Roxanne Nelson, RN, BSN

Despite the COVID-19 pandemic, oncologists still enjoyed an increase in their income as well as an increase in their overall wealth, according to the Medscape Oncologist Debt and Net Worth Report 2021.

Overall, oncologists’ average annual income rose from $377,000 in 2020 to $403,000 this year.

Although many offices closed for periods during 2020, some physicians used the Paycheck Protection Program. Others found other methods to keep their earnings relatively stable, such as switching to telehealth, cutting staff, and renegotiating leases.

The overall net worth of oncologists also increased. This year, 55% reported a net worth of $1.5 million, compared to 42% last year. A contributing factor is the rise in home prices, suggested Joel Greenwald, MD, CFP, a wealth management advisor for physicians.

The rise in the stock market also played a role, he noted. “And I’ve seen clients accumulate cash, which has added to their net worth. They cut back on spending because they were worried about big declines in income and also because there was simply less to spend money on.”

The percentage of oncologists (16%) with a net worth of more than $5 million stayed pretty much the same. Oncology remained in the upper half of the list of wealthy specialties. Topping that list are dermatology (28%), orthopedics and orthopedic surgery (25%), and plastic surgery (24%).

On the flip side, the percentage of oncologists on the lower end of the net worth scale declined from last year. Oncology was the specialty with the lowest percentage of practitioners (16%) reporting a net worth of under $500,000.
 

Expenses and debts

Similar to reports from previous years, this latest survey found that more than half of oncologists (56%) said they are paying off a mortgage on a primary residence. About a third (32%) are paying off a car loan. Credit card debt (19%), college or medical school loans (17%), childcare (14%), and medical expenses for themselves or a loved one (12%) were also reported.

When it comes to paying off school loans, oncology was near the bottom of the list of 29 medical specialties, along with nephrology, gastroenterology, and diabetes and endocrinology. Emergency medicine topped that list, followed by family medicine, pediatrics, physical medicine, and rehabilitation (all 31%).

Although the vast majority of oncologists (94%) were able to keep up with their bills, the pandemic did take a toll on some. Six percent said that they were unable to keep up with their bills, and 3% could not meet their mortgage. This is far superior to the American population at large – a quarter of adults missed a mortgage payment or rent payment because of challenges associated with the pandemic.
 

Saving and losses

Most oncologists did not take any extra steps to curtail spending – 77% reported that they had not done anything to reduce major expenses. About a quarter of respondents took significant steps to lower their expenses, such as deferring or refinancing loans (11%), switching to a different type of car (6%), or moving to a different home (5%).

Savings for tax deferred accounts this year was a mixed bag. More than half (56%) of oncologists said that they put aside the same amount every month, give or take; 11% do not regularly put money into a 401(k) retirement account or tax-deferred savings account. Compared to last year, 32% put less money into their savings accounts. Having fewer patients or working fewer hours during the pandemic may have resulted in oncologists needing more of their income, or even their full income, to pay their bills.

Similar results were seen with taxable savings. Half of oncologists were putting the same amount into bank accounts; 20% reported that they do not regularly put money into this type of account. Compared to last year, 29% put less money into taxable savings.

Most oncologists (75%) reported that they did not experience any significant financial losses during the past year. This was similar to last year (77%). The percentage of those who had losses related to their practice rose from 3% to 8%. Much of this increase was due to COVID-19.
 

Living within their means

The vast majority of oncologists live within or below their means (94%). “There are certainly folks who believe that as long as they pay their credit card every month and contribute to their 401(k) enough to get their employer match, they’re doing okay,” said Dr. Greenwald. “I would say living within one’s means is having a 3 to 6 months’ emergency fund and saving at least 20% of gross income toward retirement.”

Although most oncologists live within their means, they also have a higher than average number of credit cards. More than half (54%) have at least five; the average American has four. Nineteen percent of oncologists reported having seven or more credit cards, and none said they had no credit cards.

Mortgage payments varied considerably among respondents, from less than $100,000 (16%) to more than half a million (21%). More than a third (37%) reported having no mortgage at all. According to the Mortgage Bankers Association, the overall average size of a home mortgage loan was $344,556 in March 2020.

For household finances, 57% reported that they pool incomes to pay the bills, regardless of how much each person earns. A quarter said that they do not have joint finances with a spouse or partner, and for 13%, the person with the higher income paid a larger share.

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

Despite the COVID-19 pandemic, oncologists still enjoyed an increase in their income as well as an increase in their overall wealth, according to the Medscape Oncologist Debt and Net Worth Report 2021.

Overall, oncologists’ average annual income rose from $377,000 in 2020 to $403,000 this year.

Although many offices closed for periods during 2020, some physicians used the Paycheck Protection Program. Others found other methods to keep their earnings relatively stable, such as switching to telehealth, cutting staff, and renegotiating leases.

The overall net worth of oncologists also increased. This year, 55% reported a net worth of $1.5 million, compared to 42% last year. A contributing factor is the rise in home prices, suggested Joel Greenwald, MD, CFP, a wealth management advisor for physicians.

The rise in the stock market also played a role, he noted. “And I’ve seen clients accumulate cash, which has added to their net worth. They cut back on spending because they were worried about big declines in income and also because there was simply less to spend money on.”

The percentage of oncologists (16%) with a net worth of more than $5 million stayed pretty much the same. Oncology remained in the upper half of the list of wealthy specialties. Topping that list are dermatology (28%), orthopedics and orthopedic surgery (25%), and plastic surgery (24%).

On the flip side, the percentage of oncologists on the lower end of the net worth scale declined from last year. Oncology was the specialty with the lowest percentage of practitioners (16%) reporting a net worth of under $500,000.
 

Expenses and debts

Similar to reports from previous years, this latest survey found that more than half of oncologists (56%) said they are paying off a mortgage on a primary residence. About a third (32%) are paying off a car loan. Credit card debt (19%), college or medical school loans (17%), childcare (14%), and medical expenses for themselves or a loved one (12%) were also reported.

When it comes to paying off school loans, oncology was near the bottom of the list of 29 medical specialties, along with nephrology, gastroenterology, and diabetes and endocrinology. Emergency medicine topped that list, followed by family medicine, pediatrics, physical medicine, and rehabilitation (all 31%).

Although the vast majority of oncologists (94%) were able to keep up with their bills, the pandemic did take a toll on some. Six percent said that they were unable to keep up with their bills, and 3% could not meet their mortgage. This is far superior to the American population at large – a quarter of adults missed a mortgage payment or rent payment because of challenges associated with the pandemic.
 

Saving and losses

Most oncologists did not take any extra steps to curtail spending – 77% reported that they had not done anything to reduce major expenses. About a quarter of respondents took significant steps to lower their expenses, such as deferring or refinancing loans (11%), switching to a different type of car (6%), or moving to a different home (5%).

Savings for tax deferred accounts this year was a mixed bag. More than half (56%) of oncologists said that they put aside the same amount every month, give or take; 11% do not regularly put money into a 401(k) retirement account or tax-deferred savings account. Compared to last year, 32% put less money into their savings accounts. Having fewer patients or working fewer hours during the pandemic may have resulted in oncologists needing more of their income, or even their full income, to pay their bills.

Similar results were seen with taxable savings. Half of oncologists were putting the same amount into bank accounts; 20% reported that they do not regularly put money into this type of account. Compared to last year, 29% put less money into taxable savings.

Most oncologists (75%) reported that they did not experience any significant financial losses during the past year. This was similar to last year (77%). The percentage of those who had losses related to their practice rose from 3% to 8%. Much of this increase was due to COVID-19.
 

Living within their means

The vast majority of oncologists live within or below their means (94%). “There are certainly folks who believe that as long as they pay their credit card every month and contribute to their 401(k) enough to get their employer match, they’re doing okay,” said Dr. Greenwald. “I would say living within one’s means is having a 3 to 6 months’ emergency fund and saving at least 20% of gross income toward retirement.”

Although most oncologists live within their means, they also have a higher than average number of credit cards. More than half (54%) have at least five; the average American has four. Nineteen percent of oncologists reported having seven or more credit cards, and none said they had no credit cards.

Mortgage payments varied considerably among respondents, from less than $100,000 (16%) to more than half a million (21%). More than a third (37%) reported having no mortgage at all. According to the Mortgage Bankers Association, the overall average size of a home mortgage loan was $344,556 in March 2020.

For household finances, 57% reported that they pool incomes to pay the bills, regardless of how much each person earns. A quarter said that they do not have joint finances with a spouse or partner, and for 13%, the person with the higher income paid a larger share.

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

Despite the COVID-19 pandemic, oncologists still enjoyed an increase in their income as well as an increase in their overall wealth, according to the Medscape Oncologist Debt and Net Worth Report 2021.

Overall, oncologists’ average annual income rose from $377,000 in 2020 to $403,000 this year.

Although many offices closed for periods during 2020, some physicians used the Paycheck Protection Program. Others found other methods to keep their earnings relatively stable, such as switching to telehealth, cutting staff, and renegotiating leases.

The overall net worth of oncologists also increased. This year, 55% reported a net worth of $1.5 million, compared to 42% last year. A contributing factor is the rise in home prices, suggested Joel Greenwald, MD, CFP, a wealth management advisor for physicians.

The rise in the stock market also played a role, he noted. “And I’ve seen clients accumulate cash, which has added to their net worth. They cut back on spending because they were worried about big declines in income and also because there was simply less to spend money on.”

The percentage of oncologists (16%) with a net worth of more than $5 million stayed pretty much the same. Oncology remained in the upper half of the list of wealthy specialties. Topping that list are dermatology (28%), orthopedics and orthopedic surgery (25%), and plastic surgery (24%).

On the flip side, the percentage of oncologists on the lower end of the net worth scale declined from last year. Oncology was the specialty with the lowest percentage of practitioners (16%) reporting a net worth of under $500,000.
 

Expenses and debts

Similar to reports from previous years, this latest survey found that more than half of oncologists (56%) said they are paying off a mortgage on a primary residence. About a third (32%) are paying off a car loan. Credit card debt (19%), college or medical school loans (17%), childcare (14%), and medical expenses for themselves or a loved one (12%) were also reported.

When it comes to paying off school loans, oncology was near the bottom of the list of 29 medical specialties, along with nephrology, gastroenterology, and diabetes and endocrinology. Emergency medicine topped that list, followed by family medicine, pediatrics, physical medicine, and rehabilitation (all 31%).

Although the vast majority of oncologists (94%) were able to keep up with their bills, the pandemic did take a toll on some. Six percent said that they were unable to keep up with their bills, and 3% could not meet their mortgage. This is far superior to the American population at large – a quarter of adults missed a mortgage payment or rent payment because of challenges associated with the pandemic.
 

Saving and losses

Most oncologists did not take any extra steps to curtail spending – 77% reported that they had not done anything to reduce major expenses. About a quarter of respondents took significant steps to lower their expenses, such as deferring or refinancing loans (11%), switching to a different type of car (6%), or moving to a different home (5%).

Savings for tax deferred accounts this year was a mixed bag. More than half (56%) of oncologists said that they put aside the same amount every month, give or take; 11% do not regularly put money into a 401(k) retirement account or tax-deferred savings account. Compared to last year, 32% put less money into their savings accounts. Having fewer patients or working fewer hours during the pandemic may have resulted in oncologists needing more of their income, or even their full income, to pay their bills.

Similar results were seen with taxable savings. Half of oncologists were putting the same amount into bank accounts; 20% reported that they do not regularly put money into this type of account. Compared to last year, 29% put less money into taxable savings.

Most oncologists (75%) reported that they did not experience any significant financial losses during the past year. This was similar to last year (77%). The percentage of those who had losses related to their practice rose from 3% to 8%. Much of this increase was due to COVID-19.
 

Living within their means

The vast majority of oncologists live within or below their means (94%). “There are certainly folks who believe that as long as they pay their credit card every month and contribute to their 401(k) enough to get their employer match, they’re doing okay,” said Dr. Greenwald. “I would say living within one’s means is having a 3 to 6 months’ emergency fund and saving at least 20% of gross income toward retirement.”

Although most oncologists live within their means, they also have a higher than average number of credit cards. More than half (54%) have at least five; the average American has four. Nineteen percent of oncologists reported having seven or more credit cards, and none said they had no credit cards.

Mortgage payments varied considerably among respondents, from less than $100,000 (16%) to more than half a million (21%). More than a third (37%) reported having no mortgage at all. According to the Mortgage Bankers Association, the overall average size of a home mortgage loan was $344,556 in March 2020.

For household finances, 57% reported that they pool incomes to pay the bills, regardless of how much each person earns. A quarter said that they do not have joint finances with a spouse or partner, and for 13%, the person with the higher income paid a larger share.

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

A COVID-19 booster shot may be beneficial for patients with cancer who are undergoing treatment, according to new findings from an Israeli case-control study.

The seropositivity rate among the patients with cancer remained high (87%) about 4 months after the patients had received the second BNT162b2 (Pfizer/BioNTech) vaccination. However, the median IgG titer in the patients and the control persons who were without cancer decreased over time. Notably, in a previous analysis that the authors conducted and in the current one, the IgG titers were statistically significantly lower in the patients with cancer as compared to control persons.

The correlation between antibody levels following vaccination and clinical protection has yet to be proven, but the accumulating evidence supports antibody response as a possible correlate of disease protection.

“Our data can’t predict if a third booster dose is necessary,” said study author Salomon M. Stemmer, MD, professor at the Institute of Oncology of Rabin Medical Center, Petah Tikva, Israel. “It does seem quite logical that a booster dose will cause an increase in IgG levels.”

The findings were published Aug. 11, 2021, in a research letter in JAMA Oncology.

In their previous study, Dr. Stemmer and colleagues compared the rates of anti–spike antibody response to the initial shot of the BNT162b2 vaccine among 102 adults with solid-tumor cancers who were undergoing treatment with that of 78 healthy control persons. They found that a high percentage of patients undergoing treatment for cancer (90%) achieved a sufficient antibody response to the BNT162b2 vaccine.
 

Booster endorsed

Responses to COVID-19 vaccination have varied among patients with cancer. For patients with solid tumors, responses have been good even while the patients were receiving systemic therapy. However, among patients with blood cancers, particularly those receiving immunosuppressive therapies, responses have been poor. Studies have identified factors associated with a poor response, but it has been unclear whether to recommend booster shots.

In August the Food and Drug Administration authorized a third dose of either the Pfizer or the Moderna COVID-19 vaccine for all individuals with compromised immune systems. Those eligible for a third dose include solid-organ transplant recipients, those undergoing cancer treatments, and people with autoimmune diseases that suppress their immune systems.
 

IgG titers lower in cancer patients

In the current analysis, the authors evaluated the anti-S response in the patients with cancer approximately 4 months after they had received the second vaccine dose. They compared the responses in those patients with the responses in a control group.

The cohort included 95 patients from the prior study and 66 control persons. The most common malignancies were gastrointestinal (26%), lung (25%), and breast (18%).

All patients were receiving systemic therapy. Chemotherapy was the most common (28%), followed by immunotherapy (21%) and combination chemotherapy/biological therapy (20%).

At a median of 123 days after the second vaccination, 83 patients with cancer (87%) and all of the control patients (100%) were seropositive for anti-S IgG antibodies. The median titer levels were significantly lower among case patients as compared with control patients (417 AU/mL [interquartile range, 136-895] vs. 1,220 AU/mL [IQR, 588-1,987]; P < .001)

There was a 3.6-fold range in median titer values across tumor types and an even wider range (8.8-fold) across the different types of treatment. The lowest titers were observed among patients who had received immunotherapy plus chemotherapy/biological therapy (median [IQR], 94.4 [49.4-191] AU/mL vs. 147 [62.8-339] AU/mL).

In an exploratory multivariable analysis, treatments with chemotherapy plus immunotherapy and immunotherapy plus biological therapy were significantly associated with lower IgG titers.
 

No downside for cancer patients

The Biden administration announced a plan to begin booster COVID-19 vaccinations for all American adults in September, with recommendations that the third vaccine be given at least 8 months after the second mRNA vaccine dose.

Jeremy M. Levin, DPhil, the chairman and CEO of Ovid Therapeutics, explained that, concerning boosters, “it is inconceivable that we will have all data at this stage.

“Knowledge about how boosters work and don’t work and when you should ideally have them is imperfect,” he told this news organization. “However, we can have a lot of confidence in the fact that hundreds of millions of people have received the vaccine, so we know a lot about the safety and efficacy.”

Immunocompromised adults represent less than 5% of the total population, and most of the available data on vaccination are from patients who have undergone solid-organ transplant, Dr. Levin explained. Studies have shown that their response is less robust to vaccination in comparison with adults in the general population.

“Although it is still preliminary, the strongest data come from Israel,” he said, “where they found that the booster was highly effective and doubled the number of transplant patients who developed antibodies.”

But data are not yet available in the setting of cancer. “But even though we don’t have the data yet, the answer is that no matter, the booster process is essential,” he said. “The evidence we have is that boosters raise the immune response, and it is the best data we have now.”

Martin J. Edelman, MD, chair, department of hematology/oncology, Fox Chase Cancer Center, Philadelphia, noted that the current recommendation is that patients who are immunocompromised receive a booster immediately.

At his health system, this is interpreted to include patients who have undergone the following treatments: Transplant (solid-organ and bone marrow transplant), hemodialysis, hematologic malignancy treatment, active immunosuppressive (chemotherapy, chemoimmunotherapy, and nonhormonal or single-agent immunotherapy) treatment, rheumatology treatments, and high-dose steroids.

“As for cancer patients, we are making arrangements to vaccinate patients who meet the above criteria now,” he said. “There is no known downside to receiving booster immediately. While there may be less of a response than waiting for completion of treatment, we know that patients on active therapy are frequently able to mount a response, and any response is better than none.”

Dr. Edelman added that this area is changing very rapidly. “We will modify our approach as information and guidance from appropriate organizations, such as the FDA and CDC, become available.”

Dr. Stemmer has received institutional research grants from CAN-FITE, AstraZeneca, Bioline RX, BMS, Halozyme, Clovis Oncology, CTG Pharma, Exelixis, Geicam, Incyte, Lilly, Moderna, Teva Pharmaceuticals, and Roche, and owns stocks and options in CTG Pharma, DocBoxMD, Tyrnovo, VYPE, Cytora, and CAN-FITE. Dr. Edelman has received personal fees and other compensation from Windmil, Biomarker Strategies, AstraZeneca, Takeda, GlaxoSmithKline, Apexigen, Nektar, Bristol-Myers Squibb, Armo, Bergen Bio, and Apexigen outside the submitted work. He has submitted a patent for epigenetic modifications to increase susceptibility to radiopharmaceuticals and is a paid adviser for Kanaph and Flame. Dr. Levin is chairman and CEO of Ovid Therapeutics.

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

A COVID-19 booster shot may be beneficial for patients with cancer who are undergoing treatment, according to new findings from an Israeli case-control study.

The seropositivity rate among the patients with cancer remained high (87%) about 4 months after the patients had received the second BNT162b2 (Pfizer/BioNTech) vaccination. However, the median IgG titer in the patients and the control persons who were without cancer decreased over time. Notably, in a previous analysis that the authors conducted and in the current one, the IgG titers were statistically significantly lower in the patients with cancer as compared to control persons.

The correlation between antibody levels following vaccination and clinical protection has yet to be proven, but the accumulating evidence supports antibody response as a possible correlate of disease protection.

“Our data can’t predict if a third booster dose is necessary,” said study author Salomon M. Stemmer, MD, professor at the Institute of Oncology of Rabin Medical Center, Petah Tikva, Israel. “It does seem quite logical that a booster dose will cause an increase in IgG levels.”

The findings were published Aug. 11, 2021, in a research letter in JAMA Oncology.

