AVAHO

Multicancer early-detection blood (MCED) tests are the focus of intensive development. What techniques do these tests use? What potential do they show? Suzette Delaloge, MD, MSc, oncologist, breast cancer specialist, and director of the individualized cancer prevention program (Interception) at the Gustave Roussy Institute in Villejuif, France, looks into these “liquid biopsies” and shares her reservations about their potential marketing, especially to the organized care plans.

Question: What are the general principles underpinning these MCED tests?

Suzette Delaloge, MD, MSc: Despite their specificities, the general idea is to detect certain cancer markers in various body fluids (blood, urine, saliva, etc.), for example, molecules released by cancer cells (cytokines, inflammatory proteins, leptin, etc.) or distinctive features of the DNA in tumor cells. In blood, these molecules can be found in plasma or in serum. In urine, it’s more about detecting kidney, bladder, and urinary tract cancers.

Q: What sort of time frame are we looking at for these MCED tests to be used in routine practice?

Dr. Delaloge: They first appeared around 10 years ago. Development of these tests has intensified in recent years. There are numerous research laboratories, both public and private, that are developing different early-detection tests for cancer.

Some of these development processes are about to come to an end and are expected to be in regular, concrete use within 5-10 years. For the most advanced developments, the main biologic material researched and analyzed is DNA from cancer cells. We all have fragments of DNA from dead cells in our plasma (apoptosis), but cancer cells release more of these than others, and most importantly, their DNA has distinctive characteristics. The idea is to develop tests capable of detecting these characteristics.

Liquid biopsies based on genomic biomarkers could make MCED a reality, especially for cancers for which there is no standard screening process. But at this stage of the research, there are limitations, including low sensitivity for detecting stage I cancers in validation studies and an increased risk for overdiagnosis.

Q: What specific set of characteristics are the most advanced approaches based on?

Dr. Delaloge: They’re based on the analysis of DNA methylation, a biological process by which CH3 methyl groups are added to the DNA molecule and that determines gene expression. This phenomenon differs depending on whether the cell is cancerous. Among the tests currently under development making use of this specific characteristic is the Galleri test, which is the most advanced of them all.

A previous British National Health Service study, SYMPLIFY, which was published in 2023 by researchers at the University of Oxford, was conducted in symptomatic patients attending a health center. It offers promising results in a diagnostic situation. It has nothing at all to do with screening here. A large, randomized English study, NHS-Galleri, is underway, this time involving the general population, with the aim of assessing the potential benefit of the same test as screening in 140,000 people between ages 50 and 77 years.

In the SYMPLIFY study, which was carried out in symptomatic patients attending a health center, the Galleri MCED test had a positive predictive value of 75.5%, a negative predictive value of 97.6%, a sensitivity of 66.3%, and a specificity of 98.4%. Sensitivity increased with age and cancer stage from 24.2% at stage I to 95.3% at stage IV. For cases for which a cancer signal was detected in patients with cancer, the prediction of the original site of the cancer by the MCED test was accurate in 85.2% of cases. This large-scale prospective evaluation of an MCED diagnostic test confirms its feasibility in a symptomatic population but is not yet sufficiently accurate to “confirm or rule out the presence of cancer.” According to the authors, “in cases in which the MCED test detects a cancer signal in this context, the probability of a diagnosis of cancer being made is considerably higher and may identify cancers at sites other than those suspected during the initial referral phase, thus reducing delays in diagnosis.” A negative test means a lower likelihood of cancer but not so low that proper investigation can be ruled out. Further tests will be needed to optimize use of a negative predictive value.

Q: Does MCED testing concern all types of cancer?

Dr. Delaloge: The Galleri test is based on full profiling of DNA methylation. This allows for early diagnosis of cancer even before it can be seen on imaging tests. The issue with these tests is that they aren’t that good at early diagnosis of the most common types of cancer (breast, colorectal, cervical, etc.) for which we already have more efficient means such as the fecal immunochemical test for colorectal cancer, mammography, HPV testing, and so on.

These blood tests would thus not be aimed at replacing routine screening but rather at screening asymptomatic individuals or those with nonspecific signs for cancers for which we have few or no screening measures and which are on the rise, such as deep tumors and cancer diagnosed at a late stage, namely pancreas, bile duct, ovarian, esophageal, lung, stomach, etc.

The results from the studies published are promising, but others are underway to confirm the benefit of these MCEDs. The challenge is to identify cancer at an early stage, at a stage where it will be easier to cure the patient and control its growth using treatments that are less onerous for the patient and that have fewer aftereffects but not at the expense of a massive increase in overdiagnosis, as seen with prostate-specific antigen levels in prostate cancer a few years ago!

Q: What would be the focus of these MCED tests?

Dr. Delaloge: We must be alert to the risk for the market development of MCED tests. For now, they are mostly, especially the Galleri test, developed in the general population to screen for types of cancer that could not be detected in any other way but also because it’s the most financially beneficial situation. The designers want to position themselves in the general population, regardless of whether this means they’ll have to test hundreds of people to find one for whom the test is beneficial. What’s more, developing tests in isolation, without considering their place in ad hoc treatment pathways, is not realistic. It’s likely that some of these tests will be marketed within the next 10 years, but the health care systems destined to receive them are not remotely ready to do so.

Q: An even more recent publication, from late July 2023, is even more exciting in relation to early detection of lung cancer using circulating DNA sequencing. What are your thoughts on it?

Dr. Delaloge: Initially overtaken by other technologies in favor of MCED approaches, DNA sequencing as a technique to detect somatic mutations seems to have reentered the competition with this new-generation research. The authors published some very interesting results, especially for stage I lung cancer with a very high sensitivity of 75%. [Editor’s note: A machine-learning model using genome-wide mutational profiles combined with other features and followed by CT imaging detected more than 90% of patients with lung cancer, including those with stage I and II disease.]

This research illustrates the difficulty of providing high performance while covering a broad range of cancers. Here, the good results mainly concern lung cancer. Researchers and health care authorities must be alert to ensuring that MCED tests prove themselves in terms of sensitivity and specificity in responding to a medical need and in their impact on specific mortality. This craze for MCED tests must not hinder the development of “single-cancer” technologies that may be much better for detecting specific cancers. This recent publication is interesting in this respect, because this sequencing test seems to be particularly good at detecting lung cancer.

Q: Another approach used in MCED tests is based on analyzing the size of DNA fragments in the blood. Can you explain how this works?

Dr. Delaloge: When cancer is not present, the size of DNA fragments in cells is much more homogeneous. Here also, the benefit of MCED based on this technique rests on the very early detection of cancers that are less common than those for which we already have good screening methods available.

Other approaches, still at the experimental stage, detect certain proteins, certain inflammatory molecules, RNA, etc. But for many researchers, the future will involve pairing tests on the basis of circulating DNA in the blood with the detection of specific molecules indicating the presence of cancer to obtain early screening tests that are even more effective or that possibly even allow us to identify an appropriate treatment at an early stage.

The development of a simple test based on a blood draw that allows us to screen early for all cancers and that would replace all current screening measures is, therefore, not imminent, although it could potentially be on the horizon in years to come. Alongside this, an important issue is the benefit of cancer screening in the general population vs. in a targeted population with a specific risk. The latter option is in development but requires an individualized screening pathway based on blood testing and current screening methods: imaging, etc. It also depends on an individual’s cancer risk profile such as age, personal and family medical history, genetic predisposition, and so on.

According to recent modeling, these multicancer tests could theoretically prevent a minimum of 2,000 deaths from cancer per 100,000 people between ages 50 and 79 years screened per year (17% fewer deaths from cancer per year).

This article was translated from the Medscape French Edition. A version appeared on Medscape.com.

Multicancer early-detection blood (MCED) tests are the focus of intensive development. What techniques do these tests use? What potential do they show? Suzette Delaloge, MD, MSc, oncologist, breast cancer specialist, and director of the individualized cancer prevention program (Interception) at the Gustave Roussy Institute in Villejuif, France, looks into these “liquid biopsies” and shares her reservations about their potential marketing, especially to the organized care plans.

Question: What are the general principles underpinning these MCED tests?

Suzette Delaloge, MD, MSc: Despite their specificities, the general idea is to detect certain cancer markers in various body fluids (blood, urine, saliva, etc.), for example, molecules released by cancer cells (cytokines, inflammatory proteins, leptin, etc.) or distinctive features of the DNA in tumor cells. In blood, these molecules can be found in plasma or in serum. In urine, it’s more about detecting kidney, bladder, and urinary tract cancers.

Q: What sort of time frame are we looking at for these MCED tests to be used in routine practice?

Dr. Delaloge: They first appeared around 10 years ago. Development of these tests has intensified in recent years. There are numerous research laboratories, both public and private, that are developing different early-detection tests for cancer.

Some of these development processes are about to come to an end and are expected to be in regular, concrete use within 5-10 years. For the most advanced developments, the main biologic material researched and analyzed is DNA from cancer cells. We all have fragments of DNA from dead cells in our plasma (apoptosis), but cancer cells release more of these than others, and most importantly, their DNA has distinctive characteristics. The idea is to develop tests capable of detecting these characteristics.

Liquid biopsies based on genomic biomarkers could make MCED a reality, especially for cancers for which there is no standard screening process. But at this stage of the research, there are limitations, including low sensitivity for detecting stage I cancers in validation studies and an increased risk for overdiagnosis.

Q: What specific set of characteristics are the most advanced approaches based on?

Dr. Delaloge: They’re based on the analysis of DNA methylation, a biological process by which CH3 methyl groups are added to the DNA molecule and that determines gene expression. This phenomenon differs depending on whether the cell is cancerous. Among the tests currently under development making use of this specific characteristic is the Galleri test, which is the most advanced of them all.

A previous British National Health Service study, SYMPLIFY, which was published in 2023 by researchers at the University of Oxford, was conducted in symptomatic patients attending a health center. It offers promising results in a diagnostic situation. It has nothing at all to do with screening here. A large, randomized English study, NHS-Galleri, is underway, this time involving the general population, with the aim of assessing the potential benefit of the same test as screening in 140,000 people between ages 50 and 77 years.

In the SYMPLIFY study, which was carried out in symptomatic patients attending a health center, the Galleri MCED test had a positive predictive value of 75.5%, a negative predictive value of 97.6%, a sensitivity of 66.3%, and a specificity of 98.4%. Sensitivity increased with age and cancer stage from 24.2% at stage I to 95.3% at stage IV. For cases for which a cancer signal was detected in patients with cancer, the prediction of the original site of the cancer by the MCED test was accurate in 85.2% of cases. This large-scale prospective evaluation of an MCED diagnostic test confirms its feasibility in a symptomatic population but is not yet sufficiently accurate to “confirm or rule out the presence of cancer.” According to the authors, “in cases in which the MCED test detects a cancer signal in this context, the probability of a diagnosis of cancer being made is considerably higher and may identify cancers at sites other than those suspected during the initial referral phase, thus reducing delays in diagnosis.” A negative test means a lower likelihood of cancer but not so low that proper investigation can be ruled out. Further tests will be needed to optimize use of a negative predictive value.

Q: Does MCED testing concern all types of cancer?

Dr. Delaloge: The Galleri test is based on full profiling of DNA methylation. This allows for early diagnosis of cancer even before it can be seen on imaging tests. The issue with these tests is that they aren’t that good at early diagnosis of the most common types of cancer (breast, colorectal, cervical, etc.) for which we already have more efficient means such as the fecal immunochemical test for colorectal cancer, mammography, HPV testing, and so on.

These blood tests would thus not be aimed at replacing routine screening but rather at screening asymptomatic individuals or those with nonspecific signs for cancers for which we have few or no screening measures and which are on the rise, such as deep tumors and cancer diagnosed at a late stage, namely pancreas, bile duct, ovarian, esophageal, lung, stomach, etc.

The results from the studies published are promising, but others are underway to confirm the benefit of these MCEDs. The challenge is to identify cancer at an early stage, at a stage where it will be easier to cure the patient and control its growth using treatments that are less onerous for the patient and that have fewer aftereffects but not at the expense of a massive increase in overdiagnosis, as seen with prostate-specific antigen levels in prostate cancer a few years ago!

Q: What would be the focus of these MCED tests?

Dr. Delaloge: We must be alert to the risk for the market development of MCED tests. For now, they are mostly, especially the Galleri test, developed in the general population to screen for types of cancer that could not be detected in any other way but also because it’s the most financially beneficial situation. The designers want to position themselves in the general population, regardless of whether this means they’ll have to test hundreds of people to find one for whom the test is beneficial. What’s more, developing tests in isolation, without considering their place in ad hoc treatment pathways, is not realistic. It’s likely that some of these tests will be marketed within the next 10 years, but the health care systems destined to receive them are not remotely ready to do so.

Q: An even more recent publication, from late July 2023, is even more exciting in relation to early detection of lung cancer using circulating DNA sequencing. What are your thoughts on it?

Dr. Delaloge: Initially overtaken by other technologies in favor of MCED approaches, DNA sequencing as a technique to detect somatic mutations seems to have reentered the competition with this new-generation research. The authors published some very interesting results, especially for stage I lung cancer with a very high sensitivity of 75%. [Editor’s note: A machine-learning model using genome-wide mutational profiles combined with other features and followed by CT imaging detected more than 90% of patients with lung cancer, including those with stage I and II disease.]

This research illustrates the difficulty of providing high performance while covering a broad range of cancers. Here, the good results mainly concern lung cancer. Researchers and health care authorities must be alert to ensuring that MCED tests prove themselves in terms of sensitivity and specificity in responding to a medical need and in their impact on specific mortality. This craze for MCED tests must not hinder the development of “single-cancer” technologies that may be much better for detecting specific cancers. This recent publication is interesting in this respect, because this sequencing test seems to be particularly good at detecting lung cancer.

Q: Another approach used in MCED tests is based on analyzing the size of DNA fragments in the blood. Can you explain how this works?

Dr. Delaloge: When cancer is not present, the size of DNA fragments in cells is much more homogeneous. Here also, the benefit of MCED based on this technique rests on the very early detection of cancers that are less common than those for which we already have good screening methods available.

Other approaches, still at the experimental stage, detect certain proteins, certain inflammatory molecules, RNA, etc. But for many researchers, the future will involve pairing tests on the basis of circulating DNA in the blood with the detection of specific molecules indicating the presence of cancer to obtain early screening tests that are even more effective or that possibly even allow us to identify an appropriate treatment at an early stage.

The development of a simple test based on a blood draw that allows us to screen early for all cancers and that would replace all current screening measures is, therefore, not imminent, although it could potentially be on the horizon in years to come. Alongside this, an important issue is the benefit of cancer screening in the general population vs. in a targeted population with a specific risk. The latter option is in development but requires an individualized screening pathway based on blood testing and current screening methods: imaging, etc. It also depends on an individual’s cancer risk profile such as age, personal and family medical history, genetic predisposition, and so on.

According to recent modeling, these multicancer tests could theoretically prevent a minimum of 2,000 deaths from cancer per 100,000 people between ages 50 and 79 years screened per year (17% fewer deaths from cancer per year).

This article was translated from the Medscape French Edition. A version appeared on Medscape.com.

Multicancer early-detection blood (MCED) tests are the focus of intensive development. What techniques do these tests use? What potential do they show? Suzette Delaloge, MD, MSc, oncologist, breast cancer specialist, and director of the individualized cancer prevention program (Interception) at the Gustave Roussy Institute in Villejuif, France, looks into these “liquid biopsies” and shares her reservations about their potential marketing, especially to the organized care plans.

Question: What are the general principles underpinning these MCED tests?

