made Seeley Lake an ideal place to track the long-term health of people inundated by wildfire pollution.

So far, researchers have found that people’s lung capacity declined in the first 2 years after the smoke cleared. Chris Migliaccio, PhD, an immunologist with the University of Montana, Missoula, and associates found the percentage of residents whose lung function sank below normal thresholds more than doubled in the first year after the fire and remained low a year after that.

“There’s something wrong there,” Dr. Migliaccio said.

While it’s long been known that smoke can be dangerous when in the thick of it – triggering asthma attacks, cardiac arrests, hospitalizations and more – the Seeley Lake research confirmed what public health experts feared: Wildfire haze can have consequences long after it’s gone.

That doesn’t bode well for the 78 million people in the western United States now confronting historic wildfires.

Toxic air from fires has blanketed California and the Pacific Northwest for weeks now, causing some of the world’s worst air quality. California fires have burned roughly 2.3 million acres so far this year, and the wildfire season isn’t over yet. Oregon estimates 500,000 people in the state have been under a notice to either prepare to evacuate or leave. Smoke from the West Coast blazes has drifted as far away as Europe.

Extreme wildfires are predicted to become a regular occurrence because of climate change. And, as more people increasingly settle in fire-prone places, the risks increase. That’s shifted wildfires from being a perennial reality for rural mountain towns to becoming an annual threat for areas across the West.

Perry Hystad, PhD, an associate professor at Oregon State University, Corvallis, said the Seeley Lake research offers unique insights into wildfire smoke’s impact, which until recently had largely been unexplored. He said similar studies are likely to follow because of this fire season.

“This is the question that everybody is asking,” Dr. Hystad said. “‘I’ve been sitting in smoke for 2 weeks, how concerned should I be?’”

Dr. Migliaccio wants to know whether the lung damage he saw in Seeley Lake is reversible – or even treatable. (Think of an inhaler for asthma or other medication that prevents swollen airways.)

But those discoveries will have to wait. The team hasn’t been able to return to Seeley Lake this year because of the coronavirus pandemic.

Dr. Migliaccio said more research is needed on whether wildfire smoke damages organs besides the lungs, and whether routine exposure makes people more susceptible to diseases.

The combination of the fire season and the pandemic has spurred other questions as well, like whether heavy smoke exposure could lead to more COVID-19 deaths. A recent study showed a spike in influenza cases following major fire seasons.

“Now you have the combination of flu season and COVID and the wildfires,” Dr. Migliaccio said. “How are all these things going to interact come late fall or winter?”
 

A case study

Seeley Lake has long known smoke. It sits in a narrow valley between vast stretches of thick forests.

On a recent September day, Boyd Gossard stood on his back porch and pointed toward the mountains that were ablaze in 2017.

Mr. Gossard, 80, expects to have some summer days veiled in haze. But that year, he said, he could hardly see his neighbor’s house a few hundred feet away.

“I’ve seen a lot of smoke in my career,” said Mr. Gossard, who worked in timber management and served as a wildland firefighter. “But having to just live in it like this was very different. It got to you after a while.”

When Missoula County health officials urged people to leave town and flee the hazardous smoke, many residents stayed close to home. Some said their jobs wouldn’t let them leave. Others didn’t have a place to go – or the money to get there.

Health officials warned those who stayed to avoid exercising and breathing too hard, to remain inside, and to follow steps to make their homes as smoke free as possible. The health department also worked to get air filters to those who needed them most.

But when flames got too close, some people had to sleep outside in campsites on the other side of town.
 

Understanding the science of smoke

One of the known dangers of smoke is particulate matter. Smaller than the width of a human hair, it can bypass a body’s defenses, lodging deep into lungs. Lu Hu, PhD, an atmospheric chemist with the University of Montana, said air quality reports are based on how much of that pollution is in the air.

“It’s like lead; there’s no safe level, but still we have a safety measure for what’s allowable,” Dr. Hu said. “Some things kill you fast and some things kill you slowly.”

While air quality measurements can gauge the overall amount of pollution, they can’t assess which specific toxins people are inhaling. Dr. Hu is collaborating with other scientists to better predict how smoke travels and what pollutants people actually breathe.

He said smoke’s chemistry changes based on how far it travels and what’s burning, among other factors.

