TOPLINE:

Naturally occurring glucose fluctuations affect cognitive function in people with type 1 diabetes, according to a new study. It matters less whether glucose is considerably higher or lower than the patient’s usual glucose level. Rather, cognition is slower when the glucose was atypical for that particular individual, with variations between different individuals.

METHODOLOGY:

• The investigators used continuous glucose monitoring (CGM) digital sensors and smartphone-based cognitive tests (cognitive ecological momentary assessment [EMA]) to collect repeated, high-frequency glucose and cognitive data. Glucose data were collected every 5 minutes; cognitive data were collected three times daily for 15 days as participants went about their daily lives.
• The study included 200 participants (mean [standard deviation] age, 47.5 [15.6] years; 53.5% female; 86% White; mean A1c, 7.5 mmol/mol [1.3]).
• Using CGM and EMA, the researchers obtained “intensive” longitudinal measurements of glucose as well as cognition (processing speed and sustained attention).
• Hierarchical Bayesian modeling estimated dynamic, within-person associations between glucose and cognition, and data-driven lasso regression identified identify clinical characteristics that predicted differences from person to person in cognitive vulnerability to glucose fluctuations.

TAKEAWAY:

• Cognitive performance was reduced both at low and high glucose levels, “reflecting vulnerability to glucose fluctuations.”
• Large glucose fluctuations were associated with slower as well as less accurate processing speed, although slight glucose elevations (relative to the individual’s own means) were associated with faster processing speed, regardless of the absolute level (eg, euglycemic vs hyperglycemic) of those means.
• By contrast, glucose fluctuations were unrelated to sustained attention.
• The researchers identified seven clinical characteristics that predicted individual differences in cognitive vulnerability to glucose fluctuations: Older age, time in hypoglycemia, lifetime severe hypoglycemic events, microvascular complications, glucose variability, fatigue, and larger neck circumference.

IN PRACTICE:

“Our results demonstrate that people can differ a lot from one another in how their brains are impacted by glucose,” co-senior author Laura Germine, PhD, director of the Laboratory for Brain and Cognitive Health Technology, McLean Hospital, Boston, said in a news release. “We found that minimizing glucose fluctuations in daily life is important for optimizing processing speed, and this is especially true for people who are older or have other diabetes-related health conditions.”

SOURCE:

Zoë Hawks, PhD, research investigator, McLean Hospital, Boston, was the lead and corresponding author on the study. It was published online on March 18 in Digital Medicine.

LIMITATIONS:

The researchers required 24-hour access to a smartphone with reliable Internet access, which might have biased sampling toward people of higher economic status. Moreover, the present sample was predominantly White and non-Hispanic, so findings may not be generalizable to other populations.

DISCLOSURES:

The research was supported by grants from the National Institutes of Health, the Brain and Behavior Research Foundation, and the Alzheimer’s Association. Dr. Hawks received consulting fees from Blueprint Health. The other authors’ disclosures were listed in the original paper.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Naturally occurring glucose fluctuations affect cognitive function in people with type 1 diabetes, according to a new study. It matters less whether glucose is considerably higher or lower than the patient’s usual glucose level. Rather, cognition is slower when the glucose was atypical for that particular individual, with variations between different individuals.

METHODOLOGY:

• The investigators used continuous glucose monitoring (CGM) digital sensors and smartphone-based cognitive tests (cognitive ecological momentary assessment [EMA]) to collect repeated, high-frequency glucose and cognitive data. Glucose data were collected every 5 minutes; cognitive data were collected three times daily for 15 days as participants went about their daily lives.
• The study included 200 participants (mean [standard deviation] age, 47.5 [15.6] years; 53.5% female; 86% White; mean A1c, 7.5 mmol/mol [1.3]).
• Using CGM and EMA, the researchers obtained “intensive” longitudinal measurements of glucose as well as cognition (processing speed and sustained attention).
• Hierarchical Bayesian modeling estimated dynamic, within-person associations between glucose and cognition, and data-driven lasso regression identified identify clinical characteristics that predicted differences from person to person in cognitive vulnerability to glucose fluctuations.

TAKEAWAY:

• Cognitive performance was reduced both at low and high glucose levels, “reflecting vulnerability to glucose fluctuations.”
• Large glucose fluctuations were associated with slower as well as less accurate processing speed, although slight glucose elevations (relative to the individual’s own means) were associated with faster processing speed, regardless of the absolute level (eg, euglycemic vs hyperglycemic) of those means.
• By contrast, glucose fluctuations were unrelated to sustained attention.
• The researchers identified seven clinical characteristics that predicted individual differences in cognitive vulnerability to glucose fluctuations: Older age, time in hypoglycemia, lifetime severe hypoglycemic events, microvascular complications, glucose variability, fatigue, and larger neck circumference.

IN PRACTICE:

“Our results demonstrate that people can differ a lot from one another in how their brains are impacted by glucose,” co-senior author Laura Germine, PhD, director of the Laboratory for Brain and Cognitive Health Technology, McLean Hospital, Boston, said in a news release. “We found that minimizing glucose fluctuations in daily life is important for optimizing processing speed, and this is especially true for people who are older or have other diabetes-related health conditions.”

SOURCE:

Zoë Hawks, PhD, research investigator, McLean Hospital, Boston, was the lead and corresponding author on the study. It was published online on March 18 in Digital Medicine.

LIMITATIONS:

The researchers required 24-hour access to a smartphone with reliable Internet access, which might have biased sampling toward people of higher economic status. Moreover, the present sample was predominantly White and non-Hispanic, so findings may not be generalizable to other populations.

DISCLOSURES:

The research was supported by grants from the National Institutes of Health, the Brain and Behavior Research Foundation, and the Alzheimer’s Association. Dr. Hawks received consulting fees from Blueprint Health. The other authors’ disclosures were listed in the original paper.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Naturally occurring glucose fluctuations affect cognitive function in people with type 1 diabetes, according to a new study. It matters less whether glucose is considerably higher or lower than the patient’s usual glucose level. Rather, cognition is slower when the glucose was atypical for that particular individual, with variations between different individuals.

METHODOLOGY:

• The investigators used continuous glucose monitoring (CGM) digital sensors and smartphone-based cognitive tests (cognitive ecological momentary assessment [EMA]) to collect repeated, high-frequency glucose and cognitive data. Glucose data were collected every 5 minutes; cognitive data were collected three times daily for 15 days as participants went about their daily lives.
• The study included 200 participants (mean [standard deviation] age, 47.5 [15.6] years; 53.5% female; 86% White; mean A1c, 7.5 mmol/mol [1.3]).
• Using CGM and EMA, the researchers obtained “intensive” longitudinal measurements of glucose as well as cognition (processing speed and sustained attention).
• Hierarchical Bayesian modeling estimated dynamic, within-person associations between glucose and cognition, and data-driven lasso regression identified identify clinical characteristics that predicted differences from person to person in cognitive vulnerability to glucose fluctuations.

TAKEAWAY:

• Cognitive performance was reduced both at low and high glucose levels, “reflecting vulnerability to glucose fluctuations.”
• Large glucose fluctuations were associated with slower as well as less accurate processing speed, although slight glucose elevations (relative to the individual’s own means) were associated with faster processing speed, regardless of the absolute level (eg, euglycemic vs hyperglycemic) of those means.
• By contrast, glucose fluctuations were unrelated to sustained attention.
• The researchers identified seven clinical characteristics that predicted individual differences in cognitive vulnerability to glucose fluctuations: Older age, time in hypoglycemia, lifetime severe hypoglycemic events, microvascular complications, glucose variability, fatigue, and larger neck circumference.

IN PRACTICE:

“Our results demonstrate that people can differ a lot from one another in how their brains are impacted by glucose,” co-senior author Laura Germine, PhD, director of the Laboratory for Brain and Cognitive Health Technology, McLean Hospital, Boston, said in a news release. “We found that minimizing glucose fluctuations in daily life is important for optimizing processing speed, and this is especially true for people who are older or have other diabetes-related health conditions.”

SOURCE:

Zoë Hawks, PhD, research investigator, McLean Hospital, Boston, was the lead and corresponding author on the study. It was published online on March 18 in Digital Medicine.

LIMITATIONS:

The researchers required 24-hour access to a smartphone with reliable Internet access, which might have biased sampling toward people of higher economic status. Moreover, the present sample was predominantly White and non-Hispanic, so findings may not be generalizable to other populations.

DISCLOSURES:

The research was supported by grants from the National Institutes of Health, the Brain and Behavior Research Foundation, and the Alzheimer’s Association. Dr. Hawks received consulting fees from Blueprint Health. The other authors’ disclosures were listed in the original paper.
 

A version of this article appeared on Medscape.com.

The Advanced Breast Cancer (ABC) 7th International Consensus Conference Guidelines for Advanced Breast Cancer will soon be released. This news organization discussed the new guidelines with Fatima Cardoso, MD, director of the Breast Unit at Champalimaud Clinical Center, Lisbon, Portugal. Dr. Cardoso is president of the ABC Global Alliance and chair of the guidelines committee. The interview has been edited for length and clarity.

Where do the ABC International Consensus Guidelines come from?

The 7th International Consensus Conference for Advanced Breast Cancer was held in November 2023. This is an international conference that takes place every 2 years. At the conference, we discuss new data that have come out in the past 2 years regarding advanced and metastatic breast cancer, and whether they should impact the guidelines or not. We look at whether there is any new treatment that is ready for clinical practice that wasn’t available 2 years ago. We look at whether there is anything else that has changed in the past 2 years.
 

How do the ABC International Consensus Guidelines differ from other guidelines, such as those from the National Comprehensive Cancer Network (NCCN), American Society of Clinical Oncology (ASCO), or the European Society for Medical Oncology (ESMO)?

These guidelines have some characteristics that are different from the NCCN guidelines. One of the major differences is that the ABC guidelines are developed together with patients and patient advocates. Patients and patient advocates are members of the consensus panel where we discuss important issues around this disease and how to manage it. We also do not discuss drugs exclusively because there are other needs for patients with advanced breast cancer, and we issue recommendations regarding the global care of these patients.
 

Can you tell me about the other issues discussed in the guidelines besides drugs?

For example, in the more general recommendations, we revisited the proper definition of endocrine resistance. A lot of clinical trials are based on selecting a population that is considered to be endocrine sensitive or endocrine resistant, but the definition is very heterogeneous. We have updated the definition because there have been quite a few advances in this particular subtype of cancer. This [new] definition of endocrine resistance and sensitivity will be used and implemented in the different clinical trials, allowing for a better interpretation of the results, with clear impact on clinical practice.
 

What subtype of metastatic breast cancer had the biggest advances in terms of drugs in the guidelines?

The subtype that had the biggest advances in the new guidelines is the hormonal-dependent breast cancer, the ER-positive, HER2-negative. For that particular subtype, we have new drugs either already approved or in the process of being evaluated. Some of them have been approved in the United States but not yet in Europe by the European Medicines Agency (EMA). We are starting to discuss whether these drugs should be approved, and if they are, how we should use them. It is relevant to know what the cost-effectiveness is of each new treatment, as well and the balance between efficacy and toxicity. Sometimes data are too preliminary and we need longer follow-up or more important endpoints, such as survival.

Elacestrant is one of the drugs that has been approved by the US Food and Drug Administration (FDA), and it is very controversial because the benefit it provides on progression-free survival is modest and we still lack data on survival. So, there was a discussion on whether to consider this drug as an option or wait until we have survival data. The majority on the panel thought we could consider elacestrant as a potential new option, when we do not have other endocrine options available.

We issued a recommendation on a drug that is not FDA approved because we think the FDA is going to approve it quite soon. The drug is capivasertib and it blocks the PIK3CA pathway. [Editor’s note: The drug has since been approved by the FDA.] We have a drug that targets this pathway, alpelisib, but it is quite toxic so it is not widely used. Capivasertib has a better toxicity profile so we believe it could be a good addition to our armamentarium for this particular subtype of breast cancer.

We have lots of new data about the antibody-drug conjugates, the ADCs. Initially, we had more data for HER2-positive and triple-negative disease, but now studies have been done to show the value of the ADCs also in the ER-positive, HER2-negative subtype, and so they are now options. In particular, we have trastuzumab deruxtecan for patients with HER2-low disease. Most of the HER2-low tumors are also hormone receptor–positive.
 

The ABC Guidelines discuss tough clinical situations. Can you explain?

The guidelines also discuss issues that in clinical practice are quite difficult because we don’t have strong data. There are certain tough clinical situations. One example is how to treat a woman who has metastatic disease and is pregnant. We discuss the possibilities of treatment in that situation and also what other support these patients need. We discussed that the only available therapy we can use is chemotherapy. We cannot use endocrine therapy, nor biological agents such as anti-HER2 agents and immunotherapy. So, this raises a lot of concerns for how to treat these women without hurting the fetus. But in these guidelines, we discuss other needs of these patients. It’s a hot topic in the US and we did issue a recommendation: that in some situations where the life of the mother may be at risk because we are not able to provide the most adequate treatment, then they should be free to choose to terminate the pregnancy.

It is important to realize that you can’t give most of the new treatments — and ones that have an impact on survival — to a woman when she is pregnant.
 

What other tough clinical situations do you discuss in the new guidelines?

We discuss someone who has metastatic disease and is HIV-positive. Can we use CDK4/6 inhibitors? Can we use immunotherapy? What are the recent data? We have very little data to show that we can possibly use immunotherapy, but we do not have any safety data regarding the CDK4/6 inhibitors.

It’s important to note that people who are HIV-positive tend to have a worse mortality rate from cancer and also suffer from more toxicity. Very often, there is a need to reduce the doses of the treatments we are going to give. The guidelines provide guidance on these issues so that in clinical practice, doctors can have some help managing these difficult situations.

Another example of a tough clinical situation is how to treat an elderly, frail patient who has metastatic disease. We discuss what geriatric evaluations you need to perform before deciding the treatment. We discuss the need very often to reduce the starting dose and then adapt according to what the patient can tolerate.

We have discussed quite a lot of topics that are really patient-oriented and clinically oriented. The aim is to help everyone in clinical practice to provide the best available care.
 

Do you want to expand a bit on the elderly, frail patient and what you have in the guidelines about that?

A very important message is that it doesn’t matter what age your ID card says; it’s the biological age that is important. There are some people who are in their 80s, but they are very fit and they have a very active, normal life. There are other people who are in their 50s and they struggle. It’s important to perform a geriatric evaluation to determine the probability of tolerating a cancer treatment, and we normally use a simple tool called G8. If this tool shows fragility, then it is crucial to have a full geriatric assessment and a full physical exam.

It’s also very important to look for drug-drug interactions in the elderly because these patients often take many different therapies for other diseases.

Another issue is chronic undertreatment in the elderly. If you look just at chronological age and you don’t provide the optimal treatment, there will be increased mortality.

We also recommend starting elderly patients on a lower dose. There are not strong data for that, but we think it is clinical common sense to start at a lower dose. Then, if there is good tolerance, you can move to the usual dose.

Often, the elderly are excluded from clinical trials. Some of the clinical trials for some of the newer agents have included elderly patients. For example, there were some elderly patients in the CDK4/6 inhibitor trials. We know that these patients can receive these treatments with a reduction in dose.

Very frail elderly patients are often excluded from clinical trials. If we continue to do that, we will never know how to treat them.
 