Suzette Delaloge, MD, MSc: Despite their specificities, the general idea is to detect certain cancer markers in various body fluids (blood, urine, saliva, etc.), for example, molecules released by cancer cells (cytokines, inflammatory proteins, leptin, etc.) or distinctive features of the DNA in tumor cells. In blood, these molecules can be found in plasma or in serum. In urine, it’s more about detecting kidney, bladder, and urinary tract cancers.

Q: What sort of time frame are we looking at for these MCED tests to be used in routine practice?

Dr. Delaloge: They first appeared around 10 years ago. Development of these tests has intensified in recent years. There are numerous research laboratories, both public and private, that are developing different early-detection tests for cancer.

Some of these development processes are about to come to an end and are expected to be in regular, concrete use within 5-10 years. For the most advanced developments, the main biologic material researched and analyzed is DNA from cancer cells. We all have fragments of DNA from dead cells in our plasma (apoptosis), but cancer cells release more of these than others, and most importantly, their DNA has distinctive characteristics. The idea is to develop tests capable of detecting these characteristics.

Liquid biopsies based on genomic biomarkers could make MCED a reality, especially for cancers for which there is no standard screening process. But at this stage of the research, there are limitations, including low sensitivity for detecting stage I cancers in validation studies and an increased risk for overdiagnosis.

Q: What specific set of characteristics are the most advanced approaches based on?

Dr. Delaloge: They’re based on the analysis of DNA methylation, a biological process by which CH3 methyl groups are added to the DNA molecule and that determines gene expression. This phenomenon differs depending on whether the cell is cancerous. Among the tests currently under development making use of this specific characteristic is the Galleri test, which is the most advanced of them all.

A previous British National Health Service study, SYMPLIFY, which was published in 2023 by researchers at the University of Oxford, was conducted in symptomatic patients attending a health center. It offers promising results in a diagnostic situation. It has nothing at all to do with screening here. A large, randomized English study, NHS-Galleri, is underway, this time involving the general population, with the aim of assessing the potential benefit of the same test as screening in 140,000 people between ages 50 and 77 years.

In the SYMPLIFY study, which was carried out in symptomatic patients attending a health center, the Galleri MCED test had a positive predictive value of 75.5%, a negative predictive value of 97.6%, a sensitivity of 66.3%, and a specificity of 98.4%. Sensitivity increased with age and cancer stage from 24.2% at stage I to 95.3% at stage IV. For cases for which a cancer signal was detected in patients with cancer, the prediction of the original site of the cancer by the MCED test was accurate in 85.2% of cases. This large-scale prospective evaluation of an MCED diagnostic test confirms its feasibility in a symptomatic population but is not yet sufficiently accurate to “confirm or rule out the presence of cancer.” According to the authors, “in cases in which the MCED test detects a cancer signal in this context, the probability of a diagnosis of cancer being made is considerably higher and may identify cancers at sites other than those suspected during the initial referral phase, thus reducing delays in diagnosis.” A negative test means a lower likelihood of cancer but not so low that proper investigation can be ruled out. Further tests will be needed to optimize use of a negative predictive value.

Q: Does MCED testing concern all types of cancer?

Dr. Delaloge: The Galleri test is based on full profiling of DNA methylation. This allows for early diagnosis of cancer even before it can be seen on imaging tests. The issue with these tests is that they aren’t that good at early diagnosis of the most common types of cancer (breast, colorectal, cervical, etc.) for which we already have more efficient means such as the fecal immunochemical test for colorectal cancer, mammography, HPV testing, and so on.

These blood tests would thus not be aimed at replacing routine screening but rather at screening asymptomatic individuals or those with nonspecific signs for cancers for which we have few or no screening measures and which are on the rise, such as deep tumors and cancer diagnosed at a late stage, namely pancreas, bile duct, ovarian, esophageal, lung, stomach, etc.

The results from the studies published are promising, but others are underway to confirm the benefit of these MCEDs. The challenge is to identify cancer at an early stage, at a stage where it will be easier to cure the patient and control its growth using treatments that are less onerous for the patient and that have fewer aftereffects but not at the expense of a massive increase in overdiagnosis, as seen with prostate-specific antigen levels in prostate cancer a few years ago!

Q: What would be the focus of these MCED tests?

Dr. Delaloge: We must be alert to the risk for the market development of MCED tests. For now, they are mostly, especially the Galleri test, developed in the general population to screen for types of cancer that could not be detected in any other way but also because it’s the most financially beneficial situation. The designers want to position themselves in the general population, regardless of whether this means they’ll have to test hundreds of people to find one for whom the test is beneficial. What’s more, developing tests in isolation, without considering their place in ad hoc treatment pathways, is not realistic. It’s likely that some of these tests will be marketed within the next 10 years, but the health care systems destined to receive them are not remotely ready to do so.

Q: An even more recent publication, from late July 2023, is even more exciting in relation to early detection of lung cancer using circulating DNA sequencing. What are your thoughts on it?

Dr. Delaloge: Initially overtaken by other technologies in favor of MCED approaches, DNA sequencing as a technique to detect somatic mutations seems to have reentered the competition with this new-generation research. The authors published some very interesting results, especially for stage I lung cancer with a very high sensitivity of 75%. [Editor’s note: A machine-learning model using genome-wide mutational profiles combined with other features and followed by CT imaging detected more than 90% of patients with lung cancer, including those with stage I and II disease.]

This research illustrates the difficulty of providing high performance while covering a broad range of cancers. Here, the good results mainly concern lung cancer. Researchers and health care authorities must be alert to ensuring that MCED tests prove themselves in terms of sensitivity and specificity in responding to a medical need and in their impact on specific mortality. This craze for MCED tests must not hinder the development of “single-cancer” technologies that may be much better for detecting specific cancers. This recent publication is interesting in this respect, because this sequencing test seems to be particularly good at detecting lung cancer.

Q: Another approach used in MCED tests is based on analyzing the size of DNA fragments in the blood. Can you explain how this works?

Dr. Delaloge: When cancer is not present, the size of DNA fragments in cells is much more homogeneous. Here also, the benefit of MCED based on this technique rests on the very early detection of cancers that are less common than those for which we already have good screening methods available.

Other approaches, still at the experimental stage, detect certain proteins, certain inflammatory molecules, RNA, etc. But for many researchers, the future will involve pairing tests on the basis of circulating DNA in the blood with the detection of specific molecules indicating the presence of cancer to obtain early screening tests that are even more effective or that possibly even allow us to identify an appropriate treatment at an early stage.

The development of a simple test based on a blood draw that allows us to screen early for all cancers and that would replace all current screening measures is, therefore, not imminent, although it could potentially be on the horizon in years to come. Alongside this, an important issue is the benefit of cancer screening in the general population vs. in a targeted population with a specific risk. The latter option is in development but requires an individualized screening pathway based on blood testing and current screening methods: imaging, etc. It also depends on an individual’s cancer risk profile such as age, personal and family medical history, genetic predisposition, and so on.

According to recent modeling, these multicancer tests could theoretically prevent a minimum of 2,000 deaths from cancer per 100,000 people between ages 50 and 79 years screened per year (17% fewer deaths from cancer per year).

This article was translated from the Medscape French Edition. A version appeared on Medscape.com.

The updated draft recommendation from the U.S. Preventive Services Task Force that would lower the recommended start age for routine screening mammograms by a decade for all average-risk women is not justified, experts argue in a “dissenting view” published in the New England Journal of Medicine.

The proposed change would affect more than 20 million U.S. women, and it’s “hard to see any potential benefits associated with lowering the starting age,” coauthor Steven Woloshin, MD, with Dartmouth Cancer Center, Lebanon, N.H., said in an NEJM podcast.

Back in May, when USPSTF released the draft recommendation, task force member John Wong, MD, with Tufts Medical Center, Boston, said in an interview, “It is now clear that screening every other year starting at age 40 has the potential to save about 20% more lives among all women.”

But, according to Dr. Woloshin, there is no recent evidence that mortality from breast cancer is increasing in young women.

In fact, the United States has seen a steady decrease in breast cancer mortality, especially among younger women. Breast cancer mortality among women under 50 “has been cut in half over the past 30 years,” Dr. Woloshin and coauthors explained.

Another wrinkle: The task force did not base its recent recommendation on randomized trial data. In fact, there have been no new randomized trials of screening mammography for women in their 40s since 2016. Instead, the task force relied on statistical models to “estimate what might happen if the starting age were lowered,” Dr. Woloshin and colleagues said.

Relying on a statistical model, however, “is problematic because it has some very optimistic assumptions about the benefit of mammography,” Dr. Woloshin said in the podcast. For instance, the models assume that screening mammography reduces breast cancer mortality by about 25%.

That 25% reduction is “far greater than what’s reported in the meta-analyses of the available randomized trials,” Dr. Woloshin explained. The meta-analyses report about a 16% reduction for all the trials combined and an estimated 13% for trials at low risk of bias. But “even these meta-analyses are likely to overstate the effect of screening since the trials were done before the major advances in treatment.”

In their own calculations, Dr. Woloshin and colleagues found that lowering the screening age to 40 came with a small potential benefit and a substantial risk for harm.

Combing data from the National Cancer Institute, the team reported that the risk for death for women in their 40s from any cause over the next 10 years was about 3% whether or not they received their biennial mammogram.

The risk for death from breast cancer in that time was 0.23% with mammograms – about 2 in every 1,000 women – and 0.31% without. “That’s 1 less breast cancer death per 1,000 women screened for 10 years,” Dr. Woloshin said.

Put another way, with mammography screening, “the chance of not dying from breast cancer over the next 10 years increases from 99.7% to 99.8%,” Dr. Woloshin said.

The benefit is arguably small, while the harms appear quite significant, Dr. Woloshin said. About 36% of women who begin screening at age 40 would have at least one false alarm over 10 years, and almost 7% would have a false alarm requiring a biopsy in that time frame.
 

Ease or exacerbate racial disparity?

Another argument that the USPSTF highlighted for lowering the screening age: Research indicates that Black women get breast cancer at younger ages and are more likely to die of the disease, compared with White women.

Dr. Woloshin and coauthors, however, also took issue with the view that lowering the screening age could reduce disparities between Black and White women.

“There’s no question that there are substantial differences between Black and White women in terms of breast cancer mortality, but there’s actually very little disparity in breast cancer screening – about 60% of Black and White women in their 40s are screened regularly in the United States,” Dr. Woloshin explained in the podcast.

Therefore, it’s “really hard to imagine” how recommending the same intervention to both groups could possibly reduce the disparity, he said.

“The disparity is not a reflection of screening. It reflects differences in cancer biology,” he added. “Black women are at higher risk for more aggressive, fast-growing cancers that are less likely to be caught by screening and unfortunately are less likely to benefit from treatment.”

Earlier screening would also not address the problems facing poor women, who tend to be disproportionately Black, such as lower quality of available medical services, follow-up delays after abnormal scans, treatment delays, and less use of adjuvant therapy, Dr. Woloshin cautioned.

In Dr. Woloshin’s view, lowering the screening age, which broadens the eligible population, may actually “exacerbate problems contributing to disparity by diverting resources toward expanded screening rather than doing what we know works by ensuring that high-quality treatments are more readily accessible to poor women with breast cancer.”
 

Reconsider the change?

Because task force recommendations are so influential, Dr. Woloshin and colleagues worry that mammography screening for women in their 40s will probably become a performance measure.

“Our concern is that, rather than fostering informed decisions, clinicians and practices are going to be judged and rewarded and punished based on compliance with this quality metric,” Dr. Woloshin said.

That’s a problem, he noted, “because women should be able to make the decision for themselves rather than having this be a public health imperative, which is imposed by physicians and practices who are incentivized to meet a quality metric.”

The hope, said Dr. Woloshin, is that this prospective piece will help influence the task force to “reconsider the recommendation, because we think that the bottom line is that their models are insufficient to support a new imperative. The benefits are really limited, and there are really common and important harms for healthy women.”

The comment period for the draft recommendation is now closed, and a final decision from the task force is forthcoming.

The research had no funding. Dr. Woloshin has no relevant disclosures.

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

The updated draft recommendation from the U.S. Preventive Services Task Force that would lower the recommended start age for routine screening mammograms by a decade for all average-risk women is not justified, experts argue in a “dissenting view” published in the New England Journal of Medicine.

The proposed change would affect more than 20 million U.S. women, and it’s “hard to see any potential benefits associated with lowering the starting age,” coauthor Steven Woloshin, MD, with Dartmouth Cancer Center, Lebanon, N.H., said in an NEJM podcast.

Back in May, when USPSTF released the draft recommendation, task force member John Wong, MD, with Tufts Medical Center, Boston, said in an interview, “It is now clear that screening every other year starting at age 40 has the potential to save about 20% more lives among all women.”

But, according to Dr. Woloshin, there is no recent evidence that mortality from breast cancer is increasing in young women.

In fact, the United States has seen a steady decrease in breast cancer mortality, especially among younger women. Breast cancer mortality among women under 50 “has been cut in half over the past 30 years,” Dr. Woloshin and coauthors explained.

Another wrinkle: The task force did not base its recent recommendation on randomized trial data. In fact, there have been no new randomized trials of screening mammography for women in their 40s since 2016. Instead, the task force relied on statistical models to “estimate what might happen if the starting age were lowered,” Dr. Woloshin and colleagues said.

Relying on a statistical model, however, “is problematic because it has some very optimistic assumptions about the benefit of mammography,” Dr. Woloshin said in the podcast. For instance, the models assume that screening mammography reduces breast cancer mortality by about 25%.

That 25% reduction is “far greater than what’s reported in the meta-analyses of the available randomized trials,” Dr. Woloshin explained. The meta-analyses report about a 16% reduction for all the trials combined and an estimated 13% for trials at low risk of bias. But “even these meta-analyses are likely to overstate the effect of screening since the trials were done before the major advances in treatment.”

In their own calculations, Dr. Woloshin and colleagues found that lowering the screening age to 40 came with a small potential benefit and a substantial risk for harm.

Combing data from the National Cancer Institute, the team reported that the risk for death for women in their 40s from any cause over the next 10 years was about 3% whether or not they received their biennial mammogram.

The risk for death from breast cancer in that time was 0.23% with mammograms – about 2 in every 1,000 women – and 0.31% without. “That’s 1 less breast cancer death per 1,000 women screened for 10 years,” Dr. Woloshin said.

Put another way, with mammography screening, “the chance of not dying from breast cancer over the next 10 years increases from 99.7% to 99.8%,” Dr. Woloshin said.

The benefit is arguably small, while the harms appear quite significant, Dr. Woloshin said. About 36% of women who begin screening at age 40 would have at least one false alarm over 10 years, and almost 7% would have a false alarm requiring a biopsy in that time frame.
 

Ease or exacerbate racial disparity?

Another argument that the USPSTF highlighted for lowering the screening age: Research indicates that Black women get breast cancer at younger ages and are more likely to die of the disease, compared with White women.

Dr. Woloshin and coauthors, however, also took issue with the view that lowering the screening age could reduce disparities between Black and White women.

“There’s no question that there are substantial differences between Black and White women in terms of breast cancer mortality, but there’s actually very little disparity in breast cancer screening – about 60% of Black and White women in their 40s are screened regularly in the United States,” Dr. Woloshin explained in the podcast.

Therefore, it’s “really hard to imagine” how recommending the same intervention to both groups could possibly reduce the disparity, he said.

“The disparity is not a reflection of screening. It reflects differences in cancer biology,” he added. “Black women are at higher risk for more aggressive, fast-growing cancers that are less likely to be caught by screening and unfortunately are less likely to benefit from treatment.”