Over the past few years, teams of researchers drove trucks along fire lines to collect smoke samples. Other scientists boarded cargo planes and flew into smoke plumes to take samples right from a fire’s source. Still others stationed at a mountain lookout captured smoke drifting in from nearby fires. And ground-level machines at a Missoula site logged data over 2 summers.

Bob Yokelson, PhD, a longtime smoke researcher with the University of Montana, said scientists are getting closer to understanding its contents. And, he said, “it’s not all bad news.”

Temperature and sunlight can change some pollutants over time. Some dangerous particles seem to disappear. But others, such as ozone, can increase as smoke ages.

Dr. Yokelson said scientists are still a long way from determining a safe level of exposure to the hundred-odd pollutants in smoke.

“We can complete the circle by measuring not only what’s in smoke, but measuring what’s happening to the people who breathe it,” Dr. Yokelson said. “That’s where the future of health research on smoke is going to go.”
 

Coping with nowhere to flee

In the meantime, those studying wildland smoke hope what they’ve learned so far can better prepare people to live in the haze when evacuation isn’t an option.

Joan Wollan, 82, was one of the Seeley Lake study participants. She stayed put during the 2017 fire because her house at the time sat on a border of the evacuation zone. The air made her eyes burn and her husband cough. She ordered air filters to create cleaner air inside her home, which helped.

On a recent day, the air in Mrs. Wollan’s new neighborhood in Missoula turned that familiar gray-orange as traces of fires from elsewhere appeared. Local health officials warned that western Montana could get hit by some of the worst air quality the state had seen since those 2017 fires.

If it got bad enough, Mrs. Wollan said, she’d get the filters out of storage or look for a way to get to cleaner air – “if there is someplace in Montana that isn’t smoky.”

KHN (Kaiser Health News) is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

When researchers arrived in Seeley Lake, Mont., a town tucked in the northern Rockies, 3 years ago, they could still smell the smoke a day after it cleared from devastating wildfires. Their plan was to chart how long it took for people to recover from living for 7 weeks surrounded by relentless smoke.

They still don’t know, because most residents haven’t recovered. In fact, they’ve gotten worse.

Forest fires had funneled hazardous air into Seeley Lake, a town of fewer than 2,000 people, for 49 days. The air quality was so bad that on some days the monitoring stations couldn’t measure the extent of the pollution. The intensity of the smoke and the length of time residents had been trapped in it were unprecedented, prompting county officials to issue their first evacuation orders because of smoke, not fire risk.

Many people stayed. That made Seeley Lake an ideal place to track the long-term health of people inundated by wildfire pollution.

So far, researchers have found that people’s lung capacity declined in the first 2 years after the smoke cleared. Chris Migliaccio, PhD, an immunologist with the University of Montana, Missoula, and associates found the percentage of residents whose lung function sank below normal thresholds more than doubled in the first year after the fire and remained low a year after that.

“There’s something wrong there,” Dr. Migliaccio said.

While it’s long been known that smoke can be dangerous when in the thick of it – triggering asthma attacks, cardiac arrests, hospitalizations and more – the Seeley Lake research confirmed what public health experts feared: Wildfire haze can have consequences long after it’s gone.

That doesn’t bode well for the 78 million people in the western United States now confronting historic wildfires.

Toxic air from fires has blanketed California and the Pacific Northwest for weeks now, causing some of the world’s worst air quality. California fires have burned roughly 2.3 million acres so far this year, and the wildfire season isn’t over yet. Oregon estimates 500,000 people in the state have been under a notice to either prepare to evacuate or leave. Smoke from the West Coast blazes has drifted as far away as Europe.

Extreme wildfires are predicted to become a regular occurrence because of climate change. And, as more people increasingly settle in fire-prone places, the risks increase. That’s shifted wildfires from being a perennial reality for rural mountain towns to becoming an annual threat for areas across the West.

Perry Hystad, PhD, an associate professor at Oregon State University, Corvallis, said the Seeley Lake research offers unique insights into wildfire smoke’s impact, which until recently had largely been unexplored. He said similar studies are likely to follow because of this fire season.

“This is the question that everybody is asking,” Dr. Hystad said. “‘I’ve been sitting in smoke for 2 weeks, how concerned should I be?’”