Is there anything you would like to add about the ABC Guidelines that we haven’t talked about?

In the general statement of the guidelines, we mention two things that I think are important for people to know. The first is that during the COVID-19 pandemic, a lot of cancer patients, particularly those with advanced disease, were not offered access to ventilators. Remember, we didn’t have enough ventilators for everyone, so there were exclusion criteria, and one of the exclusion criteria was having cancer. Cancer patients shouldn’t be excluded from having life-saving treatment based solely on the cancer diagnosis. There are many different cancers and many different stages of the disease.

Access to intensive care units is sometimes needed temporarily for a patient with advanced breast cancer. The new treatments, such as immunotherapies and ADCs, can have significant and life-threatening toxicities. You can die from some of these side effects. All over the world, this is a difficult situation because of the bias among many healthcare providers regarding access to intensive care units for cancer patients. It’s a bias we are fighting against.

The second thing we discuss in the beginning of the new guidelines is what is happening to cancer patients during periods of war or conflict. For example, in Ukraine, many of the patients were able to run away and go to another country, but all their health information was lost because the hospitals were destroyed. Patients arrive in a new country and they don’t have any information on the type of cancer they have nor the type of treatment they were undergoing. It was very difficult, for example, for the doctors in Poland to know how to continue to treat the Ukrainian patients. So, in the guidelines, we discuss how we can find a way to ensure that a patient has a copy of their important health data.

Dr. Cardoso, MD, has disclosed the following relevant financial relationships:Personal financial interest in form of consultancy role for: Amgen; Astellas/Medivation; AstraZeneca; Celgene; Daiichi-Sankyo; Eisai; GE Oncology; Genentech; Gilead; GlaxoSmithKline; Iqvia; Macrogenics; Medscape; Merck-Sharp; Merus BV; Mylan; Mundipharma; Novartis; Pfizer; Pierre-Fabre; prIME Oncology; Roche; Sanofi; Samsung Bioepis; Seagen; Teva; Touchime.

Institutional financial support for clinical trials from: Amgen; AstraZeneca; Bayer; Boehringer Ingelheim; Bristol Myers Squibb; Bayer; Daiichi; Eisai; Fresenius GmbH; Genentech; GlaxoSmithKline; Ipsen; Incyte; Nektar Therapeutics; Nerviano; Novartis; Macrogenics; Medigene; MedImmune; Merck; Millennium; Pfizer; Pierre-Fabre; Roche; Sanofi-Aventis; Sonus; Tesaro; Tigris; Wilex; Wyeth.

A version of this article appeared on Medscape.com.

The Advanced Breast Cancer (ABC) 7th International Consensus Conference Guidelines for Advanced Breast Cancer will soon be released. This news organization discussed the new guidelines with Fatima Cardoso, MD, director of the Breast Unit at Champalimaud Clinical Center, Lisbon, Portugal. Dr. Cardoso is president of the ABC Global Alliance and chair of the guidelines committee. The interview has been edited for length and clarity.

Where do the ABC International Consensus Guidelines come from?

The 7th International Consensus Conference for Advanced Breast Cancer was held in November 2023. This is an international conference that takes place every 2 years. At the conference, we discuss new data that have come out in the past 2 years regarding advanced and metastatic breast cancer, and whether they should impact the guidelines or not. We look at whether there is any new treatment that is ready for clinical practice that wasn’t available 2 years ago. We look at whether there is anything else that has changed in the past 2 years.
 

How do the ABC International Consensus Guidelines differ from other guidelines, such as those from the National Comprehensive Cancer Network (NCCN), American Society of Clinical Oncology (ASCO), or the European Society for Medical Oncology (ESMO)?

These guidelines have some characteristics that are different from the NCCN guidelines. One of the major differences is that the ABC guidelines are developed together with patients and patient advocates. Patients and patient advocates are members of the consensus panel where we discuss important issues around this disease and how to manage it. We also do not discuss drugs exclusively because there are other needs for patients with advanced breast cancer, and we issue recommendations regarding the global care of these patients.
 

Can you tell me about the other issues discussed in the guidelines besides drugs?

For example, in the more general recommendations, we revisited the proper definition of endocrine resistance. A lot of clinical trials are based on selecting a population that is considered to be endocrine sensitive or endocrine resistant, but the definition is very heterogeneous. We have updated the definition because there have been quite a few advances in this particular subtype of cancer. This [new] definition of endocrine resistance and sensitivity will be used and implemented in the different clinical trials, allowing for a better interpretation of the results, with clear impact on clinical practice.
 

What subtype of metastatic breast cancer had the biggest advances in terms of drugs in the guidelines?

The subtype that had the biggest advances in the new guidelines is the hormonal-dependent breast cancer, the ER-positive, HER2-negative. For that particular subtype, we have new drugs either already approved or in the process of being evaluated. Some of them have been approved in the United States but not yet in Europe by the European Medicines Agency (EMA). We are starting to discuss whether these drugs should be approved, and if they are, how we should use them. It is relevant to know what the cost-effectiveness is of each new treatment, as well and the balance between efficacy and toxicity. Sometimes data are too preliminary and we need longer follow-up or more important endpoints, such as survival.

Elacestrant is one of the drugs that has been approved by the US Food and Drug Administration (FDA), and it is very controversial because the benefit it provides on progression-free survival is modest and we still lack data on survival. So, there was a discussion on whether to consider this drug as an option or wait until we have survival data. The majority on the panel thought we could consider elacestrant as a potential new option, when we do not have other endocrine options available.

We issued a recommendation on a drug that is not FDA approved because we think the FDA is going to approve it quite soon. The drug is capivasertib and it blocks the PIK3CA pathway. [Editor’s note: The drug has since been approved by the FDA.] We have a drug that targets this pathway, alpelisib, but it is quite toxic so it is not widely used. Capivasertib has a better toxicity profile so we believe it could be a good addition to our armamentarium for this particular subtype of breast cancer.

We have lots of new data about the antibody-drug conjugates, the ADCs. Initially, we had more data for HER2-positive and triple-negative disease, but now studies have been done to show the value of the ADCs also in the ER-positive, HER2-negative subtype, and so they are now options. In particular, we have trastuzumab deruxtecan for patients with HER2-low disease. Most of the HER2-low tumors are also hormone receptor–positive.
 

The ABC Guidelines discuss tough clinical situations. Can you explain?

The guidelines also discuss issues that in clinical practice are quite difficult because we don’t have strong data. There are certain tough clinical situations. One example is how to treat a woman who has metastatic disease and is pregnant. We discuss the possibilities of treatment in that situation and also what other support these patients need. We discussed that the only available therapy we can use is chemotherapy. We cannot use endocrine therapy, nor biological agents such as anti-HER2 agents and immunotherapy. So, this raises a lot of concerns for how to treat these women without hurting the fetus. But in these guidelines, we discuss other needs of these patients. It’s a hot topic in the US and we did issue a recommendation: that in some situations where the life of the mother may be at risk because we are not able to provide the most adequate treatment, then they should be free to choose to terminate the pregnancy.

It is important to realize that you can’t give most of the new treatments — and ones that have an impact on survival — to a woman when she is pregnant.
 

What other tough clinical situations do you discuss in the new guidelines?

We discuss someone who has metastatic disease and is HIV-positive. Can we use CDK4/6 inhibitors? Can we use immunotherapy? What are the recent data? We have very little data to show that we can possibly use immunotherapy, but we do not have any safety data regarding the CDK4/6 inhibitors.

It’s important to note that people who are HIV-positive tend to have a worse mortality rate from cancer and also suffer from more toxicity. Very often, there is a need to reduce the doses of the treatments we are going to give. The guidelines provide guidance on these issues so that in clinical practice, doctors can have some help managing these difficult situations.

Another example of a tough clinical situation is how to treat an elderly, frail patient who has metastatic disease. We discuss what geriatric evaluations you need to perform before deciding the treatment. We discuss the need very often to reduce the starting dose and then adapt according to what the patient can tolerate.

We have discussed quite a lot of topics that are really patient-oriented and clinically oriented. The aim is to help everyone in clinical practice to provide the best available care.
 

Do you want to expand a bit on the elderly, frail patient and what you have in the guidelines about that?

A very important message is that it doesn’t matter what age your ID card says; it’s the biological age that is important. There are some people who are in their 80s, but they are very fit and they have a very active, normal life. There are other people who are in their 50s and they struggle. It’s important to perform a geriatric evaluation to determine the probability of tolerating a cancer treatment, and we normally use a simple tool called G8. If this tool shows fragility, then it is crucial to have a full geriatric assessment and a full physical exam.

It’s also very important to look for drug-drug interactions in the elderly because these patients often take many different therapies for other diseases.

Another issue is chronic undertreatment in the elderly. If you look just at chronological age and you don’t provide the optimal treatment, there will be increased mortality.

We also recommend starting elderly patients on a lower dose. There are not strong data for that, but we think it is clinical common sense to start at a lower dose. Then, if there is good tolerance, you can move to the usual dose.

Often, the elderly are excluded from clinical trials. Some of the clinical trials for some of the newer agents have included elderly patients. For example, there were some elderly patients in the CDK4/6 inhibitor trials. We know that these patients can receive these treatments with a reduction in dose.

Very frail elderly patients are often excluded from clinical trials. If we continue to do that, we will never know how to treat them.
 

Is there anything you would like to add about the ABC Guidelines that we haven’t talked about?

In the general statement of the guidelines, we mention two things that I think are important for people to know. The first is that during the COVID-19 pandemic, a lot of cancer patients, particularly those with advanced disease, were not offered access to ventilators. Remember, we didn’t have enough ventilators for everyone, so there were exclusion criteria, and one of the exclusion criteria was having cancer. Cancer patients shouldn’t be excluded from having life-saving treatment based solely on the cancer diagnosis. There are many different cancers and many different stages of the disease.

Access to intensive care units is sometimes needed temporarily for a patient with advanced breast cancer. The new treatments, such as immunotherapies and ADCs, can have significant and life-threatening toxicities. You can die from some of these side effects. All over the world, this is a difficult situation because of the bias among many healthcare providers regarding access to intensive care units for cancer patients. It’s a bias we are fighting against.

The second thing we discuss in the beginning of the new guidelines is what is happening to cancer patients during periods of war or conflict. For example, in Ukraine, many of the patients were able to run away and go to another country, but all their health information was lost because the hospitals were destroyed. Patients arrive in a new country and they don’t have any information on the type of cancer they have nor the type of treatment they were undergoing. It was very difficult, for example, for the doctors in Poland to know how to continue to treat the Ukrainian patients. So, in the guidelines, we discuss how we can find a way to ensure that a patient has a copy of their important health data.

Dr. Cardoso, MD, has disclosed the following relevant financial relationships:Personal financial interest in form of consultancy role for: Amgen; Astellas/Medivation; AstraZeneca; Celgene; Daiichi-Sankyo; Eisai; GE Oncology; Genentech; Gilead; GlaxoSmithKline; Iqvia; Macrogenics; Medscape; Merck-Sharp; Merus BV; Mylan; Mundipharma; Novartis; Pfizer; Pierre-Fabre; prIME Oncology; Roche; Sanofi; Samsung Bioepis; Seagen; Teva; Touchime.

Institutional financial support for clinical trials from: Amgen; AstraZeneca; Bayer; Boehringer Ingelheim; Bristol Myers Squibb; Bayer; Daiichi; Eisai; Fresenius GmbH; Genentech; GlaxoSmithKline; Ipsen; Incyte; Nektar Therapeutics; Nerviano; Novartis; Macrogenics; Medigene; MedImmune; Merck; Millennium; Pfizer; Pierre-Fabre; Roche; Sanofi-Aventis; Sonus; Tesaro; Tigris; Wilex; Wyeth.

A version of this article appeared on Medscape.com.

The Advanced Breast Cancer (ABC) 7th International Consensus Conference Guidelines for Advanced Breast Cancer will soon be released. This news organization discussed the new guidelines with Fatima Cardoso, MD, director of the Breast Unit at Champalimaud Clinical Center, Lisbon, Portugal. Dr. Cardoso is president of the ABC Global Alliance and chair of the guidelines committee. The interview has been edited for length and clarity.

Where do the ABC International Consensus Guidelines come from?

The 7th International Consensus Conference for Advanced Breast Cancer was held in November 2023. This is an international conference that takes place every 2 years. At the conference, we discuss new data that have come out in the past 2 years regarding advanced and metastatic breast cancer, and whether they should impact the guidelines or not. We look at whether there is any new treatment that is ready for clinical practice that wasn’t available 2 years ago. We look at whether there is anything else that has changed in the past 2 years.
 

How do the ABC International Consensus Guidelines differ from other guidelines, such as those from the National Comprehensive Cancer Network (NCCN), American Society of Clinical Oncology (ASCO), or the European Society for Medical Oncology (ESMO)?

These guidelines have some characteristics that are different from the NCCN guidelines. One of the major differences is that the ABC guidelines are developed together with patients and patient advocates. Patients and patient advocates are members of the consensus panel where we discuss important issues around this disease and how to manage it. We also do not discuss drugs exclusively because there are other needs for patients with advanced breast cancer, and we issue recommendations regarding the global care of these patients.
 

Can you tell me about the other issues discussed in the guidelines besides drugs?

For example, in the more general recommendations, we revisited the proper definition of endocrine resistance. A lot of clinical trials are based on selecting a population that is considered to be endocrine sensitive or endocrine resistant, but the definition is very heterogeneous. We have updated the definition because there have been quite a few advances in this particular subtype of cancer. This [new] definition of endocrine resistance and sensitivity will be used and implemented in the different clinical trials, allowing for a better interpretation of the results, with clear impact on clinical practice.
 

What subtype of metastatic breast cancer had the biggest advances in terms of drugs in the guidelines?

The subtype that had the biggest advances in the new guidelines is the hormonal-dependent breast cancer, the ER-positive, HER2-negative. For that particular subtype, we have new drugs either already approved or in the process of being evaluated. Some of them have been approved in the United States but not yet in Europe by the European Medicines Agency (EMA). We are starting to discuss whether these drugs should be approved, and if they are, how we should use them. It is relevant to know what the cost-effectiveness is of each new treatment, as well and the balance between efficacy and toxicity. Sometimes data are too preliminary and we need longer follow-up or more important endpoints, such as survival.

Elacestrant is one of the drugs that has been approved by the US Food and Drug Administration (FDA), and it is very controversial because the benefit it provides on progression-free survival is modest and we still lack data on survival. So, there was a discussion on whether to consider this drug as an option or wait until we have survival data. The majority on the panel thought we could consider elacestrant as a potential new option, when we do not have other endocrine options available.

We issued a recommendation on a drug that is not FDA approved because we think the FDA is going to approve it quite soon. The drug is capivasertib and it blocks the PIK3CA pathway. [Editor’s note: The drug has since been approved by the FDA.] We have a drug that targets this pathway, alpelisib, but it is quite toxic so it is not widely used. Capivasertib has a better toxicity profile so we believe it could be a good addition to our armamentarium for this particular subtype of breast cancer.

We have lots of new data about the antibody-drug conjugates, the ADCs. Initially, we had more data for HER2-positive and triple-negative disease, but now studies have been done to show the value of the ADCs also in the ER-positive, HER2-negative subtype, and so they are now options. In particular, we have trastuzumab deruxtecan for patients with HER2-low disease. Most of the HER2-low tumors are also hormone receptor–positive.
 