Earlier screening would also not address the problems facing poor women, who tend to be disproportionately Black, such as lower quality of available medical services, follow-up delays after abnormal scans, treatment delays, and less use of adjuvant therapy, Dr. Woloshin cautioned.

In Dr. Woloshin’s view, lowering the screening age, which broadens the eligible population, may actually “exacerbate problems contributing to disparity by diverting resources toward expanded screening rather than doing what we know works by ensuring that high-quality treatments are more readily accessible to poor women with breast cancer.”
 

Reconsider the change?

Because task force recommendations are so influential, Dr. Woloshin and colleagues worry that mammography screening for women in their 40s will probably become a performance measure.

“Our concern is that, rather than fostering informed decisions, clinicians and practices are going to be judged and rewarded and punished based on compliance with this quality metric,” Dr. Woloshin said.

That’s a problem, he noted, “because women should be able to make the decision for themselves rather than having this be a public health imperative, which is imposed by physicians and practices who are incentivized to meet a quality metric.”

The hope, said Dr. Woloshin, is that this prospective piece will help influence the task force to “reconsider the recommendation, because we think that the bottom line is that their models are insufficient to support a new imperative. The benefits are really limited, and there are really common and important harms for healthy women.”

The comment period for the draft recommendation is now closed, and a final decision from the task force is forthcoming.

The research had no funding. Dr. Woloshin has no relevant disclosures.

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

The updated draft recommendation from the U.S. Preventive Services Task Force that would lower the recommended start age for routine screening mammograms by a decade for all average-risk women is not justified, experts argue in a “dissenting view” published in the New England Journal of Medicine.

The proposed change would affect more than 20 million U.S. women, and it’s “hard to see any potential benefits associated with lowering the starting age,” coauthor Steven Woloshin, MD, with Dartmouth Cancer Center, Lebanon, N.H., said in an NEJM podcast.

Back in May, when USPSTF released the draft recommendation, task force member John Wong, MD, with Tufts Medical Center, Boston, said in an interview, “It is now clear that screening every other year starting at age 40 has the potential to save about 20% more lives among all women.”

But, according to Dr. Woloshin, there is no recent evidence that mortality from breast cancer is increasing in young women.

In fact, the United States has seen a steady decrease in breast cancer mortality, especially among younger women. Breast cancer mortality among women under 50 “has been cut in half over the past 30 years,” Dr. Woloshin and coauthors explained.

Another wrinkle: The task force did not base its recent recommendation on randomized trial data. In fact, there have been no new randomized trials of screening mammography for women in their 40s since 2016. Instead, the task force relied on statistical models to “estimate what might happen if the starting age were lowered,” Dr. Woloshin and colleagues said.

Relying on a statistical model, however, “is problematic because it has some very optimistic assumptions about the benefit of mammography,” Dr. Woloshin said in the podcast. For instance, the models assume that screening mammography reduces breast cancer mortality by about 25%.

That 25% reduction is “far greater than what’s reported in the meta-analyses of the available randomized trials,” Dr. Woloshin explained. The meta-analyses report about a 16% reduction for all the trials combined and an estimated 13% for trials at low risk of bias. But “even these meta-analyses are likely to overstate the effect of screening since the trials were done before the major advances in treatment.”

In their own calculations, Dr. Woloshin and colleagues found that lowering the screening age to 40 came with a small potential benefit and a substantial risk for harm.

Combing data from the National Cancer Institute, the team reported that the risk for death for women in their 40s from any cause over the next 10 years was about 3% whether or not they received their biennial mammogram.

The risk for death from breast cancer in that time was 0.23% with mammograms – about 2 in every 1,000 women – and 0.31% without. “That’s 1 less breast cancer death per 1,000 women screened for 10 years,” Dr. Woloshin said.

Put another way, with mammography screening, “the chance of not dying from breast cancer over the next 10 years increases from 99.7% to 99.8%,” Dr. Woloshin said.

The benefit is arguably small, while the harms appear quite significant, Dr. Woloshin said. About 36% of women who begin screening at age 40 would have at least one false alarm over 10 years, and almost 7% would have a false alarm requiring a biopsy in that time frame.
 

Ease or exacerbate racial disparity?

Another argument that the USPSTF highlighted for lowering the screening age: Research indicates that Black women get breast cancer at younger ages and are more likely to die of the disease, compared with White women.

Dr. Woloshin and coauthors, however, also took issue with the view that lowering the screening age could reduce disparities between Black and White women.

“There’s no question that there are substantial differences between Black and White women in terms of breast cancer mortality, but there’s actually very little disparity in breast cancer screening – about 60% of Black and White women in their 40s are screened regularly in the United States,” Dr. Woloshin explained in the podcast.

Therefore, it’s “really hard to imagine” how recommending the same intervention to both groups could possibly reduce the disparity, he said.

“The disparity is not a reflection of screening. It reflects differences in cancer biology,” he added. “Black women are at higher risk for more aggressive, fast-growing cancers that are less likely to be caught by screening and unfortunately are less likely to benefit from treatment.”

Earlier screening would also not address the problems facing poor women, who tend to be disproportionately Black, such as lower quality of available medical services, follow-up delays after abnormal scans, treatment delays, and less use of adjuvant therapy, Dr. Woloshin cautioned.

In Dr. Woloshin’s view, lowering the screening age, which broadens the eligible population, may actually “exacerbate problems contributing to disparity by diverting resources toward expanded screening rather than doing what we know works by ensuring that high-quality treatments are more readily accessible to poor women with breast cancer.”
 

Reconsider the change?

Because task force recommendations are so influential, Dr. Woloshin and colleagues worry that mammography screening for women in their 40s will probably become a performance measure.

“Our concern is that, rather than fostering informed decisions, clinicians and practices are going to be judged and rewarded and punished based on compliance with this quality metric,” Dr. Woloshin said.

That’s a problem, he noted, “because women should be able to make the decision for themselves rather than having this be a public health imperative, which is imposed by physicians and practices who are incentivized to meet a quality metric.”

The hope, said Dr. Woloshin, is that this prospective piece will help influence the task force to “reconsider the recommendation, because we think that the bottom line is that their models are insufficient to support a new imperative. The benefits are really limited, and there are really common and important harms for healthy women.”

The comment period for the draft recommendation is now closed, and a final decision from the task force is forthcoming.

The research had no funding. Dr. Woloshin has no relevant disclosures.

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

CHICAGO – The US Department of Veterans Affairs (VA) top medical officer told the Association of VA Hematology/Oncology (AVAHO) oncology members that they are at the forefront of the agency’s push to expand care for veterans who may have been injured by exposure to hazardous materials on the job.

“All of you are playing a critical role in implementing the PACT Act, the signature legislative achievement of the Biden administration,” said Shereef Elnahal, MD, MBA, the VA Under Secretary for Health, in a keynote address at the 2023 annual meeting of AVAHO. “But more importantly, if we do our jobs right, it could be the largest expansion of veterans’ benefits in the history of this country. That requires us to have the capacity to deliver care to so many more individuals.”

The VA has provided more than 4.1 million free toxic exposure screenings to veterans since President Biden signed the PACT Act (The Sergeant First Class Heath Robinson Honoring our Promise to Address Comprehensive Toxics Act) in August 2022. The legislation prioritizes claims for cancer, terminal illnesses, and homelessness, and the White House says it has allowed the Veterans Health Administration and the Veterans Benefits Administration to grow at the fastest rates in 2 decades. 

“Almost every type of solid tumor is now considered a presumptive condition associated with burden of exposure to veterans deployed anywhere in Central Command, either in the Persian Gulf War or the post-9/11 conflicts,” said Under Secretary Elnahal, who was confirmed in his job by the Senate in July 2022. 

Implementing the PACT Act “requires all of us to make investments and further strengthen our system’s care for oncology,” he said. It is also crucial, to reduce “leakage into the community,” referring to veterans who leave the VA for private care. “I know for a fact that the care that veterans get when they have oncology services available in our direct-care system within VA is better. That's not a contention. That is proven by different peer-reviewed studies over the years. And I think that comparison is only intensifying when it comes to how much better evidence-based care our veterans receive at the hands of all of you across the country.”

Elnahal highlighted the development of a “2-way” cancer registry that will allow the National Institute and the VA to exchange cancer diagnosis and treatment data with state registries. “This will give the VA access to critical data in a complete way—to what veterans have experienced, especially veterans who are getting parts of their care in one place and parts of their care in a different place.”

On the data front, he also noted that “the PACT Act also requires us to research the future and determine the next set of presumptive conditions that are related to the hazards of serving our country. It requires that we have robust data sets to be able to gain those insights.”
More globally, Elnahal said the VA can play a crucial role in the Cancer Moonshot Program: “We can win the race, and VA can contribute asymmetrically to that race, to make cancer a chronic condition.”

He highlighted efforts within the VA to battle cancer such as programs to reduce disparities, boost cancer screening, treat rural veterans via a national teleoncology service, and implement the Close to Me program to bring infusion services to veterans in isolated regions.

But Elnahal’s presentation was not entirely rosy. He warned that 40% of veterans are being served outside the VA. “That's sort of a rule-of-thumb threshold when you start looking more like a payer than a provider.”

He also noted that while the VA hired 54,000 people in just the past year—6.2% growth—it takes a long time to bring workers on board. “That’s why I'm holding every single leader in our system accountable for reducing onboarding times by at least a month,” he said. The AVAHO audience enthusiastically applauded.

CHICAGO – The US Department of Veterans Affairs (VA) top medical officer told the Association of VA Hematology/Oncology (AVAHO) oncology members that they are at the forefront of the agency’s push to expand care for veterans who may have been injured by exposure to hazardous materials on the job.

“All of you are playing a critical role in implementing the PACT Act, the signature legislative achievement of the Biden administration,” said Shereef Elnahal, MD, MBA, the VA Under Secretary for Health, in a keynote address at the 2023 annual meeting of AVAHO. “But more importantly, if we do our jobs right, it could be the largest expansion of veterans’ benefits in the history of this country. That requires us to have the capacity to deliver care to so many more individuals.”

The VA has provided more than 4.1 million free toxic exposure screenings to veterans since President Biden signed the PACT Act (The Sergeant First Class Heath Robinson Honoring our Promise to Address Comprehensive Toxics Act) in August 2022. The legislation prioritizes claims for cancer, terminal illnesses, and homelessness, and the White House says it has allowed the Veterans Health Administration and the Veterans Benefits Administration to grow at the fastest rates in 2 decades. 

“Almost every type of solid tumor is now considered a presumptive condition associated with burden of exposure to veterans deployed anywhere in Central Command, either in the Persian Gulf War or the post-9/11 conflicts,” said Under Secretary Elnahal, who was confirmed in his job by the Senate in July 2022. 

Implementing the PACT Act “requires all of us to make investments and further strengthen our system’s care for oncology,” he said. It is also crucial, to reduce “leakage into the community,” referring to veterans who leave the VA for private care. “I know for a fact that the care that veterans get when they have oncology services available in our direct-care system within VA is better. That's not a contention. That is proven by different peer-reviewed studies over the years. And I think that comparison is only intensifying when it comes to how much better evidence-based care our veterans receive at the hands of all of you across the country.”

Elnahal highlighted the development of a “2-way” cancer registry that will allow the National Institute and the VA to exchange cancer diagnosis and treatment data with state registries. “This will give the VA access to critical data in a complete way—to what veterans have experienced, especially veterans who are getting parts of their care in one place and parts of their care in a different place.”

On the data front, he also noted that “the PACT Act also requires us to research the future and determine the next set of presumptive conditions that are related to the hazards of serving our country. It requires that we have robust data sets to be able to gain those insights.”
More globally, Elnahal said the VA can play a crucial role in the Cancer Moonshot Program: “We can win the race, and VA can contribute asymmetrically to that race, to make cancer a chronic condition.”

He highlighted efforts within the VA to battle cancer such as programs to reduce disparities, boost cancer screening, treat rural veterans via a national teleoncology service, and implement the Close to Me program to bring infusion services to veterans in isolated regions.

But Elnahal’s presentation was not entirely rosy. He warned that 40% of veterans are being served outside the VA. “That's sort of a rule-of-thumb threshold when you start looking more like a payer than a provider.”

He also noted that while the VA hired 54,000 people in just the past year—6.2% growth—it takes a long time to bring workers on board. “That’s why I'm holding every single leader in our system accountable for reducing onboarding times by at least a month,” he said. The AVAHO audience enthusiastically applauded.

CHICAGO – The US Department of Veterans Affairs (VA) top medical officer told the Association of VA Hematology/Oncology (AVAHO) oncology members that they are at the forefront of the agency’s push to expand care for veterans who may have been injured by exposure to hazardous materials on the job.

“All of you are playing a critical role in implementing the PACT Act, the signature legislative achievement of the Biden administration,” said Shereef Elnahal, MD, MBA, the VA Under Secretary for Health, in a keynote address at the 2023 annual meeting of AVAHO. “But more importantly, if we do our jobs right, it could be the largest expansion of veterans’ benefits in the history of this country. That requires us to have the capacity to deliver care to so many more individuals.”

The VA has provided more than 4.1 million free toxic exposure screenings to veterans since President Biden signed the PACT Act (The Sergeant First Class Heath Robinson Honoring our Promise to Address Comprehensive Toxics Act) in August 2022. The legislation prioritizes claims for cancer, terminal illnesses, and homelessness, and the White House says it has allowed the Veterans Health Administration and the Veterans Benefits Administration to grow at the fastest rates in 2 decades. 

“Almost every type of solid tumor is now considered a presumptive condition associated with burden of exposure to veterans deployed anywhere in Central Command, either in the Persian Gulf War or the post-9/11 conflicts,” said Under Secretary Elnahal, who was confirmed in his job by the Senate in July 2022. 

Implementing the PACT Act “requires all of us to make investments and further strengthen our system’s care for oncology,” he said. It is also crucial, to reduce “leakage into the community,” referring to veterans who leave the VA for private care. “I know for a fact that the care that veterans get when they have oncology services available in our direct-care system within VA is better. That's not a contention. That is proven by different peer-reviewed studies over the years. And I think that comparison is only intensifying when it comes to how much better evidence-based care our veterans receive at the hands of all of you across the country.”

Elnahal highlighted the development of a “2-way” cancer registry that will allow the National Institute and the VA to exchange cancer diagnosis and treatment data with state registries. “This will give the VA access to critical data in a complete way—to what veterans have experienced, especially veterans who are getting parts of their care in one place and parts of their care in a different place.”

On the data front, he also noted that “the PACT Act also requires us to research the future and determine the next set of presumptive conditions that are related to the hazards of serving our country. It requires that we have robust data sets to be able to gain those insights.”
More globally, Elnahal said the VA can play a crucial role in the Cancer Moonshot Program: “We can win the race, and VA can contribute asymmetrically to that race, to make cancer a chronic condition.”

He highlighted efforts within the VA to battle cancer such as programs to reduce disparities, boost cancer screening, treat rural veterans via a national teleoncology service, and implement the Close to Me program to bring infusion services to veterans in isolated regions.

But Elnahal’s presentation was not entirely rosy. He warned that 40% of veterans are being served outside the VA. “That's sort of a rule-of-thumb threshold when you start looking more like a payer than a provider.”

He also noted that while the VA hired 54,000 people in just the past year—6.2% growth—it takes a long time to bring workers on board. “That’s why I'm holding every single leader in our system accountable for reducing onboarding times by at least a month,” he said. The AVAHO audience enthusiastically applauded.