In their previous study, Dr. Stemmer and colleagues compared the rates of anti–spike antibody response to the initial shot of the BNT162b2 vaccine among 102 adults with solid-tumor cancers who were undergoing treatment with that of 78 healthy control persons. They found that a high percentage of patients undergoing treatment for cancer (90%) achieved a sufficient antibody response to the BNT162b2 vaccine.
 

Booster endorsed

Responses to COVID-19 vaccination have varied among patients with cancer. For patients with solid tumors, responses have been good even while the patients were receiving systemic therapy. However, among patients with blood cancers, particularly those receiving immunosuppressive therapies, responses have been poor. Studies have identified factors associated with a poor response, but it has been unclear whether to recommend booster shots.

In August the Food and Drug Administration authorized a third dose of either the Pfizer or the Moderna COVID-19 vaccine for all individuals with compromised immune systems. Those eligible for a third dose include solid-organ transplant recipients, those undergoing cancer treatments, and people with autoimmune diseases that suppress their immune systems.
 

IgG titers lower in cancer patients

In the current analysis, the authors evaluated the anti-S response in the patients with cancer approximately 4 months after they had received the second vaccine dose. They compared the responses in those patients with the responses in a control group.

The cohort included 95 patients from the prior study and 66 control persons. The most common malignancies were gastrointestinal (26%), lung (25%), and breast (18%).

All patients were receiving systemic therapy. Chemotherapy was the most common (28%), followed by immunotherapy (21%) and combination chemotherapy/biological therapy (20%).

At a median of 123 days after the second vaccination, 83 patients with cancer (87%) and all of the control patients (100%) were seropositive for anti-S IgG antibodies. The median titer levels were significantly lower among case patients as compared with control patients (417 AU/mL [interquartile range, 136-895] vs. 1,220 AU/mL [IQR, 588-1,987]; P < .001)

There was a 3.6-fold range in median titer values across tumor types and an even wider range (8.8-fold) across the different types of treatment. The lowest titers were observed among patients who had received immunotherapy plus chemotherapy/biological therapy (median [IQR], 94.4 [49.4-191] AU/mL vs. 147 [62.8-339] AU/mL).

In an exploratory multivariable analysis, treatments with chemotherapy plus immunotherapy and immunotherapy plus biological therapy were significantly associated with lower IgG titers.
 

No downside for cancer patients

The Biden administration announced a plan to begin booster COVID-19 vaccinations for all American adults in September, with recommendations that the third vaccine be given at least 8 months after the second mRNA vaccine dose.

Jeremy M. Levin, DPhil, the chairman and CEO of Ovid Therapeutics, explained that, concerning boosters, “it is inconceivable that we will have all data at this stage.

“Knowledge about how boosters work and don’t work and when you should ideally have them is imperfect,” he told this news organization. “However, we can have a lot of confidence in the fact that hundreds of millions of people have received the vaccine, so we know a lot about the safety and efficacy.”

Immunocompromised adults represent less than 5% of the total population, and most of the available data on vaccination are from patients who have undergone solid-organ transplant, Dr. Levin explained. Studies have shown that their response is less robust to vaccination in comparison with adults in the general population.

“Although it is still preliminary, the strongest data come from Israel,” he said, “where they found that the booster was highly effective and doubled the number of transplant patients who developed antibodies.”

But data are not yet available in the setting of cancer. “But even though we don’t have the data yet, the answer is that no matter, the booster process is essential,” he said. “The evidence we have is that boosters raise the immune response, and it is the best data we have now.”

Martin J. Edelman, MD, chair, department of hematology/oncology, Fox Chase Cancer Center, Philadelphia, noted that the current recommendation is that patients who are immunocompromised receive a booster immediately.

At his health system, this is interpreted to include patients who have undergone the following treatments: Transplant (solid-organ and bone marrow transplant), hemodialysis, hematologic malignancy treatment, active immunosuppressive (chemotherapy, chemoimmunotherapy, and nonhormonal or single-agent immunotherapy) treatment, rheumatology treatments, and high-dose steroids.

“As for cancer patients, we are making arrangements to vaccinate patients who meet the above criteria now,” he said. “There is no known downside to receiving booster immediately. While there may be less of a response than waiting for completion of treatment, we know that patients on active therapy are frequently able to mount a response, and any response is better than none.”

Dr. Edelman added that this area is changing very rapidly. “We will modify our approach as information and guidance from appropriate organizations, such as the FDA and CDC, become available.”

Dr. Stemmer has received institutional research grants from CAN-FITE, AstraZeneca, Bioline RX, BMS, Halozyme, Clovis Oncology, CTG Pharma, Exelixis, Geicam, Incyte, Lilly, Moderna, Teva Pharmaceuticals, and Roche, and owns stocks and options in CTG Pharma, DocBoxMD, Tyrnovo, VYPE, Cytora, and CAN-FITE. Dr. Edelman has received personal fees and other compensation from Windmil, Biomarker Strategies, AstraZeneca, Takeda, GlaxoSmithKline, Apexigen, Nektar, Bristol-Myers Squibb, Armo, Bergen Bio, and Apexigen outside the submitted work. He has submitted a patent for epigenetic modifications to increase susceptibility to radiopharmaceuticals and is a paid adviser for Kanaph and Flame. Dr. Levin is chairman and CEO of Ovid Therapeutics.

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

A COVID-19 booster shot may be beneficial for patients with cancer who are undergoing treatment, according to new findings from an Israeli case-control study.

The seropositivity rate among the patients with cancer remained high (87%) about 4 months after the patients had received the second BNT162b2 (Pfizer/BioNTech) vaccination. However, the median IgG titer in the patients and the control persons who were without cancer decreased over time. Notably, in a previous analysis that the authors conducted and in the current one, the IgG titers were statistically significantly lower in the patients with cancer as compared to control persons.

The correlation between antibody levels following vaccination and clinical protection has yet to be proven, but the accumulating evidence supports antibody response as a possible correlate of disease protection.

“Our data can’t predict if a third booster dose is necessary,” said study author Salomon M. Stemmer, MD, professor at the Institute of Oncology of Rabin Medical Center, Petah Tikva, Israel. “It does seem quite logical that a booster dose will cause an increase in IgG levels.”

The findings were published Aug. 11, 2021, in a research letter in JAMA Oncology.

In their previous study, Dr. Stemmer and colleagues compared the rates of anti–spike antibody response to the initial shot of the BNT162b2 vaccine among 102 adults with solid-tumor cancers who were undergoing treatment with that of 78 healthy control persons. They found that a high percentage of patients undergoing treatment for cancer (90%) achieved a sufficient antibody response to the BNT162b2 vaccine.
 

Booster endorsed

Responses to COVID-19 vaccination have varied among patients with cancer. For patients with solid tumors, responses have been good even while the patients were receiving systemic therapy. However, among patients with blood cancers, particularly those receiving immunosuppressive therapies, responses have been poor. Studies have identified factors associated with a poor response, but it has been unclear whether to recommend booster shots.

In August the Food and Drug Administration authorized a third dose of either the Pfizer or the Moderna COVID-19 vaccine for all individuals with compromised immune systems. Those eligible for a third dose include solid-organ transplant recipients, those undergoing cancer treatments, and people with autoimmune diseases that suppress their immune systems.
 

IgG titers lower in cancer patients

In the current analysis, the authors evaluated the anti-S response in the patients with cancer approximately 4 months after they had received the second vaccine dose. They compared the responses in those patients with the responses in a control group.

The cohort included 95 patients from the prior study and 66 control persons. The most common malignancies were gastrointestinal (26%), lung (25%), and breast (18%).

All patients were receiving systemic therapy. Chemotherapy was the most common (28%), followed by immunotherapy (21%) and combination chemotherapy/biological therapy (20%).

At a median of 123 days after the second vaccination, 83 patients with cancer (87%) and all of the control patients (100%) were seropositive for anti-S IgG antibodies. The median titer levels were significantly lower among case patients as compared with control patients (417 AU/mL [interquartile range, 136-895] vs. 1,220 AU/mL [IQR, 588-1,987]; P < .001)

There was a 3.6-fold range in median titer values across tumor types and an even wider range (8.8-fold) across the different types of treatment. The lowest titers were observed among patients who had received immunotherapy plus chemotherapy/biological therapy (median [IQR], 94.4 [49.4-191] AU/mL vs. 147 [62.8-339] AU/mL).

In an exploratory multivariable analysis, treatments with chemotherapy plus immunotherapy and immunotherapy plus biological therapy were significantly associated with lower IgG titers.
 

No downside for cancer patients

The Biden administration announced a plan to begin booster COVID-19 vaccinations for all American adults in September, with recommendations that the third vaccine be given at least 8 months after the second mRNA vaccine dose.

Jeremy M. Levin, DPhil, the chairman and CEO of Ovid Therapeutics, explained that, concerning boosters, “it is inconceivable that we will have all data at this stage.

“Knowledge about how boosters work and don’t work and when you should ideally have them is imperfect,” he told this news organization. “However, we can have a lot of confidence in the fact that hundreds of millions of people have received the vaccine, so we know a lot about the safety and efficacy.”

Immunocompromised adults represent less than 5% of the total population, and most of the available data on vaccination are from patients who have undergone solid-organ transplant, Dr. Levin explained. Studies have shown that their response is less robust to vaccination in comparison with adults in the general population.

“Although it is still preliminary, the strongest data come from Israel,” he said, “where they found that the booster was highly effective and doubled the number of transplant patients who developed antibodies.”

But data are not yet available in the setting of cancer. “But even though we don’t have the data yet, the answer is that no matter, the booster process is essential,” he said. “The evidence we have is that boosters raise the immune response, and it is the best data we have now.”

Martin J. Edelman, MD, chair, department of hematology/oncology, Fox Chase Cancer Center, Philadelphia, noted that the current recommendation is that patients who are immunocompromised receive a booster immediately.

At his health system, this is interpreted to include patients who have undergone the following treatments: Transplant (solid-organ and bone marrow transplant), hemodialysis, hematologic malignancy treatment, active immunosuppressive (chemotherapy, chemoimmunotherapy, and nonhormonal or single-agent immunotherapy) treatment, rheumatology treatments, and high-dose steroids.

“As for cancer patients, we are making arrangements to vaccinate patients who meet the above criteria now,” he said. “There is no known downside to receiving booster immediately. While there may be less of a response than waiting for completion of treatment, we know that patients on active therapy are frequently able to mount a response, and any response is better than none.”

Dr. Edelman added that this area is changing very rapidly. “We will modify our approach as information and guidance from appropriate organizations, such as the FDA and CDC, become available.”

Dr. Stemmer has received institutional research grants from CAN-FITE, AstraZeneca, Bioline RX, BMS, Halozyme, Clovis Oncology, CTG Pharma, Exelixis, Geicam, Incyte, Lilly, Moderna, Teva Pharmaceuticals, and Roche, and owns stocks and options in CTG Pharma, DocBoxMD, Tyrnovo, VYPE, Cytora, and CAN-FITE. Dr. Edelman has received personal fees and other compensation from Windmil, Biomarker Strategies, AstraZeneca, Takeda, GlaxoSmithKline, Apexigen, Nektar, Bristol-Myers Squibb, Armo, Bergen Bio, and Apexigen outside the submitted work. He has submitted a patent for epigenetic modifications to increase susceptibility to radiopharmaceuticals and is a paid adviser for Kanaph and Flame. Dr. Levin is chairman and CEO of Ovid Therapeutics.

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

A remote monitoring system was highly effective in managing symptoms and improving quality of life among patients with cancer who were receiving chemotherapy, say researchers reporting the first clinical trial of the new approach.

The study tested the Advanced Symptom Management System (ASyMS) for patients with various cancer types who were undergoing treatment at cancer centers in several European countries. The study primarily focused on patients who were being treated with curative intent.

The 24-hour monitoring system optimized symptom management in a manner safe, secure, and in “real time,” the team reports. This is particularly relevant during the COVID-19 pandemic, they note.

“Our findings suggest that an evidence based remote monitoring intervention, such as ASyMS, has potential for implementation into routine care to make a meaningful difference to people with cancer,” the authors conclude.

The findings were published online in BMJ.

The results show that “ASyMS can be implemented across multiple countries within diverse health care systems,” commented lead author Roma Maguire, PhD, a professor of digital health and care at the University of Strathclyde, in Glasgow, and director of the Health and Care Futures initiative.

So far, the system has only been used in clinical research studies, but “our findings do suggest that it is feasible to implement our system on a wider scale,” she added.

The study cohort included 829 patients with various cancers, including nonmetastatic breast cancer, colorectal cancer, Hodgkin disease, and non-Hodgkin lymphoma. The patients were receiving first-line adjuvant chemotherapy or chemotherapy for the first time in 5 years. They were recruited from 12 cancer centers in Austria, Greece, Norway, the Republic of Ireland, and the United Kingdom.

Patients were randomly assigned to receive ASyMS (n = 415) or standard care (n = 414) during six cycles of chemotherapy.

The primary outcome was symptom burden, as determined using the Memorial Symptom Assessment Scale. Secondary outcomes included health-related quality of life, as determined by results on the Functional Assessment of Cancer Therapy–General, the Supportive Care Needs Survey–Short Form, the State-Trait Anxiety Inventory–Revised, the Communication and Attitudinal Self-Efficacy scale for cancer, and the Work Limitations Questionnaire.

Patients in the intervention group completed a daily symptom questionnaire on a handheld ASyMS device, which generated alerts to health care professionals if any intervention was needed. The patients were also provided with advice and information on how to manage their symptoms themselves.

Among patients using ASyMS, symptom burden remained at prechemotherapy levels over all six chemotherapy cycles. Conversely, the control group reported an increase in symptom burden from cycle 1; symptom burden slowly decreased during the remaining chemotherapy cycles.

Overall, the investigators found that, among the patients who used ASyMS, psychological and physical symptoms were significantly reduced, along with the level of distress associated with each symptom.

In addition, for the patients who used ASyMS, health-related quality-of-life scores were higher across all cycles. The authors note that the improvements in health-related quality of life are consistent with findings from recent trials of the use of remote monitoring systems in chemotherapy care. The intervention group also experienced significant improvements regarding the need for supportive care.

Improvements in symptom burden differed among countries. The greatest improvements were seen among patients with breast cancer, Hodgkin disease, or non-Hodgkin lymphoma in Austria, Ireland, and the United Kingdom. The reasons for these differences are unclear, the authors note. ASyMS was developed in the United Kingdom, and it’s possible that ASyMS is more effective in countries that have health care systems similar to the system in the United Kingdom, they suggest.

The incidence of adverse events was similar for the two groups, although the rate of neutropenia was higher among patients using ASyMS (n = 125; 64%) in comparison with the standard-care group ( n = 71; 36%). Three deaths occurred in each study arm. The number of planned hospital admissions was similar between the two groups (34 vs. 38), as was the number of unplanned hospital admissions (120 vs. 109). No ASyMS device-related incidents were reported.

The trial was funded by the European Commission and was sponsored by the University of Strathclyde. Dr. Maguire has disclosed no relevant financial relationships.

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

A remote monitoring system was highly effective in managing symptoms and improving quality of life among patients with cancer who were receiving chemotherapy, say researchers reporting the first clinical trial of the new approach.

The study tested the Advanced Symptom Management System (ASyMS) for patients with various cancer types who were undergoing treatment at cancer centers in several European countries. The study primarily focused on patients who were being treated with curative intent.

The 24-hour monitoring system optimized symptom management in a manner safe, secure, and in “real time,” the team reports. This is particularly relevant during the COVID-19 pandemic, they note.

“Our findings suggest that an evidence based remote monitoring intervention, such as ASyMS, has potential for implementation into routine care to make a meaningful difference to people with cancer,” the authors conclude.

The findings were published online in BMJ.

The results show that “ASyMS can be implemented across multiple countries within diverse health care systems,” commented lead author Roma Maguire, PhD, a professor of digital health and care at the University of Strathclyde, in Glasgow, and director of the Health and Care Futures initiative.

So far, the system has only been used in clinical research studies, but “our findings do suggest that it is feasible to implement our system on a wider scale,” she added.

The study cohort included 829 patients with various cancers, including nonmetastatic breast cancer, colorectal cancer, Hodgkin disease, and non-Hodgkin lymphoma. The patients were receiving first-line adjuvant chemotherapy or chemotherapy for the first time in 5 years. They were recruited from 12 cancer centers in Austria, Greece, Norway, the Republic of Ireland, and the United Kingdom.

Patients were randomly assigned to receive ASyMS (n = 415) or standard care (n = 414) during six cycles of chemotherapy.

The primary outcome was symptom burden, as determined using the Memorial Symptom Assessment Scale. Secondary outcomes included health-related quality of life, as determined by results on the Functional Assessment of Cancer Therapy–General, the Supportive Care Needs Survey–Short Form, the State-Trait Anxiety Inventory–Revised, the Communication and Attitudinal Self-Efficacy scale for cancer, and the Work Limitations Questionnaire.

Patients in the intervention group completed a daily symptom questionnaire on a handheld ASyMS device, which generated alerts to health care professionals if any intervention was needed. The patients were also provided with advice and information on how to manage their symptoms themselves.

Among patients using ASyMS, symptom burden remained at prechemotherapy levels over all six chemotherapy cycles. Conversely, the control group reported an increase in symptom burden from cycle 1; symptom burden slowly decreased during the remaining chemotherapy cycles.

Overall, the investigators found that, among the patients who used ASyMS, psychological and physical symptoms were significantly reduced, along with the level of distress associated with each symptom.

In addition, for the patients who used ASyMS, health-related quality-of-life scores were higher across all cycles. The authors note that the improvements in health-related quality of life are consistent with findings from recent trials of the use of remote monitoring systems in chemotherapy care. The intervention group also experienced significant improvements regarding the need for supportive care.

Improvements in symptom burden differed among countries. The greatest improvements were seen among patients with breast cancer, Hodgkin disease, or non-Hodgkin lymphoma in Austria, Ireland, and the United Kingdom. The reasons for these differences are unclear, the authors note. ASyMS was developed in the United Kingdom, and it’s possible that ASyMS is more effective in countries that have health care systems similar to the system in the United Kingdom, they suggest.

The incidence of adverse events was similar for the two groups, although the rate of neutropenia was higher among patients using ASyMS (n = 125; 64%) in comparison with the standard-care group ( n = 71; 36%). Three deaths occurred in each study arm. The number of planned hospital admissions was similar between the two groups (34 vs. 38), as was the number of unplanned hospital admissions (120 vs. 109). No ASyMS device-related incidents were reported.

The trial was funded by the European Commission and was sponsored by the University of Strathclyde. Dr. Maguire has disclosed no relevant financial relationships.

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

A remote monitoring system was highly effective in managing symptoms and improving quality of life among patients with cancer who were receiving chemotherapy, say researchers reporting the first clinical trial of the new approach.

The study tested the Advanced Symptom Management System (ASyMS) for patients with various cancer types who were undergoing treatment at cancer centers in several European countries. The study primarily focused on patients who were being treated with curative intent.

The 24-hour monitoring system optimized symptom management in a manner safe, secure, and in “real time,” the team reports. This is particularly relevant during the COVID-19 pandemic, they note.

“Our findings suggest that an evidence based remote monitoring intervention, such as ASyMS, has potential for implementation into routine care to make a meaningful difference to people with cancer,” the authors conclude.

The findings were published online in BMJ.

The results show that “ASyMS can be implemented across multiple countries within diverse health care systems,” commented lead author Roma Maguire, PhD, a professor of digital health and care at the University of Strathclyde, in Glasgow, and director of the Health and Care Futures initiative.

So far, the system has only been used in clinical research studies, but “our findings do suggest that it is feasible to implement our system on a wider scale,” she added.

The study cohort included 829 patients with various cancers, including nonmetastatic breast cancer, colorectal cancer, Hodgkin disease, and non-Hodgkin lymphoma. The patients were receiving first-line adjuvant chemotherapy or chemotherapy for the first time in 5 years. They were recruited from 12 cancer centers in Austria, Greece, Norway, the Republic of Ireland, and the United Kingdom.