The ABC Guidelines discuss tough clinical situations. Can you explain?

The guidelines also discuss issues that in clinical practice are quite difficult because we don’t have strong data. There are certain tough clinical situations. One example is how to treat a woman who has metastatic disease and is pregnant. We discuss the possibilities of treatment in that situation and also what other support these patients need. We discussed that the only available therapy we can use is chemotherapy. We cannot use endocrine therapy, nor biological agents such as anti-HER2 agents and immunotherapy. So, this raises a lot of concerns for how to treat these women without hurting the fetus. But in these guidelines, we discuss other needs of these patients. It’s a hot topic in the US and we did issue a recommendation: that in some situations where the life of the mother may be at risk because we are not able to provide the most adequate treatment, then they should be free to choose to terminate the pregnancy.

It is important to realize that you can’t give most of the new treatments — and ones that have an impact on survival — to a woman when she is pregnant.
 

What other tough clinical situations do you discuss in the new guidelines?

We discuss someone who has metastatic disease and is HIV-positive. Can we use CDK4/6 inhibitors? Can we use immunotherapy? What are the recent data? We have very little data to show that we can possibly use immunotherapy, but we do not have any safety data regarding the CDK4/6 inhibitors.

It’s important to note that people who are HIV-positive tend to have a worse mortality rate from cancer and also suffer from more toxicity. Very often, there is a need to reduce the doses of the treatments we are going to give. The guidelines provide guidance on these issues so that in clinical practice, doctors can have some help managing these difficult situations.

Another example of a tough clinical situation is how to treat an elderly, frail patient who has metastatic disease. We discuss what geriatric evaluations you need to perform before deciding the treatment. We discuss the need very often to reduce the starting dose and then adapt according to what the patient can tolerate.

We have discussed quite a lot of topics that are really patient-oriented and clinically oriented. The aim is to help everyone in clinical practice to provide the best available care.
 

Do you want to expand a bit on the elderly, frail patient and what you have in the guidelines about that?

A very important message is that it doesn’t matter what age your ID card says; it’s the biological age that is important. There are some people who are in their 80s, but they are very fit and they have a very active, normal life. There are other people who are in their 50s and they struggle. It’s important to perform a geriatric evaluation to determine the probability of tolerating a cancer treatment, and we normally use a simple tool called G8. If this tool shows fragility, then it is crucial to have a full geriatric assessment and a full physical exam.

It’s also very important to look for drug-drug interactions in the elderly because these patients often take many different therapies for other diseases.

Another issue is chronic undertreatment in the elderly. If you look just at chronological age and you don’t provide the optimal treatment, there will be increased mortality.

We also recommend starting elderly patients on a lower dose. There are not strong data for that, but we think it is clinical common sense to start at a lower dose. Then, if there is good tolerance, you can move to the usual dose.

Often, the elderly are excluded from clinical trials. Some of the clinical trials for some of the newer agents have included elderly patients. For example, there were some elderly patients in the CDK4/6 inhibitor trials. We know that these patients can receive these treatments with a reduction in dose.

Very frail elderly patients are often excluded from clinical trials. If we continue to do that, we will never know how to treat them.
 

Is there anything you would like to add about the ABC Guidelines that we haven’t talked about?

In the general statement of the guidelines, we mention two things that I think are important for people to know. The first is that during the COVID-19 pandemic, a lot of cancer patients, particularly those with advanced disease, were not offered access to ventilators. Remember, we didn’t have enough ventilators for everyone, so there were exclusion criteria, and one of the exclusion criteria was having cancer. Cancer patients shouldn’t be excluded from having life-saving treatment based solely on the cancer diagnosis. There are many different cancers and many different stages of the disease.

Access to intensive care units is sometimes needed temporarily for a patient with advanced breast cancer. The new treatments, such as immunotherapies and ADCs, can have significant and life-threatening toxicities. You can die from some of these side effects. All over the world, this is a difficult situation because of the bias among many healthcare providers regarding access to intensive care units for cancer patients. It’s a bias we are fighting against.

The second thing we discuss in the beginning of the new guidelines is what is happening to cancer patients during periods of war or conflict. For example, in Ukraine, many of the patients were able to run away and go to another country, but all their health information was lost because the hospitals were destroyed. Patients arrive in a new country and they don’t have any information on the type of cancer they have nor the type of treatment they were undergoing. It was very difficult, for example, for the doctors in Poland to know how to continue to treat the Ukrainian patients. So, in the guidelines, we discuss how we can find a way to ensure that a patient has a copy of their important health data.

Dr. Cardoso, MD, has disclosed the following relevant financial relationships:Personal financial interest in form of consultancy role for: Amgen; Astellas/Medivation; AstraZeneca; Celgene; Daiichi-Sankyo; Eisai; GE Oncology; Genentech; Gilead; GlaxoSmithKline; Iqvia; Macrogenics; Medscape; Merck-Sharp; Merus BV; Mylan; Mundipharma; Novartis; Pfizer; Pierre-Fabre; prIME Oncology; Roche; Sanofi; Samsung Bioepis; Seagen; Teva; Touchime.

Institutional financial support for clinical trials from: Amgen; AstraZeneca; Bayer; Boehringer Ingelheim; Bristol Myers Squibb; Bayer; Daiichi; Eisai; Fresenius GmbH; Genentech; GlaxoSmithKline; Ipsen; Incyte; Nektar Therapeutics; Nerviano; Novartis; Macrogenics; Medigene; MedImmune; Merck; Millennium; Pfizer; Pierre-Fabre; Roche; Sanofi-Aventis; Sonus; Tesaro; Tigris; Wilex; Wyeth.

A version of this article appeared on Medscape.com.

Symptoms of sleep apnea, including snorting, gasping, or paused breathing during sleep, are associated with a significantly greater risk for problems with cognitive and memory problems, results from a large study showed.

Data from a representative sample of US adults show that those who reported sleep apnea symptoms were about 50% more likely to also report cognitive issues versus their counterparts without such symptoms.

“For clinicians, these findings suggest a potential benefit of considering sleep apnea as a possible contributing or exacerbating factor in individuals experiencing memory or cognitive problems. This could prompt further evaluation for sleep apnea, particularly in at-risk individuals,” said study investigator Dominique Low, MD, MPH, Department of Neurology, Boston Medical Center.

The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
 

Need to Raise Awareness

The findings are based on 4257 adults who participated in the 2017-2018 National Health and Nutrition Examination Survey and completed questionnaires covering sleep, memory, cognition, and decision-making abilities.

Those who reported snorting, gasping, or breathing pauses during sleep were categorized as experiencing sleep apnea symptoms. Those who reported memory trouble, periods of confusion, difficulty concentrating, or decision-making problems were classified as having memory or cognitive symptoms.

Overall, 1079 participants reported symptoms of sleep apnea. Compared with people without sleep apnea, those with symptoms were more likely to have cognitive problems (33% vs 20%) and have greater odds of having memory or cognitive symptoms, even after adjusting for age, gender, race, and education (adjusted odds ratio, 2.02; P < .001).

“While the study did not establish a cause-and-effect relationship, the findings suggest the importance of raising awareness about the potential link between sleep and cognitive function. Early identification and treatment may improve overall health and potentially lead to a better quality of life,” Dr. Low said.

Limitations of the study include self-reported data on sleep apnea symptoms and cognitive issues sourced from one survey.
 

Consistent Data

Reached for comment, Matthew Pase, PhD, with the Turner Institute for Brain and Mental Health, Monash University, Melbourne, Australia, said the results are similar to earlier work that found a link between obstructive sleep apnea and cognition.

For example, in a recent study, the presence of mild to severe OSA, identified using overnight polysomnography in five community-based cohorts with more than 5900 adults, was associated with poorer cognitive test performance, Dr. Pase said.

“These and other results underscore the importance of healthy sleep for optimal brain health. Future research is needed to test if treating OSA and other sleep disorders can reduce the risk of cognitive impairment,” Dr. Pase said.

Yet, in its latest statement on the topic, the US Preventive Services Task Force concluded there remains insufficient evidence to weigh the balance of benefits and harms of screening for OSA among asymptomatic adults and those with unrecognized symptoms.

The study had no specific funding. Dr. Low and Dr. Pase had no relevant disclosures.
 

A version of this article appeared on Medscape.com.

Symptoms of sleep apnea, including snorting, gasping, or paused breathing during sleep, are associated with a significantly greater risk for problems with cognitive and memory problems, results from a large study showed.

Data from a representative sample of US adults show that those who reported sleep apnea symptoms were about 50% more likely to also report cognitive issues versus their counterparts without such symptoms.

“For clinicians, these findings suggest a potential benefit of considering sleep apnea as a possible contributing or exacerbating factor in individuals experiencing memory or cognitive problems. This could prompt further evaluation for sleep apnea, particularly in at-risk individuals,” said study investigator Dominique Low, MD, MPH, Department of Neurology, Boston Medical Center.

The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
 

Need to Raise Awareness

The findings are based on 4257 adults who participated in the 2017-2018 National Health and Nutrition Examination Survey and completed questionnaires covering sleep, memory, cognition, and decision-making abilities.

Those who reported snorting, gasping, or breathing pauses during sleep were categorized as experiencing sleep apnea symptoms. Those who reported memory trouble, periods of confusion, difficulty concentrating, or decision-making problems were classified as having memory or cognitive symptoms.

Overall, 1079 participants reported symptoms of sleep apnea. Compared with people without sleep apnea, those with symptoms were more likely to have cognitive problems (33% vs 20%) and have greater odds of having memory or cognitive symptoms, even after adjusting for age, gender, race, and education (adjusted odds ratio, 2.02; P < .001).

“While the study did not establish a cause-and-effect relationship, the findings suggest the importance of raising awareness about the potential link between sleep and cognitive function. Early identification and treatment may improve overall health and potentially lead to a better quality of life,” Dr. Low said.

Limitations of the study include self-reported data on sleep apnea symptoms and cognitive issues sourced from one survey.
 

Consistent Data

Reached for comment, Matthew Pase, PhD, with the Turner Institute for Brain and Mental Health, Monash University, Melbourne, Australia, said the results are similar to earlier work that found a link between obstructive sleep apnea and cognition.

For example, in a recent study, the presence of mild to severe OSA, identified using overnight polysomnography in five community-based cohorts with more than 5900 adults, was associated with poorer cognitive test performance, Dr. Pase said.

“These and other results underscore the importance of healthy sleep for optimal brain health. Future research is needed to test if treating OSA and other sleep disorders can reduce the risk of cognitive impairment,” Dr. Pase said.

Yet, in its latest statement on the topic, the US Preventive Services Task Force concluded there remains insufficient evidence to weigh the balance of benefits and harms of screening for OSA among asymptomatic adults and those with unrecognized symptoms.

The study had no specific funding. Dr. Low and Dr. Pase had no relevant disclosures.
 

A version of this article appeared on Medscape.com.

Symptoms of sleep apnea, including snorting, gasping, or paused breathing during sleep, are associated with a significantly greater risk for problems with cognitive and memory problems, results from a large study showed.

Data from a representative sample of US adults show that those who reported sleep apnea symptoms were about 50% more likely to also report cognitive issues versus their counterparts without such symptoms.

“For clinicians, these findings suggest a potential benefit of considering sleep apnea as a possible contributing or exacerbating factor in individuals experiencing memory or cognitive problems. This could prompt further evaluation for sleep apnea, particularly in at-risk individuals,” said study investigator Dominique Low, MD, MPH, Department of Neurology, Boston Medical Center.

The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
 

Need to Raise Awareness

The findings are based on 4257 adults who participated in the 2017-2018 National Health and Nutrition Examination Survey and completed questionnaires covering sleep, memory, cognition, and decision-making abilities.

Those who reported snorting, gasping, or breathing pauses during sleep were categorized as experiencing sleep apnea symptoms. Those who reported memory trouble, periods of confusion, difficulty concentrating, or decision-making problems were classified as having memory or cognitive symptoms.

Overall, 1079 participants reported symptoms of sleep apnea. Compared with people without sleep apnea, those with symptoms were more likely to have cognitive problems (33% vs 20%) and have greater odds of having memory or cognitive symptoms, even after adjusting for age, gender, race, and education (adjusted odds ratio, 2.02; P < .001).

“While the study did not establish a cause-and-effect relationship, the findings suggest the importance of raising awareness about the potential link between sleep and cognitive function. Early identification and treatment may improve overall health and potentially lead to a better quality of life,” Dr. Low said.

Limitations of the study include self-reported data on sleep apnea symptoms and cognitive issues sourced from one survey.
 

Consistent Data

Reached for comment, Matthew Pase, PhD, with the Turner Institute for Brain and Mental Health, Monash University, Melbourne, Australia, said the results are similar to earlier work that found a link between obstructive sleep apnea and cognition.

For example, in a recent study, the presence of mild to severe OSA, identified using overnight polysomnography in five community-based cohorts with more than 5900 adults, was associated with poorer cognitive test performance, Dr. Pase said.

“These and other results underscore the importance of healthy sleep for optimal brain health. Future research is needed to test if treating OSA and other sleep disorders can reduce the risk of cognitive impairment,” Dr. Pase said.

Yet, in its latest statement on the topic, the US Preventive Services Task Force concluded there remains insufficient evidence to weigh the balance of benefits and harms of screening for OSA among asymptomatic adults and those with unrecognized symptoms.

The study had no specific funding. Dr. Low and Dr. Pase had no relevant disclosures.
 

A version of this article appeared on Medscape.com.

Most survivors of childhood cancer don’t meet surveillance guidelines that recommend screening for adult cancers or other long-term adverse effects of treatment, according to a new study.

Among childhood cancer survivors in Ontario, Canada, who faced an elevated risk due to chemotherapy or radiation treatments, 53% followed screening recommendations for cardiomyopathy, 13% met colorectal cancer screening guidelines, and 6% adhered to breast cancer screening guidelines.

“Although over 80% of children newly diagnosed with cancer will become long-term survivors, as many as four out of five of these survivors will develop a serious or life-threatening late effect of their cancer therapy by age 45,” lead author Jennifer Shuldiner, PhD, MPH, a scientist at Women’s College Hospital Institute for Health Systems Solutions and Virtual Care in Toronto, told this news organization.

For instance, the risk for colorectal cancer in childhood cancer survivors is two to three times higher than it is among the general population, and the risk for breast cancer is similar between those who underwent chest radiation and those with a BRCA mutation. As many as 50% of those who received anthracycline chemotherapy or radiation involving the heart later develop cardiotoxicity.

The North American Children’s Oncology Group has published long-term follow-up guidelines for survivors of childhood cancer, yet many survivors don’t follow them because of lack of awareness or other barriers, said Dr. Shuldiner.

“Prior research has shown that many survivors do not complete these recommended tests,” she said. “With better knowledge of this at-risk population, we can design, test, and implement appropriate interventions and supports to tackle the issues.”

The study was published online on March 11 in CMAJ. 
 

Changes in Adherence 

The researchers conducted a retrospective population-based cohort study analyzing Ontario healthcare administrative data for adult survivors of childhood cancer diagnosed between 1986 and 2014 who faced an elevated risk for therapy-related colorectal cancer, breast cancer, or cardiomyopathy. The research team then assessed long-term adherence to the North American Children’s Oncology Group guidelines and predictors of adherence.