WASHINGTON – Adding the PD-1 inhibitor pembrolizumab to the established combination of dabrafenib and trametinib (DT) significantly improves survival outcomes in BRAF V600E-mutated anaplastic thyroid cancer - particularly when administered in a neoadjuvant fashion, prior to surgery. Overall survival rates in the study exceeded 5 years.

“The very long median overall survival in the study’s neoadjuvant group is quite remarkable for a group of patients who used to have a very poor prognosis,” senior author Maria E. Cabanillas, MD, associate professor in the department of endocrine neoplasia and hormonal disorders at the University of Texas MD Anderson Cancer Center in Houston, said in an interview.

“This median overall survival definitely exceeds any other treatments thus far in BRAF-mutated anaplastic thyroid cancer.”

The research was presented at the annual meeting of the American Thyroid Association.

Anaplastic thyroid cancer, though rare, is the most aggressive form of thyroid cancer. It accounts for just 1% of the cancers but causes about 50% of thyroid cancer mortality.

The historical median overall survival is 5-6 months.

With research in recent years showing that as many as 40% of anaplastic thyroid cancers harbor BRAF V600E mutations, the door has opened for potential benefits with the combination of the BRAF inhibitor dabrafenib with the MEK-inhibitor drug trametinib.

The treatment combination was shown in research that included the phase 2 ROAR trial to yield important responses. It was approved by the Food and Drug Administration in 2018 for locally advanced or metastatic BRAF V600E-mutant anaplastic thyroid cancer, as well as other cancers.

However, a key caveat of DT is that patients eventually develop resistance mutations, leading to disease progression.

To overcome the problem, Dr. Cabanillas and her team found two key strategies that show promise – the addition of immunotherapy, such as pembrolizumab to DT, and the use of a neoadjuvant approach, with surgery performed after an initial response to the triplet therapy.
 

Triple therapy showed highly favorable results

In a study presented at the 2022 ATA annual meeting, researchers reported on the triple therapy of BRAF/MEK inhibitors vemurafenib and cobimetinib plus immunotherapy with atezolizumab. Results were highly favorable, with an overall response rate of 72% and an impressive 2-year survival of 67%.

However, a major limitation was that the study lacked a control arm. In the current study, the addition of pembrolizumab to DT was compared with DT alone. The investigators also sought to determine the survival benefits of a neoadjuvant strategy.

For the study, first author Sarah Hamidi, MD, also of the MD Anderson Cancer Center, and her colleagues identified 94 patients with BRAF-mutated anaplastic thyroid cancer who were treated either with first‐line DT or DT plus pembrolizumab between 2014 and 2023, either outside of a trial or in a reported clinical trial.

The study compared three treatment regimens – DT alone (n = 23), DT with pembrolizumab added before or after disease progression (n = 48), and DT with neoadjuvant pembrolizumab added prior to or after surgery (n = 23).

There were no significant differences in baseline characteristics between the groups. Metastatic disease was present at the start of treatment among 87.0% of the DT group, 79.2% of the pembrolizumab group prior to or after disease progression, and 65.2% of the neoadjuvant pembrolizumab group.

The median follow-up of the three groups was 102 months, 28 months, and 42 months, respectively. The median overall survival was 9 months with DT alone, vs. 17 months with DT plus pembrolizumab before or after progression and 63 months with neoadjuvant pembrolizumab plus DT (P < .001).

The 12- and 24-month survival rates with DT alone were 33.7% and 28.9%, respectively; for DT plus pembrolizumab before or after progression, the rates were 60.2% and 36.5%; and for neoadjuvant pembrolizumab plus DT, the rates were 80.7% and 74.5%.

In an analysis that did not include the neoadjuvant group, median progression-free survival was significantly longer with DT plus pembrolizumab as an initial treatment (11.0 months) compared with DT alone (4.0 months; P  =  .049).

A subanalysis that evaluated the timing of the addition of pembrolizumab to DT before or after disease progression showed no significant differences between the two in median overall survival (17 months vs. 16 months; P = .554).

“This is valuable information, especially for centers where pembrolizumab cannot be easily obtained as a first-line therapy for anaplastic thyroid cancer,” Dr. Hamidi said in presenting the findings.

She noted, however, that the results should be interpreted with caution, given the small number of patients who received pembrolizumab before progression (n = 34) and especially after progression (n = 14).

In terms of safety, there were no grade 5 adverse events (AEs); 32.4% of patients experienced immune‐related AEs, most frequently, colitis and hepatitis.
 

Therapies “improve survival”

Overall, the results are important, Dr. Cabanillas said.

The results are “very exciting when you think about the fact that 10 years ago, patients with anaplastic thyroid cancer had a median overall survival measured in months, and now we see that those with a BRAF mutation have a real chance at survival when managed appropriately from the start,” she told this news organization.

She noted that a key caveat is the study’s retrospective nature. Other important considerations are that pembrolizumab adds toxicity as well as cost, and it is largely used off label in anaplastic thyroid cancer.

Nevertheless, “it does feel like there needs to be a call to action in the guidelines for this disease so that it includes neoadjuvant DT or DT plus pembrolizumab as the primary treatment of patients with BRAF-mutated anaplastic thyroid cancer because the initial treatment is critical here,” Dr. Cabanillas said.

She added that a phase 2 trial with neoadjuvant DT plus pembrolizumab is ongoing. Enrollment is expected to be completed soon.

Commenting on the findings, Sarimar Agosto Salgado, MD, of the department of head and neck – endocrine oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Fla., who was a comoderator of the session, said the results are encouraging.

“These findings are promising because they open the landscape of options of therapies that we can provide these patients,” she said in an interview.

“Anaplastic thyroid cancer has been a disease with a very short survival despite aggressive therapies, but we are seeing that not only have these therapies been able to improve survival but also patients’ quality of life.”

Particularly encouraging is how quickly the therapies can work, Dr. Salgado added.

“Many times when patients present to the clinic, the rapid response to these systemic therapies can even [allow them to avoid] having a tracheostomy, and we’re also seeing that some of these patients are able to go from unresectable disease to resectable disease, and then by having the main tumor out, their survival improves.

“So, this is definitely a big ray of hope for these patients.”

Dr. Cabanillas has received research funding from Merck. Dr. Hamidi has disclosed no relevant financial relationships. Dr. Salgado has relationships with Lilly and Exelixis.
 

A version of this article appeared on Medscape.com.

WASHINGTON – Adding the PD-1 inhibitor pembrolizumab to the established combination of dabrafenib and trametinib (DT) significantly improves survival outcomes in BRAF V600E-mutated anaplastic thyroid cancer - particularly when administered in a neoadjuvant fashion, prior to surgery. Overall survival rates in the study exceeded 5 years.

“The very long median overall survival in the study’s neoadjuvant group is quite remarkable for a group of patients who used to have a very poor prognosis,” senior author Maria E. Cabanillas, MD, associate professor in the department of endocrine neoplasia and hormonal disorders at the University of Texas MD Anderson Cancer Center in Houston, said in an interview.

“This median overall survival definitely exceeds any other treatments thus far in BRAF-mutated anaplastic thyroid cancer.”

The research was presented at the annual meeting of the American Thyroid Association.

Anaplastic thyroid cancer, though rare, is the most aggressive form of thyroid cancer. It accounts for just 1% of the cancers but causes about 50% of thyroid cancer mortality.

The historical median overall survival is 5-6 months.

With research in recent years showing that as many as 40% of anaplastic thyroid cancers harbor BRAF V600E mutations, the door has opened for potential benefits with the combination of the BRAF inhibitor dabrafenib with the MEK-inhibitor drug trametinib.

The treatment combination was shown in research that included the phase 2 ROAR trial to yield important responses. It was approved by the Food and Drug Administration in 2018 for locally advanced or metastatic BRAF V600E-mutant anaplastic thyroid cancer, as well as other cancers.

However, a key caveat of DT is that patients eventually develop resistance mutations, leading to disease progression.

To overcome the problem, Dr. Cabanillas and her team found two key strategies that show promise – the addition of immunotherapy, such as pembrolizumab to DT, and the use of a neoadjuvant approach, with surgery performed after an initial response to the triplet therapy.
 

Triple therapy showed highly favorable results

In a study presented at the 2022 ATA annual meeting, researchers reported on the triple therapy of BRAF/MEK inhibitors vemurafenib and cobimetinib plus immunotherapy with atezolizumab. Results were highly favorable, with an overall response rate of 72% and an impressive 2-year survival of 67%.

However, a major limitation was that the study lacked a control arm. In the current study, the addition of pembrolizumab to DT was compared with DT alone. The investigators also sought to determine the survival benefits of a neoadjuvant strategy.

For the study, first author Sarah Hamidi, MD, also of the MD Anderson Cancer Center, and her colleagues identified 94 patients with BRAF-mutated anaplastic thyroid cancer who were treated either with first‐line DT or DT plus pembrolizumab between 2014 and 2023, either outside of a trial or in a reported clinical trial.

The study compared three treatment regimens – DT alone (n = 23), DT with pembrolizumab added before or after disease progression (n = 48), and DT with neoadjuvant pembrolizumab added prior to or after surgery (n = 23).

There were no significant differences in baseline characteristics between the groups. Metastatic disease was present at the start of treatment among 87.0% of the DT group, 79.2% of the pembrolizumab group prior to or after disease progression, and 65.2% of the neoadjuvant pembrolizumab group.

The median follow-up of the three groups was 102 months, 28 months, and 42 months, respectively. The median overall survival was 9 months with DT alone, vs. 17 months with DT plus pembrolizumab before or after progression and 63 months with neoadjuvant pembrolizumab plus DT (P < .001).

The 12- and 24-month survival rates with DT alone were 33.7% and 28.9%, respectively; for DT plus pembrolizumab before or after progression, the rates were 60.2% and 36.5%; and for neoadjuvant pembrolizumab plus DT, the rates were 80.7% and 74.5%.

In an analysis that did not include the neoadjuvant group, median progression-free survival was significantly longer with DT plus pembrolizumab as an initial treatment (11.0 months) compared with DT alone (4.0 months; P  =  .049).

A subanalysis that evaluated the timing of the addition of pembrolizumab to DT before or after disease progression showed no significant differences between the two in median overall survival (17 months vs. 16 months; P = .554).

“This is valuable information, especially for centers where pembrolizumab cannot be easily obtained as a first-line therapy for anaplastic thyroid cancer,” Dr. Hamidi said in presenting the findings.

She noted, however, that the results should be interpreted with caution, given the small number of patients who received pembrolizumab before progression (n = 34) and especially after progression (n = 14).

In terms of safety, there were no grade 5 adverse events (AEs); 32.4% of patients experienced immune‐related AEs, most frequently, colitis and hepatitis.
 

Therapies “improve survival”

Overall, the results are important, Dr. Cabanillas said.

The results are “very exciting when you think about the fact that 10 years ago, patients with anaplastic thyroid cancer had a median overall survival measured in months, and now we see that those with a BRAF mutation have a real chance at survival when managed appropriately from the start,” she told this news organization.

She noted that a key caveat is the study’s retrospective nature. Other important considerations are that pembrolizumab adds toxicity as well as cost, and it is largely used off label in anaplastic thyroid cancer.

Nevertheless, “it does feel like there needs to be a call to action in the guidelines for this disease so that it includes neoadjuvant DT or DT plus pembrolizumab as the primary treatment of patients with BRAF-mutated anaplastic thyroid cancer because the initial treatment is critical here,” Dr. Cabanillas said.

She added that a phase 2 trial with neoadjuvant DT plus pembrolizumab is ongoing. Enrollment is expected to be completed soon.

Commenting on the findings, Sarimar Agosto Salgado, MD, of the department of head and neck – endocrine oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Fla., who was a comoderator of the session, said the results are encouraging.

“These findings are promising because they open the landscape of options of therapies that we can provide these patients,” she said in an interview.

“Anaplastic thyroid cancer has been a disease with a very short survival despite aggressive therapies, but we are seeing that not only have these therapies been able to improve survival but also patients’ quality of life.”

Particularly encouraging is how quickly the therapies can work, Dr. Salgado added.

“Many times when patients present to the clinic, the rapid response to these systemic therapies can even [allow them to avoid] having a tracheostomy, and we’re also seeing that some of these patients are able to go from unresectable disease to resectable disease, and then by having the main tumor out, their survival improves.

“So, this is definitely a big ray of hope for these patients.”

Dr. Cabanillas has received research funding from Merck. Dr. Hamidi has disclosed no relevant financial relationships. Dr. Salgado has relationships with Lilly and Exelixis.
 

A version of this article appeared on Medscape.com.

WASHINGTON – Adding the PD-1 inhibitor pembrolizumab to the established combination of dabrafenib and trametinib (DT) significantly improves survival outcomes in BRAF V600E-mutated anaplastic thyroid cancer - particularly when administered in a neoadjuvant fashion, prior to surgery. Overall survival rates in the study exceeded 5 years.

“The very long median overall survival in the study’s neoadjuvant group is quite remarkable for a group of patients who used to have a very poor prognosis,” senior author Maria E. Cabanillas, MD, associate professor in the department of endocrine neoplasia and hormonal disorders at the University of Texas MD Anderson Cancer Center in Houston, said in an interview.

“This median overall survival definitely exceeds any other treatments thus far in BRAF-mutated anaplastic thyroid cancer.”

The research was presented at the annual meeting of the American Thyroid Association.

Anaplastic thyroid cancer, though rare, is the most aggressive form of thyroid cancer. It accounts for just 1% of the cancers but causes about 50% of thyroid cancer mortality.

The historical median overall survival is 5-6 months.

With research in recent years showing that as many as 40% of anaplastic thyroid cancers harbor BRAF V600E mutations, the door has opened for potential benefits with the combination of the BRAF inhibitor dabrafenib with the MEK-inhibitor drug trametinib.

The treatment combination was shown in research that included the phase 2 ROAR trial to yield important responses. It was approved by the Food and Drug Administration in 2018 for locally advanced or metastatic BRAF V600E-mutant anaplastic thyroid cancer, as well as other cancers.

However, a key caveat of DT is that patients eventually develop resistance mutations, leading to disease progression.

To overcome the problem, Dr. Cabanillas and her team found two key strategies that show promise – the addition of immunotherapy, such as pembrolizumab to DT, and the use of a neoadjuvant approach, with surgery performed after an initial response to the triplet therapy.
 

Triple therapy showed highly favorable results

In a study presented at the 2022 ATA annual meeting, researchers reported on the triple therapy of BRAF/MEK inhibitors vemurafenib and cobimetinib plus immunotherapy with atezolizumab. Results were highly favorable, with an overall response rate of 72% and an impressive 2-year survival of 67%.

However, a major limitation was that the study lacked a control arm. In the current study, the addition of pembrolizumab to DT was compared with DT alone. The investigators also sought to determine the survival benefits of a neoadjuvant strategy.

For the study, first author Sarah Hamidi, MD, also of the MD Anderson Cancer Center, and her colleagues identified 94 patients with BRAF-mutated anaplastic thyroid cancer who were treated either with first‐line DT or DT plus pembrolizumab between 2014 and 2023, either outside of a trial or in a reported clinical trial.

The study compared three treatment regimens – DT alone (n = 23), DT with pembrolizumab added before or after disease progression (n = 48), and DT with neoadjuvant pembrolizumab added prior to or after surgery (n = 23).

There were no significant differences in baseline characteristics between the groups. Metastatic disease was present at the start of treatment among 87.0% of the DT group, 79.2% of the pembrolizumab group prior to or after disease progression, and 65.2% of the neoadjuvant pembrolizumab group.