Patients were randomly assigned to receive ASyMS (n = 415) or standard care (n = 414) during six cycles of chemotherapy.

The primary outcome was symptom burden, as determined using the Memorial Symptom Assessment Scale. Secondary outcomes included health-related quality of life, as determined by results on the Functional Assessment of Cancer Therapy–General, the Supportive Care Needs Survey–Short Form, the State-Trait Anxiety Inventory–Revised, the Communication and Attitudinal Self-Efficacy scale for cancer, and the Work Limitations Questionnaire.

Patients in the intervention group completed a daily symptom questionnaire on a handheld ASyMS device, which generated alerts to health care professionals if any intervention was needed. The patients were also provided with advice and information on how to manage their symptoms themselves.

Among patients using ASyMS, symptom burden remained at prechemotherapy levels over all six chemotherapy cycles. Conversely, the control group reported an increase in symptom burden from cycle 1; symptom burden slowly decreased during the remaining chemotherapy cycles.

Overall, the investigators found that, among the patients who used ASyMS, psychological and physical symptoms were significantly reduced, along with the level of distress associated with each symptom.

In addition, for the patients who used ASyMS, health-related quality-of-life scores were higher across all cycles. The authors note that the improvements in health-related quality of life are consistent with findings from recent trials of the use of remote monitoring systems in chemotherapy care. The intervention group also experienced significant improvements regarding the need for supportive care.

Improvements in symptom burden differed among countries. The greatest improvements were seen among patients with breast cancer, Hodgkin disease, or non-Hodgkin lymphoma in Austria, Ireland, and the United Kingdom. The reasons for these differences are unclear, the authors note. ASyMS was developed in the United Kingdom, and it’s possible that ASyMS is more effective in countries that have health care systems similar to the system in the United Kingdom, they suggest.

The incidence of adverse events was similar for the two groups, although the rate of neutropenia was higher among patients using ASyMS (n = 125; 64%) in comparison with the standard-care group ( n = 71; 36%). Three deaths occurred in each study arm. The number of planned hospital admissions was similar between the two groups (34 vs. 38), as was the number of unplanned hospital admissions (120 vs. 109). No ASyMS device-related incidents were reported.

The trial was funded by the European Commission and was sponsored by the University of Strathclyde. Dr. Maguire has disclosed no relevant financial relationships.

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

A case report describes a novel helmet device that generates a noninvasive oscillating magnetic field and that shrunk a glioblastoma tumor by about a third.

This is the first time that the wearable Oncomagnetic device was tried with a patient.

The patient had end-stage recurrent glioblastoma and had undergone all standard therapy options. He wore the device for 5 weeks but died from an unrelated injury, so the treatment period was cut short.

A brain scan showed a 31% reduction of contrast-enhanced tumor volume, and an autopsy of his brain confirmed the rapid response to the treatment.

The case study was published online on July 22, 2021, in Frontiers in Oncology.

“I believe that there is a great potential with this device,” said study author David S. Baskin, MD, director of the Kenneth R. Peak Center for Brain and Pituitary Tumor Treatment in the department of neurosurgery at Houston Methodist Hospital. “This is a very exciting time.”

The team is now treating several patients with glioblastoma under compassionate use.

In an independent comment, Adilia Hormigo, MD, PhD, director of the neuro-oncology program at the Tisch Cancer Institute, Mount Sinai Health System, New York, noted that a clinical trial is needed to evaluate the device. “But this is an interesting idea, and we have to be open-minded in treating this fatal disease.”
 

Oscillating magnetic fields

The Oncomagnetic device consists of three oncoscillators that are attached to the outside of a helmet and are connected to a microprocessor-based electronic controller powered by a rechargeable battery.

It consists of a series of rotating magnets that produce oscillating magnetic fields that cover the entire brain, including the upper part of the brain stem. The device induces rapid apoptosis of glioblastoma cells, Dr. Baskin explained. Its mechanism of action involves disruption of the electron transport in the mitochondrial respiratory chain, causing an elevation of reactive oxygen species and caspase-dependent cancer cell death.

Dr. Baskin emphasized that the new Oncomagnetic device is very different from the Optune device (Novocare), which is already approved by the Food and Drug Administration and has been shown to increase survival among patients with glioblastoma. Optune uses tumor-treating fields (TTFs), which are electromagnetic waves that are delivered via an electric field generator through four transducer arrays that are placed on a shaved scalp. Preclinical studies indicated that the TTFs disrupt cell division by disrupting several steps in the mitotic process that are crucial for cell division.

Both of these devices “are using a type of external maneuver” rather than invasive intracranial approaches, said Dr. Hormingo. The experimental Oncomagnetic device may have an advantage in that it needs to be worn by the patient for fewer hours, she commented. A better understanding of the physics and underlying mechanism is needed, however. Clinical trials are an essential next step.
 

Most common brain cancer in adults

Glioblastoma is the most common malignant tumor of the brain in adults. Outcomes continue to be dismal. In more than 40 years, median survival has only modestly improved.

“We haven’t gotten very far with glioblastoma despite millions of dollars in research,” Dr. Baskin said. “With treatment, survival is about 15 months, and those are not very good months.”
 

Out of the box

Standard treatments for glioblastoma include surgery, radiotherapy, and chemotherapy, and many patients cannot tolerate some of these, Dr. Baskin noted. Hence, there is a great need for a different therapeutic approach that yields better outcomes with lower toxicity.

“We didn’t want to develop another chemotherapeutic agent that would help you live another 2 months,” he said in an interview. “We were trying to think out of the box.

“If you want to do something that will really make a difference in an aggressive tumor like glioblastoma, you have to attack something so basic that the tumor can’t evade it,” he said. “For example, with temozolomide, if it is unmethylated, the tumor can repair the DNA damage from the chemotherapy. Even if you’re sensitive to begin with, over time, the tumor will eventually become resistant.”

The new device stems from work by Dr. Baskin and colleagues on mitochondria, which he describes as the powerhouse of the cell. “Mitochondrial DNA can’t repair itself, so if you damage the mitochondria, you will damage the cell, and theoretically, it cannot repair itself,” he said.

In preclinical models, the oscillating magnetic fields generated by the new device were shown to kill patient-derived glioblastoma cells in cell culture without having cytotoxic effects on cortical neurons and normal human astrocytes. Animal studies also showed that it was effective and nontoxic, explained Dr. Baskin.

However, getting the device to human clinical trials has been slow going. “We wanted to start an early-phase trial for an investigational device, but the FDA is overwhelmed with COVID-related applications,” he said. “That has taken priority, and we understand that. So we were able to evaluate it on a patient through compassionate use via the [Food and Drug Administration]–approved Expanded Access Program.”
 

Exciting possibilities

The patient was a 53-year-old man who had undergone radiotherapy and chemotherapy, and the tumor was progressing. Imaging revealed the presence of leptomeningeal disease, which is associated with a poor outcome and a median survival of 3.5-3.9 months.

The patient was fitted with the helmet device and wore it under supervision for the first 3 days of treatment, during which time the strength of the oscillating magnetic fields was escalated. After this initial supervised phase, the treatment continued at home without supervision, using the same regimen as on the third day.

Treatment was first administered for 2 hours while under supervision and was then gradually increased to a maximum of 6 hours per day. The patient was evaluated clinically on days 7, 16, 30, and 44 after initiation of treatment. No serious adverse events were reported during treatment. The patient’s wife reported subjective improvement in speech and cognitive function.

Dr. Baskin noted that the patient had been experiencing falls for the past year and a half before treatment was initiated. “And then he tripped and fell and sustained a head injury that he subsequently died from,” he said.

Autopsy results confirmed the rapid response to treatment, and tumor shrinkage appeared to correlate with the treatment dose.

“Our results in the laboratory and with this patient open a new world of noninvasive and nontoxic therapy for brain cancer, with many exciting possibilities for the future,” Dr. Baskin commented.

He said his team has experimented with this approach with other tumor types in the laboratory, including triple-negative breast cancer and lung cancer. “We’ve only tried it in a culture so far, but it seems to melt the cancer cells,” he said.

The work was supported by a grant from the Translational Research Initiative of the Houston Methodist Research Institute and several foundations. Dr. Baskin and two coauthors are listed as inventors on a U.S. patent application filed by Houston Methodist Hospital for the device used in this report.

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

A case report describes a novel helmet device that generates a noninvasive oscillating magnetic field and that shrunk a glioblastoma tumor by about a third.

This is the first time that the wearable Oncomagnetic device was tried with a patient.

The patient had end-stage recurrent glioblastoma and had undergone all standard therapy options. He wore the device for 5 weeks but died from an unrelated injury, so the treatment period was cut short.

A brain scan showed a 31% reduction of contrast-enhanced tumor volume, and an autopsy of his brain confirmed the rapid response to the treatment.

The case study was published online on July 22, 2021, in Frontiers in Oncology.

“I believe that there is a great potential with this device,” said study author David S. Baskin, MD, director of the Kenneth R. Peak Center for Brain and Pituitary Tumor Treatment in the department of neurosurgery at Houston Methodist Hospital. “This is a very exciting time.”

The team is now treating several patients with glioblastoma under compassionate use.

In an independent comment, Adilia Hormigo, MD, PhD, director of the neuro-oncology program at the Tisch Cancer Institute, Mount Sinai Health System, New York, noted that a clinical trial is needed to evaluate the device. “But this is an interesting idea, and we have to be open-minded in treating this fatal disease.”
 

Oscillating magnetic fields

The Oncomagnetic device consists of three oncoscillators that are attached to the outside of a helmet and are connected to a microprocessor-based electronic controller powered by a rechargeable battery.

It consists of a series of rotating magnets that produce oscillating magnetic fields that cover the entire brain, including the upper part of the brain stem. The device induces rapid apoptosis of glioblastoma cells, Dr. Baskin explained. Its mechanism of action involves disruption of the electron transport in the mitochondrial respiratory chain, causing an elevation of reactive oxygen species and caspase-dependent cancer cell death.

Dr. Baskin emphasized that the new Oncomagnetic device is very different from the Optune device (Novocare), which is already approved by the Food and Drug Administration and has been shown to increase survival among patients with glioblastoma. Optune uses tumor-treating fields (TTFs), which are electromagnetic waves that are delivered via an electric field generator through four transducer arrays that are placed on a shaved scalp. Preclinical studies indicated that the TTFs disrupt cell division by disrupting several steps in the mitotic process that are crucial for cell division.

Both of these devices “are using a type of external maneuver” rather than invasive intracranial approaches, said Dr. Hormingo. The experimental Oncomagnetic device may have an advantage in that it needs to be worn by the patient for fewer hours, she commented. A better understanding of the physics and underlying mechanism is needed, however. Clinical trials are an essential next step.
 

Most common brain cancer in adults

Glioblastoma is the most common malignant tumor of the brain in adults. Outcomes continue to be dismal. In more than 40 years, median survival has only modestly improved.

“We haven’t gotten very far with glioblastoma despite millions of dollars in research,” Dr. Baskin said. “With treatment, survival is about 15 months, and those are not very good months.”
 

Out of the box

Standard treatments for glioblastoma include surgery, radiotherapy, and chemotherapy, and many patients cannot tolerate some of these, Dr. Baskin noted. Hence, there is a great need for a different therapeutic approach that yields better outcomes with lower toxicity.

“We didn’t want to develop another chemotherapeutic agent that would help you live another 2 months,” he said in an interview. “We were trying to think out of the box.

“If you want to do something that will really make a difference in an aggressive tumor like glioblastoma, you have to attack something so basic that the tumor can’t evade it,” he said. “For example, with temozolomide, if it is unmethylated, the tumor can repair the DNA damage from the chemotherapy. Even if you’re sensitive to begin with, over time, the tumor will eventually become resistant.”

The new device stems from work by Dr. Baskin and colleagues on mitochondria, which he describes as the powerhouse of the cell. “Mitochondrial DNA can’t repair itself, so if you damage the mitochondria, you will damage the cell, and theoretically, it cannot repair itself,” he said.

In preclinical models, the oscillating magnetic fields generated by the new device were shown to kill patient-derived glioblastoma cells in cell culture without having cytotoxic effects on cortical neurons and normal human astrocytes. Animal studies also showed that it was effective and nontoxic, explained Dr. Baskin.

However, getting the device to human clinical trials has been slow going. “We wanted to start an early-phase trial for an investigational device, but the FDA is overwhelmed with COVID-related applications,” he said. “That has taken priority, and we understand that. So we were able to evaluate it on a patient through compassionate use via the [Food and Drug Administration]–approved Expanded Access Program.”
 

Exciting possibilities

The patient was a 53-year-old man who had undergone radiotherapy and chemotherapy, and the tumor was progressing. Imaging revealed the presence of leptomeningeal disease, which is associated with a poor outcome and a median survival of 3.5-3.9 months.

The patient was fitted with the helmet device and wore it under supervision for the first 3 days of treatment, during which time the strength of the oscillating magnetic fields was escalated. After this initial supervised phase, the treatment continued at home without supervision, using the same regimen as on the third day.

Treatment was first administered for 2 hours while under supervision and was then gradually increased to a maximum of 6 hours per day. The patient was evaluated clinically on days 7, 16, 30, and 44 after initiation of treatment. No serious adverse events were reported during treatment. The patient’s wife reported subjective improvement in speech and cognitive function.

Dr. Baskin noted that the patient had been experiencing falls for the past year and a half before treatment was initiated. “And then he tripped and fell and sustained a head injury that he subsequently died from,” he said.

Autopsy results confirmed the rapid response to treatment, and tumor shrinkage appeared to correlate with the treatment dose.

“Our results in the laboratory and with this patient open a new world of noninvasive and nontoxic therapy for brain cancer, with many exciting possibilities for the future,” Dr. Baskin commented.

He said his team has experimented with this approach with other tumor types in the laboratory, including triple-negative breast cancer and lung cancer. “We’ve only tried it in a culture so far, but it seems to melt the cancer cells,” he said.

The work was supported by a grant from the Translational Research Initiative of the Houston Methodist Research Institute and several foundations. Dr. Baskin and two coauthors are listed as inventors on a U.S. patent application filed by Houston Methodist Hospital for the device used in this report.

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

A case report describes a novel helmet device that generates a noninvasive oscillating magnetic field and that shrunk a glioblastoma tumor by about a third.

This is the first time that the wearable Oncomagnetic device was tried with a patient.

The patient had end-stage recurrent glioblastoma and had undergone all standard therapy options. He wore the device for 5 weeks but died from an unrelated injury, so the treatment period was cut short.

A brain scan showed a 31% reduction of contrast-enhanced tumor volume, and an autopsy of his brain confirmed the rapid response to the treatment.

The case study was published online on July 22, 2021, in Frontiers in Oncology.

“I believe that there is a great potential with this device,” said study author David S. Baskin, MD, director of the Kenneth R. Peak Center for Brain and Pituitary Tumor Treatment in the department of neurosurgery at Houston Methodist Hospital. “This is a very exciting time.”

The team is now treating several patients with glioblastoma under compassionate use.

In an independent comment, Adilia Hormigo, MD, PhD, director of the neuro-oncology program at the Tisch Cancer Institute, Mount Sinai Health System, New York, noted that a clinical trial is needed to evaluate the device. “But this is an interesting idea, and we have to be open-minded in treating this fatal disease.”
 

Oscillating magnetic fields

The Oncomagnetic device consists of three oncoscillators that are attached to the outside of a helmet and are connected to a microprocessor-based electronic controller powered by a rechargeable battery.

It consists of a series of rotating magnets that produce oscillating magnetic fields that cover the entire brain, including the upper part of the brain stem. The device induces rapid apoptosis of glioblastoma cells, Dr. Baskin explained. Its mechanism of action involves disruption of the electron transport in the mitochondrial respiratory chain, causing an elevation of reactive oxygen species and caspase-dependent cancer cell death.

Dr. Baskin emphasized that the new Oncomagnetic device is very different from the Optune device (Novocare), which is already approved by the Food and Drug Administration and has been shown to increase survival among patients with glioblastoma. Optune uses tumor-treating fields (TTFs), which are electromagnetic waves that are delivered via an electric field generator through four transducer arrays that are placed on a shaved scalp. Preclinical studies indicated that the TTFs disrupt cell division by disrupting several steps in the mitotic process that are crucial for cell division.

Both of these devices “are using a type of external maneuver” rather than invasive intracranial approaches, said Dr. Hormingo. The experimental Oncomagnetic device may have an advantage in that it needs to be worn by the patient for fewer hours, she commented. A better understanding of the physics and underlying mechanism is needed, however. Clinical trials are an essential next step.
 

Most common brain cancer in adults

Glioblastoma is the most common malignant tumor of the brain in adults. Outcomes continue to be dismal. In more than 40 years, median survival has only modestly improved.

“We haven’t gotten very far with glioblastoma despite millions of dollars in research,” Dr. Baskin said. “With treatment, survival is about 15 months, and those are not very good months.”
 

Out of the box

Standard treatments for glioblastoma include surgery, radiotherapy, and chemotherapy, and many patients cannot tolerate some of these, Dr. Baskin noted. Hence, there is a great need for a different therapeutic approach that yields better outcomes with lower toxicity.

“We didn’t want to develop another chemotherapeutic agent that would help you live another 2 months,” he said in an interview. “We were trying to think out of the box.

“If you want to do something that will really make a difference in an aggressive tumor like glioblastoma, you have to attack something so basic that the tumor can’t evade it,” he said. “For example, with temozolomide, if it is unmethylated, the tumor can repair the DNA damage from the chemotherapy. Even if you’re sensitive to begin with, over time, the tumor will eventually become resistant.”

The new device stems from work by Dr. Baskin and colleagues on mitochondria, which he describes as the powerhouse of the cell. “Mitochondrial DNA can’t repair itself, so if you damage the mitochondria, you will damage the cell, and theoretically, it cannot repair itself,” he said.

In preclinical models, the oscillating magnetic fields generated by the new device were shown to kill patient-derived glioblastoma cells in cell culture without having cytotoxic effects on cortical neurons and normal human astrocytes. Animal studies also showed that it was effective and nontoxic, explained Dr. Baskin.

However, getting the device to human clinical trials has been slow going. “We wanted to start an early-phase trial for an investigational device, but the FDA is overwhelmed with COVID-related applications,” he said. “That has taken priority, and we understand that. So we were able to evaluate it on a patient through compassionate use via the [Food and Drug Administration]–approved Expanded Access Program.”
 

Exciting possibilities

The patient was a 53-year-old man who had undergone radiotherapy and chemotherapy, and the tumor was progressing. Imaging revealed the presence of leptomeningeal disease, which is associated with a poor outcome and a median survival of 3.5-3.9 months.

The patient was fitted with the helmet device and wore it under supervision for the first 3 days of treatment, during which time the strength of the oscillating magnetic fields was escalated. After this initial supervised phase, the treatment continued at home without supervision, using the same regimen as on the third day.

Treatment was first administered for 2 hours while under supervision and was then gradually increased to a maximum of 6 hours per day. The patient was evaluated clinically on days 7, 16, 30, and 44 after initiation of treatment. No serious adverse events were reported during treatment. The patient’s wife reported subjective improvement in speech and cognitive function.

Dr. Baskin noted that the patient had been experiencing falls for the past year and a half before treatment was initiated. “And then he tripped and fell and sustained a head injury that he subsequently died from,” he said.

Autopsy results confirmed the rapid response to treatment, and tumor shrinkage appeared to correlate with the treatment dose.

“Our results in the laboratory and with this patient open a new world of noninvasive and nontoxic therapy for brain cancer, with many exciting possibilities for the future,” Dr. Baskin commented.

He said his team has experimented with this approach with other tumor types in the laboratory, including triple-negative breast cancer and lung cancer. “We’ve only tried it in a culture so far, but it seems to melt the cancer cells,” he said.