Among 3241 survivors, 3205 (99%) were at elevated risk for cardiomyopathy, 327 (10%) were at elevated risk for colorectal cancer, and 234 (7%) were at elevated risk for breast cancer. In addition, 2806 (87%) were at risk for one late effect, 345 (11%) were at risk for two late effects, and 90 (3%) were at risk for three late effects.

Overall, 53%, 13%, and 6% were adherent to their recommended surveillance for cardiomyopathy, colorectal cancer, and breast cancer, respectively. Over time, adherence increased for colorectal cancer and cardiomyopathy but decreased for breast cancer.

In addition, patients who were older at diagnosis were more likely to follow screening guidelines for colorectal and breast cancers, whereas those who were younger at diagnosis were more likely to follow screening guidelines for cardiomyopathy.

During a median follow-up of 7.8 years, the proportion of time spent adherent was 43% for cardiomyopathy, 14% for colorectal cancer, and 10% for breast cancer.

Survivors who attended a long-term follow-up clinic in the previous year had low adherence rates as well, though they were higher than in the rest of the cohort. In this group, the proportion of time that was spent adherent was 71% for cardiomyopathy, 27% for colorectal cancer, and 15% for breast cancer.

Shuldiner and colleagues are launching a research trial to determine whether a provincial support system can help childhood cancer survivors receive the recommended surveillance. The support system provides information about screening recommendations to survivors as well as reminders and sends key information to their family doctors.

“We now understand that childhood cancer survivors need help to complete the recommended tests,” said Dr. Shuldiner. “If the trial is successful, we hope it will be implemented in Ontario.” 
 

Survivorship Care Plans 

Low screening rates may result from a lack of awareness about screening recommendations and the negative long-term effects of cancer treatments, the study authors wrote. Cancer survivors, caregivers, family physicians, specialists, and survivor support groups can share the responsibility of spreading awareness and adhering to guidelines, they noted. In some cases, a survivorship care plan (SCP) may help.

“SCPs are intended to improve adherence by providing follow-up information and facilitating the transition from cancer treatment to survivorship and from pediatric to adult care,” Adam Yan, MD, a staff oncologist and oncology informatics lead at the Hospital for Sick Children in Toronto, told this news organization.

Dr. Yan, who wasn’t involved with this study, has researched surveillance adherence for secondary cancers and cardiac dysfunction among childhood cancer survivors. He and his colleagues found that screening rates were typically low among survivors who faced high risks for cardiac dysfunction and breast, colorectal, or skin cancers.

However, having a survivorship care plan seemed to help, and survivors treated after 1990 were more likely to have an SCP.

“SCP possession by high-risk survivors was associated with increased breast, skin, and cardiac surveillance,” he said. “It is uncertain whether SCP possession leads to adherence or whether SCP possession is a marker of survivors who are focused on their health and thus likely to adhere to preventive health practices, including surveillance.”

The study was funded by the Canadian Institutes of Health Research and ICES, which receives support from the Ontario Ministry of Health and the Ministry of Long-Term Care. Dr. Shuldiner received a Canadian Institutes of Health Research Health System Impact Postdoctoral Fellowship in support of the work. Dr. Yan disclosed no relevant financial relationships. 
 

A version of this article appeared on Medscape.com.

Most survivors of childhood cancer don’t meet surveillance guidelines that recommend screening for adult cancers or other long-term adverse effects of treatment, according to a new study.

Among childhood cancer survivors in Ontario, Canada, who faced an elevated risk due to chemotherapy or radiation treatments, 53% followed screening recommendations for cardiomyopathy, 13% met colorectal cancer screening guidelines, and 6% adhered to breast cancer screening guidelines.

“Although over 80% of children newly diagnosed with cancer will become long-term survivors, as many as four out of five of these survivors will develop a serious or life-threatening late effect of their cancer therapy by age 45,” lead author Jennifer Shuldiner, PhD, MPH, a scientist at Women’s College Hospital Institute for Health Systems Solutions and Virtual Care in Toronto, told this news organization.

For instance, the risk for colorectal cancer in childhood cancer survivors is two to three times higher than it is among the general population, and the risk for breast cancer is similar between those who underwent chest radiation and those with a BRCA mutation. As many as 50% of those who received anthracycline chemotherapy or radiation involving the heart later develop cardiotoxicity.

The North American Children’s Oncology Group has published long-term follow-up guidelines for survivors of childhood cancer, yet many survivors don’t follow them because of lack of awareness or other barriers, said Dr. Shuldiner.

“Prior research has shown that many survivors do not complete these recommended tests,” she said. “With better knowledge of this at-risk population, we can design, test, and implement appropriate interventions and supports to tackle the issues.”

The study was published online on March 11 in CMAJ. 
 

Changes in Adherence 

The researchers conducted a retrospective population-based cohort study analyzing Ontario healthcare administrative data for adult survivors of childhood cancer diagnosed between 1986 and 2014 who faced an elevated risk for therapy-related colorectal cancer, breast cancer, or cardiomyopathy. The research team then assessed long-term adherence to the North American Children’s Oncology Group guidelines and predictors of adherence.

Among 3241 survivors, 3205 (99%) were at elevated risk for cardiomyopathy, 327 (10%) were at elevated risk for colorectal cancer, and 234 (7%) were at elevated risk for breast cancer. In addition, 2806 (87%) were at risk for one late effect, 345 (11%) were at risk for two late effects, and 90 (3%) were at risk for three late effects.

Overall, 53%, 13%, and 6% were adherent to their recommended surveillance for cardiomyopathy, colorectal cancer, and breast cancer, respectively. Over time, adherence increased for colorectal cancer and cardiomyopathy but decreased for breast cancer.

In addition, patients who were older at diagnosis were more likely to follow screening guidelines for colorectal and breast cancers, whereas those who were younger at diagnosis were more likely to follow screening guidelines for cardiomyopathy.

During a median follow-up of 7.8 years, the proportion of time spent adherent was 43% for cardiomyopathy, 14% for colorectal cancer, and 10% for breast cancer.

Survivors who attended a long-term follow-up clinic in the previous year had low adherence rates as well, though they were higher than in the rest of the cohort. In this group, the proportion of time that was spent adherent was 71% for cardiomyopathy, 27% for colorectal cancer, and 15% for breast cancer.

Shuldiner and colleagues are launching a research trial to determine whether a provincial support system can help childhood cancer survivors receive the recommended surveillance. The support system provides information about screening recommendations to survivors as well as reminders and sends key information to their family doctors.

“We now understand that childhood cancer survivors need help to complete the recommended tests,” said Dr. Shuldiner. “If the trial is successful, we hope it will be implemented in Ontario.” 
 

Survivorship Care Plans 

Low screening rates may result from a lack of awareness about screening recommendations and the negative long-term effects of cancer treatments, the study authors wrote. Cancer survivors, caregivers, family physicians, specialists, and survivor support groups can share the responsibility of spreading awareness and adhering to guidelines, they noted. In some cases, a survivorship care plan (SCP) may help.

“SCPs are intended to improve adherence by providing follow-up information and facilitating the transition from cancer treatment to survivorship and from pediatric to adult care,” Adam Yan, MD, a staff oncologist and oncology informatics lead at the Hospital for Sick Children in Toronto, told this news organization.

Dr. Yan, who wasn’t involved with this study, has researched surveillance adherence for secondary cancers and cardiac dysfunction among childhood cancer survivors. He and his colleagues found that screening rates were typically low among survivors who faced high risks for cardiac dysfunction and breast, colorectal, or skin cancers.

However, having a survivorship care plan seemed to help, and survivors treated after 1990 were more likely to have an SCP.

“SCP possession by high-risk survivors was associated with increased breast, skin, and cardiac surveillance,” he said. “It is uncertain whether SCP possession leads to adherence or whether SCP possession is a marker of survivors who are focused on their health and thus likely to adhere to preventive health practices, including surveillance.”

The study was funded by the Canadian Institutes of Health Research and ICES, which receives support from the Ontario Ministry of Health and the Ministry of Long-Term Care. Dr. Shuldiner received a Canadian Institutes of Health Research Health System Impact Postdoctoral Fellowship in support of the work. Dr. Yan disclosed no relevant financial relationships. 
 

A version of this article appeared on Medscape.com.

Most survivors of childhood cancer don’t meet surveillance guidelines that recommend screening for adult cancers or other long-term adverse effects of treatment, according to a new study.

Among childhood cancer survivors in Ontario, Canada, who faced an elevated risk due to chemotherapy or radiation treatments, 53% followed screening recommendations for cardiomyopathy, 13% met colorectal cancer screening guidelines, and 6% adhered to breast cancer screening guidelines.

“Although over 80% of children newly diagnosed with cancer will become long-term survivors, as many as four out of five of these survivors will develop a serious or life-threatening late effect of their cancer therapy by age 45,” lead author Jennifer Shuldiner, PhD, MPH, a scientist at Women’s College Hospital Institute for Health Systems Solutions and Virtual Care in Toronto, told this news organization.

For instance, the risk for colorectal cancer in childhood cancer survivors is two to three times higher than it is among the general population, and the risk for breast cancer is similar between those who underwent chest radiation and those with a BRCA mutation. As many as 50% of those who received anthracycline chemotherapy or radiation involving the heart later develop cardiotoxicity.

The North American Children’s Oncology Group has published long-term follow-up guidelines for survivors of childhood cancer, yet many survivors don’t follow them because of lack of awareness or other barriers, said Dr. Shuldiner.

“Prior research has shown that many survivors do not complete these recommended tests,” she said. “With better knowledge of this at-risk population, we can design, test, and implement appropriate interventions and supports to tackle the issues.”

The study was published online on March 11 in CMAJ. 
 

Changes in Adherence 

The researchers conducted a retrospective population-based cohort study analyzing Ontario healthcare administrative data for adult survivors of childhood cancer diagnosed between 1986 and 2014 who faced an elevated risk for therapy-related colorectal cancer, breast cancer, or cardiomyopathy. The research team then assessed long-term adherence to the North American Children’s Oncology Group guidelines and predictors of adherence.

Among 3241 survivors, 3205 (99%) were at elevated risk for cardiomyopathy, 327 (10%) were at elevated risk for colorectal cancer, and 234 (7%) were at elevated risk for breast cancer. In addition, 2806 (87%) were at risk for one late effect, 345 (11%) were at risk for two late effects, and 90 (3%) were at risk for three late effects.

Overall, 53%, 13%, and 6% were adherent to their recommended surveillance for cardiomyopathy, colorectal cancer, and breast cancer, respectively. Over time, adherence increased for colorectal cancer and cardiomyopathy but decreased for breast cancer.

In addition, patients who were older at diagnosis were more likely to follow screening guidelines for colorectal and breast cancers, whereas those who were younger at diagnosis were more likely to follow screening guidelines for cardiomyopathy.

During a median follow-up of 7.8 years, the proportion of time spent adherent was 43% for cardiomyopathy, 14% for colorectal cancer, and 10% for breast cancer.

Survivors who attended a long-term follow-up clinic in the previous year had low adherence rates as well, though they were higher than in the rest of the cohort. In this group, the proportion of time that was spent adherent was 71% for cardiomyopathy, 27% for colorectal cancer, and 15% for breast cancer.

Shuldiner and colleagues are launching a research trial to determine whether a provincial support system can help childhood cancer survivors receive the recommended surveillance. The support system provides information about screening recommendations to survivors as well as reminders and sends key information to their family doctors.

“We now understand that childhood cancer survivors need help to complete the recommended tests,” said Dr. Shuldiner. “If the trial is successful, we hope it will be implemented in Ontario.” 
 

Survivorship Care Plans 

Low screening rates may result from a lack of awareness about screening recommendations and the negative long-term effects of cancer treatments, the study authors wrote. Cancer survivors, caregivers, family physicians, specialists, and survivor support groups can share the responsibility of spreading awareness and adhering to guidelines, they noted. In some cases, a survivorship care plan (SCP) may help.

“SCPs are intended to improve adherence by providing follow-up information and facilitating the transition from cancer treatment to survivorship and from pediatric to adult care,” Adam Yan, MD, a staff oncologist and oncology informatics lead at the Hospital for Sick Children in Toronto, told this news organization.

Dr. Yan, who wasn’t involved with this study, has researched surveillance adherence for secondary cancers and cardiac dysfunction among childhood cancer survivors. He and his colleagues found that screening rates were typically low among survivors who faced high risks for cardiac dysfunction and breast, colorectal, or skin cancers.

However, having a survivorship care plan seemed to help, and survivors treated after 1990 were more likely to have an SCP.

“SCP possession by high-risk survivors was associated with increased breast, skin, and cardiac surveillance,” he said. “It is uncertain whether SCP possession leads to adherence or whether SCP possession is a marker of survivors who are focused on their health and thus likely to adhere to preventive health practices, including surveillance.”

The study was funded by the Canadian Institutes of Health Research and ICES, which receives support from the Ontario Ministry of Health and the Ministry of Long-Term Care. Dr. Shuldiner received a Canadian Institutes of Health Research Health System Impact Postdoctoral Fellowship in support of the work. Dr. Yan disclosed no relevant financial relationships. 
 

A version of this article appeared on Medscape.com.

Andrew Solomon, MD, from the University of Vermont in Burlington, highlights key findings presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2024.

Dr Solomon begins by discussing a study on the potential benefits of antipyretics to manage overheating associated with exercise, a common symptom among MS patients. Results showed that MS patients who took aspirin or acetaminophen had less increase in body temperature after a maximal exercise test than those who took placebo.

He next reports on a study that examined whether a combination of two imaging biomarkers specific for MS, namely the central vein sign and the paramagnetic rim lesion, could improve diagnostic specificity. This study found that the presence of at least one of the signs contributed to improved diagnosis.

Dr Solomon then discusses a post hoc analysis of the ULTIMATE I and II trials which reconsidered how to confirm relapses of MS. The study found that follow-up MRI could distinguish relapse from pseudoexacerbations.

Finally, he reports on a study that examined the feasibility and tolerability of low-field brain MRI in MS. The equipment is smaller, portable, and more cost-effective than standard MRI and has high acceptability from patients. Although the precision of these devices needs further testing, Dr Solomon suggests that portable MRI could make MS diagnosis and monitoring available to broader populations.

--

Andrew J. Solomon, MD, Professor, Neurological Sciences, Larner College of Medicine, University of Vermont; Division Chief, Multiple Sclerosis, University Health Center, Burlington, Vermont

Andrew J. Solomon, MD, has disclosed the following relevant financial relationships: Received research grant from: Bristol Myers Squibb

Andrew Solomon, MD, from the University of Vermont in Burlington, highlights key findings presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2024.

Dr Solomon begins by discussing a study on the potential benefits of antipyretics to manage overheating associated with exercise, a common symptom among MS patients. Results showed that MS patients who took aspirin or acetaminophen had less increase in body temperature after a maximal exercise test than those who took placebo.

He next reports on a study that examined whether a combination of two imaging biomarkers specific for MS, namely the central vein sign and the paramagnetic rim lesion, could improve diagnostic specificity. This study found that the presence of at least one of the signs contributed to improved diagnosis.

Dr Solomon then discusses a post hoc analysis of the ULTIMATE I and II trials which reconsidered how to confirm relapses of MS. The study found that follow-up MRI could distinguish relapse from pseudoexacerbations.