The median follow-up of the three groups was 102 months, 28 months, and 42 months, respectively. The median overall survival was 9 months with DT alone, vs. 17 months with DT plus pembrolizumab before or after progression and 63 months with neoadjuvant pembrolizumab plus DT (P < .001).

The 12- and 24-month survival rates with DT alone were 33.7% and 28.9%, respectively; for DT plus pembrolizumab before or after progression, the rates were 60.2% and 36.5%; and for neoadjuvant pembrolizumab plus DT, the rates were 80.7% and 74.5%.

In an analysis that did not include the neoadjuvant group, median progression-free survival was significantly longer with DT plus pembrolizumab as an initial treatment (11.0 months) compared with DT alone (4.0 months; P  =  .049).

A subanalysis that evaluated the timing of the addition of pembrolizumab to DT before or after disease progression showed no significant differences between the two in median overall survival (17 months vs. 16 months; P = .554).

“This is valuable information, especially for centers where pembrolizumab cannot be easily obtained as a first-line therapy for anaplastic thyroid cancer,” Dr. Hamidi said in presenting the findings.

She noted, however, that the results should be interpreted with caution, given the small number of patients who received pembrolizumab before progression (n = 34) and especially after progression (n = 14).

In terms of safety, there were no grade 5 adverse events (AEs); 32.4% of patients experienced immune‐related AEs, most frequently, colitis and hepatitis.
 

Therapies “improve survival”

Overall, the results are important, Dr. Cabanillas said.

The results are “very exciting when you think about the fact that 10 years ago, patients with anaplastic thyroid cancer had a median overall survival measured in months, and now we see that those with a BRAF mutation have a real chance at survival when managed appropriately from the start,” she told this news organization.

She noted that a key caveat is the study’s retrospective nature. Other important considerations are that pembrolizumab adds toxicity as well as cost, and it is largely used off label in anaplastic thyroid cancer.

Nevertheless, “it does feel like there needs to be a call to action in the guidelines for this disease so that it includes neoadjuvant DT or DT plus pembrolizumab as the primary treatment of patients with BRAF-mutated anaplastic thyroid cancer because the initial treatment is critical here,” Dr. Cabanillas said.

She added that a phase 2 trial with neoadjuvant DT plus pembrolizumab is ongoing. Enrollment is expected to be completed soon.

Commenting on the findings, Sarimar Agosto Salgado, MD, of the department of head and neck – endocrine oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Fla., who was a comoderator of the session, said the results are encouraging.

“These findings are promising because they open the landscape of options of therapies that we can provide these patients,” she said in an interview.

“Anaplastic thyroid cancer has been a disease with a very short survival despite aggressive therapies, but we are seeing that not only have these therapies been able to improve survival but also patients’ quality of life.”

Particularly encouraging is how quickly the therapies can work, Dr. Salgado added.

“Many times when patients present to the clinic, the rapid response to these systemic therapies can even [allow them to avoid] having a tracheostomy, and we’re also seeing that some of these patients are able to go from unresectable disease to resectable disease, and then by having the main tumor out, their survival improves.

“So, this is definitely a big ray of hope for these patients.”

Dr. Cabanillas has received research funding from Merck. Dr. Hamidi has disclosed no relevant financial relationships. Dr. Salgado has relationships with Lilly and Exelixis.
 

A version of this article appeared on Medscape.com.

TOPLINE:

A meta-analysis finds that tea drinking may reduce the risk for colorectal cancer (CRC) by 24%, but the estimate is “uncertain,” and the actual effect on CRC risk can range from a reduction of 51% to an increase of 18%, researchers say.

METHODOLOGY:

• Researchers conducted a systematic review and meta-analysis of 15 studies (11 cohort, three case-control, and one randomized controlled trial) with nearly 2.7 million participants.
• The studies were conducted in Asia, North America, Europe, and Oceania between 1986 and 2015 and included black and green tea.
• Tea consumption was dichotomized as < 1 cup vs. ≥ 1 cups daily. A random effects model was used for data analysis.

TAKEAWAY:

• No statistically significant association was found between tea consumption and CRC risk (relative risk, 0.76).
• By geographic region, results of an American subgroup analysis suggested tea drinking might be protective against CRC (RR, 0.33), while data from the United Kingdom (RR, 1.45) and Italian (RR, 1.15) subgroups had opposite results.
• In subgroups by tea type, green tea was associated with a lower CRC risk (RR, 0.05).
• Sensitivity analysis revealed that the effect on CRC risk can range from a reduction of 51% (RR, 0.49) to an increase of 18% (RR, 1.18).

IN PRACTICE:

“Taken together, this meta-analysis suggests that tea consumption may not be linked to the development of CRC. These relationships still need to be confirmed by additional well-designed large prospective studies and randomized clinical trials,” the authors write.

SOURCE:

The study, with co–first authors Yu Huang and Qiang Chen, with the Third Hospital of Hebei Medical University, Shijiazhuang, China, was published online in BMC Gastroenterology.

LIMITATIONS:

There was a high level of heterogeneity in the original studies, as well as variations in the quantity and types of tea consumed and in the design and quality of the studies. Some studies did not account for potentially important variables, such as alcohol use and diet.

DISCLOSURES:

The study was supported by grants from the Hebei Provincial Natural Science Foundation and the Hebei Provincial Department of Science and Technology. The authors have disclosed no conflicts of interest.

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

TOPLINE:

A meta-analysis finds that tea drinking may reduce the risk for colorectal cancer (CRC) by 24%, but the estimate is “uncertain,” and the actual effect on CRC risk can range from a reduction of 51% to an increase of 18%, researchers say.

METHODOLOGY:

• Researchers conducted a systematic review and meta-analysis of 15 studies (11 cohort, three case-control, and one randomized controlled trial) with nearly 2.7 million participants.
• The studies were conducted in Asia, North America, Europe, and Oceania between 1986 and 2015 and included black and green tea.
• Tea consumption was dichotomized as < 1 cup vs. ≥ 1 cups daily. A random effects model was used for data analysis.

TAKEAWAY:

• No statistically significant association was found between tea consumption and CRC risk (relative risk, 0.76).
• By geographic region, results of an American subgroup analysis suggested tea drinking might be protective against CRC (RR, 0.33), while data from the United Kingdom (RR, 1.45) and Italian (RR, 1.15) subgroups had opposite results.
• In subgroups by tea type, green tea was associated with a lower CRC risk (RR, 0.05).
• Sensitivity analysis revealed that the effect on CRC risk can range from a reduction of 51% (RR, 0.49) to an increase of 18% (RR, 1.18).

IN PRACTICE:

“Taken together, this meta-analysis suggests that tea consumption may not be linked to the development of CRC. These relationships still need to be confirmed by additional well-designed large prospective studies and randomized clinical trials,” the authors write.

SOURCE:

The study, with co–first authors Yu Huang and Qiang Chen, with the Third Hospital of Hebei Medical University, Shijiazhuang, China, was published online in BMC Gastroenterology.

LIMITATIONS:

There was a high level of heterogeneity in the original studies, as well as variations in the quantity and types of tea consumed and in the design and quality of the studies. Some studies did not account for potentially important variables, such as alcohol use and diet.

DISCLOSURES:

The study was supported by grants from the Hebei Provincial Natural Science Foundation and the Hebei Provincial Department of Science and Technology. The authors have disclosed no conflicts of interest.

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

TOPLINE:

A meta-analysis finds that tea drinking may reduce the risk for colorectal cancer (CRC) by 24%, but the estimate is “uncertain,” and the actual effect on CRC risk can range from a reduction of 51% to an increase of 18%, researchers say.

METHODOLOGY:

• Researchers conducted a systematic review and meta-analysis of 15 studies (11 cohort, three case-control, and one randomized controlled trial) with nearly 2.7 million participants.
• The studies were conducted in Asia, North America, Europe, and Oceania between 1986 and 2015 and included black and green tea.
• Tea consumption was dichotomized as < 1 cup vs. ≥ 1 cups daily. A random effects model was used for data analysis.

TAKEAWAY:

• No statistically significant association was found between tea consumption and CRC risk (relative risk, 0.76).
• By geographic region, results of an American subgroup analysis suggested tea drinking might be protective against CRC (RR, 0.33), while data from the United Kingdom (RR, 1.45) and Italian (RR, 1.15) subgroups had opposite results.
• In subgroups by tea type, green tea was associated with a lower CRC risk (RR, 0.05).
• Sensitivity analysis revealed that the effect on CRC risk can range from a reduction of 51% (RR, 0.49) to an increase of 18% (RR, 1.18).

IN PRACTICE:

“Taken together, this meta-analysis suggests that tea consumption may not be linked to the development of CRC. These relationships still need to be confirmed by additional well-designed large prospective studies and randomized clinical trials,” the authors write.

SOURCE:

The study, with co–first authors Yu Huang and Qiang Chen, with the Third Hospital of Hebei Medical University, Shijiazhuang, China, was published online in BMC Gastroenterology.

LIMITATIONS:

There was a high level of heterogeneity in the original studies, as well as variations in the quantity and types of tea consumed and in the design and quality of the studies. Some studies did not account for potentially important variables, such as alcohol use and diet.

DISCLOSURES:

The study was supported by grants from the Hebei Provincial Natural Science Foundation and the Hebei Provincial Department of Science and Technology. The authors have disclosed no conflicts of interest.

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

TOPLINE:

Vegetarian diets may reduce the risk for gastric and colorectal cancers, according to the results of a meta-analysis.

METHODOLOGY:

• Researchers did a systematic review and meta-analysis of seven original studies (six cohorts and one case-control) involving 686,691 people.
• Pooled relative risk for gastric, colorectal, and upper gastrointestinal cancers were assessed with confidence intervals in multivariate analysis accounting for potential confounders.

TAKEAWAY:

• Compared with nonvegetarian diets, vegetarian diets were inversely associated with the risk for GI tumor development (relative risk, 0.77).
• In a subgroup analysis, vegetarian diets were negatively correlated with the risk for gastric cancer (RR, 0.41) and colorectal cancer (RR, 0.85) but not with upper GI cancer (excluding stomach; RR, 0.93).
• Vegetarian diets were negatively correlated with the risk for GI cancer in men (RR, 0.57) but not women (RR, 0.89).
• Vegetarian diets were negatively correlated with the risk for GI cancer in North American (RR, 0.76) and Asian populations (RR, 0.43) but not in European populations (RR, 0.83).

IN PRACTICE:

“The results of this systematic review indicate that adherence to vegetarian diets can reduce the risk of gastrointestinal cancers, compared with non-vegetarian diets. This study provides a reference for primary prevention strategies for gastrointestinal cancers,” the authors write.

SOURCE:

The study, with first author Tongtong Bai, of Nanjing University of Chinese Medicine, was published online on in the European Journal of Gastroenterology & Hepatology.

LIMITATIONS:

The effects of vegetarian diets on GI tumorigenesis may be influenced by gender and geographical region. The heterogeneity of effects of vegetarian diets on different GI cancers could be due to the small number of studies included and could represent chance variation. The results need to be confirmed by studies of populations in other regions. There was evidence of publication bias.

DISCLOSURES:

The study had no specific funding. The authors have disclosed no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Vegetarian diets may reduce the risk for gastric and colorectal cancers, according to the results of a meta-analysis.

METHODOLOGY:

• Researchers did a systematic review and meta-analysis of seven original studies (six cohorts and one case-control) involving 686,691 people.
• Pooled relative risk for gastric, colorectal, and upper gastrointestinal cancers were assessed with confidence intervals in multivariate analysis accounting for potential confounders.

TAKEAWAY:

• Compared with nonvegetarian diets, vegetarian diets were inversely associated with the risk for GI tumor development (relative risk, 0.77).
• In a subgroup analysis, vegetarian diets were negatively correlated with the risk for gastric cancer (RR, 0.41) and colorectal cancer (RR, 0.85) but not with upper GI cancer (excluding stomach; RR, 0.93).
• Vegetarian diets were negatively correlated with the risk for GI cancer in men (RR, 0.57) but not women (RR, 0.89).
• Vegetarian diets were negatively correlated with the risk for GI cancer in North American (RR, 0.76) and Asian populations (RR, 0.43) but not in European populations (RR, 0.83).

IN PRACTICE:

“The results of this systematic review indicate that adherence to vegetarian diets can reduce the risk of gastrointestinal cancers, compared with non-vegetarian diets. This study provides a reference for primary prevention strategies for gastrointestinal cancers,” the authors write.

SOURCE:

The study, with first author Tongtong Bai, of Nanjing University of Chinese Medicine, was published online on in the European Journal of Gastroenterology & Hepatology.

LIMITATIONS:

The effects of vegetarian diets on GI tumorigenesis may be influenced by gender and geographical region. The heterogeneity of effects of vegetarian diets on different GI cancers could be due to the small number of studies included and could represent chance variation. The results need to be confirmed by studies of populations in other regions. There was evidence of publication bias.

DISCLOSURES:

The study had no specific funding. The authors have disclosed no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Vegetarian diets may reduce the risk for gastric and colorectal cancers, according to the results of a meta-analysis.

METHODOLOGY:

• Researchers did a systematic review and meta-analysis of seven original studies (six cohorts and one case-control) involving 686,691 people.
• Pooled relative risk for gastric, colorectal, and upper gastrointestinal cancers were assessed with confidence intervals in multivariate analysis accounting for potential confounders.

TAKEAWAY:

• Compared with nonvegetarian diets, vegetarian diets were inversely associated with the risk for GI tumor development (relative risk, 0.77).
• In a subgroup analysis, vegetarian diets were negatively correlated with the risk for gastric cancer (RR, 0.41) and colorectal cancer (RR, 0.85) but not with upper GI cancer (excluding stomach; RR, 0.93).
• Vegetarian diets were negatively correlated with the risk for GI cancer in men (RR, 0.57) but not women (RR, 0.89).
• Vegetarian diets were negatively correlated with the risk for GI cancer in North American (RR, 0.76) and Asian populations (RR, 0.43) but not in European populations (RR, 0.83).

IN PRACTICE:

“The results of this systematic review indicate that adherence to vegetarian diets can reduce the risk of gastrointestinal cancers, compared with non-vegetarian diets. This study provides a reference for primary prevention strategies for gastrointestinal cancers,” the authors write.

SOURCE:

The study, with first author Tongtong Bai, of Nanjing University of Chinese Medicine, was published online on in the European Journal of Gastroenterology & Hepatology.

LIMITATIONS:

The effects of vegetarian diets on GI tumorigenesis may be influenced by gender and geographical region. The heterogeneity of effects of vegetarian diets on different GI cancers could be due to the small number of studies included and could represent chance variation. The results need to be confirmed by studies of populations in other regions. There was evidence of publication bias.

DISCLOSURES:

The study had no specific funding. The authors have disclosed no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

When patients deal directly with their insurance companies for answers about copayments and other issues, they are more likely to experience delays in cancer care and to be nonadherent.

METHODOLOGY:

• Navigating the complexities of insurance coverage is difficult for cancer patients, and the clinical impact of managing these intricacies remains unclear.
• To understand the issue, investigators surveyed 510 insured cancer patients in the United States about how often they estimate out-of-pocket costs for medications, doctors’ visits, and lab tests and scans, as well as how often they ask their insurance company to help them understand their coverage and how often they appeal coverage decisions.
• The team then correlated the answers with how often patients reported postponing or skipping doctors’ appointments and lab tests and how often they delayed filling prescriptions or skipped doses.
• Breast, colorectal, lung, and prostate cancer were the most common diagnoses among respondents.