The work was supported by a grant from the Translational Research Initiative of the Houston Methodist Research Institute and several foundations. Dr. Baskin and two coauthors are listed as inventors on a U.S. patent application filed by Houston Methodist Hospital for the device used in this report.

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

Terminally ill patients with advanced cancer may not be receiving adequate pain management, according to new findings.

There has been a sharp decrease in access to opioids during the past decade, and many patients are going to emergency departments for pain treatment.

Overall, during the study period (2007-2017), there was a 34% reduction in the number of opioid prescriptions filled per patient and a 38% reduction in the total dose of opioids filled near the end of life.

There was a dramatic drop in the use of long-acting opioids, which can provide patients with more consistent pain relief and are important for managing severe cancer pain. The investigators’ results show that during the study period, the number of long-acting opioid prescriptions filled per patient fell by 50%.

“We do believe that the decline in cancer patients’ access to opioids near the end of life is likely attributable to the efforts to curtail opioid misuse,” commented lead author Andrea Enzinger, MD, a medical oncologist at Dana-Farber Cancer Institute, Boston.

The study was published online July 22 in the Journal of Clinical Oncology.

“The study provides fascinating data that support our clinical observations,” said Marcin Chwistek, MD, FAAHPM, director of the supportive oncology and palliative care program at Fox Chase Cancer Center, Philadelphia, who was asked for comment. “Primarily, we have noticed a heightened reluctance on the parts of patients with cancer, including those with advanced cancer, to take opioids in general.”
 

Many factors involved

The crisis of opioid misuse and abuse led to the implementation of regulations to curb inappropriate prescribing. But these restrictions on opioid prescribing may have unintended consequences for patients with advanced, incurable malignancies who are experiencing pain.

“Many but not all opioid regulations specifically exclude cancer patients,” said Dr. Enzinger. “However, the cumulative effect of these regulations may have had a chilling effect on providers’ comfort or willingness to prescribe opioids, even for cancer pain.”

She said in an interview that the prescribing of opioids has become much more difficult. Prescribers are often required to sign an opioid agreement with patients prior to providing them with opioids. Health care professionals may need to use a two-factor authentication to prescribe, and prescribers in 49 of 50 U.S. states are required to check electronic prescription drug monitoring programs prior to providing the prescription.

“After the medications are prescribed, insurance companies require prior-authorization paperwork before filling the medications, particularly for long-acting opioids or high-dose opioids,” Dr. Enzinger said. “These barriers pile up and make the whole process onerous and time consuming.”

Patient factors may also have contributed to the decline in use.

“Cancer patients are often very hesitant to use opioids to treat their pain, as they worry about becoming addicted or being labeled a ‘pill seeker,’” she explained. “Also, the added regulations, such as requirements for prior authorization paperwork, signing opioid agreements, and so on, may add to the stigma of opioid therapy and send a message to patients that these medications are inherently dangerous.”

Dr. Enzinger added that there are legitimate reasons why patients may not want to use opioids and that these should be respected. “But addiction risk should really not weigh into the decisions about pain management for patients who are dying from cancer,” she said.
 

Decline in opioid dose and prescriptions

Dr. Enzinger and colleagues used administrative data from the Centers for Medicare & Medicaid Services to identify 270,632 Medicare fee-for-service patients who had cancers that were associated with poor prognoses and who died from 2007 to 2017. During this period, the opioid crisis was first recognized. There followed legislative reforms and subsequent declines in population-based opioid prescribing.

Among the patients in the study, the most common cancers were lung, colorectal, pancreatic, prostate, and breast cancers; 166,962 patients (61.7%) were enrolled in hospice before death. This percentage increased from 57.1% in 2007 to 66.2% in 2017 (P for trend < .001).

From 2007 to 2017, the proportion of patients filling greater than or equal to 1 opioid prescriptions declined from 42.0% to 35.5%. The proportion declined faster from 2012-2017 than from 2007-2011.

The proportion of patients who filled prescriptions for long-acting opioids dropped from 18.1% to 11.5%. Here again, the decline was faster from 2012-2017 than from 2007-2011. Prescriptions for strong short-acting opioids declined from 31.7% to 28.5%. Prescribing was initially stable from 2007-2011 and began to decline in 2012. Conversely, prescriptions for weak short-acting opioids dropped from 8.4% to 6.5% from 2007-2011 and then stabilized after 2012.

The mean daily dose fell 24.5%, from 85.6 morphine milligram equivalents per day (MMED) to 64.6 MMED. Overall, the total amount of opioids prescribed per decedent fell 38.0%, from 1,075 MMEs per person to 666 MMEs.

At the same time, the proportion of patients who visited EDs increased 50.8%, from 13.2% to 19.9%.
 

Experts weigh in

Approached for an independent comment, Amit Barochia, MD, a hematologist/oncologist with Health First Medical Group, Titusville, Fla., commented that the decline could be due, in part, to greater vigilance and awareness by physicians in light of more stringent requirements and of federal and state regulations. “Some physicians are avoiding prescribing opioids due to more regulations and requirements as well, which is routing patients to the ER for pain relief,” he said.

Dr. Barochia agreed that some of the decline could be due to patient factors. “I do think that some of the patients are hesitant about considering opioid use for better pain relief, in part due to fear of addiction as well as complications arising from their use,” he said. “This is likely resulting from more awareness in the community about their adverse effects.

“That awareness could come from aggressive media coverage as well as social media,” he continued. “It is also true that there is a difficulty in getting authorization for certain opioid products, which is delaying the onset of a proper pain regimen that would help to provide adequate pain relief early on.”

For patients with advanced cancer, earlier referral to palliative care would be beneficial, Dr. Barochia pointed out, because this would allow for a more in-depth discussion about pain in addition to addressing the physical and mental symptoms associated with cancer.

Fox Chase Cancer Center’s Dr. Chwistek noted that patients and their caregivers are often apprehensive about the potential adverse effects of opioids, because they often hear about community-based opioid overdoses and are fearful of taking the medications. “Additionally, it has become increasingly challenging to fill opioid prescriptions at local pharmacies, due to quantity limitations, ubiquitous need for prior authorizations, and stigma,” he said.

The fear of addiction is often brought up by the patients during clinic visits, and insurers and pharmacies have imposed many limits on opioid prescribing. “Most of these can be overcome with prior authorizations, but not always, and prior authorizations are time consuming, confusing, and very frustrating for patients,” he said in an interview.

These findings suggest that not enough patients are getting optimal palliative care. “One of the primary tenets of palliative care is optimal symptom control, including pain,” said Dr. Chwistek. “Palliative care teams have the experience and insight needed to help patients overcome the barriers to appropriate pain control. Education, support, and advocacy are critical to ensure that patients’ pain is appropriately addressed.”

The study was funded by a grant from the Agency for Healthcare Research and Quality of the U.S. Department of Health and Human Services.

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

Terminally ill patients with advanced cancer may not be receiving adequate pain management, according to new findings.

There has been a sharp decrease in access to opioids during the past decade, and many patients are going to emergency departments for pain treatment.

Overall, during the study period (2007-2017), there was a 34% reduction in the number of opioid prescriptions filled per patient and a 38% reduction in the total dose of opioids filled near the end of life.

There was a dramatic drop in the use of long-acting opioids, which can provide patients with more consistent pain relief and are important for managing severe cancer pain. The investigators’ results show that during the study period, the number of long-acting opioid prescriptions filled per patient fell by 50%.

“We do believe that the decline in cancer patients’ access to opioids near the end of life is likely attributable to the efforts to curtail opioid misuse,” commented lead author Andrea Enzinger, MD, a medical oncologist at Dana-Farber Cancer Institute, Boston.

The study was published online July 22 in the Journal of Clinical Oncology.

“The study provides fascinating data that support our clinical observations,” said Marcin Chwistek, MD, FAAHPM, director of the supportive oncology and palliative care program at Fox Chase Cancer Center, Philadelphia, who was asked for comment. “Primarily, we have noticed a heightened reluctance on the parts of patients with cancer, including those with advanced cancer, to take opioids in general.”
 

Many factors involved

The crisis of opioid misuse and abuse led to the implementation of regulations to curb inappropriate prescribing. But these restrictions on opioid prescribing may have unintended consequences for patients with advanced, incurable malignancies who are experiencing pain.

“Many but not all opioid regulations specifically exclude cancer patients,” said Dr. Enzinger. “However, the cumulative effect of these regulations may have had a chilling effect on providers’ comfort or willingness to prescribe opioids, even for cancer pain.”

She said in an interview that the prescribing of opioids has become much more difficult. Prescribers are often required to sign an opioid agreement with patients prior to providing them with opioids. Health care professionals may need to use a two-factor authentication to prescribe, and prescribers in 49 of 50 U.S. states are required to check electronic prescription drug monitoring programs prior to providing the prescription.

“After the medications are prescribed, insurance companies require prior-authorization paperwork before filling the medications, particularly for long-acting opioids or high-dose opioids,” Dr. Enzinger said. “These barriers pile up and make the whole process onerous and time consuming.”

Patient factors may also have contributed to the decline in use.

“Cancer patients are often very hesitant to use opioids to treat their pain, as they worry about becoming addicted or being labeled a ‘pill seeker,’” she explained. “Also, the added regulations, such as requirements for prior authorization paperwork, signing opioid agreements, and so on, may add to the stigma of opioid therapy and send a message to patients that these medications are inherently dangerous.”

Dr. Enzinger added that there are legitimate reasons why patients may not want to use opioids and that these should be respected. “But addiction risk should really not weigh into the decisions about pain management for patients who are dying from cancer,” she said.
 

Decline in opioid dose and prescriptions

Dr. Enzinger and colleagues used administrative data from the Centers for Medicare & Medicaid Services to identify 270,632 Medicare fee-for-service patients who had cancers that were associated with poor prognoses and who died from 2007 to 2017. During this period, the opioid crisis was first recognized. There followed legislative reforms and subsequent declines in population-based opioid prescribing.

Among the patients in the study, the most common cancers were lung, colorectal, pancreatic, prostate, and breast cancers; 166,962 patients (61.7%) were enrolled in hospice before death. This percentage increased from 57.1% in 2007 to 66.2% in 2017 (P for trend < .001).

From 2007 to 2017, the proportion of patients filling greater than or equal to 1 opioid prescriptions declined from 42.0% to 35.5%. The proportion declined faster from 2012-2017 than from 2007-2011.

The proportion of patients who filled prescriptions for long-acting opioids dropped from 18.1% to 11.5%. Here again, the decline was faster from 2012-2017 than from 2007-2011. Prescriptions for strong short-acting opioids declined from 31.7% to 28.5%. Prescribing was initially stable from 2007-2011 and began to decline in 2012. Conversely, prescriptions for weak short-acting opioids dropped from 8.4% to 6.5% from 2007-2011 and then stabilized after 2012.

The mean daily dose fell 24.5%, from 85.6 morphine milligram equivalents per day (MMED) to 64.6 MMED. Overall, the total amount of opioids prescribed per decedent fell 38.0%, from 1,075 MMEs per person to 666 MMEs.

At the same time, the proportion of patients who visited EDs increased 50.8%, from 13.2% to 19.9%.
 

Experts weigh in

Approached for an independent comment, Amit Barochia, MD, a hematologist/oncologist with Health First Medical Group, Titusville, Fla., commented that the decline could be due, in part, to greater vigilance and awareness by physicians in light of more stringent requirements and of federal and state regulations. “Some physicians are avoiding prescribing opioids due to more regulations and requirements as well, which is routing patients to the ER for pain relief,” he said.

Dr. Barochia agreed that some of the decline could be due to patient factors. “I do think that some of the patients are hesitant about considering opioid use for better pain relief, in part due to fear of addiction as well as complications arising from their use,” he said. “This is likely resulting from more awareness in the community about their adverse effects.

“That awareness could come from aggressive media coverage as well as social media,” he continued. “It is also true that there is a difficulty in getting authorization for certain opioid products, which is delaying the onset of a proper pain regimen that would help to provide adequate pain relief early on.”

For patients with advanced cancer, earlier referral to palliative care would be beneficial, Dr. Barochia pointed out, because this would allow for a more in-depth discussion about pain in addition to addressing the physical and mental symptoms associated with cancer.

Fox Chase Cancer Center’s Dr. Chwistek noted that patients and their caregivers are often apprehensive about the potential adverse effects of opioids, because they often hear about community-based opioid overdoses and are fearful of taking the medications. “Additionally, it has become increasingly challenging to fill opioid prescriptions at local pharmacies, due to quantity limitations, ubiquitous need for prior authorizations, and stigma,” he said.

The fear of addiction is often brought up by the patients during clinic visits, and insurers and pharmacies have imposed many limits on opioid prescribing. “Most of these can be overcome with prior authorizations, but not always, and prior authorizations are time consuming, confusing, and very frustrating for patients,” he said in an interview.

These findings suggest that not enough patients are getting optimal palliative care. “One of the primary tenets of palliative care is optimal symptom control, including pain,” said Dr. Chwistek. “Palliative care teams have the experience and insight needed to help patients overcome the barriers to appropriate pain control. Education, support, and advocacy are critical to ensure that patients’ pain is appropriately addressed.”

The study was funded by a grant from the Agency for Healthcare Research and Quality of the U.S. Department of Health and Human Services.

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

Terminally ill patients with advanced cancer may not be receiving adequate pain management, according to new findings.

There has been a sharp decrease in access to opioids during the past decade, and many patients are going to emergency departments for pain treatment.

Overall, during the study period (2007-2017), there was a 34% reduction in the number of opioid prescriptions filled per patient and a 38% reduction in the total dose of opioids filled near the end of life.

There was a dramatic drop in the use of long-acting opioids, which can provide patients with more consistent pain relief and are important for managing severe cancer pain. The investigators’ results show that during the study period, the number of long-acting opioid prescriptions filled per patient fell by 50%.

“We do believe that the decline in cancer patients’ access to opioids near the end of life is likely attributable to the efforts to curtail opioid misuse,” commented lead author Andrea Enzinger, MD, a medical oncologist at Dana-Farber Cancer Institute, Boston.

The study was published online July 22 in the Journal of Clinical Oncology.

“The study provides fascinating data that support our clinical observations,” said Marcin Chwistek, MD, FAAHPM, director of the supportive oncology and palliative care program at Fox Chase Cancer Center, Philadelphia, who was asked for comment. “Primarily, we have noticed a heightened reluctance on the parts of patients with cancer, including those with advanced cancer, to take opioids in general.”
 

Many factors involved

The crisis of opioid misuse and abuse led to the implementation of regulations to curb inappropriate prescribing. But these restrictions on opioid prescribing may have unintended consequences for patients with advanced, incurable malignancies who are experiencing pain.

“Many but not all opioid regulations specifically exclude cancer patients,” said Dr. Enzinger. “However, the cumulative effect of these regulations may have had a chilling effect on providers’ comfort or willingness to prescribe opioids, even for cancer pain.”

She said in an interview that the prescribing of opioids has become much more difficult. Prescribers are often required to sign an opioid agreement with patients prior to providing them with opioids. Health care professionals may need to use a two-factor authentication to prescribe, and prescribers in 49 of 50 U.S. states are required to check electronic prescription drug monitoring programs prior to providing the prescription.

“After the medications are prescribed, insurance companies require prior-authorization paperwork before filling the medications, particularly for long-acting opioids or high-dose opioids,” Dr. Enzinger said. “These barriers pile up and make the whole process onerous and time consuming.”

Patient factors may also have contributed to the decline in use.

“Cancer patients are often very hesitant to use opioids to treat their pain, as they worry about becoming addicted or being labeled a ‘pill seeker,’” she explained. “Also, the added regulations, such as requirements for prior authorization paperwork, signing opioid agreements, and so on, may add to the stigma of opioid therapy and send a message to patients that these medications are inherently dangerous.”

Dr. Enzinger added that there are legitimate reasons why patients may not want to use opioids and that these should be respected. “But addiction risk should really not weigh into the decisions about pain management for patients who are dying from cancer,” she said.
 

Decline in opioid dose and prescriptions

Dr. Enzinger and colleagues used administrative data from the Centers for Medicare & Medicaid Services to identify 270,632 Medicare fee-for-service patients who had cancers that were associated with poor prognoses and who died from 2007 to 2017. During this period, the opioid crisis was first recognized. There followed legislative reforms and subsequent declines in population-based opioid prescribing.

Among the patients in the study, the most common cancers were lung, colorectal, pancreatic, prostate, and breast cancers; 166,962 patients (61.7%) were enrolled in hospice before death. This percentage increased from 57.1% in 2007 to 66.2% in 2017 (P for trend < .001).

From 2007 to 2017, the proportion of patients filling greater than or equal to 1 opioid prescriptions declined from 42.0% to 35.5%. The proportion declined faster from 2012-2017 than from 2007-2011.

The proportion of patients who filled prescriptions for long-acting opioids dropped from 18.1% to 11.5%. Here again, the decline was faster from 2012-2017 than from 2007-2011. Prescriptions for strong short-acting opioids declined from 31.7% to 28.5%. Prescribing was initially stable from 2007-2011 and began to decline in 2012. Conversely, prescriptions for weak short-acting opioids dropped from 8.4% to 6.5% from 2007-2011 and then stabilized after 2012.

The mean daily dose fell 24.5%, from 85.6 morphine milligram equivalents per day (MMED) to 64.6 MMED. Overall, the total amount of opioids prescribed per decedent fell 38.0%, from 1,075 MMEs per person to 666 MMEs.

At the same time, the proportion of patients who visited EDs increased 50.8%, from 13.2% to 19.9%.
 

Experts weigh in

Approached for an independent comment, Amit Barochia, MD, a hematologist/oncologist with Health First Medical Group, Titusville, Fla., commented that the decline could be due, in part, to greater vigilance and awareness by physicians in light of more stringent requirements and of federal and state regulations. “Some physicians are avoiding prescribing opioids due to more regulations and requirements as well, which is routing patients to the ER for pain relief,” he said.

Dr. Barochia agreed that some of the decline could be due to patient factors. “I do think that some of the patients are hesitant about considering opioid use for better pain relief, in part due to fear of addiction as well as complications arising from their use,” he said. “This is likely resulting from more awareness in the community about their adverse effects.

“That awareness could come from aggressive media coverage as well as social media,” he continued. “It is also true that there is a difficulty in getting authorization for certain opioid products, which is delaying the onset of a proper pain regimen that would help to provide adequate pain relief early on.”

For patients with advanced cancer, earlier referral to palliative care would be beneficial, Dr. Barochia pointed out, because this would allow for a more in-depth discussion about pain in addition to addressing the physical and mental symptoms associated with cancer.

Fox Chase Cancer Center’s Dr. Chwistek noted that patients and their caregivers are often apprehensive about the potential adverse effects of opioids, because they often hear about community-based opioid overdoses and are fearful of taking the medications. “Additionally, it has become increasingly challenging to fill opioid prescriptions at local pharmacies, due to quantity limitations, ubiquitous need for prior authorizations, and stigma,” he said.

The fear of addiction is often brought up by the patients during clinic visits, and insurers and pharmacies have imposed many limits on opioid prescribing. “Most of these can be overcome with prior authorizations, but not always, and prior authorizations are time consuming, confusing, and very frustrating for patients,” he said in an interview.

These findings suggest that not enough patients are getting optimal palliative care. “One of the primary tenets of palliative care is optimal symptom control, including pain,” said Dr. Chwistek. “Palliative care teams have the experience and insight needed to help patients overcome the barriers to appropriate pain control. Education, support, and advocacy are critical to ensure that patients’ pain is appropriately addressed.”

The study was funded by a grant from the Agency for Healthcare Research and Quality of the U.S. Department of Health and Human Services.

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

Travel distance is an important determinant of access to abortion care in the United States, new findings show.

Increases in median travel distance to the nearest abortion care facility were associated with significant reductions in median abortion rate.

The abortion rate was 21.1 per 1,000 female residents of reproductive age among those who lived less than 5 miles from a facility, but that number dropped to 3.9/1,000 for those living 120 miles or further away.