Dr. Migliaccio wants to know whether the lung damage he saw in Seeley Lake is reversible – or even treatable. (Think of an inhaler for asthma or other medication that prevents swollen airways.)

But those discoveries will have to wait. The team hasn’t been able to return to Seeley Lake this year because of the coronavirus pandemic.

Dr. Migliaccio said more research is needed on whether wildfire smoke damages organs besides the lungs, and whether routine exposure makes people more susceptible to diseases.

The combination of the fire season and the pandemic has spurred other questions as well, like whether heavy smoke exposure could lead to more COVID-19 deaths. A recent study showed a spike in influenza cases following major fire seasons.

“Now you have the combination of flu season and COVID and the wildfires,” Dr. Migliaccio said. “How are all these things going to interact come late fall or winter?”
 

A case study

Seeley Lake has long known smoke. It sits in a narrow valley between vast stretches of thick forests.

On a recent September day, Boyd Gossard stood on his back porch and pointed toward the mountains that were ablaze in 2017.

Mr. Gossard, 80, expects to have some summer days veiled in haze. But that year, he said, he could hardly see his neighbor’s house a few hundred feet away.

“I’ve seen a lot of smoke in my career,” said Mr. Gossard, who worked in timber management and served as a wildland firefighter. “But having to just live in it like this was very different. It got to you after a while.”

When Missoula County health officials urged people to leave town and flee the hazardous smoke, many residents stayed close to home. Some said their jobs wouldn’t let them leave. Others didn’t have a place to go – or the money to get there.

Health officials warned those who stayed to avoid exercising and breathing too hard, to remain inside, and to follow steps to make their homes as smoke free as possible. The health department also worked to get air filters to those who needed them most.

But when flames got too close, some people had to sleep outside in campsites on the other side of town.
 

Understanding the science of smoke

One of the known dangers of smoke is particulate matter. Smaller than the width of a human hair, it can bypass a body’s defenses, lodging deep into lungs. Lu Hu, PhD, an atmospheric chemist with the University of Montana, said air quality reports are based on how much of that pollution is in the air.

“It’s like lead; there’s no safe level, but still we have a safety measure for what’s allowable,” Dr. Hu said. “Some things kill you fast and some things kill you slowly.”

While air quality measurements can gauge the overall amount of pollution, they can’t assess which specific toxins people are inhaling. Dr. Hu is collaborating with other scientists to better predict how smoke travels and what pollutants people actually breathe.

He said smoke’s chemistry changes based on how far it travels and what’s burning, among other factors.

Over the past few years, teams of researchers drove trucks along fire lines to collect smoke samples. Other scientists boarded cargo planes and flew into smoke plumes to take samples right from a fire’s source. Still others stationed at a mountain lookout captured smoke drifting in from nearby fires. And ground-level machines at a Missoula site logged data over 2 summers.

Bob Yokelson, PhD, a longtime smoke researcher with the University of Montana, said scientists are getting closer to understanding its contents. And, he said, “it’s not all bad news.”

Temperature and sunlight can change some pollutants over time. Some dangerous particles seem to disappear. But others, such as ozone, can increase as smoke ages.

Dr. Yokelson said scientists are still a long way from determining a safe level of exposure to the hundred-odd pollutants in smoke.

“We can complete the circle by measuring not only what’s in smoke, but measuring what’s happening to the people who breathe it,” Dr. Yokelson said. “That’s where the future of health research on smoke is going to go.”
 

Coping with nowhere to flee

In the meantime, those studying wildland smoke hope what they’ve learned so far can better prepare people to live in the haze when evacuation isn’t an option.

Joan Wollan, 82, was one of the Seeley Lake study participants. She stayed put during the 2017 fire because her house at the time sat on a border of the evacuation zone. The air made her eyes burn and her husband cough. She ordered air filters to create cleaner air inside her home, which helped.

On a recent day, the air in Mrs. Wollan’s new neighborhood in Missoula turned that familiar gray-orange as traces of fires from elsewhere appeared. Local health officials warned that western Montana could get hit by some of the worst air quality the state had seen since those 2017 fires.

If it got bad enough, Mrs. Wollan said, she’d get the filters out of storage or look for a way to get to cleaner air – “if there is someplace in Montana that isn’t smoky.”

KHN (Kaiser Health News) is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.