TAKEAWAY:

• Overall, 55% of participants said they “never” or “rarely” engaged in any insurance-related cost tasks. The most frequently performed administrative tasks included finding out the cost before filling a prescription (28%) or before undergoing lab tests or scans (20%), as well as estimating the cost before agreeing to a treatment (20%), asking an insurance company for help understanding coverage (18%), or appealing a denial (17%).
• After adjusting for age, race/ethnicity, education, and monthly out-of-pocket costs, participants who engaged in any cost task were 18% more likely to experience treatment delays or forgo care.
• Every additional cost task or increase in frequency of a cost task was associated with 32% higher frequency of treatment delay or nonadherence.
• Age, race, and monthly out-of-pocket costs were more strongly associated with treatment delays/nonadherence than cost-task burden. Younger patients and Black patients were more likely than others to experience cost-related delays/nonadherence.

IN PRACTICE:

• “Reductions to administrative burden on patients, whether through patient-level education interventions, the adaptation of hospital-based navigation programs, or policy-focused changes to insurance systems, will be crucial” for helping patients with cancer to overcome administrative burdens and improve access to care, the authors said.

SOURCE:

• The study, led by Meredith Doherty, PhD, of the University of Pennsylvania, Philadelphia, was published in Cancer Epidemiology, Biomarkers and Prevention.

LIMITATIONS:

The survey was voluntary, which raises the possibility of self-selection bias. Recall bias may also have occurred, particularly among patients farther out from diagnosis and treatment. The investigators did not include uninsured patients and did not stratify patients by insurance type, and they did not measure or account for health care literacy.

DISCLOSURES:

The study was funded by the American Cancer Society. The investigators have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

When patients deal directly with their insurance companies for answers about copayments and other issues, they are more likely to experience delays in cancer care and to be nonadherent.

METHODOLOGY:

• Navigating the complexities of insurance coverage is difficult for cancer patients, and the clinical impact of managing these intricacies remains unclear.
• To understand the issue, investigators surveyed 510 insured cancer patients in the United States about how often they estimate out-of-pocket costs for medications, doctors’ visits, and lab tests and scans, as well as how often they ask their insurance company to help them understand their coverage and how often they appeal coverage decisions.
• The team then correlated the answers with how often patients reported postponing or skipping doctors’ appointments and lab tests and how often they delayed filling prescriptions or skipped doses.
• Breast, colorectal, lung, and prostate cancer were the most common diagnoses among respondents.

TAKEAWAY:

• Overall, 55% of participants said they “never” or “rarely” engaged in any insurance-related cost tasks. The most frequently performed administrative tasks included finding out the cost before filling a prescription (28%) or before undergoing lab tests or scans (20%), as well as estimating the cost before agreeing to a treatment (20%), asking an insurance company for help understanding coverage (18%), or appealing a denial (17%).
• After adjusting for age, race/ethnicity, education, and monthly out-of-pocket costs, participants who engaged in any cost task were 18% more likely to experience treatment delays or forgo care.
• Every additional cost task or increase in frequency of a cost task was associated with 32% higher frequency of treatment delay or nonadherence.
• Age, race, and monthly out-of-pocket costs were more strongly associated with treatment delays/nonadherence than cost-task burden. Younger patients and Black patients were more likely than others to experience cost-related delays/nonadherence.

IN PRACTICE:

• “Reductions to administrative burden on patients, whether through patient-level education interventions, the adaptation of hospital-based navigation programs, or policy-focused changes to insurance systems, will be crucial” for helping patients with cancer to overcome administrative burdens and improve access to care, the authors said.

SOURCE:

• The study, led by Meredith Doherty, PhD, of the University of Pennsylvania, Philadelphia, was published in Cancer Epidemiology, Biomarkers and Prevention.

LIMITATIONS:

The survey was voluntary, which raises the possibility of self-selection bias. Recall bias may also have occurred, particularly among patients farther out from diagnosis and treatment. The investigators did not include uninsured patients and did not stratify patients by insurance type, and they did not measure or account for health care literacy.

DISCLOSURES:

The study was funded by the American Cancer Society. The investigators have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

When patients deal directly with their insurance companies for answers about copayments and other issues, they are more likely to experience delays in cancer care and to be nonadherent.

METHODOLOGY:

• Navigating the complexities of insurance coverage is difficult for cancer patients, and the clinical impact of managing these intricacies remains unclear.
• To understand the issue, investigators surveyed 510 insured cancer patients in the United States about how often they estimate out-of-pocket costs for medications, doctors’ visits, and lab tests and scans, as well as how often they ask their insurance company to help them understand their coverage and how often they appeal coverage decisions.
• The team then correlated the answers with how often patients reported postponing or skipping doctors’ appointments and lab tests and how often they delayed filling prescriptions or skipped doses.
• Breast, colorectal, lung, and prostate cancer were the most common diagnoses among respondents.

TAKEAWAY:

• Overall, 55% of participants said they “never” or “rarely” engaged in any insurance-related cost tasks. The most frequently performed administrative tasks included finding out the cost before filling a prescription (28%) or before undergoing lab tests or scans (20%), as well as estimating the cost before agreeing to a treatment (20%), asking an insurance company for help understanding coverage (18%), or appealing a denial (17%).
• After adjusting for age, race/ethnicity, education, and monthly out-of-pocket costs, participants who engaged in any cost task were 18% more likely to experience treatment delays or forgo care.
• Every additional cost task or increase in frequency of a cost task was associated with 32% higher frequency of treatment delay or nonadherence.
• Age, race, and monthly out-of-pocket costs were more strongly associated with treatment delays/nonadherence than cost-task burden. Younger patients and Black patients were more likely than others to experience cost-related delays/nonadherence.

IN PRACTICE:

• “Reductions to administrative burden on patients, whether through patient-level education interventions, the adaptation of hospital-based navigation programs, or policy-focused changes to insurance systems, will be crucial” for helping patients with cancer to overcome administrative burdens and improve access to care, the authors said.

SOURCE:

• The study, led by Meredith Doherty, PhD, of the University of Pennsylvania, Philadelphia, was published in Cancer Epidemiology, Biomarkers and Prevention.

LIMITATIONS:

The survey was voluntary, which raises the possibility of self-selection bias. Recall bias may also have occurred, particularly among patients farther out from diagnosis and treatment. The investigators did not include uninsured patients and did not stratify patients by insurance type, and they did not measure or account for health care literacy.

DISCLOSURES:

The study was funded by the American Cancer Society. The investigators have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Cutaneous immune-related adverse events are associated with improved overall and progression-free survival among patients treated with immune checkpoint inhibitors (ICIs).

METHODOLOGY:

• Emerging evidence suggests that the presence of cutaneous immune-related adverse events may be linked with favorable outcomes among patients with cancer who receive ICIs.
• Researchers conducted a systematic review and meta-analysis that included 23 studies and a total of 22,749 patients with cancer who received ICI treatment; studies compared outcomes among patients with and those without cutaneous immune-related adverse events.
• The major outcomes evaluated in the analysis were overall survival and progression-free survival (PFS); subgroup analyses assessed cutaneous immune-related adverse event type, cancer type, and other factors.

TAKEAWAY:

• The occurrence of cutaneous immune-related adverse events was associated with improved PFS (hazard ratio, 0.52; P < .001) and overall survival (HR, 0.61; P < .001).
• In the subgroup analysis, patients with eczematous (HR, 0.69), lichenoid or lichen planus–like skin lesions (HR, 0.51), pruritus without rash (HR, 0.70), psoriasis (HR, 0.63), or vitiligo (HR, 0.30) demonstrated a significant overall survival advantage. Vitiligo was the only adverse event associated with a PFS advantage (HR, 0.28).
• Among patients with melanoma, analyses revealed a significant association between the incidence of cutaneous immune-related adverse events and improved overall survival (HR, 0.51) and PFS (HR, 0.45). The authors highlighted similar findings among patients with non–small cell lung cancer (HR, 0.50 for overall survival and 0.61 for PFS).

IN PRACTICE:

“These data suggest that [cutaneous immune-related adverse events] may have useful prognostic value in ICI treatment,” the authors concluded.

SOURCE:

The analysis, led by Fei Wang, MD, Zhong Da Hospital, School of Medicine, Southeast University, Nanjing, China, was published online in JAMA Dermatology.

LIMITATIONS:

Most of the data came from retrospective studies, and there were limited data on specific patient subgroups. The Egger tests, used to assess potential publication bias in meta-analyses, revealed publication bias.

DISCLOSURES:

No disclosures were reported. The study was supported by a grant from the Postgraduate Research and Practice Innovation Program of Jiangsu Province.

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

TOPLINE:

Cutaneous immune-related adverse events are associated with improved overall and progression-free survival among patients treated with immune checkpoint inhibitors (ICIs).

METHODOLOGY:

• Emerging evidence suggests that the presence of cutaneous immune-related adverse events may be linked with favorable outcomes among patients with cancer who receive ICIs.
• Researchers conducted a systematic review and meta-analysis that included 23 studies and a total of 22,749 patients with cancer who received ICI treatment; studies compared outcomes among patients with and those without cutaneous immune-related adverse events.
• The major outcomes evaluated in the analysis were overall survival and progression-free survival (PFS); subgroup analyses assessed cutaneous immune-related adverse event type, cancer type, and other factors.

TAKEAWAY:

• The occurrence of cutaneous immune-related adverse events was associated with improved PFS (hazard ratio, 0.52; P < .001) and overall survival (HR, 0.61; P < .001).
• In the subgroup analysis, patients with eczematous (HR, 0.69), lichenoid or lichen planus–like skin lesions (HR, 0.51), pruritus without rash (HR, 0.70), psoriasis (HR, 0.63), or vitiligo (HR, 0.30) demonstrated a significant overall survival advantage. Vitiligo was the only adverse event associated with a PFS advantage (HR, 0.28).
• Among patients with melanoma, analyses revealed a significant association between the incidence of cutaneous immune-related adverse events and improved overall survival (HR, 0.51) and PFS (HR, 0.45). The authors highlighted similar findings among patients with non–small cell lung cancer (HR, 0.50 for overall survival and 0.61 for PFS).

IN PRACTICE:

“These data suggest that [cutaneous immune-related adverse events] may have useful prognostic value in ICI treatment,” the authors concluded.

SOURCE:

The analysis, led by Fei Wang, MD, Zhong Da Hospital, School of Medicine, Southeast University, Nanjing, China, was published online in JAMA Dermatology.

LIMITATIONS:

Most of the data came from retrospective studies, and there were limited data on specific patient subgroups. The Egger tests, used to assess potential publication bias in meta-analyses, revealed publication bias.

DISCLOSURES:

No disclosures were reported. The study was supported by a grant from the Postgraduate Research and Practice Innovation Program of Jiangsu Province.

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

TOPLINE:

Cutaneous immune-related adverse events are associated with improved overall and progression-free survival among patients treated with immune checkpoint inhibitors (ICIs).

METHODOLOGY:

• Emerging evidence suggests that the presence of cutaneous immune-related adverse events may be linked with favorable outcomes among patients with cancer who receive ICIs.
• Researchers conducted a systematic review and meta-analysis that included 23 studies and a total of 22,749 patients with cancer who received ICI treatment; studies compared outcomes among patients with and those without cutaneous immune-related adverse events.
• The major outcomes evaluated in the analysis were overall survival and progression-free survival (PFS); subgroup analyses assessed cutaneous immune-related adverse event type, cancer type, and other factors.

TAKEAWAY:

• The occurrence of cutaneous immune-related adverse events was associated with improved PFS (hazard ratio, 0.52; P < .001) and overall survival (HR, 0.61; P < .001).
• In the subgroup analysis, patients with eczematous (HR, 0.69), lichenoid or lichen planus–like skin lesions (HR, 0.51), pruritus without rash (HR, 0.70), psoriasis (HR, 0.63), or vitiligo (HR, 0.30) demonstrated a significant overall survival advantage. Vitiligo was the only adverse event associated with a PFS advantage (HR, 0.28).
• Among patients with melanoma, analyses revealed a significant association between the incidence of cutaneous immune-related adverse events and improved overall survival (HR, 0.51) and PFS (HR, 0.45). The authors highlighted similar findings among patients with non–small cell lung cancer (HR, 0.50 for overall survival and 0.61 for PFS).

IN PRACTICE:

“These data suggest that [cutaneous immune-related adverse events] may have useful prognostic value in ICI treatment,” the authors concluded.

SOURCE:

The analysis, led by Fei Wang, MD, Zhong Da Hospital, School of Medicine, Southeast University, Nanjing, China, was published online in JAMA Dermatology.

LIMITATIONS:

Most of the data came from retrospective studies, and there were limited data on specific patient subgroups. The Egger tests, used to assess potential publication bias in meta-analyses, revealed publication bias.

DISCLOSURES:

No disclosures were reported. The study was supported by a grant from the Postgraduate Research and Practice Innovation Program of Jiangsu Province.

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

Having grown up with sickle cell disease (SCD), Titilope Fasipe, MD, PhD, codirector of the sickle cell program at Texas Children’s Hospital in Houston, knows firsthand the physical pain, mental anguish, and dread that have long accompanied this condition. So few child patients lived to reach adulthood that until recently, SCD was considered a pediatric disease.

These days, thanks to transformative advances in treating SCD that have substantially improved survival, Dr. Fasipe’s mission for a new generation of patients and their families is to replace their pain and fear with relief and hope.

Courtesy Racheal Adetayo Artistry

“If you grow up thinking that you’re going to die when you’re 18, it changes your world and your viewpoints, and it impacts your mental health,” she told this news organization.

“We are trying to make sure our children and their families know that there is a new story for sickle cell disease, and you don’t have to use any age as your prediction marker for your lifespan,” Dr. Fasipe said.

SCD, which affects about 100,000 people nationwide, is an inherited blood disorder, with the majority of patients – but not all – being of African descent. This condition is characterized by pain crises, or vaso-occlusive episodes, triggered when cells that are sickled get stuck and impede blood flow. These crises can come on suddenly and range from mild to severe.

Dr. Fasipe was born in Nigeria, where rates of SCD are among the world’s highest. She attended elementary school in the United States, where her father was studying theology, before returning to Nigeria with her family at age 11.

Back in those days, in both nations only about 50% of children with SCD lived beyond their 18th birthday. The survival rates in Nigeria and sub-Saharan Africa countries continue to be poor. In some more developed regions elsewhere, advances such as universal newborn screening, penicillin prophylaxis, pneumococcal vaccination, stroke screening, and hydroxyurea therapy have yielded substantial improvements, with 95% or more patients with SCD reaching their 18th birthday.

“With measures such as newborn screening, we can immediately start prevention measures in sickle cell disease, such as prevention of infection, which was the number one reason why children were dying,” Dr. Fasipe explained. “With global initiatives, we want that story to be the same in sub-Saharan Africa as well.”
 

Cousin’s early death inspires medical studies

In an essay published by Texas Medical Center that describes her childhood experiences, Dr. Fasipe recounts a pivotal event in her life: The heartbreaking death of her beloved cousin at the age of just 17, from a complication of SCD. This bereavement fueled Dr. Fasipe’s determination to pursue a medical career, to do all that she could to prevent such losses.

“Having sickle cell disease myself wasn’t the trigger that made me become a doctor. But when Femi [her cousin] died, I thought: ‘This shouldn’t happen,’ ” Dr. Fasipe wrote.

When she applied to medical school back in the United States, she declared in her application essay: “I want to cure sickle cell.”