Overall, in a model of 3,107 U.S. counties that included 62.5 million women of reproductive age, there were an estimated 696,760 abortions (at a mean rate of 11.1/1,000). The authors estimate that if abortion services were integrated into primary care, an additional 18,190 abortions would be performed (mean rate, 11.4/1,000).

Similarly, if telemedicine became widely available in this setting, this would allow approximately 70,920 abortions (mean rate 12.3/1,000). The study was published online in JAMA Open Network.

Reducing travel distances to abortion facilities would increase access, but additional clinics and providers would be needed to meet the demand. But as the population density of many counties with poor access is low, innovative strategies are also needed.

Integrating abortion into primary care or making medication abortion care available by telemedicine may decrease this unmet need, and lead author Kirsten Thompson, MPH, noted that there is growing evidence that both solutions are quite feasible to implement.

“A study published in 2018 has led primary care providers to adopt the same regimen for miscarriage care, showing that they are interested and capable, despite the barriers posed by the mifepristone [Risk Evaluation and Mitigation Strategy] program for these patients,” said Ms. Thompson, who is program and communications director, Bixby Center for Global Reproductive Health, University of California, San Francisco. “Medical education programs designed specifically for primary care providers have trained family medicine and other clinicians in abortion care for over a decade.”

As for telemedicine, Ms. Thompson explained that, during the pandemic, a preliminary injunction in a federal court case and then the Food and Drug Administration suspended enforcement of the in-person requirements of the mifepristone REMS. “In states that allow medical abortion care by telemedicine, providers have been able to offer remote care when medically appropriate, including mailing medical abortion pills to patients at home,” she said. “Researchers have already published evidence on the safety of and patient satisfaction with this approach.”

However, there are two main barriers to the widespread adoption of medical abortion by telemedicine in the United States. “One is the potentially temporary nature of the FDA’s enforcement discretion and second, are the 19 states with laws that ban it, singling out medical abortion as somehow different from other forms of care by telemedicine,” she said.
 

Study details

About one in four women in the United States will terminate a pregnancy during their lifetime, but the issue is highly contentious and many states have implemented policies that restrict access to abortion care. The authors pointed out that studies have documented clinic closures and women being unable to obtain abortion care, with low-income women and non-White women being disproportionately affected. Increased travel to a provider has also been associated with delays in care as well as increased costs and stress.

Prior research has shown that the further a woman lives from a facility, the less likely she is to obtain abortion care. In this study, Ms. Thompson and colleagues examined the association between travel distance to the nearest abortion care facility and the abortion rate, and then modeled the effect of reduced travel distance on rates.

They first conducted a cross-sectional geographic analysis using the American Community Survey and the U.S. Census to calculate county-level abortion rates per 1,000 women aged between 15 and 44 years. The 2015 data covered 1,948 counties in 27 states.

Abortion rates were then estimated for 3,107 counties in 48 states and the effect of different travel distance scenarios on the abortion rate was also estimated by multivariable model. Data were collected from April 2018 to October 2019.

There were 37.3 million women of reproductive age residing in the 27 states, and a total of 428,720 reported abortions (mean rate, 11.5/1,000; median rate, 9.9/1,000 women).

When looking at all 48 states, the population-weighted mean travel distance to the nearest facility was 25.6 miles, with a median travel distance of 8.2 miles.

A multivariable model showed that a greater travel distance was associated with lower abortion rates. When compared with traveling less than 5 miles, the abortion rate declined by 0.05/1,000 for women traveling between 5 to less than 15 miles for care, 0.22 for those traveling 15 to less than 30 miles, 0.34 for 30 to less than 60 miles, 0.43 for 60 to less than 120 miles, and 0.73 for those traveling 120 miles or more.

They estimated that, if all travel was under 30 miles, there would be a 2.6% increase or 18,190 additional abortions. A simulation also showed that there would be a 10.2% increase (70,920 additional abortions) using medication via telemedicine.
 

Solutions are feasible

Approached for an independent comment, Sarah W. Prager, MD, MAS, professor of obstetrics and gynecology and division chief, complex family planning, at the University of Washington, Seattle, agreed that the solutions proposed by the authors were feasible.

“More than a third of abortions that are eligible are now done with medication,” she said, “And 89% of abortions are done in the first trimester.”

What this means is that early first-trimester abortions can conceivably be performed in the primary care setting. “Any primary care clinician – whether it’s a family practice or internal medicine physician, or nurse practitioner or nurse midwife – can all be trained to do aspiration or prescribe medication in the first trimester,” said Dr. Prager. “So it could easily be integrated into primary care settings if there was motivation for that to happen.”

However, she emphasized that more is involved than just training the provider. “The whole clinic has to buy into it,” Dr. Prager explained. “The nurses have to be willing to assist, you need the medical assistants, the scheduler or person who works the front desk – the whole clinic system has to buy into it and that’s where it becomes more challenging.”

The individual provider may be willing, but the system may still not be allowing that to happen. “This is also where telemedicine can come in, where the medication can be mailed so it can circumvent the problem to a certain extent,” Dr. Prager added. “You don’t have to have the infrastructure in the same way.”

But many states already have laws in place to make that illegal, especially for abortion care even if they allow it for similar types of care.

Another expert also weighed in and agreed that these two solutions can potentially be implemented.

“The concept of decreased rates of abortion associated with greater distances traveled is not new, but what is unique to this manuscript is the estimations that the authors conducted in understanding the impact of expanding access to abortion among primary care and telehealth providers,” said Catherine Cansino, MD, MPH, associate clinical professor in the department of obstetrics and gynecology, University of California, Davis.

“The study provides convincing evidence regarding the need to strengthen infrastructures that support expansion of these services in primary care settings, among physicians and advanced care practitioners,” she said. “Training to provide medical abortion and first-trimester surgical abortion is simple. Many primary care providers are already doing gynecologic procedures – IUD insertions, colposcopies, endometrial biopsies.”

Thus, she noted, adding abortion care “to their toolkit isn’t too far of a stretch.”

As for telemedicine, Dr. Cansino pointed out how the COVID-19 pandemic has also expanded what both patients and providers think are safe options for providing and receiving good care. “Consultations through telemedicine coupled with access to medications for medical abortion through local pharmacies or express mail is definitely safe and feasible.”

The study was supported by the William and Flora Hewlett Foundation and by an anonymous foundation for general operating support (Ms Thompson). Ms. Thompson reported receiving personal fees from GenBioPro outside the submitted work. Dr. Cansino and Dr. Prager have no disclosures.

Travel distance is an important determinant of access to abortion care in the United States, new findings show.

Increases in median travel distance to the nearest abortion care facility were associated with significant reductions in median abortion rate.

The abortion rate was 21.1 per 1,000 female residents of reproductive age among those who lived less than 5 miles from a facility, but that number dropped to 3.9/1,000 for those living 120 miles or further away.

Overall, in a model of 3,107 U.S. counties that included 62.5 million women of reproductive age, there were an estimated 696,760 abortions (at a mean rate of 11.1/1,000). The authors estimate that if abortion services were integrated into primary care, an additional 18,190 abortions would be performed (mean rate, 11.4/1,000).

Similarly, if telemedicine became widely available in this setting, this would allow approximately 70,920 abortions (mean rate 12.3/1,000). The study was published online in JAMA Open Network.

Reducing travel distances to abortion facilities would increase access, but additional clinics and providers would be needed to meet the demand. But as the population density of many counties with poor access is low, innovative strategies are also needed.

Integrating abortion into primary care or making medication abortion care available by telemedicine may decrease this unmet need, and lead author Kirsten Thompson, MPH, noted that there is growing evidence that both solutions are quite feasible to implement.

“A study published in 2018 has led primary care providers to adopt the same regimen for miscarriage care, showing that they are interested and capable, despite the barriers posed by the mifepristone [Risk Evaluation and Mitigation Strategy] program for these patients,” said Ms. Thompson, who is program and communications director, Bixby Center for Global Reproductive Health, University of California, San Francisco. “Medical education programs designed specifically for primary care providers have trained family medicine and other clinicians in abortion care for over a decade.”

As for telemedicine, Ms. Thompson explained that, during the pandemic, a preliminary injunction in a federal court case and then the Food and Drug Administration suspended enforcement of the in-person requirements of the mifepristone REMS. “In states that allow medical abortion care by telemedicine, providers have been able to offer remote care when medically appropriate, including mailing medical abortion pills to patients at home,” she said. “Researchers have already published evidence on the safety of and patient satisfaction with this approach.”

However, there are two main barriers to the widespread adoption of medical abortion by telemedicine in the United States. “One is the potentially temporary nature of the FDA’s enforcement discretion and second, are the 19 states with laws that ban it, singling out medical abortion as somehow different from other forms of care by telemedicine,” she said.
 

Study details

About one in four women in the United States will terminate a pregnancy during their lifetime, but the issue is highly contentious and many states have implemented policies that restrict access to abortion care. The authors pointed out that studies have documented clinic closures and women being unable to obtain abortion care, with low-income women and non-White women being disproportionately affected. Increased travel to a provider has also been associated with delays in care as well as increased costs and stress.

Prior research has shown that the further a woman lives from a facility, the less likely she is to obtain abortion care. In this study, Ms. Thompson and colleagues examined the association between travel distance to the nearest abortion care facility and the abortion rate, and then modeled the effect of reduced travel distance on rates.

They first conducted a cross-sectional geographic analysis using the American Community Survey and the U.S. Census to calculate county-level abortion rates per 1,000 women aged between 15 and 44 years. The 2015 data covered 1,948 counties in 27 states.

Abortion rates were then estimated for 3,107 counties in 48 states and the effect of different travel distance scenarios on the abortion rate was also estimated by multivariable model. Data were collected from April 2018 to October 2019.

There were 37.3 million women of reproductive age residing in the 27 states, and a total of 428,720 reported abortions (mean rate, 11.5/1,000; median rate, 9.9/1,000 women).

When looking at all 48 states, the population-weighted mean travel distance to the nearest facility was 25.6 miles, with a median travel distance of 8.2 miles.

A multivariable model showed that a greater travel distance was associated with lower abortion rates. When compared with traveling less than 5 miles, the abortion rate declined by 0.05/1,000 for women traveling between 5 to less than 15 miles for care, 0.22 for those traveling 15 to less than 30 miles, 0.34 for 30 to less than 60 miles, 0.43 for 60 to less than 120 miles, and 0.73 for those traveling 120 miles or more.

They estimated that, if all travel was under 30 miles, there would be a 2.6% increase or 18,190 additional abortions. A simulation also showed that there would be a 10.2% increase (70,920 additional abortions) using medication via telemedicine.
 

Solutions are feasible

Approached for an independent comment, Sarah W. Prager, MD, MAS, professor of obstetrics and gynecology and division chief, complex family planning, at the University of Washington, Seattle, agreed that the solutions proposed by the authors were feasible.

“More than a third of abortions that are eligible are now done with medication,” she said, “And 89% of abortions are done in the first trimester.”

What this means is that early first-trimester abortions can conceivably be performed in the primary care setting. “Any primary care clinician – whether it’s a family practice or internal medicine physician, or nurse practitioner or nurse midwife – can all be trained to do aspiration or prescribe medication in the first trimester,” said Dr. Prager. “So it could easily be integrated into primary care settings if there was motivation for that to happen.”

However, she emphasized that more is involved than just training the provider. “The whole clinic has to buy into it,” Dr. Prager explained. “The nurses have to be willing to assist, you need the medical assistants, the scheduler or person who works the front desk – the whole clinic system has to buy into it and that’s where it becomes more challenging.”

The individual provider may be willing, but the system may still not be allowing that to happen. “This is also where telemedicine can come in, where the medication can be mailed so it can circumvent the problem to a certain extent,” Dr. Prager added. “You don’t have to have the infrastructure in the same way.”

But many states already have laws in place to make that illegal, especially for abortion care even if they allow it for similar types of care.

Another expert also weighed in and agreed that these two solutions can potentially be implemented.

“The concept of decreased rates of abortion associated with greater distances traveled is not new, but what is unique to this manuscript is the estimations that the authors conducted in understanding the impact of expanding access to abortion among primary care and telehealth providers,” said Catherine Cansino, MD, MPH, associate clinical professor in the department of obstetrics and gynecology, University of California, Davis.

“The study provides convincing evidence regarding the need to strengthen infrastructures that support expansion of these services in primary care settings, among physicians and advanced care practitioners,” she said. “Training to provide medical abortion and first-trimester surgical abortion is simple. Many primary care providers are already doing gynecologic procedures – IUD insertions, colposcopies, endometrial biopsies.”

Thus, she noted, adding abortion care “to their toolkit isn’t too far of a stretch.”

As for telemedicine, Dr. Cansino pointed out how the COVID-19 pandemic has also expanded what both patients and providers think are safe options for providing and receiving good care. “Consultations through telemedicine coupled with access to medications for medical abortion through local pharmacies or express mail is definitely safe and feasible.”

The study was supported by the William and Flora Hewlett Foundation and by an anonymous foundation for general operating support (Ms Thompson). Ms. Thompson reported receiving personal fees from GenBioPro outside the submitted work. Dr. Cansino and Dr. Prager have no disclosures.

Travel distance is an important determinant of access to abortion care in the United States, new findings show.

Increases in median travel distance to the nearest abortion care facility were associated with significant reductions in median abortion rate.

The abortion rate was 21.1 per 1,000 female residents of reproductive age among those who lived less than 5 miles from a facility, but that number dropped to 3.9/1,000 for those living 120 miles or further away.

Overall, in a model of 3,107 U.S. counties that included 62.5 million women of reproductive age, there were an estimated 696,760 abortions (at a mean rate of 11.1/1,000). The authors estimate that if abortion services were integrated into primary care, an additional 18,190 abortions would be performed (mean rate, 11.4/1,000).

Similarly, if telemedicine became widely available in this setting, this would allow approximately 70,920 abortions (mean rate 12.3/1,000). The study was published online in JAMA Open Network.

Reducing travel distances to abortion facilities would increase access, but additional clinics and providers would be needed to meet the demand. But as the population density of many counties with poor access is low, innovative strategies are also needed.

Integrating abortion into primary care or making medication abortion care available by telemedicine may decrease this unmet need, and lead author Kirsten Thompson, MPH, noted that there is growing evidence that both solutions are quite feasible to implement.

“A study published in 2018 has led primary care providers to adopt the same regimen for miscarriage care, showing that they are interested and capable, despite the barriers posed by the mifepristone [Risk Evaluation and Mitigation Strategy] program for these patients,” said Ms. Thompson, who is program and communications director, Bixby Center for Global Reproductive Health, University of California, San Francisco. “Medical education programs designed specifically for primary care providers have trained family medicine and other clinicians in abortion care for over a decade.”

As for telemedicine, Ms. Thompson explained that, during the pandemic, a preliminary injunction in a federal court case and then the Food and Drug Administration suspended enforcement of the in-person requirements of the mifepristone REMS. “In states that allow medical abortion care by telemedicine, providers have been able to offer remote care when medically appropriate, including mailing medical abortion pills to patients at home,” she said. “Researchers have already published evidence on the safety of and patient satisfaction with this approach.”

However, there are two main barriers to the widespread adoption of medical abortion by telemedicine in the United States. “One is the potentially temporary nature of the FDA’s enforcement discretion and second, are the 19 states with laws that ban it, singling out medical abortion as somehow different from other forms of care by telemedicine,” she said.
 

Study details

About one in four women in the United States will terminate a pregnancy during their lifetime, but the issue is highly contentious and many states have implemented policies that restrict access to abortion care. The authors pointed out that studies have documented clinic closures and women being unable to obtain abortion care, with low-income women and non-White women being disproportionately affected. Increased travel to a provider has also been associated with delays in care as well as increased costs and stress.

Prior research has shown that the further a woman lives from a facility, the less likely she is to obtain abortion care. In this study, Ms. Thompson and colleagues examined the association between travel distance to the nearest abortion care facility and the abortion rate, and then modeled the effect of reduced travel distance on rates.

They first conducted a cross-sectional geographic analysis using the American Community Survey and the U.S. Census to calculate county-level abortion rates per 1,000 women aged between 15 and 44 years. The 2015 data covered 1,948 counties in 27 states.

Abortion rates were then estimated for 3,107 counties in 48 states and the effect of different travel distance scenarios on the abortion rate was also estimated by multivariable model. Data were collected from April 2018 to October 2019.

There were 37.3 million women of reproductive age residing in the 27 states, and a total of 428,720 reported abortions (mean rate, 11.5/1,000; median rate, 9.9/1,000 women).

When looking at all 48 states, the population-weighted mean travel distance to the nearest facility was 25.6 miles, with a median travel distance of 8.2 miles.

A multivariable model showed that a greater travel distance was associated with lower abortion rates. When compared with traveling less than 5 miles, the abortion rate declined by 0.05/1,000 for women traveling between 5 to less than 15 miles for care, 0.22 for those traveling 15 to less than 30 miles, 0.34 for 30 to less than 60 miles, 0.43 for 60 to less than 120 miles, and 0.73 for those traveling 120 miles or more.

They estimated that, if all travel was under 30 miles, there would be a 2.6% increase or 18,190 additional abortions. A simulation also showed that there would be a 10.2% increase (70,920 additional abortions) using medication via telemedicine.
 

Solutions are feasible

Approached for an independent comment, Sarah W. Prager, MD, MAS, professor of obstetrics and gynecology and division chief, complex family planning, at the University of Washington, Seattle, agreed that the solutions proposed by the authors were feasible.

“More than a third of abortions that are eligible are now done with medication,” she said, “And 89% of abortions are done in the first trimester.”

What this means is that early first-trimester abortions can conceivably be performed in the primary care setting. “Any primary care clinician – whether it’s a family practice or internal medicine physician, or nurse practitioner or nurse midwife – can all be trained to do aspiration or prescribe medication in the first trimester,” said Dr. Prager. “So it could easily be integrated into primary care settings if there was motivation for that to happen.”

However, she emphasized that more is involved than just training the provider. “The whole clinic has to buy into it,” Dr. Prager explained. “The nurses have to be willing to assist, you need the medical assistants, the scheduler or person who works the front desk – the whole clinic system has to buy into it and that’s where it becomes more challenging.”

The individual provider may be willing, but the system may still not be allowing that to happen. “This is also where telemedicine can come in, where the medication can be mailed so it can circumvent the problem to a certain extent,” Dr. Prager added. “You don’t have to have the infrastructure in the same way.”

But many states already have laws in place to make that illegal, especially for abortion care even if they allow it for similar types of care.

Another expert also weighed in and agreed that these two solutions can potentially be implemented.

“The concept of decreased rates of abortion associated with greater distances traveled is not new, but what is unique to this manuscript is the estimations that the authors conducted in understanding the impact of expanding access to abortion among primary care and telehealth providers,” said Catherine Cansino, MD, MPH, associate clinical professor in the department of obstetrics and gynecology, University of California, Davis.

“The study provides convincing evidence regarding the need to strengthen infrastructures that support expansion of these services in primary care settings, among physicians and advanced care practitioners,” she said. “Training to provide medical abortion and first-trimester surgical abortion is simple. Many primary care providers are already doing gynecologic procedures – IUD insertions, colposcopies, endometrial biopsies.”

Thus, she noted, adding abortion care “to their toolkit isn’t too far of a stretch.”

As for telemedicine, Dr. Cansino pointed out how the COVID-19 pandemic has also expanded what both patients and providers think are safe options for providing and receiving good care. “Consultations through telemedicine coupled with access to medications for medical abortion through local pharmacies or express mail is definitely safe and feasible.”

The study was supported by the William and Flora Hewlett Foundation and by an anonymous foundation for general operating support (Ms Thompson). Ms. Thompson reported receiving personal fees from GenBioPro outside the submitted work. Dr. Cansino and Dr. Prager have no disclosures.