Finally, he reports on a study that examined the feasibility and tolerability of low-field brain MRI in MS. The equipment is smaller, portable, and more cost-effective than standard MRI and has high acceptability from patients. Although the precision of these devices needs further testing, Dr Solomon suggests that portable MRI could make MS diagnosis and monitoring available to broader populations.

--

Andrew J. Solomon, MD, Professor, Neurological Sciences, Larner College of Medicine, University of Vermont; Division Chief, Multiple Sclerosis, University Health Center, Burlington, Vermont

Andrew J. Solomon, MD, has disclosed the following relevant financial relationships: Received research grant from: Bristol Myers Squibb

Andrew Solomon, MD, from the University of Vermont in Burlington, highlights key findings presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2024.

Dr Solomon begins by discussing a study on the potential benefits of antipyretics to manage overheating associated with exercise, a common symptom among MS patients. Results showed that MS patients who took aspirin or acetaminophen had less increase in body temperature after a maximal exercise test than those who took placebo.

He next reports on a study that examined whether a combination of two imaging biomarkers specific for MS, namely the central vein sign and the paramagnetic rim lesion, could improve diagnostic specificity. This study found that the presence of at least one of the signs contributed to improved diagnosis.

Dr Solomon then discusses a post hoc analysis of the ULTIMATE I and II trials which reconsidered how to confirm relapses of MS. The study found that follow-up MRI could distinguish relapse from pseudoexacerbations.

Finally, he reports on a study that examined the feasibility and tolerability of low-field brain MRI in MS. The equipment is smaller, portable, and more cost-effective than standard MRI and has high acceptability from patients. Although the precision of these devices needs further testing, Dr Solomon suggests that portable MRI could make MS diagnosis and monitoring available to broader populations.

--

Andrew J. Solomon, MD, Professor, Neurological Sciences, Larner College of Medicine, University of Vermont; Division Chief, Multiple Sclerosis, University Health Center, Burlington, Vermont

Andrew J. Solomon, MD, has disclosed the following relevant financial relationships: Received research grant from: Bristol Myers Squibb

Minimally invasive cytoreductive surgery for epithelial ovarian cancer appears to be safe and does not compromise survival, compared with open surgery, when patients have completely resected tumors.

This was a finding of a retrospective study presented by Judy Hayek, MD, during an oral abstract session at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer, in San Diego.

Among 2,412 women in the National Cancer Database with tumor-free surgical margins (R0 resections) after interval debulking surgery (IDS), the median overall survival (OS) was 46 months for those who had undergone an open procedure or minimally invasive surgery (MIS) that was converted to an open procedure. In contrast, the median OS was 51 months for patients who underwent laparoscopic or robot-assisted minimally invasive surgery, reported Dr. Hayek, a gynecologic oncology fellow at SUNY Downstate Health Sciences University in Brooklyn, New York.

“R0 resection at the time of interval debulking surgery has similar survival outcomes by minimally invasive surgery versus laparotomy, while R0 resection via laparotomy is associated with higher perioperative mortality. There is no interaction between the extent of surgery and the impact of MIS on survival,” she said during her presentation.

The session included a debate on the pros and cons of minimally invasive vs. open surgery in this population.
 

Growing Use of MIS

Over the last decade, minimally invasive surgery for interval debulking was shown to be safe and feasible. More recently, two studies using National Cancer Database cohorts showed that survival was similar and perioperative outcomes were better with a minimally invasive approach at the time of IDS for patients with early disease, Dr. Hayek said (Obstet Gynecol 2017 Jul;130(1):71-79; and Gynecol Oncol 2023 May:172:130-137).

Potential limitations of MIS include the absence of haptic feedback compared with open surgery, and the possibility that limited visualization of the surgical field could lead to missed residual disease and subsequent poor outcomes for patients who were presumed to have complete gross resections, she said.
 

Outcomes Compared

Dr. Hayek and colleagues conducted their study to evaluate survival outcomes after R0 resections by MIS or laparotomy in IDS for patients with advanced epithelial ovarian cancer.

As noted before, they looked at outcomes for 2,412 women with stage IIIC or IV cancers of all histology types who were diagnosed from 2010 through 2019. A total of 624 patients (25.9%) had minimally invasive procedures, and 1,788 (74.1%) had open surgery or MIS that had been converted to open procedures.

Of the minimally invasive procedures, 48.7% were robot-assisted, and the remainder were laparoscopic.

Over the decade of the study, the frequency of minimally invasive surgery steadily increased, from 11.9% of all procedures in 2010 to 36.5% in 2019.

Also as noted, there was no difference in median overall survival, at 46 months for open/converted procedures vs. 51 months for minimally invasive procedures.

As might be expected, the mean length of stay was shorter with the less invasive surgery: 3.3 days compared with 5.3 days with open surgery (P less than .001). In addition, 30-day and 90-day mortality rates were also lower with MIS, at 0.8% and 1.9%, respectively, compared with 1.6% and 3.5% with laparotomy (P = .006 for 30-day mortality, and .003 for 90-day).

There were also no differences in overall survival between the procedure types when the cases were stratified according to extent of surgery. Within the minimally invasive surgery groups there were no differences in median OS for patients whose surgery was performed laparoscopically or with robotic assistance.

The study was limited by a lack of data on either patient-specific tumor burden, neoadjuvant chemotherapy use, progression-free survival, cause of death, or surgical morbidity, Dr. Hayek acknowledged.
 

MIS Use Debatable: CON

Despite the good outcomes with minimally invasive techniques in this favorable-risk population, critics contend that MIS interval cytoreduction is too risky in the majority of cases.

In the debate portion of the session, Kara Long Roche, MD, an associate attending in the section of ovarian cancer surgery at Memorial Sloan Kettering Cancer Center in New York, argued that the potential for MIS missing residual disease is too great.

“We know from almost every retrospective and prospective study done that the volume of residual disease after debulking, whether primary or interval, is the most important prognostic factor for our patients that we can modify,” she said.

Rather than debating morbidity, mortality, or criteria for resection, “I would argue that the question we need to debate is can MIS interval debulking achieve a completeness of resection, i.e., volume of residual disease?” she said.

Dr. Roche contended that retrospective studies such as that reported by Dr. Hayek cannot adequately answer this question because of selection bias. Patients selected for MIS have better responses to neoadjuvant chemotherapy and more favorable tumor biology; and, therefore, overall survival may not be the optimal endpoint for retrospective studies.

In addition, neoadjuvant chemotherapy does not automatically preclude the need for extensive upper abdominal surgery since almost half of patients who receive neoadjuvant chemotherapy are found to have bulky upper abdominal disease at the time of debulking.

Dr. Roche especially cautioned against what she called the WNL or “We Never Looked” phenomenon, in which patients are found on open surgery and organ mobilization to have disease that was not evident on presurgical imaging.

She acknowledged that for some patients the risks of laparotomy are likely to outweigh the benefit of a radical resection, and stressed that for such patients forgoing surgery or optimizing perioperative care may be more important than the size of the incision.

MIS IDS should be the exception, not the rule. We need prospective data with appropriate endpoints. We need surgical quality control in both arms, and we need to continue to focus on surgical education and training so that our trainees can graduate doing these procedures via any approach,” she concluded.
 

Debate: PRO

Arguing in favor of MIS for ovarian cancer, J. Alejandro Rauh-Hain, MD, MPH, associate professor of gynecologic oncology at the University of Texas MD Anderson Cancer Center in Houston, told attendees “the only bias I have is that I actually love doing open surgery, but I’m going to try to convince you that there is a potential role for minimally invasive surgery in the future for selected patients with ovarian cancer after neoadjuvant chemotherapy.”

He noted that several studies have convincingly shown that neoadjuvant chemotherapy does not adversely affect oncologic outcomes for patients with advanced-stage ovarian cancer, and decreases perioperative morbidity in patients who receive it, including reductions in serious adverse events, risk of stoma, and 30-day postoperative mortality.

In addition, low use of neoadjuvant chemotherapy is associated with increased risks for 90-day postoperative deaths in both low- and high surgical volume centers in the US, according to unpublished National Cancer Database data.

Dr. Rauh-Hain noted that neoadjuvant chemotherapy use has steadily increased from 2010 through 2020, and added that in 2022, 32% of interval cytoreductive surgeries in the United States were performed with a minimally invasive approach.

To get a better handle on the MIS vs. open-surgery question, Dr. Rauh-Hain and colleagues at MD Anderson and 13 other centers in the United States, Canada, and Europe are currently recruiting patients for the Laparoscopic Cytoreduction After Neoadjuvant Chemotherapy (LANCE) trial. In this phase 3 noninferiority study, patients with stage IIIC-IV ovarian, primary peritoneal, or fallopian tube cancer who have complete or partial responses and CA125 normalization after three or four cycles of neoadjuvant chemotherapy will be randomized to laparotomy or MIS, followed by adjuvant platinum- and taxane-based chemotherapy.

The study by Hayek et al. was internally supported. Dr. Hayek and Dr. Roche reported having no conflicts of interest. Dr. Rauh-Hain disclosed financial relationships with Guidepoint Consulting, and the Schlesinger Group.

Minimally invasive cytoreductive surgery for epithelial ovarian cancer appears to be safe and does not compromise survival, compared with open surgery, when patients have completely resected tumors.

This was a finding of a retrospective study presented by Judy Hayek, MD, during an oral abstract session at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer, in San Diego.

Among 2,412 women in the National Cancer Database with tumor-free surgical margins (R0 resections) after interval debulking surgery (IDS), the median overall survival (OS) was 46 months for those who had undergone an open procedure or minimally invasive surgery (MIS) that was converted to an open procedure. In contrast, the median OS was 51 months for patients who underwent laparoscopic or robot-assisted minimally invasive surgery, reported Dr. Hayek, a gynecologic oncology fellow at SUNY Downstate Health Sciences University in Brooklyn, New York.

“R0 resection at the time of interval debulking surgery has similar survival outcomes by minimally invasive surgery versus laparotomy, while R0 resection via laparotomy is associated with higher perioperative mortality. There is no interaction between the extent of surgery and the impact of MIS on survival,” she said during her presentation.

The session included a debate on the pros and cons of minimally invasive vs. open surgery in this population.
 

Growing Use of MIS

Over the last decade, minimally invasive surgery for interval debulking was shown to be safe and feasible. More recently, two studies using National Cancer Database cohorts showed that survival was similar and perioperative outcomes were better with a minimally invasive approach at the time of IDS for patients with early disease, Dr. Hayek said (Obstet Gynecol 2017 Jul;130(1):71-79; and Gynecol Oncol 2023 May:172:130-137).

Potential limitations of MIS include the absence of haptic feedback compared with open surgery, and the possibility that limited visualization of the surgical field could lead to missed residual disease and subsequent poor outcomes for patients who were presumed to have complete gross resections, she said.
 

Outcomes Compared

Dr. Hayek and colleagues conducted their study to evaluate survival outcomes after R0 resections by MIS or laparotomy in IDS for patients with advanced epithelial ovarian cancer.

As noted before, they looked at outcomes for 2,412 women with stage IIIC or IV cancers of all histology types who were diagnosed from 2010 through 2019. A total of 624 patients (25.9%) had minimally invasive procedures, and 1,788 (74.1%) had open surgery or MIS that had been converted to open procedures.

Of the minimally invasive procedures, 48.7% were robot-assisted, and the remainder were laparoscopic.

Over the decade of the study, the frequency of minimally invasive surgery steadily increased, from 11.9% of all procedures in 2010 to 36.5% in 2019.

Also as noted, there was no difference in median overall survival, at 46 months for open/converted procedures vs. 51 months for minimally invasive procedures.

As might be expected, the mean length of stay was shorter with the less invasive surgery: 3.3 days compared with 5.3 days with open surgery (P less than .001). In addition, 30-day and 90-day mortality rates were also lower with MIS, at 0.8% and 1.9%, respectively, compared with 1.6% and 3.5% with laparotomy (P = .006 for 30-day mortality, and .003 for 90-day).

There were also no differences in overall survival between the procedure types when the cases were stratified according to extent of surgery. Within the minimally invasive surgery groups there were no differences in median OS for patients whose surgery was performed laparoscopically or with robotic assistance.

The study was limited by a lack of data on either patient-specific tumor burden, neoadjuvant chemotherapy use, progression-free survival, cause of death, or surgical morbidity, Dr. Hayek acknowledged.
 

MIS Use Debatable: CON

Despite the good outcomes with minimally invasive techniques in this favorable-risk population, critics contend that MIS interval cytoreduction is too risky in the majority of cases.

In the debate portion of the session, Kara Long Roche, MD, an associate attending in the section of ovarian cancer surgery at Memorial Sloan Kettering Cancer Center in New York, argued that the potential for MIS missing residual disease is too great.

“We know from almost every retrospective and prospective study done that the volume of residual disease after debulking, whether primary or interval, is the most important prognostic factor for our patients that we can modify,” she said.

Rather than debating morbidity, mortality, or criteria for resection, “I would argue that the question we need to debate is can MIS interval debulking achieve a completeness of resection, i.e., volume of residual disease?” she said.

Dr. Roche contended that retrospective studies such as that reported by Dr. Hayek cannot adequately answer this question because of selection bias. Patients selected for MIS have better responses to neoadjuvant chemotherapy and more favorable tumor biology; and, therefore, overall survival may not be the optimal endpoint for retrospective studies.

In addition, neoadjuvant chemotherapy does not automatically preclude the need for extensive upper abdominal surgery since almost half of patients who receive neoadjuvant chemotherapy are found to have bulky upper abdominal disease at the time of debulking.

Dr. Roche especially cautioned against what she called the WNL or “We Never Looked” phenomenon, in which patients are found on open surgery and organ mobilization to have disease that was not evident on presurgical imaging.

She acknowledged that for some patients the risks of laparotomy are likely to outweigh the benefit of a radical resection, and stressed that for such patients forgoing surgery or optimizing perioperative care may be more important than the size of the incision.

MIS IDS should be the exception, not the rule. We need prospective data with appropriate endpoints. We need surgical quality control in both arms, and we need to continue to focus on surgical education and training so that our trainees can graduate doing these procedures via any approach,” she concluded.
 

Debate: PRO

Arguing in favor of MIS for ovarian cancer, J. Alejandro Rauh-Hain, MD, MPH, associate professor of gynecologic oncology at the University of Texas MD Anderson Cancer Center in Houston, told attendees “the only bias I have is that I actually love doing open surgery, but I’m going to try to convince you that there is a potential role for minimally invasive surgery in the future for selected patients with ovarian cancer after neoadjuvant chemotherapy.”

He noted that several studies have convincingly shown that neoadjuvant chemotherapy does not adversely affect oncologic outcomes for patients with advanced-stage ovarian cancer, and decreases perioperative morbidity in patients who receive it, including reductions in serious adverse events, risk of stoma, and 30-day postoperative mortality.

In addition, low use of neoadjuvant chemotherapy is associated with increased risks for 90-day postoperative deaths in both low- and high surgical volume centers in the US, according to unpublished National Cancer Database data.

Dr. Rauh-Hain noted that neoadjuvant chemotherapy use has steadily increased from 2010 through 2020, and added that in 2022, 32% of interval cytoreductive surgeries in the United States were performed with a minimally invasive approach.