By the time Dr. Fasipe was ready to undertake residency and fellowship applications, her essay had shifted to focus on pediatrics “specifically because I want to reach sickle cell patients before they’ve defined how their lives are going to be,” she said. “I want to give them hope.”
 

Hope for a cure

Fast-forwarding to this point in Dr. Fasipe’s career, she noted that her dream of a cure for SCD is no longer a distant aspiration, thanks to the advent of stem cell transplantation and more recently, gene therapy. These advancements have elevated her hope for a cure to an entirely new level.

Each new treatment comes with caveats. Stem cell transplantation requires a matching donor, leaving the majority of patients ineligible. And while gene therapy eliminates the need for a donor, treatment can reportedly cost nearly $3 million. Nevertheless, Dr. Fasipe emphasized the promise that these new advancements represent.

“The scientists that work in these spaces do appreciate these [accessibility barriers], and the expectation is these therapies will be more accessible with time and effort,” she said. “We’ve got to start somewhere, and it’s exciting that they’re making these early successes.”
 

Advice for clinicians

With firsthand knowledge of how it feels to be the patient, as well as on the clinician side of SCD treatment, Dr. Fasipe advises colleagues on some ways that they can improve care while boosting their patients’ hope:

Speak with empathy

Acknowledge the ‘elephant in the room’; the pain that patients with SCD can experience is real.

“When I’m managing any patient with pain, I first acknowledge the suffering because while we may not understand what that person is going through, acknowledgment is part of showing empathy,” she explains.

Seek out resources

Patients with SCD may typically seek treatment in primary care, where expertise in the disease may be lacking, and general practitioners may feel frustrated that there are limited treatment options.

“If you do find yourself treating a sickle cell disease patient, you may not have all of the answers, but there are good resources, whether it’s a nearby sickle cell disease centers or national guidelines,” Dr. Fasipe said.

Access to treatment

With research, including a recent study, showing that only about 25% of patients with SCD are prescribed hydroxyurea and even fewer – only about 5% – receive more recently approved SCD treatments, clinicians should be proactive by making sure that patients receive needed treatments.

“Clearly medicines like hydroxyurea are not as optimized in this community space as they should be, and then there are newer therapies that families, patients, and even providers may not be aware of, so it is important to be informed of the guidelines and provide all patients with comprehensive, high-quality care,” Dr. Fasipe said.

In the ED, patients with SCD are ‘care-seeking,’ not drug-seeking

Due to the sometimes rapid onset of severe pain symptoms, patients with SCD commonly wind up in the emergency department. In this time of an opioid epidemic, patients too often are suspected of merely seeking drugs.

“Sickle cell disease tends to get lumped into a category of a disease of pain, but pain is subjective and it is difficult to quantify, so unfortunately, patients can be labeled as potentially drug-seeking,” Dr. Fasipe explained, citing an article that detailed this problem.

Consequently, patients may have particularly negative experiences in the emergency department, but the use of resources such as a sickle cell disease point-of-care tool developed by the American College of Emergency Physicians and the American Society of Hematology can help improve care for those patients.

“One of the [point-of-care recommendations] before even managing the pain is that physicians show compassion by acknowledging the patient’s pain and that they understand why pain with sickle cell disease might look different than other types of pain,” Dr. Fasipe said.
 

Building trust

Encounters such as negative emergency department experiences can perpetuate a deeper issue of distrust between those with SCD and the medical community, which originated in long-held, well-documented racial disparities in health care.

“We know historically and even today that there are difficulties facing our families who are impacted by sickle cell disease, and they are related to structural racism and socioeconomic barriers,” Dr. Fasipe explained.

With these issues in mind, she said, “I refer to sickle cell disease as the medical representation of the Black experience in America.” However, she added, the good news is “we are now doing our best now to improve that.”

Among key efforts in building trust is the inclusion of patients with SCD and their families in as many aspects of research and clinical care as possible.

“In the global health care community, it is imperative to invite people with sickle cell disease and from the community to the decision-making table,” she noted.

“Now, when we’re talking about research for therapies, their expectation is that research trials and other initiatives for sickle cell disease must have input from the community; there are no initiatives for sickle cell disease that do not have input from the community.

“The patients and community members may not be experts on the science of sickle cell, but they’re experts on the lived experience and that’s very important when you’re thinking about new bringing in a new therapy.”
 

Forward momentum

Meanwhile, Dr. Fasipe observed, with the collective, advocacy-driven, forward momentum of the SCD community as a whole, things should only continue to improve.

“Because of the various barriers, some progress may not be immediately around the corner, but I do have confidence that this current generation of children with sickle cell will have improved health equity by the time they reach adulthood,” she said.

“I believe in this future, so I’m doing the work now, and it’s a promise I tell parents: I want your future adult child to live their best life, and we’re working hard to ensure that that becomes their future reality.”
 

Sickle cell disease awareness

September is National Sickle Cell Disease Awareness Month, and the National Heart, Lung, and Blood Institute offers a comprehensive website that clinicians can pass along to their patients, with information ranging from fact sheets on the disease and treatments to social media resources and inspiring stories of people with the disease.

In a comment, Lewis Hsu, MD, PhD, chief medical officer of the Sickle Cell Disease Association of America, underscored the uniquely important contributions of people like Dr. Fasipe, in providing inspiration to patients and clinicians alike.

“I have worked with several physicians, nurses, psychologists, and public health specialists who have sickle cell disease,” said Dr. Hsu, who is a pediatric hematologist who also serves as director of the Sickle Cell Center and professor of pediatrics for the University of Illinois at Chicago.

“They are ambassadors who have the trust of both patients and healthcare providers,” Dr. Hsu said.

In addition to providing inspiration of resilience, such care providers can serve as “communication bridges,” he explained.

“When they are conference speakers, everybody wants to hear them; when they sit on advisory committees or focus groups, they can help find the compromise or set the priorities.”

“Their impact on the whole sickle cell community is very large,” Dr. Hsu said.

Having grown up with sickle cell disease (SCD), Titilope Fasipe, MD, PhD, codirector of the sickle cell program at Texas Children’s Hospital in Houston, knows firsthand the physical pain, mental anguish, and dread that have long accompanied this condition. So few child patients lived to reach adulthood that until recently, SCD was considered a pediatric disease.

These days, thanks to transformative advances in treating SCD that have substantially improved survival, Dr. Fasipe’s mission for a new generation of patients and their families is to replace their pain and fear with relief and hope.

Courtesy Racheal Adetayo Artistry

“If you grow up thinking that you’re going to die when you’re 18, it changes your world and your viewpoints, and it impacts your mental health,” she told this news organization.

“We are trying to make sure our children and their families know that there is a new story for sickle cell disease, and you don’t have to use any age as your prediction marker for your lifespan,” Dr. Fasipe said.

SCD, which affects about 100,000 people nationwide, is an inherited blood disorder, with the majority of patients – but not all – being of African descent. This condition is characterized by pain crises, or vaso-occlusive episodes, triggered when cells that are sickled get stuck and impede blood flow. These crises can come on suddenly and range from mild to severe.

Dr. Fasipe was born in Nigeria, where rates of SCD are among the world’s highest. She attended elementary school in the United States, where her father was studying theology, before returning to Nigeria with her family at age 11.

Back in those days, in both nations only about 50% of children with SCD lived beyond their 18th birthday. The survival rates in Nigeria and sub-Saharan Africa countries continue to be poor. In some more developed regions elsewhere, advances such as universal newborn screening, penicillin prophylaxis, pneumococcal vaccination, stroke screening, and hydroxyurea therapy have yielded substantial improvements, with 95% or more patients with SCD reaching their 18th birthday.

“With measures such as newborn screening, we can immediately start prevention measures in sickle cell disease, such as prevention of infection, which was the number one reason why children were dying,” Dr. Fasipe explained. “With global initiatives, we want that story to be the same in sub-Saharan Africa as well.”
 

Cousin’s early death inspires medical studies

In an essay published by Texas Medical Center that describes her childhood experiences, Dr. Fasipe recounts a pivotal event in her life: The heartbreaking death of her beloved cousin at the age of just 17, from a complication of SCD. This bereavement fueled Dr. Fasipe’s determination to pursue a medical career, to do all that she could to prevent such losses.

“Having sickle cell disease myself wasn’t the trigger that made me become a doctor. But when Femi [her cousin] died, I thought: ‘This shouldn’t happen,’ ” Dr. Fasipe wrote.

When she applied to medical school back in the United States, she declared in her application essay: “I want to cure sickle cell.”

By the time Dr. Fasipe was ready to undertake residency and fellowship applications, her essay had shifted to focus on pediatrics “specifically because I want to reach sickle cell patients before they’ve defined how their lives are going to be,” she said. “I want to give them hope.”
 

Hope for a cure

Fast-forwarding to this point in Dr. Fasipe’s career, she noted that her dream of a cure for SCD is no longer a distant aspiration, thanks to the advent of stem cell transplantation and more recently, gene therapy. These advancements have elevated her hope for a cure to an entirely new level.

Each new treatment comes with caveats. Stem cell transplantation requires a matching donor, leaving the majority of patients ineligible. And while gene therapy eliminates the need for a donor, treatment can reportedly cost nearly $3 million. Nevertheless, Dr. Fasipe emphasized the promise that these new advancements represent.

“The scientists that work in these spaces do appreciate these [accessibility barriers], and the expectation is these therapies will be more accessible with time and effort,” she said. “We’ve got to start somewhere, and it’s exciting that they’re making these early successes.”
 

Advice for clinicians

With firsthand knowledge of how it feels to be the patient, as well as on the clinician side of SCD treatment, Dr. Fasipe advises colleagues on some ways that they can improve care while boosting their patients’ hope:

Speak with empathy

Acknowledge the ‘elephant in the room’; the pain that patients with SCD can experience is real.

“When I’m managing any patient with pain, I first acknowledge the suffering because while we may not understand what that person is going through, acknowledgment is part of showing empathy,” she explains.

Seek out resources

Patients with SCD may typically seek treatment in primary care, where expertise in the disease may be lacking, and general practitioners may feel frustrated that there are limited treatment options.

“If you do find yourself treating a sickle cell disease patient, you may not have all of the answers, but there are good resources, whether it’s a nearby sickle cell disease centers or national guidelines,” Dr. Fasipe said.

Access to treatment

With research, including a recent study, showing that only about 25% of patients with SCD are prescribed hydroxyurea and even fewer – only about 5% – receive more recently approved SCD treatments, clinicians should be proactive by making sure that patients receive needed treatments.

“Clearly medicines like hydroxyurea are not as optimized in this community space as they should be, and then there are newer therapies that families, patients, and even providers may not be aware of, so it is important to be informed of the guidelines and provide all patients with comprehensive, high-quality care,” Dr. Fasipe said.

In the ED, patients with SCD are ‘care-seeking,’ not drug-seeking

Due to the sometimes rapid onset of severe pain symptoms, patients with SCD commonly wind up in the emergency department. In this time of an opioid epidemic, patients too often are suspected of merely seeking drugs.

“Sickle cell disease tends to get lumped into a category of a disease of pain, but pain is subjective and it is difficult to quantify, so unfortunately, patients can be labeled as potentially drug-seeking,” Dr. Fasipe explained, citing an article that detailed this problem.

Consequently, patients may have particularly negative experiences in the emergency department, but the use of resources such as a sickle cell disease point-of-care tool developed by the American College of Emergency Physicians and the American Society of Hematology can help improve care for those patients.

“One of the [point-of-care recommendations] before even managing the pain is that physicians show compassion by acknowledging the patient’s pain and that they understand why pain with sickle cell disease might look different than other types of pain,” Dr. Fasipe said.
 

Building trust

Encounters such as negative emergency department experiences can perpetuate a deeper issue of distrust between those with SCD and the medical community, which originated in long-held, well-documented racial disparities in health care.

“We know historically and even today that there are difficulties facing our families who are impacted by sickle cell disease, and they are related to structural racism and socioeconomic barriers,” Dr. Fasipe explained.

With these issues in mind, she said, “I refer to sickle cell disease as the medical representation of the Black experience in America.” However, she added, the good news is “we are now doing our best now to improve that.”

Among key efforts in building trust is the inclusion of patients with SCD and their families in as many aspects of research and clinical care as possible.

“In the global health care community, it is imperative to invite people with sickle cell disease and from the community to the decision-making table,” she noted.

“Now, when we’re talking about research for therapies, their expectation is that research trials and other initiatives for sickle cell disease must have input from the community; there are no initiatives for sickle cell disease that do not have input from the community.

“The patients and community members may not be experts on the science of sickle cell, but they’re experts on the lived experience and that’s very important when you’re thinking about new bringing in a new therapy.”
 

Forward momentum

Meanwhile, Dr. Fasipe observed, with the collective, advocacy-driven, forward momentum of the SCD community as a whole, things should only continue to improve.

“Because of the various barriers, some progress may not be immediately around the corner, but I do have confidence that this current generation of children with sickle cell will have improved health equity by the time they reach adulthood,” she said.

“I believe in this future, so I’m doing the work now, and it’s a promise I tell parents: I want your future adult child to live their best life, and we’re working hard to ensure that that becomes their future reality.”
 

Sickle cell disease awareness

September is National Sickle Cell Disease Awareness Month, and the National Heart, Lung, and Blood Institute offers a comprehensive website that clinicians can pass along to their patients, with information ranging from fact sheets on the disease and treatments to social media resources and inspiring stories of people with the disease.

In a comment, Lewis Hsu, MD, PhD, chief medical officer of the Sickle Cell Disease Association of America, underscored the uniquely important contributions of people like Dr. Fasipe, in providing inspiration to patients and clinicians alike.

“I have worked with several physicians, nurses, psychologists, and public health specialists who have sickle cell disease,” said Dr. Hsu, who is a pediatric hematologist who also serves as director of the Sickle Cell Center and professor of pediatrics for the University of Illinois at Chicago.

“They are ambassadors who have the trust of both patients and healthcare providers,” Dr. Hsu said.

In addition to providing inspiration of resilience, such care providers can serve as “communication bridges,” he explained.

“When they are conference speakers, everybody wants to hear them; when they sit on advisory committees or focus groups, they can help find the compromise or set the priorities.”

“Their impact on the whole sickle cell community is very large,” Dr. Hsu said.

Having grown up with sickle cell disease (SCD), Titilope Fasipe, MD, PhD, codirector of the sickle cell program at Texas Children’s Hospital in Houston, knows firsthand the physical pain, mental anguish, and dread that have long accompanied this condition. So few child patients lived to reach adulthood that until recently, SCD was considered a pediatric disease.

These days, thanks to transformative advances in treating SCD that have substantially improved survival, Dr. Fasipe’s mission for a new generation of patients and their families is to replace their pain and fear with relief and hope.

Courtesy Racheal Adetayo Artistry

“If you grow up thinking that you’re going to die when you’re 18, it changes your world and your viewpoints, and it impacts your mental health,” she told this news organization.

“We are trying to make sure our children and their families know that there is a new story for sickle cell disease, and you don’t have to use any age as your prediction marker for your lifespan,” Dr. Fasipe said.

SCD, which affects about 100,000 people nationwide, is an inherited blood disorder, with the majority of patients – but not all – being of African descent. This condition is characterized by pain crises, or vaso-occlusive episodes, triggered when cells that are sickled get stuck and impede blood flow. These crises can come on suddenly and range from mild to severe.

Dr. Fasipe was born in Nigeria, where rates of SCD are among the world’s highest. She attended elementary school in the United States, where her father was studying theology, before returning to Nigeria with her family at age 11.