A simple nasal swab may help in the diagnosis of lung cancer in smokers who have undergone CT screening and had lung nodules detected on the scan.  

Only about 5% of the nearly 1.6 million lung nodules identified as incidental findings on low-dose CT screening tests will turn out to be malignant. The new test helps to distinguish between benign and malignant nodules, say researchers reporting a validation study.  

The results show that the test identified those at low risk for cancer with a sensitivity of 96.3% and specificity of 41.7%, as well as identifying those as high risk, with a specificity of 90.4% and sensitivity of 58.2%.

The Percepta nasal swab is a first-of-its-kind genomic test, says the manufacturer Veracyte.

It is based on “field of injury” technology, which examines genomic changes in the lining of the respiratory tract for evidence of active cancer cells, coupled with a machine learning model that includes factors such as age, gender, and smoking history.

Veracyte hopes to begin to make the test available to a select number of sites in the second half of 2021. “The test is intended to be performed in the physician’s office on patients referred with suspicious lung nodules found on CT scans,” said Giulia C. Kennedy, PhD, chief scientific officer and chief medical officer at Veracyte. “This could include patients with nodules found through screening programs, as well as incidentally.”

“It will be made available as a laboratory developed test in the U.S. through Veracyte’s centralized CLIA laboratory,” she said in an interview. “In global markets, we will offer the test as an IVD product that can be performed on the nCounter instrument by laboratories locally. Outside of the United States, the test will require a CE mark, which we are equipped to support.”

Results with the test were presented during the American Society of Clinical Oncology (ASCO) 2021 Annual Meeting, which was held virtually this year.

It was first tested in a training set, which consisted of more than 1,100 patients. All were current or former smokers who had a lung nodule detected on chest CT scanning and were followed for up to 1 year or until a final diagnosis of lung cancer or benign disease.

Brushings of the nasal epithelium were prospectively collected in patients with lung nodules from multiple cohorts.

A total of 502 genes were used in the classifier, and performance was evaluated in an independent clinical validation set consisting of 249 patients.

The test identified true benign patients as low risk with 41.7% specificity and 96.3% sensitivity, resulting in a negative predictive value (NPV) of 97.1% in a population with a cancer prevalence of 25%. The risk of malignancy for patients in this low-risk group was less than 3% (1-NPV), and for this group, clinical guidelines recommend surveillance.  

Patients with true malignancies were identified as high risk, with 58.2% sensitivity and 90.4% specificity, resulting in a positive predictive value of 67.0% in a population with 25% cancer prevalence. The risk of malignancy for patients deemed to be high risk by the classifier was 67.0%, which exceeds the current guideline threshold for consideration of surgical resection or other ablative therapy if a staging evaluation confirms early stage disease, the authors point out.  

The remaining patients, who did not meet the stringent cut-offs for low or high risk, were identified as intermediate risk. In this population, the prevalence of malignancy for patients identified as intermediate risk was 20.7%, which is consistent with guidelines that provide a range for intermediate-risk patients as between 5% and 65% for whom diagnostic biopsy is recommended.
 

Help guide decisions, more data needed

Approached by this news organization for independent comment, Alexander Spira, MD, PhD, medical oncologist, Virginia Cancer Specialists, Fairfax, explained that the study provides an interesting way to look at a common finding and lung nodules and to predict whether further workup should be done.

“This could provide a role in reassurance that patients who fall into the low-risk category could be observed with serial imaging rather than proceeding to immediate biopsy,” he said. “It falls in under the ‘field of injury’ principle.”

Dr. Spira noted that although the low-risk group appears to have a negative predictive value of >90%, it doesn’t mean that the patient would require no further workup. “It would require CT surveillance rather than proceeding to immediate biopsy, and at this point it does appear promising, but I would want further follow-up in terms of outcomes,” he said.

“This does not apply to nonsmokers, which is of increasing prevalence, but with the increased use of CT screening for patients with a history of tobacco use, it may indeed have a role.”

He also pointed out that while the idea is to avoid biopsies, the smaller lesions are the ones that are concerning. “They are often tough to get at, and it would also depend on patient choice and anxiety as well, given the chance of being in that low percentage that the test misses,” said Dr. Spira. “Lastly, many pulmonologists are ordering PET scans in lieu of a biopsy, and this may also help.”

The bottom line is that this may help guide clinical decisions, but more data are needed. “Even in the low-risk category, 9.4% of patients had a malignancy, which is still a high miss rate,” he added.

The study was funded by Veracyte. Dr. Kennedy is employed by Veracyte. Dr. Spira has reported no relevant financial relationships.

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

A simple nasal swab may help in the diagnosis of lung cancer in smokers who have undergone CT screening and had lung nodules detected on the scan.  

Only about 5% of the nearly 1.6 million lung nodules identified as incidental findings on low-dose CT screening tests will turn out to be malignant. The new test helps to distinguish between benign and malignant nodules, say researchers reporting a validation study.  

The results show that the test identified those at low risk for cancer with a sensitivity of 96.3% and specificity of 41.7%, as well as identifying those as high risk, with a specificity of 90.4% and sensitivity of 58.2%.

The Percepta nasal swab is a first-of-its-kind genomic test, says the manufacturer Veracyte.

It is based on “field of injury” technology, which examines genomic changes in the lining of the respiratory tract for evidence of active cancer cells, coupled with a machine learning model that includes factors such as age, gender, and smoking history.

Veracyte hopes to begin to make the test available to a select number of sites in the second half of 2021. “The test is intended to be performed in the physician’s office on patients referred with suspicious lung nodules found on CT scans,” said Giulia C. Kennedy, PhD, chief scientific officer and chief medical officer at Veracyte. “This could include patients with nodules found through screening programs, as well as incidentally.”

“It will be made available as a laboratory developed test in the U.S. through Veracyte’s centralized CLIA laboratory,” she said in an interview. “In global markets, we will offer the test as an IVD product that can be performed on the nCounter instrument by laboratories locally. Outside of the United States, the test will require a CE mark, which we are equipped to support.”

Results with the test were presented during the American Society of Clinical Oncology (ASCO) 2021 Annual Meeting, which was held virtually this year.

It was first tested in a training set, which consisted of more than 1,100 patients. All were current or former smokers who had a lung nodule detected on chest CT scanning and were followed for up to 1 year or until a final diagnosis of lung cancer or benign disease.

Brushings of the nasal epithelium were prospectively collected in patients with lung nodules from multiple cohorts.

A total of 502 genes were used in the classifier, and performance was evaluated in an independent clinical validation set consisting of 249 patients.

The test identified true benign patients as low risk with 41.7% specificity and 96.3% sensitivity, resulting in a negative predictive value (NPV) of 97.1% in a population with a cancer prevalence of 25%. The risk of malignancy for patients in this low-risk group was less than 3% (1-NPV), and for this group, clinical guidelines recommend surveillance.  

Patients with true malignancies were identified as high risk, with 58.2% sensitivity and 90.4% specificity, resulting in a positive predictive value of 67.0% in a population with 25% cancer prevalence. The risk of malignancy for patients deemed to be high risk by the classifier was 67.0%, which exceeds the current guideline threshold for consideration of surgical resection or other ablative therapy if a staging evaluation confirms early stage disease, the authors point out.  

The remaining patients, who did not meet the stringent cut-offs for low or high risk, were identified as intermediate risk. In this population, the prevalence of malignancy for patients identified as intermediate risk was 20.7%, which is consistent with guidelines that provide a range for intermediate-risk patients as between 5% and 65% for whom diagnostic biopsy is recommended.
 

Help guide decisions, more data needed

Approached by this news organization for independent comment, Alexander Spira, MD, PhD, medical oncologist, Virginia Cancer Specialists, Fairfax, explained that the study provides an interesting way to look at a common finding and lung nodules and to predict whether further workup should be done.

“This could provide a role in reassurance that patients who fall into the low-risk category could be observed with serial imaging rather than proceeding to immediate biopsy,” he said. “It falls in under the ‘field of injury’ principle.”

Dr. Spira noted that although the low-risk group appears to have a negative predictive value of >90%, it doesn’t mean that the patient would require no further workup. “It would require CT surveillance rather than proceeding to immediate biopsy, and at this point it does appear promising, but I would want further follow-up in terms of outcomes,” he said.

“This does not apply to nonsmokers, which is of increasing prevalence, but with the increased use of CT screening for patients with a history of tobacco use, it may indeed have a role.”

He also pointed out that while the idea is to avoid biopsies, the smaller lesions are the ones that are concerning. “They are often tough to get at, and it would also depend on patient choice and anxiety as well, given the chance of being in that low percentage that the test misses,” said Dr. Spira. “Lastly, many pulmonologists are ordering PET scans in lieu of a biopsy, and this may also help.”

The bottom line is that this may help guide clinical decisions, but more data are needed. “Even in the low-risk category, 9.4% of patients had a malignancy, which is still a high miss rate,” he added.

The study was funded by Veracyte. Dr. Kennedy is employed by Veracyte. Dr. Spira has reported no relevant financial relationships.

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

A simple nasal swab may help in the diagnosis of lung cancer in smokers who have undergone CT screening and had lung nodules detected on the scan.  

Only about 5% of the nearly 1.6 million lung nodules identified as incidental findings on low-dose CT screening tests will turn out to be malignant. The new test helps to distinguish between benign and malignant nodules, say researchers reporting a validation study.  

The results show that the test identified those at low risk for cancer with a sensitivity of 96.3% and specificity of 41.7%, as well as identifying those as high risk, with a specificity of 90.4% and sensitivity of 58.2%.

The Percepta nasal swab is a first-of-its-kind genomic test, says the manufacturer Veracyte.

It is based on “field of injury” technology, which examines genomic changes in the lining of the respiratory tract for evidence of active cancer cells, coupled with a machine learning model that includes factors such as age, gender, and smoking history.

Veracyte hopes to begin to make the test available to a select number of sites in the second half of 2021. “The test is intended to be performed in the physician’s office on patients referred with suspicious lung nodules found on CT scans,” said Giulia C. Kennedy, PhD, chief scientific officer and chief medical officer at Veracyte. “This could include patients with nodules found through screening programs, as well as incidentally.”

“It will be made available as a laboratory developed test in the U.S. through Veracyte’s centralized CLIA laboratory,” she said in an interview. “In global markets, we will offer the test as an IVD product that can be performed on the nCounter instrument by laboratories locally. Outside of the United States, the test will require a CE mark, which we are equipped to support.”

Results with the test were presented during the American Society of Clinical Oncology (ASCO) 2021 Annual Meeting, which was held virtually this year.

It was first tested in a training set, which consisted of more than 1,100 patients. All were current or former smokers who had a lung nodule detected on chest CT scanning and were followed for up to 1 year or until a final diagnosis of lung cancer or benign disease.

Brushings of the nasal epithelium were prospectively collected in patients with lung nodules from multiple cohorts.

A total of 502 genes were used in the classifier, and performance was evaluated in an independent clinical validation set consisting of 249 patients.

The test identified true benign patients as low risk with 41.7% specificity and 96.3% sensitivity, resulting in a negative predictive value (NPV) of 97.1% in a population with a cancer prevalence of 25%. The risk of malignancy for patients in this low-risk group was less than 3% (1-NPV), and for this group, clinical guidelines recommend surveillance.  

Patients with true malignancies were identified as high risk, with 58.2% sensitivity and 90.4% specificity, resulting in a positive predictive value of 67.0% in a population with 25% cancer prevalence. The risk of malignancy for patients deemed to be high risk by the classifier was 67.0%, which exceeds the current guideline threshold for consideration of surgical resection or other ablative therapy if a staging evaluation confirms early stage disease, the authors point out.  

The remaining patients, who did not meet the stringent cut-offs for low or high risk, were identified as intermediate risk. In this population, the prevalence of malignancy for patients identified as intermediate risk was 20.7%, which is consistent with guidelines that provide a range for intermediate-risk patients as between 5% and 65% for whom diagnostic biopsy is recommended.
 

Help guide decisions, more data needed

Approached by this news organization for independent comment, Alexander Spira, MD, PhD, medical oncologist, Virginia Cancer Specialists, Fairfax, explained that the study provides an interesting way to look at a common finding and lung nodules and to predict whether further workup should be done.

“This could provide a role in reassurance that patients who fall into the low-risk category could be observed with serial imaging rather than proceeding to immediate biopsy,” he said. “It falls in under the ‘field of injury’ principle.”

Dr. Spira noted that although the low-risk group appears to have a negative predictive value of >90%, it doesn’t mean that the patient would require no further workup. “It would require CT surveillance rather than proceeding to immediate biopsy, and at this point it does appear promising, but I would want further follow-up in terms of outcomes,” he said.

“This does not apply to nonsmokers, which is of increasing prevalence, but with the increased use of CT screening for patients with a history of tobacco use, it may indeed have a role.”

He also pointed out that while the idea is to avoid biopsies, the smaller lesions are the ones that are concerning. “They are often tough to get at, and it would also depend on patient choice and anxiety as well, given the chance of being in that low percentage that the test misses,” said Dr. Spira. “Lastly, many pulmonologists are ordering PET scans in lieu of a biopsy, and this may also help.”

The bottom line is that this may help guide clinical decisions, but more data are needed. “Even in the low-risk category, 9.4% of patients had a malignancy, which is still a high miss rate,” he added.

The study was funded by Veracyte. Dr. Kennedy is employed by Veracyte. Dr. Spira has reported no relevant financial relationships.

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

Working night shifts has been associated with an increased risk for certain cancers, as well as other health disorders. Indeed, the World Health Organization’s International Agency for Research on Cancer (IARC) has classified night shift work as “probably carcinogenic to humans.”

But why night shift should elevate the risk for cancer has been unclear.

A new study shows that a simulated night shift schedule significantly altered the normal circadian rhythmicity of genes that are involved in cancer hallmark pathways. It also found that this circadian misalignment caused circadian dysregulation of genes involved in key DNA repair pathways.

“Taken together, these findings suggest that night shift schedules throw off the timing of expression of cancer-related genes in a way that reduces the effectiveness of the body’s DNA repair processes when they are most needed,” said co-corresponding author Jason McDermott, a computational scientist with the Pacific Northwest National Laboratory’s biological sciences division in Richland, Wash.

The study was published online in the Journal of Pineal Research.
 

Study conducted among volunteers 

The study was carried out among healthy volunteers who were subjected to simulated night shift or day shift schedules.

The cohort comprised 14 adults between the ages of 22 and 34 years who had normal nighttime sleep schedules. They were randomly assigned (seven in each group) to a simulated day shift schedule that involved 3 days of daytime wakefulness (6 a.m.-10 p.m.), or a simulated night shift schedule involving 3 days of nighttime wakefulness (6 p.m.-10 a.m.).

After the 3 days of simulated shift work, all participants were then kept in a constant routine protocol (used to study humans’ internally generated biological rhythms independent of any external influences). As part of the protocol, they were kept awake for 24 hours in a semi-reclined posture under laboratory conditions with constant light exposure and room temperature and evenly distributed food intake (hourly isocaloric snacks).

Blood samples were collected at 3-hour intervals and used for leukocyte transcriptome analysis and DNA damage assessment.

The authors found that the circadian expression of canonical clock genes was substantially altered by the simulated night shift schedule vs. the day shift schedule. Four genes (CRY1, CRY2, PER2, and NR1D2) lost their normal day-shift rhythmicity following the night shift schedule, and NPAS2 gene expression was not rhythmic during the day shift but exhibited circadian rhythmicity in the simulated night shift condition. Three other genes (NR1D1, PER3, and DBP) were significantly rhythmic during both shifts.

The team also looked at the effect of night shift on circadian rhythmicity in cancer hallmark genes, using a panel of 726 genes. The analysis showed that:

• 257 (35.4%) were rhythmic after at least one of the two simulated shift work conditions.
• 113 (15.6%) were rhythmic in day shift only.
• 96 (13.2%) were rhythmic during night shift only.
• 48 (6.6%) were rhythmic during both shifts.

A subset of 10 (1.4%) genes exhibited a significant phase advance (3.7 to 8.3 hours) or phase delay (2.8 to 7.0 hours) during the night shift vs. the day shift.

Thus, the authors concluded, shift work caused significant disturbances in the rhythmicity of gene expression in cancer hallmark pathways.

Findings also showed that night shift work increases endogenous and exogenous DNA damage. Endogenous DNA damage was generally higher after the night shift compared to the day shift, and across the 24-hour constant routine the percentage of cells with BRCA1 and g H2AX foci was significantly higher for night shift.
 

Next steps

The team said that the next step is to conduct the same experiment with real-world shift workers who have been consistently on day or night shifts for many years to determine whether in night workers the unrepaired DNA damage builds up over time, which could ultimately increase the risk for cancer.

If what happens in real-world shift workers is consistent with the current findings, this work could eventually be used to develop prevention strategies and drugs that could address the mistiming of DNA repair processes, they suggested.  

“Night shift workers face considerable health disparities, ranging from increased risks of metabolic and cardiovascular disease to mental health disorders and cancer,” co-senior author Hans Van Dongen, PhD, a professor at Washington State University in Pullman and director of the WSU Sleep and Performance Research Center, Spokane, said in a statement. “It is high time that we find diagnosis and treatment solutions for this underserved group of essential workers so that the medical community can address their unique health challenges.”

The study was supported by start-up funds from Washington State University and a Center for Human Health and the Environment grant from North Carolina State University, and in part by the United States Army Medical Research and Development Command, the National Institutes of Health, CDMRP (Congressionally Directed Medical Research Programs) Peer Reviewed Cancer Research Program award, and the BRAVE investment.

The authors have disclosed no relevant financial relationships.

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

Working night shifts has been associated with an increased risk for certain cancers, as well as other health disorders. Indeed, the World Health Organization’s International Agency for Research on Cancer (IARC) has classified night shift work as “probably carcinogenic to humans.”

But why night shift should elevate the risk for cancer has been unclear.

A new study shows that a simulated night shift schedule significantly altered the normal circadian rhythmicity of genes that are involved in cancer hallmark pathways. It also found that this circadian misalignment caused circadian dysregulation of genes involved in key DNA repair pathways.

“Taken together, these findings suggest that night shift schedules throw off the timing of expression of cancer-related genes in a way that reduces the effectiveness of the body’s DNA repair processes when they are most needed,” said co-corresponding author Jason McDermott, a computational scientist with the Pacific Northwest National Laboratory’s biological sciences division in Richland, Wash.

The study was published online in the Journal of Pineal Research.
 

Study conducted among volunteers 

The study was carried out among healthy volunteers who were subjected to simulated night shift or day shift schedules.

The cohort comprised 14 adults between the ages of 22 and 34 years who had normal nighttime sleep schedules. They were randomly assigned (seven in each group) to a simulated day shift schedule that involved 3 days of daytime wakefulness (6 a.m.-10 p.m.), or a simulated night shift schedule involving 3 days of nighttime wakefulness (6 p.m.-10 a.m.).

After the 3 days of simulated shift work, all participants were then kept in a constant routine protocol (used to study humans’ internally generated biological rhythms independent of any external influences). As part of the protocol, they were kept awake for 24 hours in a semi-reclined posture under laboratory conditions with constant light exposure and room temperature and evenly distributed food intake (hourly isocaloric snacks).

Blood samples were collected at 3-hour intervals and used for leukocyte transcriptome analysis and DNA damage assessment.

The authors found that the circadian expression of canonical clock genes was substantially altered by the simulated night shift schedule vs. the day shift schedule. Four genes (CRY1, CRY2, PER2, and NR1D2) lost their normal day-shift rhythmicity following the night shift schedule, and NPAS2 gene expression was not rhythmic during the day shift but exhibited circadian rhythmicity in the simulated night shift condition. Three other genes (NR1D1, PER3, and DBP) were significantly rhythmic during both shifts.