To get a better handle on the MIS vs. open-surgery question, Dr. Rauh-Hain and colleagues at MD Anderson and 13 other centers in the United States, Canada, and Europe are currently recruiting patients for the Laparoscopic Cytoreduction After Neoadjuvant Chemotherapy (LANCE) trial. In this phase 3 noninferiority study, patients with stage IIIC-IV ovarian, primary peritoneal, or fallopian tube cancer who have complete or partial responses and CA125 normalization after three or four cycles of neoadjuvant chemotherapy will be randomized to laparotomy or MIS, followed by adjuvant platinum- and taxane-based chemotherapy.

The study by Hayek et al. was internally supported. Dr. Hayek and Dr. Roche reported having no conflicts of interest. Dr. Rauh-Hain disclosed financial relationships with Guidepoint Consulting, and the Schlesinger Group.

Minimally invasive cytoreductive surgery for epithelial ovarian cancer appears to be safe and does not compromise survival, compared with open surgery, when patients have completely resected tumors.

This was a finding of a retrospective study presented by Judy Hayek, MD, during an oral abstract session at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer, in San Diego.

Among 2,412 women in the National Cancer Database with tumor-free surgical margins (R0 resections) after interval debulking surgery (IDS), the median overall survival (OS) was 46 months for those who had undergone an open procedure or minimally invasive surgery (MIS) that was converted to an open procedure. In contrast, the median OS was 51 months for patients who underwent laparoscopic or robot-assisted minimally invasive surgery, reported Dr. Hayek, a gynecologic oncology fellow at SUNY Downstate Health Sciences University in Brooklyn, New York.

“R0 resection at the time of interval debulking surgery has similar survival outcomes by minimally invasive surgery versus laparotomy, while R0 resection via laparotomy is associated with higher perioperative mortality. There is no interaction between the extent of surgery and the impact of MIS on survival,” she said during her presentation.

The session included a debate on the pros and cons of minimally invasive vs. open surgery in this population.
 

Growing Use of MIS

Over the last decade, minimally invasive surgery for interval debulking was shown to be safe and feasible. More recently, two studies using National Cancer Database cohorts showed that survival was similar and perioperative outcomes were better with a minimally invasive approach at the time of IDS for patients with early disease, Dr. Hayek said (Obstet Gynecol 2017 Jul;130(1):71-79; and Gynecol Oncol 2023 May:172:130-137).

Potential limitations of MIS include the absence of haptic feedback compared with open surgery, and the possibility that limited visualization of the surgical field could lead to missed residual disease and subsequent poor outcomes for patients who were presumed to have complete gross resections, she said.
 

Outcomes Compared

Dr. Hayek and colleagues conducted their study to evaluate survival outcomes after R0 resections by MIS or laparotomy in IDS for patients with advanced epithelial ovarian cancer.

As noted before, they looked at outcomes for 2,412 women with stage IIIC or IV cancers of all histology types who were diagnosed from 2010 through 2019. A total of 624 patients (25.9%) had minimally invasive procedures, and 1,788 (74.1%) had open surgery or MIS that had been converted to open procedures.

Of the minimally invasive procedures, 48.7% were robot-assisted, and the remainder were laparoscopic.

Over the decade of the study, the frequency of minimally invasive surgery steadily increased, from 11.9% of all procedures in 2010 to 36.5% in 2019.

Also as noted, there was no difference in median overall survival, at 46 months for open/converted procedures vs. 51 months for minimally invasive procedures.

As might be expected, the mean length of stay was shorter with the less invasive surgery: 3.3 days compared with 5.3 days with open surgery (P less than .001). In addition, 30-day and 90-day mortality rates were also lower with MIS, at 0.8% and 1.9%, respectively, compared with 1.6% and 3.5% with laparotomy (P = .006 for 30-day mortality, and .003 for 90-day).

There were also no differences in overall survival between the procedure types when the cases were stratified according to extent of surgery. Within the minimally invasive surgery groups there were no differences in median OS for patients whose surgery was performed laparoscopically or with robotic assistance.

The study was limited by a lack of data on either patient-specific tumor burden, neoadjuvant chemotherapy use, progression-free survival, cause of death, or surgical morbidity, Dr. Hayek acknowledged.
 

MIS Use Debatable: CON

Despite the good outcomes with minimally invasive techniques in this favorable-risk population, critics contend that MIS interval cytoreduction is too risky in the majority of cases.

In the debate portion of the session, Kara Long Roche, MD, an associate attending in the section of ovarian cancer surgery at Memorial Sloan Kettering Cancer Center in New York, argued that the potential for MIS missing residual disease is too great.

“We know from almost every retrospective and prospective study done that the volume of residual disease after debulking, whether primary or interval, is the most important prognostic factor for our patients that we can modify,” she said.

Rather than debating morbidity, mortality, or criteria for resection, “I would argue that the question we need to debate is can MIS interval debulking achieve a completeness of resection, i.e., volume of residual disease?” she said.

Dr. Roche contended that retrospective studies such as that reported by Dr. Hayek cannot adequately answer this question because of selection bias. Patients selected for MIS have better responses to neoadjuvant chemotherapy and more favorable tumor biology; and, therefore, overall survival may not be the optimal endpoint for retrospective studies.

In addition, neoadjuvant chemotherapy does not automatically preclude the need for extensive upper abdominal surgery since almost half of patients who receive neoadjuvant chemotherapy are found to have bulky upper abdominal disease at the time of debulking.

Dr. Roche especially cautioned against what she called the WNL or “We Never Looked” phenomenon, in which patients are found on open surgery and organ mobilization to have disease that was not evident on presurgical imaging.

She acknowledged that for some patients the risks of laparotomy are likely to outweigh the benefit of a radical resection, and stressed that for such patients forgoing surgery or optimizing perioperative care may be more important than the size of the incision.

MIS IDS should be the exception, not the rule. We need prospective data with appropriate endpoints. We need surgical quality control in both arms, and we need to continue to focus on surgical education and training so that our trainees can graduate doing these procedures via any approach,” she concluded.
 

Debate: PRO

Arguing in favor of MIS for ovarian cancer, J. Alejandro Rauh-Hain, MD, MPH, associate professor of gynecologic oncology at the University of Texas MD Anderson Cancer Center in Houston, told attendees “the only bias I have is that I actually love doing open surgery, but I’m going to try to convince you that there is a potential role for minimally invasive surgery in the future for selected patients with ovarian cancer after neoadjuvant chemotherapy.”

He noted that several studies have convincingly shown that neoadjuvant chemotherapy does not adversely affect oncologic outcomes for patients with advanced-stage ovarian cancer, and decreases perioperative morbidity in patients who receive it, including reductions in serious adverse events, risk of stoma, and 30-day postoperative mortality.

In addition, low use of neoadjuvant chemotherapy is associated with increased risks for 90-day postoperative deaths in both low- and high surgical volume centers in the US, according to unpublished National Cancer Database data.

Dr. Rauh-Hain noted that neoadjuvant chemotherapy use has steadily increased from 2010 through 2020, and added that in 2022, 32% of interval cytoreductive surgeries in the United States were performed with a minimally invasive approach.

To get a better handle on the MIS vs. open-surgery question, Dr. Rauh-Hain and colleagues at MD Anderson and 13 other centers in the United States, Canada, and Europe are currently recruiting patients for the Laparoscopic Cytoreduction After Neoadjuvant Chemotherapy (LANCE) trial. In this phase 3 noninferiority study, patients with stage IIIC-IV ovarian, primary peritoneal, or fallopian tube cancer who have complete or partial responses and CA125 normalization after three or four cycles of neoadjuvant chemotherapy will be randomized to laparotomy or MIS, followed by adjuvant platinum- and taxane-based chemotherapy.

The study by Hayek et al. was internally supported. Dr. Hayek and Dr. Roche reported having no conflicts of interest. Dr. Rauh-Hain disclosed financial relationships with Guidepoint Consulting, and the Schlesinger Group.

In the not-too-distant future, immunotherapy might be administered to cancer patients in their homes.

The possibility is being driven by the development of subcutaneous formulations of commonly used immune checkpoint inhibitors for non–small cell lung cancer (NSCLC) and other indications, including pembrolizumab, nivolumab, durvalumab, atezolizumab, and amivantamab.

Instead of waiting anywhere from 30 minutes to several hours for infusions into their veins, patients would spend just a few minutes being injected under the loose skin of their abdomens or thighs. Clinicians would save time and money, and patients would leave the clinic much sooner than normal. The ease of subcutaneous injections also opens up an opportunity for home treatment, a potential boon for people who don’t want to spend their remaining time on hospital visits.

“In the future, I hope we can deliver these medicines at home,” said Hazel O’Sullivan, MBBCh, a medical lung cancer oncologist at Cork University, Ireland, who explained the issues during a session at the 2024 European Lung Cancer Congress.

She was the discussant on two studies at the meeting that highlighted the latest developments in the field, the IMscin002 study of subcutaneous atezolizumab and the PALOMA study of subcutaneous amivantamab, both mostly in NSCLC patients.

Subcutaneous atezolizumab was approved recently in Europe after its maker, Genentech/Roche, made a convincing case that its pharmacokinetics, efficacy, and safety are comparable to the intravenous (IV) version. The U.S. Food and Drug Administration is considering approval; Genentech/Roche anticipates a decision in 2024.

IMscin002 randomized 179 stage 2-4 NSCLC patients evenly to IV or subcutaneous atezolizumab for the first three cycles, then switched them for three more cycles.

Participants were then asked what version they preferred and what they wanted to continue with.

Seventy-one percent said they liked the subcutaneous version better and 80% opted to continue with it. Their main reasons were because they spent less time in the clinic and it was more comfortable.

When asked about the potential for home administration, presenter Federico Cappuzzo, MD, PhD, a medical lung cancer oncologist in Rome, said that it could be “an important option in the future,” particularly in isolated areas far away from hospitals.

The authors of new research are currently evaluating whether home administration is possible. Nurses are administering atezolizumab to patients in their homes with telemedicine monitoring.

The other subcutaneous study presented at the meeting, the PALOMA trial with amivantamab, had only 19 subjects. Administration took no more than 10 minutes, versus potentially hours, especially for the first dose. Subcutaneous amivantamab was given once a month, versus every 2 weeks for the IV formulation, during the maintenance phase of treatment.

The take-home from PALOMA is that the risk of infusion reactions is lower with subcutaneous administration (16% versus 67%) but the risk of mostly mild skin rashes is higher (79% versus 36%).

Investigation is ongoing to confirm safety, pharmacokinetic, and efficacy equivalence with the IV formulation, including in combination with other medications.

When asked about home administration of amivantamab, PALOMA lead investigator Natasha Leighl, MD, a lung, and breast cancer medical oncologist at the University of Toronto, stated that patients probably need to be watched in the clinic for the first 4 months.

The atezolizumab study was funded by maker Genentech/Roche. The amivantamab study was funded by its maker, Janssen. The amivantamab investigator, Dr. Leighl, reported grants, honoraria, and travel payments from Janssen. Dr. Cappuzzo, the investigator on the atezolizumab study, reported speaker and adviser payments from Genentech/Roche. The discussant, Dr. O’Sullivan, wasn’t involved with either company but reported payments from Amgen and AstraZeneca and travel costs covered by Takeda.

In the not-too-distant future, immunotherapy might be administered to cancer patients in their homes.

The possibility is being driven by the development of subcutaneous formulations of commonly used immune checkpoint inhibitors for non–small cell lung cancer (NSCLC) and other indications, including pembrolizumab, nivolumab, durvalumab, atezolizumab, and amivantamab.

Instead of waiting anywhere from 30 minutes to several hours for infusions into their veins, patients would spend just a few minutes being injected under the loose skin of their abdomens or thighs. Clinicians would save time and money, and patients would leave the clinic much sooner than normal. The ease of subcutaneous injections also opens up an opportunity for home treatment, a potential boon for people who don’t want to spend their remaining time on hospital visits.

“In the future, I hope we can deliver these medicines at home,” said Hazel O’Sullivan, MBBCh, a medical lung cancer oncologist at Cork University, Ireland, who explained the issues during a session at the 2024 European Lung Cancer Congress.

She was the discussant on two studies at the meeting that highlighted the latest developments in the field, the IMscin002 study of subcutaneous atezolizumab and the PALOMA study of subcutaneous amivantamab, both mostly in NSCLC patients.

Subcutaneous atezolizumab was approved recently in Europe after its maker, Genentech/Roche, made a convincing case that its pharmacokinetics, efficacy, and safety are comparable to the intravenous (IV) version. The U.S. Food and Drug Administration is considering approval; Genentech/Roche anticipates a decision in 2024.

IMscin002 randomized 179 stage 2-4 NSCLC patients evenly to IV or subcutaneous atezolizumab for the first three cycles, then switched them for three more cycles.

Participants were then asked what version they preferred and what they wanted to continue with.

Seventy-one percent said they liked the subcutaneous version better and 80% opted to continue with it. Their main reasons were because they spent less time in the clinic and it was more comfortable.

When asked about the potential for home administration, presenter Federico Cappuzzo, MD, PhD, a medical lung cancer oncologist in Rome, said that it could be “an important option in the future,” particularly in isolated areas far away from hospitals.

The authors of new research are currently evaluating whether home administration is possible. Nurses are administering atezolizumab to patients in their homes with telemedicine monitoring.

The other subcutaneous study presented at the meeting, the PALOMA trial with amivantamab, had only 19 subjects. Administration took no more than 10 minutes, versus potentially hours, especially for the first dose. Subcutaneous amivantamab was given once a month, versus every 2 weeks for the IV formulation, during the maintenance phase of treatment.

The take-home from PALOMA is that the risk of infusion reactions is lower with subcutaneous administration (16% versus 67%) but the risk of mostly mild skin rashes is higher (79% versus 36%).

Investigation is ongoing to confirm safety, pharmacokinetic, and efficacy equivalence with the IV formulation, including in combination with other medications.

When asked about home administration of amivantamab, PALOMA lead investigator Natasha Leighl, MD, a lung, and breast cancer medical oncologist at the University of Toronto, stated that patients probably need to be watched in the clinic for the first 4 months.

The atezolizumab study was funded by maker Genentech/Roche. The amivantamab study was funded by its maker, Janssen. The amivantamab investigator, Dr. Leighl, reported grants, honoraria, and travel payments from Janssen. Dr. Cappuzzo, the investigator on the atezolizumab study, reported speaker and adviser payments from Genentech/Roche. The discussant, Dr. O’Sullivan, wasn’t involved with either company but reported payments from Amgen and AstraZeneca and travel costs covered by Takeda.

In the not-too-distant future, immunotherapy might be administered to cancer patients in their homes.

The possibility is being driven by the development of subcutaneous formulations of commonly used immune checkpoint inhibitors for non–small cell lung cancer (NSCLC) and other indications, including pembrolizumab, nivolumab, durvalumab, atezolizumab, and amivantamab.

Instead of waiting anywhere from 30 minutes to several hours for infusions into their veins, patients would spend just a few minutes being injected under the loose skin of their abdomens or thighs. Clinicians would save time and money, and patients would leave the clinic much sooner than normal. The ease of subcutaneous injections also opens up an opportunity for home treatment, a potential boon for people who don’t want to spend their remaining time on hospital visits.

“In the future, I hope we can deliver these medicines at home,” said Hazel O’Sullivan, MBBCh, a medical lung cancer oncologist at Cork University, Ireland, who explained the issues during a session at the 2024 European Lung Cancer Congress.