Back in those days, in both nations only about 50% of children with SCD lived beyond their 18th birthday. The survival rates in Nigeria and sub-Saharan Africa countries continue to be poor. In some more developed regions elsewhere, advances such as universal newborn screening, penicillin prophylaxis, pneumococcal vaccination, stroke screening, and hydroxyurea therapy have yielded substantial improvements, with 95% or more patients with SCD reaching their 18th birthday.

“With measures such as newborn screening, we can immediately start prevention measures in sickle cell disease, such as prevention of infection, which was the number one reason why children were dying,” Dr. Fasipe explained. “With global initiatives, we want that story to be the same in sub-Saharan Africa as well.”
 

Cousin’s early death inspires medical studies

In an essay published by Texas Medical Center that describes her childhood experiences, Dr. Fasipe recounts a pivotal event in her life: The heartbreaking death of her beloved cousin at the age of just 17, from a complication of SCD. This bereavement fueled Dr. Fasipe’s determination to pursue a medical career, to do all that she could to prevent such losses.

“Having sickle cell disease myself wasn’t the trigger that made me become a doctor. But when Femi [her cousin] died, I thought: ‘This shouldn’t happen,’ ” Dr. Fasipe wrote.

When she applied to medical school back in the United States, she declared in her application essay: “I want to cure sickle cell.”

By the time Dr. Fasipe was ready to undertake residency and fellowship applications, her essay had shifted to focus on pediatrics “specifically because I want to reach sickle cell patients before they’ve defined how their lives are going to be,” she said. “I want to give them hope.”
 

Hope for a cure

Fast-forwarding to this point in Dr. Fasipe’s career, she noted that her dream of a cure for SCD is no longer a distant aspiration, thanks to the advent of stem cell transplantation and more recently, gene therapy. These advancements have elevated her hope for a cure to an entirely new level.

Each new treatment comes with caveats. Stem cell transplantation requires a matching donor, leaving the majority of patients ineligible. And while gene therapy eliminates the need for a donor, treatment can reportedly cost nearly $3 million. Nevertheless, Dr. Fasipe emphasized the promise that these new advancements represent.

“The scientists that work in these spaces do appreciate these [accessibility barriers], and the expectation is these therapies will be more accessible with time and effort,” she said. “We’ve got to start somewhere, and it’s exciting that they’re making these early successes.”
 

Advice for clinicians

With firsthand knowledge of how it feels to be the patient, as well as on the clinician side of SCD treatment, Dr. Fasipe advises colleagues on some ways that they can improve care while boosting their patients’ hope:

Speak with empathy

Acknowledge the ‘elephant in the room’; the pain that patients with SCD can experience is real.

“When I’m managing any patient with pain, I first acknowledge the suffering because while we may not understand what that person is going through, acknowledgment is part of showing empathy,” she explains.

Seek out resources

Patients with SCD may typically seek treatment in primary care, where expertise in the disease may be lacking, and general practitioners may feel frustrated that there are limited treatment options.

“If you do find yourself treating a sickle cell disease patient, you may not have all of the answers, but there are good resources, whether it’s a nearby sickle cell disease centers or national guidelines,” Dr. Fasipe said.

Access to treatment

With research, including a recent study, showing that only about 25% of patients with SCD are prescribed hydroxyurea and even fewer – only about 5% – receive more recently approved SCD treatments, clinicians should be proactive by making sure that patients receive needed treatments.

“Clearly medicines like hydroxyurea are not as optimized in this community space as they should be, and then there are newer therapies that families, patients, and even providers may not be aware of, so it is important to be informed of the guidelines and provide all patients with comprehensive, high-quality care,” Dr. Fasipe said.

In the ED, patients with SCD are ‘care-seeking,’ not drug-seeking

Due to the sometimes rapid onset of severe pain symptoms, patients with SCD commonly wind up in the emergency department. In this time of an opioid epidemic, patients too often are suspected of merely seeking drugs.

“Sickle cell disease tends to get lumped into a category of a disease of pain, but pain is subjective and it is difficult to quantify, so unfortunately, patients can be labeled as potentially drug-seeking,” Dr. Fasipe explained, citing an article that detailed this problem.

Consequently, patients may have particularly negative experiences in the emergency department, but the use of resources such as a sickle cell disease point-of-care tool developed by the American College of Emergency Physicians and the American Society of Hematology can help improve care for those patients.

“One of the [point-of-care recommendations] before even managing the pain is that physicians show compassion by acknowledging the patient’s pain and that they understand why pain with sickle cell disease might look different than other types of pain,” Dr. Fasipe said.
 

Building trust

Encounters such as negative emergency department experiences can perpetuate a deeper issue of distrust between those with SCD and the medical community, which originated in long-held, well-documented racial disparities in health care.

“We know historically and even today that there are difficulties facing our families who are impacted by sickle cell disease, and they are related to structural racism and socioeconomic barriers,” Dr. Fasipe explained.

With these issues in mind, she said, “I refer to sickle cell disease as the medical representation of the Black experience in America.” However, she added, the good news is “we are now doing our best now to improve that.”

Among key efforts in building trust is the inclusion of patients with SCD and their families in as many aspects of research and clinical care as possible.

“In the global health care community, it is imperative to invite people with sickle cell disease and from the community to the decision-making table,” she noted.

“Now, when we’re talking about research for therapies, their expectation is that research trials and other initiatives for sickle cell disease must have input from the community; there are no initiatives for sickle cell disease that do not have input from the community.

“The patients and community members may not be experts on the science of sickle cell, but they’re experts on the lived experience and that’s very important when you’re thinking about new bringing in a new therapy.”
 

Forward momentum

Meanwhile, Dr. Fasipe observed, with the collective, advocacy-driven, forward momentum of the SCD community as a whole, things should only continue to improve.

“Because of the various barriers, some progress may not be immediately around the corner, but I do have confidence that this current generation of children with sickle cell will have improved health equity by the time they reach adulthood,” she said.

“I believe in this future, so I’m doing the work now, and it’s a promise I tell parents: I want your future adult child to live their best life, and we’re working hard to ensure that that becomes their future reality.”
 

Sickle cell disease awareness

September is National Sickle Cell Disease Awareness Month, and the National Heart, Lung, and Blood Institute offers a comprehensive website that clinicians can pass along to their patients, with information ranging from fact sheets on the disease and treatments to social media resources and inspiring stories of people with the disease.

In a comment, Lewis Hsu, MD, PhD, chief medical officer of the Sickle Cell Disease Association of America, underscored the uniquely important contributions of people like Dr. Fasipe, in providing inspiration to patients and clinicians alike.

“I have worked with several physicians, nurses, psychologists, and public health specialists who have sickle cell disease,” said Dr. Hsu, who is a pediatric hematologist who also serves as director of the Sickle Cell Center and professor of pediatrics for the University of Illinois at Chicago.

“They are ambassadors who have the trust of both patients and healthcare providers,” Dr. Hsu said.

In addition to providing inspiration of resilience, such care providers can serve as “communication bridges,” he explained.

“When they are conference speakers, everybody wants to hear them; when they sit on advisory committees or focus groups, they can help find the compromise or set the priorities.”

“Their impact on the whole sickle cell community is very large,” Dr. Hsu said.

TOPLINE:

Women who continue breast cancer screening after age 70 face a considerable risk for overdiagnosis.

METHODOLOGY:

• Overdiagnosis – the risk of detecting and treating cancers that would never have caused issues in a person’s lifetime – is increasingly recognized as a harm of breast cancer screening; however, the scope of the problem among older women remains uncertain. 
• To get an idea, investigators linked Medicare claims data with Surveillance, Epidemiology, and End Results (SEER) data for 54,635 women 70 years or older to compare the incidence of breast cancer and breast cancer–specific death among women who continued screening mammography with those who did not.
• The women all had undergone recent screening mammograms and had no history of breast cancer at study entry. Those who had a subsequent mammogram within 3 years were classified as undergoing continued screening while those who did not were classified as not undergoing continued screening.
• Overdiagnosis was defined as the difference in cumulative incidence of breast cancer between screened and unscreened women divided by the cumulative incidence among screened women. 
• Results were adjusted for potential confounders, including age, race, and ethnicity.

TAKEAWAY:

• Over 80% of women 70-84 years old and more than 60% of women 85 years or older continued screening.
• Among women 70-74 years old, the adjusted cumulative incidence of breast cancer was 6.1 cases per 100 screened women vs. 4.2 cases per 100 unscreened women; for women aged 75-84 years old, the cumulative incidence was 4.9 per 100 screened women vs. 2.6 per 100 unscreened women, and for women 85 years and older, the cumulative incidence was 2.8 vs. 1.3 per 100, respectively.
• Estimates of overdiagnosis ranged from 31% of breast cancer cases among screened women in the 70-74 age group to 54% of cases in the 85 and older group.
• The researchers found no statistically significant reduction in breast cancer–specific death associated with screening in any age or life-expectancy group. Overdiagnosis appeared to be driven by in situ and localized invasive breast cancer, not advanced breast cancer.

IN PRACTICE:

The proportion of older women who continue to receive screening mammograms and may experience breast cancer overdiagnosis is “considerable” and “increases with advancing age and with decreasing life expectancy,” the authors conclude. Given potential benefits and harms of screening in this population, “patient preferences, including risk tolerance, comfort with uncertainty, and willingness to undergo treatment, are important for informing screening decisions.”

SOURCE:

The study was led by Ilana Richman, MD, MHS, of the Yale School of Medicine, New Haven, Connecticut, and published in the Annals of Internal Medicine.

LIMITATIONS:

The definition of screening mammography in the study may have misclassified some diagnostic mammograms as screening. Using a more conservative definition of screening mammogram, which largely accounted for this misclassification, estimates for overdiagnosis were smaller, ranging from 15% of cases in the 70-74 age group to 44% of cases in the 85 and older group. Results could not be adjusted for breast density, family history, and other breast cancer risk factors not captured by the data.

DISCLOSURES:

The work was funded by the National Cancer Institute. One author reported funding from Genentech and Johnson & Johnson.

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

TOPLINE:

Women who continue breast cancer screening after age 70 face a considerable risk for overdiagnosis.

METHODOLOGY:

• Overdiagnosis – the risk of detecting and treating cancers that would never have caused issues in a person’s lifetime – is increasingly recognized as a harm of breast cancer screening; however, the scope of the problem among older women remains uncertain. 
• To get an idea, investigators linked Medicare claims data with Surveillance, Epidemiology, and End Results (SEER) data for 54,635 women 70 years or older to compare the incidence of breast cancer and breast cancer–specific death among women who continued screening mammography with those who did not.
• The women all had undergone recent screening mammograms and had no history of breast cancer at study entry. Those who had a subsequent mammogram within 3 years were classified as undergoing continued screening while those who did not were classified as not undergoing continued screening.
• Overdiagnosis was defined as the difference in cumulative incidence of breast cancer between screened and unscreened women divided by the cumulative incidence among screened women. 
• Results were adjusted for potential confounders, including age, race, and ethnicity.

TAKEAWAY:

• Over 80% of women 70-84 years old and more than 60% of women 85 years or older continued screening.
• Among women 70-74 years old, the adjusted cumulative incidence of breast cancer was 6.1 cases per 100 screened women vs. 4.2 cases per 100 unscreened women; for women aged 75-84 years old, the cumulative incidence was 4.9 per 100 screened women vs. 2.6 per 100 unscreened women, and for women 85 years and older, the cumulative incidence was 2.8 vs. 1.3 per 100, respectively.
• Estimates of overdiagnosis ranged from 31% of breast cancer cases among screened women in the 70-74 age group to 54% of cases in the 85 and older group.
• The researchers found no statistically significant reduction in breast cancer–specific death associated with screening in any age or life-expectancy group. Overdiagnosis appeared to be driven by in situ and localized invasive breast cancer, not advanced breast cancer.

IN PRACTICE:

The proportion of older women who continue to receive screening mammograms and may experience breast cancer overdiagnosis is “considerable” and “increases with advancing age and with decreasing life expectancy,” the authors conclude. Given potential benefits and harms of screening in this population, “patient preferences, including risk tolerance, comfort with uncertainty, and willingness to undergo treatment, are important for informing screening decisions.”

SOURCE:

The study was led by Ilana Richman, MD, MHS, of the Yale School of Medicine, New Haven, Connecticut, and published in the Annals of Internal Medicine.

LIMITATIONS:

The definition of screening mammography in the study may have misclassified some diagnostic mammograms as screening. Using a more conservative definition of screening mammogram, which largely accounted for this misclassification, estimates for overdiagnosis were smaller, ranging from 15% of cases in the 70-74 age group to 44% of cases in the 85 and older group. Results could not be adjusted for breast density, family history, and other breast cancer risk factors not captured by the data.

DISCLOSURES:

The work was funded by the National Cancer Institute. One author reported funding from Genentech and Johnson & Johnson.

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

TOPLINE:

Women who continue breast cancer screening after age 70 face a considerable risk for overdiagnosis.

METHODOLOGY:

• Overdiagnosis – the risk of detecting and treating cancers that would never have caused issues in a person’s lifetime – is increasingly recognized as a harm of breast cancer screening; however, the scope of the problem among older women remains uncertain. 
• To get an idea, investigators linked Medicare claims data with Surveillance, Epidemiology, and End Results (SEER) data for 54,635 women 70 years or older to compare the incidence of breast cancer and breast cancer–specific death among women who continued screening mammography with those who did not.
• The women all had undergone recent screening mammograms and had no history of breast cancer at study entry. Those who had a subsequent mammogram within 3 years were classified as undergoing continued screening while those who did not were classified as not undergoing continued screening.
• Overdiagnosis was defined as the difference in cumulative incidence of breast cancer between screened and unscreened women divided by the cumulative incidence among screened women. 
• Results were adjusted for potential confounders, including age, race, and ethnicity.

TAKEAWAY:

• Over 80% of women 70-84 years old and more than 60% of women 85 years or older continued screening.
• Among women 70-74 years old, the adjusted cumulative incidence of breast cancer was 6.1 cases per 100 screened women vs. 4.2 cases per 100 unscreened women; for women aged 75-84 years old, the cumulative incidence was 4.9 per 100 screened women vs. 2.6 per 100 unscreened women, and for women 85 years and older, the cumulative incidence was 2.8 vs. 1.3 per 100, respectively.
• Estimates of overdiagnosis ranged from 31% of breast cancer cases among screened women in the 70-74 age group to 54% of cases in the 85 and older group.
• The researchers found no statistically significant reduction in breast cancer–specific death associated with screening in any age or life-expectancy group. Overdiagnosis appeared to be driven by in situ and localized invasive breast cancer, not advanced breast cancer.

IN PRACTICE:

The proportion of older women who continue to receive screening mammograms and may experience breast cancer overdiagnosis is “considerable” and “increases with advancing age and with decreasing life expectancy,” the authors conclude. Given potential benefits and harms of screening in this population, “patient preferences, including risk tolerance, comfort with uncertainty, and willingness to undergo treatment, are important for informing screening decisions.”

SOURCE:

The study was led by Ilana Richman, MD, MHS, of the Yale School of Medicine, New Haven, Connecticut, and published in the Annals of Internal Medicine.

LIMITATIONS:

The definition of screening mammography in the study may have misclassified some diagnostic mammograms as screening. Using a more conservative definition of screening mammogram, which largely accounted for this misclassification, estimates for overdiagnosis were smaller, ranging from 15% of cases in the 70-74 age group to 44% of cases in the 85 and older group. Results could not be adjusted for breast density, family history, and other breast cancer risk factors not captured by the data.

DISCLOSURES:

The work was funded by the National Cancer Institute. One author reported funding from Genentech and Johnson & Johnson.

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