The team also looked at the effect of night shift on circadian rhythmicity in cancer hallmark genes, using a panel of 726 genes. The analysis showed that:

• 257 (35.4%) were rhythmic after at least one of the two simulated shift work conditions.
• 113 (15.6%) were rhythmic in day shift only.
• 96 (13.2%) were rhythmic during night shift only.
• 48 (6.6%) were rhythmic during both shifts.

A subset of 10 (1.4%) genes exhibited a significant phase advance (3.7 to 8.3 hours) or phase delay (2.8 to 7.0 hours) during the night shift vs. the day shift.

Thus, the authors concluded, shift work caused significant disturbances in the rhythmicity of gene expression in cancer hallmark pathways.

Findings also showed that night shift work increases endogenous and exogenous DNA damage. Endogenous DNA damage was generally higher after the night shift compared to the day shift, and across the 24-hour constant routine the percentage of cells with BRCA1 and g H2AX foci was significantly higher for night shift.
 

Next steps

The team said that the next step is to conduct the same experiment with real-world shift workers who have been consistently on day or night shifts for many years to determine whether in night workers the unrepaired DNA damage builds up over time, which could ultimately increase the risk for cancer.

If what happens in real-world shift workers is consistent with the current findings, this work could eventually be used to develop prevention strategies and drugs that could address the mistiming of DNA repair processes, they suggested.  

“Night shift workers face considerable health disparities, ranging from increased risks of metabolic and cardiovascular disease to mental health disorders and cancer,” co-senior author Hans Van Dongen, PhD, a professor at Washington State University in Pullman and director of the WSU Sleep and Performance Research Center, Spokane, said in a statement. “It is high time that we find diagnosis and treatment solutions for this underserved group of essential workers so that the medical community can address their unique health challenges.”

The study was supported by start-up funds from Washington State University and a Center for Human Health and the Environment grant from North Carolina State University, and in part by the United States Army Medical Research and Development Command, the National Institutes of Health, CDMRP (Congressionally Directed Medical Research Programs) Peer Reviewed Cancer Research Program award, and the BRAVE investment.

The authors have disclosed no relevant financial relationships.

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

Working night shifts has been associated with an increased risk for certain cancers, as well as other health disorders. Indeed, the World Health Organization’s International Agency for Research on Cancer (IARC) has classified night shift work as “probably carcinogenic to humans.”

But why night shift should elevate the risk for cancer has been unclear.

A new study shows that a simulated night shift schedule significantly altered the normal circadian rhythmicity of genes that are involved in cancer hallmark pathways. It also found that this circadian misalignment caused circadian dysregulation of genes involved in key DNA repair pathways.

“Taken together, these findings suggest that night shift schedules throw off the timing of expression of cancer-related genes in a way that reduces the effectiveness of the body’s DNA repair processes when they are most needed,” said co-corresponding author Jason McDermott, a computational scientist with the Pacific Northwest National Laboratory’s biological sciences division in Richland, Wash.

The study was published online in the Journal of Pineal Research.
 

Study conducted among volunteers 

The study was carried out among healthy volunteers who were subjected to simulated night shift or day shift schedules.

The cohort comprised 14 adults between the ages of 22 and 34 years who had normal nighttime sleep schedules. They were randomly assigned (seven in each group) to a simulated day shift schedule that involved 3 days of daytime wakefulness (6 a.m.-10 p.m.), or a simulated night shift schedule involving 3 days of nighttime wakefulness (6 p.m.-10 a.m.).

After the 3 days of simulated shift work, all participants were then kept in a constant routine protocol (used to study humans’ internally generated biological rhythms independent of any external influences). As part of the protocol, they were kept awake for 24 hours in a semi-reclined posture under laboratory conditions with constant light exposure and room temperature and evenly distributed food intake (hourly isocaloric snacks).

Blood samples were collected at 3-hour intervals and used for leukocyte transcriptome analysis and DNA damage assessment.

The authors found that the circadian expression of canonical clock genes was substantially altered by the simulated night shift schedule vs. the day shift schedule. Four genes (CRY1, CRY2, PER2, and NR1D2) lost their normal day-shift rhythmicity following the night shift schedule, and NPAS2 gene expression was not rhythmic during the day shift but exhibited circadian rhythmicity in the simulated night shift condition. Three other genes (NR1D1, PER3, and DBP) were significantly rhythmic during both shifts.

The team also looked at the effect of night shift on circadian rhythmicity in cancer hallmark genes, using a panel of 726 genes. The analysis showed that:

• 257 (35.4%) were rhythmic after at least one of the two simulated shift work conditions.
• 113 (15.6%) were rhythmic in day shift only.
• 96 (13.2%) were rhythmic during night shift only.
• 48 (6.6%) were rhythmic during both shifts.

A subset of 10 (1.4%) genes exhibited a significant phase advance (3.7 to 8.3 hours) or phase delay (2.8 to 7.0 hours) during the night shift vs. the day shift.

Thus, the authors concluded, shift work caused significant disturbances in the rhythmicity of gene expression in cancer hallmark pathways.

Findings also showed that night shift work increases endogenous and exogenous DNA damage. Endogenous DNA damage was generally higher after the night shift compared to the day shift, and across the 24-hour constant routine the percentage of cells with BRCA1 and g H2AX foci was significantly higher for night shift.
 

Next steps

The team said that the next step is to conduct the same experiment with real-world shift workers who have been consistently on day or night shifts for many years to determine whether in night workers the unrepaired DNA damage builds up over time, which could ultimately increase the risk for cancer.

If what happens in real-world shift workers is consistent with the current findings, this work could eventually be used to develop prevention strategies and drugs that could address the mistiming of DNA repair processes, they suggested.  

“Night shift workers face considerable health disparities, ranging from increased risks of metabolic and cardiovascular disease to mental health disorders and cancer,” co-senior author Hans Van Dongen, PhD, a professor at Washington State University in Pullman and director of the WSU Sleep and Performance Research Center, Spokane, said in a statement. “It is high time that we find diagnosis and treatment solutions for this underserved group of essential workers so that the medical community can address their unique health challenges.”

The study was supported by start-up funds from Washington State University and a Center for Human Health and the Environment grant from North Carolina State University, and in part by the United States Army Medical Research and Development Command, the National Institutes of Health, CDMRP (Congressionally Directed Medical Research Programs) Peer Reviewed Cancer Research Program award, and the BRAVE investment.

The authors have disclosed no relevant financial relationships.

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

A novel risk-based approach could be an effective way to triage women for mammography during times of limited capacity, such as the situation during the COVID-19 pandemic, according to new findings.

Researchers evaluated almost 2 million mammograms that had been performed at more than 90 radiology centers and found that 12% of mammograms with “high” and “very high” cancer risk rates accounted for 55% of detected cancers.

In contrast, 44% of mammograms with very low cancer risk rates accounted for 13% of detected cancers. The study was published online March 25, 2021, in JAMA Network Open.

Cancer screening programs dramatically slowed or even came to a screeching halt during 2020, when restrictions and lockdowns were in place. The American Cancer Society even recommended that “no one should go to a health care facility for routine cancer screening,” as part of COVID-19 precautions.

However, concern was voiced that the pause in screening would allow patients with asymptomatic cancers or precursor lesions to develop into a more serious disease state.

The authors pointed out that several professional associations had posted guidance for scheduling individuals for breast imaging services during the COVID-19 pandemic, but these recommendations were based on expert opinion. The investigators’ goal was to help imaging facilities optimize the number of breast cancers that could be detected during periods of reduced capacity using clinical indication and individual characteristics.

The result was a risk-based strategy for triaging mammograms during periods of decreased capacity, which lead author Diana L. Miglioretti, PhD, explained was feasible to implement. Dr. Miglioretti is division chief of biostatistics in the department of public health sciences at University of California, Davis.

“Our risk model used information that is commonly collected by radiology facilities,” she said in an interview. “Vendors of electronic medical records could create tools that pull the information from the medical record, or could create fields in the scheduling system to efficiently collect this information when the mammogram is scheduled.”

Dr. Miglioretti emphasized that, once the information is collected in a standardized manner, “it would be straightforward to use a computer program to apply our algorithm to rank women based on their likelihood of having a breast cancer detected.”

“I think it is worth the investment to create these electronic tools now, given the potential for future shutdowns or periods of reduced capacity due to a variety of reasons, such as natural disasters and cyberattacks – or another pandemic,” she said.

Some facilities are still working through backlogs of mammograms that need to be rescheduled, which would be another way that this algorithm could be used. “They could use this approach to determine who should be scheduled first by using data available in the electronic medical record,” she added.
 

Five risk groups

Dr. Miglioretti and colleagues conducted a cohort study using data that was prospectively collected from mammography examinations performed from 2014 to 2019 at 92 radiology facilities in the Breast Cancer Surveillance Consortium. The cohort included 898,415 individuals who contributed to 1.8 million mammograms.

Information that included clinical indication for screening, breast symptoms, personal history of breast cancer, age, time since last mammogram/screening interval, family history of breast cancer, breast density, and history of high-risk breast lesion was collected from self-administered questionnaires at the time of mammography or extracted from electronic health records.

Following analysis, the data was categorized into five risk groups: very high (>50), high (22-50), moderate (10-22), low (5-10), and very low (<5) cancer detection rate per 1,000 mammograms. These thresholds were chosen based on the observed cancer detection rates and clinical expertise.

Of the group, about 1.7 million mammograms were from women without a personal history of breast cancer and 156,104 mammograms were from women with a breast cancer history. Most of the cohort were aged 50-69 years at the time of imaging, and 67.9% were White (11.2% Black, 11.3% Asian or Pacific Islander, 7% Hispanic, and 2.2% were another race/ethnicity or mixed race/ethnicity).

Their results showed that 12% of mammograms with very high (89.6-122.3 cancers detected per 1,000 mammograms) or high (36.1-47.5 cancers detected per 1,000 mammograms) cancer detection rates accounted for 55% of all detected cancers. These included mammograms that were done to evaluate an abnormal test or breast lump in individuals of all ages regardless of breast cancer history.

On the opposite end, 44.2% of mammograms with very low cancer detection rates accounted for 13.1% of detected cancers and that included annual screening tests in women aged 50-69 years (3.8 cancers detected per 1,000 mammograms) and all screening mammograms in individuals younger than 50 years regardless of screening interval (2.8 cancers detected per 1000 mammograms).
 

Treat with caution

In an accompanying editorial, Sarah M. Friedewald, MD, and Dipti Gupta, MD, both from Northwestern University, Chicago, pointed out that, while the authors examined a large dataset to identify a subgroup of patients who would most likely benefit from breast imaging in a setting where capacity is limited, “these data should be used with caution as the only barometer for whether a patient merits cancer screening during a period of rationing.”

They noted that, in the context of an acute crisis, when patient volume needs to be reduced very quickly, it is often impractical for clinicians to sift through patient records in order to capture the information necessary for triage. In addition, asking nonclinical schedulers to accurately pull data at this level, at the time when the patient calls to make an appointment, is unrealistic.

In the context of the pandemic, the editorialists wrote that, while this model uses risk for breast cancer to prioritize those to be seen in the clinic, the risk for complications from COVID-19 may also be an important factor to consider. For example, an older patient may be at a higher risk for breast cancer but may also face a higher risk for COVID-related complications. Conversely, a younger woman at a lower risk for serious COVID-related disease but who has breast cancer detected early will gain more life-years than an older patient.

There are also no algorithms to account for each patient’s perceived risk for breast cancer or COVID-19, and “the downstream effect of delaying cancer diagnosis may similarly lead to unintended consequences but may take longer to become apparent,” they wrote. “Focusing efforts on the operations of accommodating as many patients as possible, such as extending clinic hours, would be preferable.”

Finally, Dr. Friedewald and Dr. Gupta concluded that “the practicality of this process during the COVID-19 pandemic and extrapolation to other emergent settings are less obvious.”

The study was supported through a Patient-centered Outcomes Research Institute program award. Dr. Miglioretti reported receiving royalties from Elsevier outside the submitted work. Several coauthors report relationships with industry. Dr. Friedewald reported receiving grants from Hologic Research during the conduct of the study. Dr. Gupta disclosed no relevant financial relationships.

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

A novel risk-based approach could be an effective way to triage women for mammography during times of limited capacity, such as the situation during the COVID-19 pandemic, according to new findings.

Researchers evaluated almost 2 million mammograms that had been performed at more than 90 radiology centers and found that 12% of mammograms with “high” and “very high” cancer risk rates accounted for 55% of detected cancers.

In contrast, 44% of mammograms with very low cancer risk rates accounted for 13% of detected cancers. The study was published online March 25, 2021, in JAMA Network Open.

Cancer screening programs dramatically slowed or even came to a screeching halt during 2020, when restrictions and lockdowns were in place. The American Cancer Society even recommended that “no one should go to a health care facility for routine cancer screening,” as part of COVID-19 precautions.

However, concern was voiced that the pause in screening would allow patients with asymptomatic cancers or precursor lesions to develop into a more serious disease state.

The authors pointed out that several professional associations had posted guidance for scheduling individuals for breast imaging services during the COVID-19 pandemic, but these recommendations were based on expert opinion. The investigators’ goal was to help imaging facilities optimize the number of breast cancers that could be detected during periods of reduced capacity using clinical indication and individual characteristics.

The result was a risk-based strategy for triaging mammograms during periods of decreased capacity, which lead author Diana L. Miglioretti, PhD, explained was feasible to implement. Dr. Miglioretti is division chief of biostatistics in the department of public health sciences at University of California, Davis.

“Our risk model used information that is commonly collected by radiology facilities,” she said in an interview. “Vendors of electronic medical records could create tools that pull the information from the medical record, or could create fields in the scheduling system to efficiently collect this information when the mammogram is scheduled.”

Dr. Miglioretti emphasized that, once the information is collected in a standardized manner, “it would be straightforward to use a computer program to apply our algorithm to rank women based on their likelihood of having a breast cancer detected.”

“I think it is worth the investment to create these electronic tools now, given the potential for future shutdowns or periods of reduced capacity due to a variety of reasons, such as natural disasters and cyberattacks – or another pandemic,” she said.

Some facilities are still working through backlogs of mammograms that need to be rescheduled, which would be another way that this algorithm could be used. “They could use this approach to determine who should be scheduled first by using data available in the electronic medical record,” she added.
 

Five risk groups

Dr. Miglioretti and colleagues conducted a cohort study using data that was prospectively collected from mammography examinations performed from 2014 to 2019 at 92 radiology facilities in the Breast Cancer Surveillance Consortium. The cohort included 898,415 individuals who contributed to 1.8 million mammograms.

Information that included clinical indication for screening, breast symptoms, personal history of breast cancer, age, time since last mammogram/screening interval, family history of breast cancer, breast density, and history of high-risk breast lesion was collected from self-administered questionnaires at the time of mammography or extracted from electronic health records.

Following analysis, the data was categorized into five risk groups: very high (>50), high (22-50), moderate (10-22), low (5-10), and very low (<5) cancer detection rate per 1,000 mammograms. These thresholds were chosen based on the observed cancer detection rates and clinical expertise.

Of the group, about 1.7 million mammograms were from women without a personal history of breast cancer and 156,104 mammograms were from women with a breast cancer history. Most of the cohort were aged 50-69 years at the time of imaging, and 67.9% were White (11.2% Black, 11.3% Asian or Pacific Islander, 7% Hispanic, and 2.2% were another race/ethnicity or mixed race/ethnicity).

Their results showed that 12% of mammograms with very high (89.6-122.3 cancers detected per 1,000 mammograms) or high (36.1-47.5 cancers detected per 1,000 mammograms) cancer detection rates accounted for 55% of all detected cancers. These included mammograms that were done to evaluate an abnormal test or breast lump in individuals of all ages regardless of breast cancer history.

On the opposite end, 44.2% of mammograms with very low cancer detection rates accounted for 13.1% of detected cancers and that included annual screening tests in women aged 50-69 years (3.8 cancers detected per 1,000 mammograms) and all screening mammograms in individuals younger than 50 years regardless of screening interval (2.8 cancers detected per 1000 mammograms).
 

Treat with caution

In an accompanying editorial, Sarah M. Friedewald, MD, and Dipti Gupta, MD, both from Northwestern University, Chicago, pointed out that, while the authors examined a large dataset to identify a subgroup of patients who would most likely benefit from breast imaging in a setting where capacity is limited, “these data should be used with caution as the only barometer for whether a patient merits cancer screening during a period of rationing.”

They noted that, in the context of an acute crisis, when patient volume needs to be reduced very quickly, it is often impractical for clinicians to sift through patient records in order to capture the information necessary for triage. In addition, asking nonclinical schedulers to accurately pull data at this level, at the time when the patient calls to make an appointment, is unrealistic.

In the context of the pandemic, the editorialists wrote that, while this model uses risk for breast cancer to prioritize those to be seen in the clinic, the risk for complications from COVID-19 may also be an important factor to consider. For example, an older patient may be at a higher risk for breast cancer but may also face a higher risk for COVID-related complications. Conversely, a younger woman at a lower risk for serious COVID-related disease but who has breast cancer detected early will gain more life-years than an older patient.

There are also no algorithms to account for each patient’s perceived risk for breast cancer or COVID-19, and “the downstream effect of delaying cancer diagnosis may similarly lead to unintended consequences but may take longer to become apparent,” they wrote. “Focusing efforts on the operations of accommodating as many patients as possible, such as extending clinic hours, would be preferable.”

Finally, Dr. Friedewald and Dr. Gupta concluded that “the practicality of this process during the COVID-19 pandemic and extrapolation to other emergent settings are less obvious.”

The study was supported through a Patient-centered Outcomes Research Institute program award. Dr. Miglioretti reported receiving royalties from Elsevier outside the submitted work. Several coauthors report relationships with industry. Dr. Friedewald reported receiving grants from Hologic Research during the conduct of the study. Dr. Gupta disclosed no relevant financial relationships.

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

A novel risk-based approach could be an effective way to triage women for mammography during times of limited capacity, such as the situation during the COVID-19 pandemic, according to new findings.

Researchers evaluated almost 2 million mammograms that had been performed at more than 90 radiology centers and found that 12% of mammograms with “high” and “very high” cancer risk rates accounted for 55% of detected cancers.

In contrast, 44% of mammograms with very low cancer risk rates accounted for 13% of detected cancers. The study was published online March 25, 2021, in JAMA Network Open.

Cancer screening programs dramatically slowed or even came to a screeching halt during 2020, when restrictions and lockdowns were in place. The American Cancer Society even recommended that “no one should go to a health care facility for routine cancer screening,” as part of COVID-19 precautions.

However, concern was voiced that the pause in screening would allow patients with asymptomatic cancers or precursor lesions to develop into a more serious disease state.

The authors pointed out that several professional associations had posted guidance for scheduling individuals for breast imaging services during the COVID-19 pandemic, but these recommendations were based on expert opinion. The investigators’ goal was to help imaging facilities optimize the number of breast cancers that could be detected during periods of reduced capacity using clinical indication and individual characteristics.

The result was a risk-based strategy for triaging mammograms during periods of decreased capacity, which lead author Diana L. Miglioretti, PhD, explained was feasible to implement. Dr. Miglioretti is division chief of biostatistics in the department of public health sciences at University of California, Davis.

“Our risk model used information that is commonly collected by radiology facilities,” she said in an interview. “Vendors of electronic medical records could create tools that pull the information from the medical record, or could create fields in the scheduling system to efficiently collect this information when the mammogram is scheduled.”

Dr. Miglioretti emphasized that, once the information is collected in a standardized manner, “it would be straightforward to use a computer program to apply our algorithm to rank women based on their likelihood of having a breast cancer detected.”

“I think it is worth the investment to create these electronic tools now, given the potential for future shutdowns or periods of reduced capacity due to a variety of reasons, such as natural disasters and cyberattacks – or another pandemic,” she said.

Some facilities are still working through backlogs of mammograms that need to be rescheduled, which would be another way that this algorithm could be used. “They could use this approach to determine who should be scheduled first by using data available in the electronic medical record,” she added.
 