She was the discussant on two studies at the meeting that highlighted the latest developments in the field, the IMscin002 study of subcutaneous atezolizumab and the PALOMA study of subcutaneous amivantamab, both mostly in NSCLC patients.

Subcutaneous atezolizumab was approved recently in Europe after its maker, Genentech/Roche, made a convincing case that its pharmacokinetics, efficacy, and safety are comparable to the intravenous (IV) version. The U.S. Food and Drug Administration is considering approval; Genentech/Roche anticipates a decision in 2024.

IMscin002 randomized 179 stage 2-4 NSCLC patients evenly to IV or subcutaneous atezolizumab for the first three cycles, then switched them for three more cycles.

Participants were then asked what version they preferred and what they wanted to continue with.

Seventy-one percent said they liked the subcutaneous version better and 80% opted to continue with it. Their main reasons were because they spent less time in the clinic and it was more comfortable.

When asked about the potential for home administration, presenter Federico Cappuzzo, MD, PhD, a medical lung cancer oncologist in Rome, said that it could be “an important option in the future,” particularly in isolated areas far away from hospitals.

The authors of new research are currently evaluating whether home administration is possible. Nurses are administering atezolizumab to patients in their homes with telemedicine monitoring.

The other subcutaneous study presented at the meeting, the PALOMA trial with amivantamab, had only 19 subjects. Administration took no more than 10 minutes, versus potentially hours, especially for the first dose. Subcutaneous amivantamab was given once a month, versus every 2 weeks for the IV formulation, during the maintenance phase of treatment.

The take-home from PALOMA is that the risk of infusion reactions is lower with subcutaneous administration (16% versus 67%) but the risk of mostly mild skin rashes is higher (79% versus 36%).

Investigation is ongoing to confirm safety, pharmacokinetic, and efficacy equivalence with the IV formulation, including in combination with other medications.

When asked about home administration of amivantamab, PALOMA lead investigator Natasha Leighl, MD, a lung, and breast cancer medical oncologist at the University of Toronto, stated that patients probably need to be watched in the clinic for the first 4 months.

The atezolizumab study was funded by maker Genentech/Roche. The amivantamab study was funded by its maker, Janssen. The amivantamab investigator, Dr. Leighl, reported grants, honoraria, and travel payments from Janssen. Dr. Cappuzzo, the investigator on the atezolizumab study, reported speaker and adviser payments from Genentech/Roche. The discussant, Dr. O’Sullivan, wasn’t involved with either company but reported payments from Amgen and AstraZeneca and travel costs covered by Takeda.

PIK3CA-related overgrowth spectrum (PROS) encompasses a set of rare disorders caused by pathogenic variants in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene. Under normal circumstances, this pathway is activated by the stimulation of tyrosine kinase receptors that leads to tightly regulated cell growth, proliferation, and migration. However, in PROS, pathogenic variants in the PI3KCA gene lead to an abnormal accumulation of the enzyme at the cell membrane, resulting in persistent activation of the PI3K/AKT/mTOR pathway and dysregulated cell overgrowth.

Excessive cell growth and proliferation leads to the overgrowth of tissues and organs characteristically seen in PROS. Because PIK3CA pathogenic variants are not present in every cell, only certain areas of the body are affected by overgrowth; these can range from isolated digits to whole limbs, the trunk, or one or more tissues or organs.

The diagnosis of PROS is typically confirmed through genetic testing of the PIK3CA gene, which can identify the specific pathogenic variants responsible for the disorder.

Here are five things to know about PROS.

1. PROS comprises a heterogeneous group of rare congenital diseases.

PROS is a term used to describe a group of rare congenital disorders that are characterized by abnormal, segmental, or lateralized growth of various body tissues and regions. These disorders are linked by a common cause: mosaic pathogenic gain-of-function variants in the PIK3CA gene. The genetic pathogenic variants that cause these disorders are not passed down from parent to child but instead result from changes to genes during embryonic development.

PROS encompasses a range of clinical entities, each with its own set of characteristics but sharing phenotypic similarities. These clinical entities include:

• Fibroadipose hyperplasia (also called fibroadipose overgrowth)
• CLOVES syndrome (congenital lipomatosis overgrowth, vascular malformations, epidermal nevi, and scoliosis/skeletal or spinal abnormalities)
• Klippel-Trenaunay syndrome
• Megalencephaly-capillary malformation (MCAP) syndrome
• Hemihyperplasia‐multiple lipomatosis syndrome
• Dysplastic megalencephaly, hemimegalencephaly, and focal cortical dysplasia
• Facial infiltrating lipomatosis (a congenital disorder that causes overgrowth of one side of the face)
• Macrodactyly
• Isolated tissue dysplasia-overgrowth phenotypes: lymphatic malformations, vascular malformations, venous malformations, lipomatosis
• CLAPO syndrome (capillary malformation of the lower lip, lymphatic malformation of the face and neck, asymmetry, and partial/generalized overgrowth)

The global epidemiologic characteristics of PROS are not well documented, but it is estimated that each of these conditions individually has a prevalence rate of fewer than 1 case per million population, and the collective prevalence of PROS-related syndromes is 14 cases per million population. Owing to its low prevalence and the variety of diseases it encompasses, PROS is classified as a rare disease.

2. PROS diseases have specific phenotypic features with common characteristics that result in overlapping phenomena.

The severity of clinical presentation varies in patients with PROS; some have tissue-specific distribution whereas others are more pleiotropic. In general, this condition is marked by segmental overgrowth of multiple tissues, including:

• Organs and other tissues: Excessive and asymmetric overgrowth can affect the skin, bones, muscles, and other structures, leading to disfigurement and functional impairments. The overgrowth typically follows a distal to proximal pattern, mostly unilateral and affecting the lower limbs.
• Brain: Enlargement of specific structures, including ventriculomegaly, a thick corpus callosum, or cerebellar tonsillar ectopia, can cause megalencephaly, which can lead to developmental delay, seizures, cortical dysplasia, and/or hydrocephalus.
• Vasculature: Capillary, venous, arteriovenous, and lymphatic malformations are common and occur in about 43% of patients. These abnormalities can contribute to additional complications, including swelling, pain, and increased risk for bleeding.
• Skin: Thickened epidermal nevi and pigmentary anomalies, such as hyperpigmentation or hypopigmentation, are common. These skin manifestations can be early signs of PROS and may aid in diagnosis.
• Skeletal system: Anomalies can include polydactyly, macrodactyly, macrodontia, and scoliosis or other spinal abnormalities.
• Lipomatosis overgrowth: This can occur with or without regional reduction of adipose tissue on the trunk and limbs.
• Lymphatic system: Isolated malformations may include dilated vascular channels lined by lymphatic endothelial cells, which may lead to fluid-filled cysts that usually grow proportionally with the growth of the affected person and may cause pain or significant morbidity if they are infiltrative.

3. Treatment for a PROS disorder may involve targeted options, surgical interventions, and supportive care.

Historically, treatment for overgrowth syndromes such as PROS primarily involved conservative management, focusing on addressing complications through surgical excision, orthopedic surgery, sclerotherapy, embolization, and compressive therapies. However, these strategies often proved insufficient, and patients frequently experienced relapse and progression of the condition. Indeed, PROS is a complex condition that requires a multifaceted treatment approach.

The discovery of the PIK3/AKT/mTOR activation pathway in these syndromes marked a significant therapeutic breakthrough. Targeted therapies, such as the use of mTOR inhibitors like sirolimus, have shown benefits in treating venous and lymphatic malformations in patients with PROS. More recently, a selective PIK3CA inhibitor, alpelisib, has been approved. This drug has demonstrated remarkable improvements in patients with various PROS phenotypes, including reductions in capillary malformations; cessation of chronic gastrointestinal bleeding; and improvements in scoliosis and cognitive function, particularly in patients with MCAP syndrome.

Supportive care is also a critical component of managing PROS. This includes surgical interventions for significant overgrowth, orthopedic care for scoliosis and leg-length discrepancies, and neurosurgical interventions for neurologic complications such as obstructive hydrocephalus and epilepsy. Vascular and lymphatic malformations may be treated with sclerotherapy, laser therapy, or medications such as sirolimus. Additionally, routine treatment for associated conditions such as cardiac and renal abnormalities, intellectual disabilities, polydactyly, coagulopathy, and hypothyroidism is essential. For those with pain, identifying and treating the underlying cause is crucial. In cases of severe persistent hypoglycemia, ongoing treatment, which may include cornstarch administration, is necessary. Owing to the complexity and varied manifestations of PROS, specialized multidisciplinary care for diagnosis, follow-up, and optimal management is recommended.

4. PROS is a heterogeneous condition, and the clinical presentation can vary widely among affected individuals.

PROS is a complex and heterogeneous condition characterized by a wide range of clinical presentations, reflecting the diversity of affected tissues and the extent of overgrowth. Phenotypes within PROS are diverse and can range from a single lesion (ie, solitary macrodactyly) to systemic diseases (ie, Klippel-Trenaunay syndrome and CLOVES syndrome).

This heterogeneity is primarily due to the timing of the onset of the somatic causative PIK3CA pathogenic variants during embryonic and fetal development, influencing the degree of mosaicism and the combination of tissues involved (eg, neural progenitor cell pathogenic variants can lead to postnatal megalencephaly and hydrocephalus). Moreover, different gain-of-function variants in PIK3CA lead to varying levels of hyperactivation of the PI3K/AKT/mTOR pathway, resulting in diverse severity of abnormal proliferation of mesodermal and ectodermal tissues from embryogenesis onward.

This spectrum of symptoms underscores the complexity and variability of PROS, necessitating a tailored approach to diagnosis and management.

5. Regular surveillance is crucial for the effective management of PROS

Comprehensive and regular monitoring is essential to address the diverse and evolving clinical manifestations of PROS. During each medical visit, it is essential to measure growth parameters, including head circumference and the length of arms, hands, legs, and feet. This assessment helps identify any new neurologic symptoms such as seizures, changes in muscle tone, or signs of Chiari malformation.

Additionally, monitoring the patient’s developmental progress, behavior, and motor skills is vital. Clinical assessments for conditions like scoliosis and abdominal examinations for organomegaly or abdominal masses are also recommended.

Imaging plays a significant role in the ongoing evaluation of PROS. Serial head MRI is advised, with the frequency depending on the initial severity of findings and the degree of brain maturation. For patients with central nervous system overgrowth or dysplasia, brain MRI every 6 months until age 2 years, followed by annual scans until age 8 years, is recommended to monitor for progressive hydrocephalus and Chiari malformation.

Further specialized assessments may be required based on individual clinical indications. These include monitoring of vascular and lymphatic malformations, radiographs of limbs in cases of limb overgrowth, and follow-up ultrasonography or MRI for truncal overgrowth. Spinal MRI is necessary for patients with scoliosis or spinal deformities.

In cases of persistent hypoglycemia, particularly those needing ongoing treatment, blood glucose monitoring and evaluation of the hypothalamic-pituitary-adrenal axis are important.

Postsurgical patients, especially those with the CLOVES phenotype or vascular malformations, should have a hematology consultation to assess thrombosis and coagulopathy risks. The use of renal ultrasonography every 3 months until age 8 years is suggested for tumor screening, such as Wilms tumor, although this practice is somewhat controversial.

These comprehensive and tailored approaches are critical in managing the complex and varied aspects of PROS, ensuring optimal care and monitoring for affected individuals.

Dr. Keppler-Noreuil is professor of pediatrics, division of genetics and metabolism, University of Wisconsin School of Medicine and Public Health; clinical director, department of pediatrics, division of genetics and metabolism; program director, medical genetics and genomics residency, Waisman Center & UW Pediatric Specialty Clinics, University of Wisconsin. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

PIK3CA-related overgrowth spectrum (PROS) encompasses a set of rare disorders caused by pathogenic variants in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene. Under normal circumstances, this pathway is activated by the stimulation of tyrosine kinase receptors that leads to tightly regulated cell growth, proliferation, and migration. However, in PROS, pathogenic variants in the PI3KCA gene lead to an abnormal accumulation of the enzyme at the cell membrane, resulting in persistent activation of the PI3K/AKT/mTOR pathway and dysregulated cell overgrowth.

Excessive cell growth and proliferation leads to the overgrowth of tissues and organs characteristically seen in PROS. Because PIK3CA pathogenic variants are not present in every cell, only certain areas of the body are affected by overgrowth; these can range from isolated digits to whole limbs, the trunk, or one or more tissues or organs.

The diagnosis of PROS is typically confirmed through genetic testing of the PIK3CA gene, which can identify the specific pathogenic variants responsible for the disorder.

Here are five things to know about PROS.

1. PROS comprises a heterogeneous group of rare congenital diseases.

PROS is a term used to describe a group of rare congenital disorders that are characterized by abnormal, segmental, or lateralized growth of various body tissues and regions. These disorders are linked by a common cause: mosaic pathogenic gain-of-function variants in the PIK3CA gene. The genetic pathogenic variants that cause these disorders are not passed down from parent to child but instead result from changes to genes during embryonic development.

PROS encompasses a range of clinical entities, each with its own set of characteristics but sharing phenotypic similarities. These clinical entities include:

• Fibroadipose hyperplasia (also called fibroadipose overgrowth)
• CLOVES syndrome (congenital lipomatosis overgrowth, vascular malformations, epidermal nevi, and scoliosis/skeletal or spinal abnormalities)
• Klippel-Trenaunay syndrome
• Megalencephaly-capillary malformation (MCAP) syndrome
• Hemihyperplasia‐multiple lipomatosis syndrome
• Dysplastic megalencephaly, hemimegalencephaly, and focal cortical dysplasia
• Facial infiltrating lipomatosis (a congenital disorder that causes overgrowth of one side of the face)
• Macrodactyly
• Isolated tissue dysplasia-overgrowth phenotypes: lymphatic malformations, vascular malformations, venous malformations, lipomatosis
• CLAPO syndrome (capillary malformation of the lower lip, lymphatic malformation of the face and neck, asymmetry, and partial/generalized overgrowth)

The global epidemiologic characteristics of PROS are not well documented, but it is estimated that each of these conditions individually has a prevalence rate of fewer than 1 case per million population, and the collective prevalence of PROS-related syndromes is 14 cases per million population. Owing to its low prevalence and the variety of diseases it encompasses, PROS is classified as a rare disease.

2. PROS diseases have specific phenotypic features with common characteristics that result in overlapping phenomena.

The severity of clinical presentation varies in patients with PROS; some have tissue-specific distribution whereas others are more pleiotropic. In general, this condition is marked by segmental overgrowth of multiple tissues, including:

• Organs and other tissues: Excessive and asymmetric overgrowth can affect the skin, bones, muscles, and other structures, leading to disfigurement and functional impairments. The overgrowth typically follows a distal to proximal pattern, mostly unilateral and affecting the lower limbs.
• Brain: Enlargement of specific structures, including ventriculomegaly, a thick corpus callosum, or cerebellar tonsillar ectopia, can cause megalencephaly, which can lead to developmental delay, seizures, cortical dysplasia, and/or hydrocephalus.
• Vasculature: Capillary, venous, arteriovenous, and lymphatic malformations are common and occur in about 43% of patients. These abnormalities can contribute to additional complications, including swelling, pain, and increased risk for bleeding.
• Skin: Thickened epidermal nevi and pigmentary anomalies, such as hyperpigmentation or hypopigmentation, are common. These skin manifestations can be early signs of PROS and may aid in diagnosis.
• Skeletal system: Anomalies can include polydactyly, macrodactyly, macrodontia, and scoliosis or other spinal abnormalities.
• Lipomatosis overgrowth: This can occur with or without regional reduction of adipose tissue on the trunk and limbs.
• Lymphatic system: Isolated malformations may include dilated vascular channels lined by lymphatic endothelial cells, which may lead to fluid-filled cysts that usually grow proportionally with the growth of the affected person and may cause pain or significant morbidity if they are infiltrative.