Five risk groups

Dr. Miglioretti and colleagues conducted a cohort study using data that was prospectively collected from mammography examinations performed from 2014 to 2019 at 92 radiology facilities in the Breast Cancer Surveillance Consortium. The cohort included 898,415 individuals who contributed to 1.8 million mammograms.

Information that included clinical indication for screening, breast symptoms, personal history of breast cancer, age, time since last mammogram/screening interval, family history of breast cancer, breast density, and history of high-risk breast lesion was collected from self-administered questionnaires at the time of mammography or extracted from electronic health records.

Following analysis, the data was categorized into five risk groups: very high (>50), high (22-50), moderate (10-22), low (5-10), and very low (<5) cancer detection rate per 1,000 mammograms. These thresholds were chosen based on the observed cancer detection rates and clinical expertise.

Of the group, about 1.7 million mammograms were from women without a personal history of breast cancer and 156,104 mammograms were from women with a breast cancer history. Most of the cohort were aged 50-69 years at the time of imaging, and 67.9% were White (11.2% Black, 11.3% Asian or Pacific Islander, 7% Hispanic, and 2.2% were another race/ethnicity or mixed race/ethnicity).

Their results showed that 12% of mammograms with very high (89.6-122.3 cancers detected per 1,000 mammograms) or high (36.1-47.5 cancers detected per 1,000 mammograms) cancer detection rates accounted for 55% of all detected cancers. These included mammograms that were done to evaluate an abnormal test or breast lump in individuals of all ages regardless of breast cancer history.

On the opposite end, 44.2% of mammograms with very low cancer detection rates accounted for 13.1% of detected cancers and that included annual screening tests in women aged 50-69 years (3.8 cancers detected per 1,000 mammograms) and all screening mammograms in individuals younger than 50 years regardless of screening interval (2.8 cancers detected per 1000 mammograms).
 

Treat with caution

In an accompanying editorial, Sarah M. Friedewald, MD, and Dipti Gupta, MD, both from Northwestern University, Chicago, pointed out that, while the authors examined a large dataset to identify a subgroup of patients who would most likely benefit from breast imaging in a setting where capacity is limited, “these data should be used with caution as the only barometer for whether a patient merits cancer screening during a period of rationing.”

They noted that, in the context of an acute crisis, when patient volume needs to be reduced very quickly, it is often impractical for clinicians to sift through patient records in order to capture the information necessary for triage. In addition, asking nonclinical schedulers to accurately pull data at this level, at the time when the patient calls to make an appointment, is unrealistic.

In the context of the pandemic, the editorialists wrote that, while this model uses risk for breast cancer to prioritize those to be seen in the clinic, the risk for complications from COVID-19 may also be an important factor to consider. For example, an older patient may be at a higher risk for breast cancer but may also face a higher risk for COVID-related complications. Conversely, a younger woman at a lower risk for serious COVID-related disease but who has breast cancer detected early will gain more life-years than an older patient.

There are also no algorithms to account for each patient’s perceived risk for breast cancer or COVID-19, and “the downstream effect of delaying cancer diagnosis may similarly lead to unintended consequences but may take longer to become apparent,” they wrote. “Focusing efforts on the operations of accommodating as many patients as possible, such as extending clinic hours, would be preferable.”

Finally, Dr. Friedewald and Dr. Gupta concluded that “the practicality of this process during the COVID-19 pandemic and extrapolation to other emergent settings are less obvious.”

The study was supported through a Patient-centered Outcomes Research Institute program award. Dr. Miglioretti reported receiving royalties from Elsevier outside the submitted work. Several coauthors report relationships with industry. Dr. Friedewald reported receiving grants from Hologic Research during the conduct of the study. Dr. Gupta disclosed no relevant financial relationships.

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

For select older patients, it is safe to switch to a lower dose of lenalidomide maintenance therapy and discontinue dexamethasone after 9 months. The regimen is safe and yields outcomes similar to those of standard, continuous lenalidomide/dexamethasone (Rd), according to new findings.

At a median follow-up of 37 months, event-free survival was 10.4 months in the experimental arm in which dexamethasone therapy was stopped (Rd-R) versus 6.9 months for standard therapy. The tailored approach also resulted in fewer adverse effects.

The authors noted that there was no difference in progression-free survival (PFS) and overall survival between the two groups.

“These results may be useful for the treatment of myeloma patients, since approximately one-third of patients not eligible for stem cell transplantation are intermediate fit, the population in our study,” said lead author Alessandra Larocca, MD, PhD, from the department of hematology-oncology of the University Hospital Città della Salute e della Scienza, Torino, Italy.

She said in an interview that they expect that these findings “may help to optimize the treatment of less-fit elderly patients by reducing the occurrence of adverse events and thus improving outcomes and preserving quality of life of these patients.”

This approach is a viable option for clinicians to consider for some patient subgroups. “This steroid-sparing approach can also be used in other combinations,” she said. “Ongoing trials are now evaluating steroid sparing in combination with monoclonal antibodies or the role of frailty-guided treatment.”

The study was published March 19, 2021, in Blood.
 

Curtailing steroids

Myeloma patients aged 75 years or older or who have comorbidities and functional impairments are an understudied population. They are more susceptible to adverse events that may negatively affect the duration of treatment and outcomes. Steroids are “scarcely tolerated” in the long term, even among younger patients, and “whether sparing dexamethasone is as effective as prolonged steroid exposure remains an open issue,” the authors wrote. There are still no clear data on the advantage of continuous steroid treatment as opposed to fixed-duration treatment for newly diagnosed patients.

In 2010, a study compared high-dose with low-dose dexamethasone. As expected, the rate of adverse events was lower among patients who received the low-dose steroid, but quite unexpectedly, deaths with high-dose dexamethasone were significantly higher than with low-dose dexamethasone.

The 1-year overall survival was 96% among patients who received the low dose of dexamethasone versus 87% with the standard high dose.

S. Vincent Rajkumar, MD, of the Mayo Clinic, Rochester, Minn., who was the lead author of the 2010 study, spoke with this new organization about the current study. “This is an important and practice-changing study,” he said. “We have already changed our practice and recommendations based on this study.”

He explained that, for transplant-ineligible patients, instead of initial therapy with bortezomib-lenalidomide-dexamethasone followed by Rd, they use lenalidomide alone without steroids.

“After 9 months of initial therapy, I now recommend we stop dexamethasone unless we are having problems controlling the myeloma, such as progressive disease,” Dr. Rajkumar said. “I congratulate the authors on a study that will improve the quality of life for our patients.”
 

Improved event-free survival

In this study, Dr. Larocca and colleagues investigated the efficacy and feasibility of a dose- and schedule-adjusted Rd regimen that was followed by maintenance Rd-R 10 mg/d and compared the regimen with continuous Rd in elderly, intermediate-fit patients who were newly diagnosed with multiple myeloma.

The primary endpoint was event-free survival, defined as progression/death from any cause, lenalidomide discontinuation, and any hematologic grade 4 or nonhematologic grade 3-4 adverse events.

The cohort consisted of 199 patients who were randomly assigned to receive either Rd-R (n = 101) or continuous Rd (n = 98). The median age was 75 years in the Rd-R arm and 76 years in the Rd arm; 52% of patients in the Rd-R group and 43% in the Rd group were classified as being intermediate fit not for age but for geriatric impairments.

With a median follow-up of 37 months, event-free survival was 10.4 months in the Rd-R arm versus 6.9 months in the Rd arm (hazard ratio, 0.70; P = .02). This benefit was maintained beyond nine cycles (median: 19.8 vs. 10.6 months for Rd-R vs. Rd; HR, 0.55; P = .03)

The median PFS was 20.2 months with Rd-R and 18.3 months with Rd (HR, 0.78; P = .16). The median overall survival was not reached. The 3-year overall survival was 74% with Rd-R and 63% with continuous Rd (HR, 0.62; P = .06). Among patients remaining on therapy after nine cycles, no difference in median PFS was observed between the two groups (24.3 vs. 18.7 months; HR, 0.73; P = .19).

Best response was similar for both groups, with an overall response rate of 78% versus 68% (P = .15). The very good partial response rate was 51% in the Rd-R arm versus 39% in the continuous Rd arm (P = .09).

Toxicities were similar between the two groups. Hematologic adverse events of at least grade 3 were reported in 26% of Rd-R patients versus 20% of Rd patients (P = .40). In both groups, the most frequent grade ≥3 hematologic toxicity was neutropenia (21% vs 18%). The most frequent grade ≥3 toxicities were nonhematologic. They occurred in 33% of Rd-R patients and 43% of Rd patients (P = .15). The most frequent nonhematologic toxicities were infections (10% vs. 12%), constitutional (3% vs. 12%), dermatologic (7% vs. 3%), and central nervous toxicities (2% vs. 6%).

The study was sponsored by Fondazione EMN Italy Onlus. Dr. Larocca has received honoraria from Amgen, Bristol-Myers Squibb, Celgene, Janssen, and GlaxoSmithKline, and has served on the advisory boards for Bristol-Myers Squibb, Celgene, Janssen, and Takeda. Several coauthors also have disclosed relationships with industry. Dr. Rajkumar disclosed no relevant financial relationships.

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

For select older patients, it is safe to switch to a lower dose of lenalidomide maintenance therapy and discontinue dexamethasone after 9 months. The regimen is safe and yields outcomes similar to those of standard, continuous lenalidomide/dexamethasone (Rd), according to new findings.

At a median follow-up of 37 months, event-free survival was 10.4 months in the experimental arm in which dexamethasone therapy was stopped (Rd-R) versus 6.9 months for standard therapy. The tailored approach also resulted in fewer adverse effects.

The authors noted that there was no difference in progression-free survival (PFS) and overall survival between the two groups.

“These results may be useful for the treatment of myeloma patients, since approximately one-third of patients not eligible for stem cell transplantation are intermediate fit, the population in our study,” said lead author Alessandra Larocca, MD, PhD, from the department of hematology-oncology of the University Hospital Città della Salute e della Scienza, Torino, Italy.

She said in an interview that they expect that these findings “may help to optimize the treatment of less-fit elderly patients by reducing the occurrence of adverse events and thus improving outcomes and preserving quality of life of these patients.”

This approach is a viable option for clinicians to consider for some patient subgroups. “This steroid-sparing approach can also be used in other combinations,” she said. “Ongoing trials are now evaluating steroid sparing in combination with monoclonal antibodies or the role of frailty-guided treatment.”

The study was published March 19, 2021, in Blood.
 

Curtailing steroids

Myeloma patients aged 75 years or older or who have comorbidities and functional impairments are an understudied population. They are more susceptible to adverse events that may negatively affect the duration of treatment and outcomes. Steroids are “scarcely tolerated” in the long term, even among younger patients, and “whether sparing dexamethasone is as effective as prolonged steroid exposure remains an open issue,” the authors wrote. There are still no clear data on the advantage of continuous steroid treatment as opposed to fixed-duration treatment for newly diagnosed patients.

In 2010, a study compared high-dose with low-dose dexamethasone. As expected, the rate of adverse events was lower among patients who received the low-dose steroid, but quite unexpectedly, deaths with high-dose dexamethasone were significantly higher than with low-dose dexamethasone.

The 1-year overall survival was 96% among patients who received the low dose of dexamethasone versus 87% with the standard high dose.

S. Vincent Rajkumar, MD, of the Mayo Clinic, Rochester, Minn., who was the lead author of the 2010 study, spoke with this new organization about the current study. “This is an important and practice-changing study,” he said. “We have already changed our practice and recommendations based on this study.”

He explained that, for transplant-ineligible patients, instead of initial therapy with bortezomib-lenalidomide-dexamethasone followed by Rd, they use lenalidomide alone without steroids.

“After 9 months of initial therapy, I now recommend we stop dexamethasone unless we are having problems controlling the myeloma, such as progressive disease,” Dr. Rajkumar said. “I congratulate the authors on a study that will improve the quality of life for our patients.”
 

Improved event-free survival

In this study, Dr. Larocca and colleagues investigated the efficacy and feasibility of a dose- and schedule-adjusted Rd regimen that was followed by maintenance Rd-R 10 mg/d and compared the regimen with continuous Rd in elderly, intermediate-fit patients who were newly diagnosed with multiple myeloma.

The primary endpoint was event-free survival, defined as progression/death from any cause, lenalidomide discontinuation, and any hematologic grade 4 or nonhematologic grade 3-4 adverse events.

The cohort consisted of 199 patients who were randomly assigned to receive either Rd-R (n = 101) or continuous Rd (n = 98). The median age was 75 years in the Rd-R arm and 76 years in the Rd arm; 52% of patients in the Rd-R group and 43% in the Rd group were classified as being intermediate fit not for age but for geriatric impairments.

With a median follow-up of 37 months, event-free survival was 10.4 months in the Rd-R arm versus 6.9 months in the Rd arm (hazard ratio, 0.70; P = .02). This benefit was maintained beyond nine cycles (median: 19.8 vs. 10.6 months for Rd-R vs. Rd; HR, 0.55; P = .03)

The median PFS was 20.2 months with Rd-R and 18.3 months with Rd (HR, 0.78; P = .16). The median overall survival was not reached. The 3-year overall survival was 74% with Rd-R and 63% with continuous Rd (HR, 0.62; P = .06). Among patients remaining on therapy after nine cycles, no difference in median PFS was observed between the two groups (24.3 vs. 18.7 months; HR, 0.73; P = .19).

Best response was similar for both groups, with an overall response rate of 78% versus 68% (P = .15). The very good partial response rate was 51% in the Rd-R arm versus 39% in the continuous Rd arm (P = .09).

Toxicities were similar between the two groups. Hematologic adverse events of at least grade 3 were reported in 26% of Rd-R patients versus 20% of Rd patients (P = .40). In both groups, the most frequent grade ≥3 hematologic toxicity was neutropenia (21% vs 18%). The most frequent grade ≥3 toxicities were nonhematologic. They occurred in 33% of Rd-R patients and 43% of Rd patients (P = .15). The most frequent nonhematologic toxicities were infections (10% vs. 12%), constitutional (3% vs. 12%), dermatologic (7% vs. 3%), and central nervous toxicities (2% vs. 6%).

The study was sponsored by Fondazione EMN Italy Onlus. Dr. Larocca has received honoraria from Amgen, Bristol-Myers Squibb, Celgene, Janssen, and GlaxoSmithKline, and has served on the advisory boards for Bristol-Myers Squibb, Celgene, Janssen, and Takeda. Several coauthors also have disclosed relationships with industry. Dr. Rajkumar disclosed no relevant financial relationships.

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

For select older patients, it is safe to switch to a lower dose of lenalidomide maintenance therapy and discontinue dexamethasone after 9 months. The regimen is safe and yields outcomes similar to those of standard, continuous lenalidomide/dexamethasone (Rd), according to new findings.

At a median follow-up of 37 months, event-free survival was 10.4 months in the experimental arm in which dexamethasone therapy was stopped (Rd-R) versus 6.9 months for standard therapy. The tailored approach also resulted in fewer adverse effects.

The authors noted that there was no difference in progression-free survival (PFS) and overall survival between the two groups.

“These results may be useful for the treatment of myeloma patients, since approximately one-third of patients not eligible for stem cell transplantation are intermediate fit, the population in our study,” said lead author Alessandra Larocca, MD, PhD, from the department of hematology-oncology of the University Hospital Città della Salute e della Scienza, Torino, Italy.

She said in an interview that they expect that these findings “may help to optimize the treatment of less-fit elderly patients by reducing the occurrence of adverse events and thus improving outcomes and preserving quality of life of these patients.”

This approach is a viable option for clinicians to consider for some patient subgroups. “This steroid-sparing approach can also be used in other combinations,” she said. “Ongoing trials are now evaluating steroid sparing in combination with monoclonal antibodies or the role of frailty-guided treatment.”

The study was published March 19, 2021, in Blood.
 

Curtailing steroids

Myeloma patients aged 75 years or older or who have comorbidities and functional impairments are an understudied population. They are more susceptible to adverse events that may negatively affect the duration of treatment and outcomes. Steroids are “scarcely tolerated” in the long term, even among younger patients, and “whether sparing dexamethasone is as effective as prolonged steroid exposure remains an open issue,” the authors wrote. There are still no clear data on the advantage of continuous steroid treatment as opposed to fixed-duration treatment for newly diagnosed patients.

In 2010, a study compared high-dose with low-dose dexamethasone. As expected, the rate of adverse events was lower among patients who received the low-dose steroid, but quite unexpectedly, deaths with high-dose dexamethasone were significantly higher than with low-dose dexamethasone.

The 1-year overall survival was 96% among patients who received the low dose of dexamethasone versus 87% with the standard high dose.

S. Vincent Rajkumar, MD, of the Mayo Clinic, Rochester, Minn., who was the lead author of the 2010 study, spoke with this new organization about the current study. “This is an important and practice-changing study,” he said. “We have already changed our practice and recommendations based on this study.”

He explained that, for transplant-ineligible patients, instead of initial therapy with bortezomib-lenalidomide-dexamethasone followed by Rd, they use lenalidomide alone without steroids.

“After 9 months of initial therapy, I now recommend we stop dexamethasone unless we are having problems controlling the myeloma, such as progressive disease,” Dr. Rajkumar said. “I congratulate the authors on a study that will improve the quality of life for our patients.”
 

Improved event-free survival

In this study, Dr. Larocca and colleagues investigated the efficacy and feasibility of a dose- and schedule-adjusted Rd regimen that was followed by maintenance Rd-R 10 mg/d and compared the regimen with continuous Rd in elderly, intermediate-fit patients who were newly diagnosed with multiple myeloma.

The primary endpoint was event-free survival, defined as progression/death from any cause, lenalidomide discontinuation, and any hematologic grade 4 or nonhematologic grade 3-4 adverse events.

The cohort consisted of 199 patients who were randomly assigned to receive either Rd-R (n = 101) or continuous Rd (n = 98). The median age was 75 years in the Rd-R arm and 76 years in the Rd arm; 52% of patients in the Rd-R group and 43% in the Rd group were classified as being intermediate fit not for age but for geriatric impairments.

With a median follow-up of 37 months, event-free survival was 10.4 months in the Rd-R arm versus 6.9 months in the Rd arm (hazard ratio, 0.70; P = .02). This benefit was maintained beyond nine cycles (median: 19.8 vs. 10.6 months for Rd-R vs. Rd; HR, 0.55; P = .03)

The median PFS was 20.2 months with Rd-R and 18.3 months with Rd (HR, 0.78; P = .16). The median overall survival was not reached. The 3-year overall survival was 74% with Rd-R and 63% with continuous Rd (HR, 0.62; P = .06). Among patients remaining on therapy after nine cycles, no difference in median PFS was observed between the two groups (24.3 vs. 18.7 months; HR, 0.73; P = .19).

Best response was similar for both groups, with an overall response rate of 78% versus 68% (P = .15). The very good partial response rate was 51% in the Rd-R arm versus 39% in the continuous Rd arm (P = .09).

Toxicities were similar between the two groups. Hematologic adverse events of at least grade 3 were reported in 26% of Rd-R patients versus 20% of Rd patients (P = .40). In both groups, the most frequent grade ≥3 hematologic toxicity was neutropenia (21% vs 18%). The most frequent grade ≥3 toxicities were nonhematologic. They occurred in 33% of Rd-R patients and 43% of Rd patients (P = .15). The most frequent nonhematologic toxicities were infections (10% vs. 12%), constitutional (3% vs. 12%), dermatologic (7% vs. 3%), and central nervous toxicities (2% vs. 6%).

The study was sponsored by Fondazione EMN Italy Onlus. Dr. Larocca has received honoraria from Amgen, Bristol-Myers Squibb, Celgene, Janssen, and GlaxoSmithKline, and has served on the advisory boards for Bristol-Myers Squibb, Celgene, Janssen, and Takeda. Several coauthors also have disclosed relationships with industry. Dr. Rajkumar disclosed no relevant financial relationships.

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