3. Treatment for a PROS disorder may involve targeted options, surgical interventions, and supportive care.

Historically, treatment for overgrowth syndromes such as PROS primarily involved conservative management, focusing on addressing complications through surgical excision, orthopedic surgery, sclerotherapy, embolization, and compressive therapies. However, these strategies often proved insufficient, and patients frequently experienced relapse and progression of the condition. Indeed, PROS is a complex condition that requires a multifaceted treatment approach.

The discovery of the PIK3/AKT/mTOR activation pathway in these syndromes marked a significant therapeutic breakthrough. Targeted therapies, such as the use of mTOR inhibitors like sirolimus, have shown benefits in treating venous and lymphatic malformations in patients with PROS. More recently, a selective PIK3CA inhibitor, alpelisib, has been approved. This drug has demonstrated remarkable improvements in patients with various PROS phenotypes, including reductions in capillary malformations; cessation of chronic gastrointestinal bleeding; and improvements in scoliosis and cognitive function, particularly in patients with MCAP syndrome.

Supportive care is also a critical component of managing PROS. This includes surgical interventions for significant overgrowth, orthopedic care for scoliosis and leg-length discrepancies, and neurosurgical interventions for neurologic complications such as obstructive hydrocephalus and epilepsy. Vascular and lymphatic malformations may be treated with sclerotherapy, laser therapy, or medications such as sirolimus. Additionally, routine treatment for associated conditions such as cardiac and renal abnormalities, intellectual disabilities, polydactyly, coagulopathy, and hypothyroidism is essential. For those with pain, identifying and treating the underlying cause is crucial. In cases of severe persistent hypoglycemia, ongoing treatment, which may include cornstarch administration, is necessary. Owing to the complexity and varied manifestations of PROS, specialized multidisciplinary care for diagnosis, follow-up, and optimal management is recommended.

4. PROS is a heterogeneous condition, and the clinical presentation can vary widely among affected individuals.

PROS is a complex and heterogeneous condition characterized by a wide range of clinical presentations, reflecting the diversity of affected tissues and the extent of overgrowth. Phenotypes within PROS are diverse and can range from a single lesion (ie, solitary macrodactyly) to systemic diseases (ie, Klippel-Trenaunay syndrome and CLOVES syndrome).

This heterogeneity is primarily due to the timing of the onset of the somatic causative PIK3CA pathogenic variants during embryonic and fetal development, influencing the degree of mosaicism and the combination of tissues involved (eg, neural progenitor cell pathogenic variants can lead to postnatal megalencephaly and hydrocephalus). Moreover, different gain-of-function variants in PIK3CA lead to varying levels of hyperactivation of the PI3K/AKT/mTOR pathway, resulting in diverse severity of abnormal proliferation of mesodermal and ectodermal tissues from embryogenesis onward.

This spectrum of symptoms underscores the complexity and variability of PROS, necessitating a tailored approach to diagnosis and management.

5. Regular surveillance is crucial for the effective management of PROS

Comprehensive and regular monitoring is essential to address the diverse and evolving clinical manifestations of PROS. During each medical visit, it is essential to measure growth parameters, including head circumference and the length of arms, hands, legs, and feet. This assessment helps identify any new neurologic symptoms such as seizures, changes in muscle tone, or signs of Chiari malformation.

Additionally, monitoring the patient’s developmental progress, behavior, and motor skills is vital. Clinical assessments for conditions like scoliosis and abdominal examinations for organomegaly or abdominal masses are also recommended.

Imaging plays a significant role in the ongoing evaluation of PROS. Serial head MRI is advised, with the frequency depending on the initial severity of findings and the degree of brain maturation. For patients with central nervous system overgrowth or dysplasia, brain MRI every 6 months until age 2 years, followed by annual scans until age 8 years, is recommended to monitor for progressive hydrocephalus and Chiari malformation.

Further specialized assessments may be required based on individual clinical indications. These include monitoring of vascular and lymphatic malformations, radiographs of limbs in cases of limb overgrowth, and follow-up ultrasonography or MRI for truncal overgrowth. Spinal MRI is necessary for patients with scoliosis or spinal deformities.

In cases of persistent hypoglycemia, particularly those needing ongoing treatment, blood glucose monitoring and evaluation of the hypothalamic-pituitary-adrenal axis are important.

Postsurgical patients, especially those with the CLOVES phenotype or vascular malformations, should have a hematology consultation to assess thrombosis and coagulopathy risks. The use of renal ultrasonography every 3 months until age 8 years is suggested for tumor screening, such as Wilms tumor, although this practice is somewhat controversial.

These comprehensive and tailored approaches are critical in managing the complex and varied aspects of PROS, ensuring optimal care and monitoring for affected individuals.

Dr. Keppler-Noreuil is professor of pediatrics, division of genetics and metabolism, University of Wisconsin School of Medicine and Public Health; clinical director, department of pediatrics, division of genetics and metabolism; program director, medical genetics and genomics residency, Waisman Center & UW Pediatric Specialty Clinics, University of Wisconsin. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

PIK3CA-related overgrowth spectrum (PROS) encompasses a set of rare disorders caused by pathogenic variants in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene. Under normal circumstances, this pathway is activated by the stimulation of tyrosine kinase receptors that leads to tightly regulated cell growth, proliferation, and migration. However, in PROS, pathogenic variants in the PI3KCA gene lead to an abnormal accumulation of the enzyme at the cell membrane, resulting in persistent activation of the PI3K/AKT/mTOR pathway and dysregulated cell overgrowth.

Excessive cell growth and proliferation leads to the overgrowth of tissues and organs characteristically seen in PROS. Because PIK3CA pathogenic variants are not present in every cell, only certain areas of the body are affected by overgrowth; these can range from isolated digits to whole limbs, the trunk, or one or more tissues or organs.

The diagnosis of PROS is typically confirmed through genetic testing of the PIK3CA gene, which can identify the specific pathogenic variants responsible for the disorder.

Here are five things to know about PROS.

1. PROS comprises a heterogeneous group of rare congenital diseases.

PROS is a term used to describe a group of rare congenital disorders that are characterized by abnormal, segmental, or lateralized growth of various body tissues and regions. These disorders are linked by a common cause: mosaic pathogenic gain-of-function variants in the PIK3CA gene. The genetic pathogenic variants that cause these disorders are not passed down from parent to child but instead result from changes to genes during embryonic development.

PROS encompasses a range of clinical entities, each with its own set of characteristics but sharing phenotypic similarities. These clinical entities include:

• Fibroadipose hyperplasia (also called fibroadipose overgrowth)
• CLOVES syndrome (congenital lipomatosis overgrowth, vascular malformations, epidermal nevi, and scoliosis/skeletal or spinal abnormalities)
• Klippel-Trenaunay syndrome
• Megalencephaly-capillary malformation (MCAP) syndrome
• Hemihyperplasia‐multiple lipomatosis syndrome
• Dysplastic megalencephaly, hemimegalencephaly, and focal cortical dysplasia
• Facial infiltrating lipomatosis (a congenital disorder that causes overgrowth of one side of the face)
• Macrodactyly
• Isolated tissue dysplasia-overgrowth phenotypes: lymphatic malformations, vascular malformations, venous malformations, lipomatosis
• CLAPO syndrome (capillary malformation of the lower lip, lymphatic malformation of the face and neck, asymmetry, and partial/generalized overgrowth)

The global epidemiologic characteristics of PROS are not well documented, but it is estimated that each of these conditions individually has a prevalence rate of fewer than 1 case per million population, and the collective prevalence of PROS-related syndromes is 14 cases per million population. Owing to its low prevalence and the variety of diseases it encompasses, PROS is classified as a rare disease.

2. PROS diseases have specific phenotypic features with common characteristics that result in overlapping phenomena.

The severity of clinical presentation varies in patients with PROS; some have tissue-specific distribution whereas others are more pleiotropic. In general, this condition is marked by segmental overgrowth of multiple tissues, including:

• Organs and other tissues: Excessive and asymmetric overgrowth can affect the skin, bones, muscles, and other structures, leading to disfigurement and functional impairments. The overgrowth typically follows a distal to proximal pattern, mostly unilateral and affecting the lower limbs.
• Brain: Enlargement of specific structures, including ventriculomegaly, a thick corpus callosum, or cerebellar tonsillar ectopia, can cause megalencephaly, which can lead to developmental delay, seizures, cortical dysplasia, and/or hydrocephalus.
• Vasculature: Capillary, venous, arteriovenous, and lymphatic malformations are common and occur in about 43% of patients. These abnormalities can contribute to additional complications, including swelling, pain, and increased risk for bleeding.
• Skin: Thickened epidermal nevi and pigmentary anomalies, such as hyperpigmentation or hypopigmentation, are common. These skin manifestations can be early signs of PROS and may aid in diagnosis.
• Skeletal system: Anomalies can include polydactyly, macrodactyly, macrodontia, and scoliosis or other spinal abnormalities.
• Lipomatosis overgrowth: This can occur with or without regional reduction of adipose tissue on the trunk and limbs.
• Lymphatic system: Isolated malformations may include dilated vascular channels lined by lymphatic endothelial cells, which may lead to fluid-filled cysts that usually grow proportionally with the growth of the affected person and may cause pain or significant morbidity if they are infiltrative.

3. Treatment for a PROS disorder may involve targeted options, surgical interventions, and supportive care.

Historically, treatment for overgrowth syndromes such as PROS primarily involved conservative management, focusing on addressing complications through surgical excision, orthopedic surgery, sclerotherapy, embolization, and compressive therapies. However, these strategies often proved insufficient, and patients frequently experienced relapse and progression of the condition. Indeed, PROS is a complex condition that requires a multifaceted treatment approach.

The discovery of the PIK3/AKT/mTOR activation pathway in these syndromes marked a significant therapeutic breakthrough. Targeted therapies, such as the use of mTOR inhibitors like sirolimus, have shown benefits in treating venous and lymphatic malformations in patients with PROS. More recently, a selective PIK3CA inhibitor, alpelisib, has been approved. This drug has demonstrated remarkable improvements in patients with various PROS phenotypes, including reductions in capillary malformations; cessation of chronic gastrointestinal bleeding; and improvements in scoliosis and cognitive function, particularly in patients with MCAP syndrome.

Supportive care is also a critical component of managing PROS. This includes surgical interventions for significant overgrowth, orthopedic care for scoliosis and leg-length discrepancies, and neurosurgical interventions for neurologic complications such as obstructive hydrocephalus and epilepsy. Vascular and lymphatic malformations may be treated with sclerotherapy, laser therapy, or medications such as sirolimus. Additionally, routine treatment for associated conditions such as cardiac and renal abnormalities, intellectual disabilities, polydactyly, coagulopathy, and hypothyroidism is essential. For those with pain, identifying and treating the underlying cause is crucial. In cases of severe persistent hypoglycemia, ongoing treatment, which may include cornstarch administration, is necessary. Owing to the complexity and varied manifestations of PROS, specialized multidisciplinary care for diagnosis, follow-up, and optimal management is recommended.

4. PROS is a heterogeneous condition, and the clinical presentation can vary widely among affected individuals.

PROS is a complex and heterogeneous condition characterized by a wide range of clinical presentations, reflecting the diversity of affected tissues and the extent of overgrowth. Phenotypes within PROS are diverse and can range from a single lesion (ie, solitary macrodactyly) to systemic diseases (ie, Klippel-Trenaunay syndrome and CLOVES syndrome).

This heterogeneity is primarily due to the timing of the onset of the somatic causative PIK3CA pathogenic variants during embryonic and fetal development, influencing the degree of mosaicism and the combination of tissues involved (eg, neural progenitor cell pathogenic variants can lead to postnatal megalencephaly and hydrocephalus). Moreover, different gain-of-function variants in PIK3CA lead to varying levels of hyperactivation of the PI3K/AKT/mTOR pathway, resulting in diverse severity of abnormal proliferation of mesodermal and ectodermal tissues from embryogenesis onward.

This spectrum of symptoms underscores the complexity and variability of PROS, necessitating a tailored approach to diagnosis and management.

5. Regular surveillance is crucial for the effective management of PROS

Comprehensive and regular monitoring is essential to address the diverse and evolving clinical manifestations of PROS. During each medical visit, it is essential to measure growth parameters, including head circumference and the length of arms, hands, legs, and feet. This assessment helps identify any new neurologic symptoms such as seizures, changes in muscle tone, or signs of Chiari malformation.

Additionally, monitoring the patient’s developmental progress, behavior, and motor skills is vital. Clinical assessments for conditions like scoliosis and abdominal examinations for organomegaly or abdominal masses are also recommended.

Imaging plays a significant role in the ongoing evaluation of PROS. Serial head MRI is advised, with the frequency depending on the initial severity of findings and the degree of brain maturation. For patients with central nervous system overgrowth or dysplasia, brain MRI every 6 months until age 2 years, followed by annual scans until age 8 years, is recommended to monitor for progressive hydrocephalus and Chiari malformation.

Further specialized assessments may be required based on individual clinical indications. These include monitoring of vascular and lymphatic malformations, radiographs of limbs in cases of limb overgrowth, and follow-up ultrasonography or MRI for truncal overgrowth. Spinal MRI is necessary for patients with scoliosis or spinal deformities.

In cases of persistent hypoglycemia, particularly those needing ongoing treatment, blood glucose monitoring and evaluation of the hypothalamic-pituitary-adrenal axis are important.

Postsurgical patients, especially those with the CLOVES phenotype or vascular malformations, should have a hematology consultation to assess thrombosis and coagulopathy risks. The use of renal ultrasonography every 3 months until age 8 years is suggested for tumor screening, such as Wilms tumor, although this practice is somewhat controversial.

These comprehensive and tailored approaches are critical in managing the complex and varied aspects of PROS, ensuring optimal care and monitoring for affected individuals.

Dr. Keppler-Noreuil is professor of pediatrics, division of genetics and metabolism, University of Wisconsin School of Medicine and Public Health; clinical director, department of pediatrics, division of genetics and metabolism; program director, medical genetics and genomics residency, Waisman Center & UW Pediatric Specialty Clinics, University of Wisconsin. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Screening for lung cancer can detect other health issues, as well.

The reason is because the low-dose CT scans used for screening cover the lower neck down to the upper abdomen, revealing far more anatomy than simply the lungs.

In fact, lung cancer screening can provide information on three of the top 10 causes of death worldwide: ischemic heart disease, chronic obstructive pulmonary disease, and, of course, lung cancer.

With lung cancer screening, “we are basically targeting many birds with one low-dose stone,” explained Jelena Spasic MD, PhD, at the European Lung Cancer Congress (ELCC) 2024.

Dr. Spasic, a medical oncologist at the Institute for Oncology and Radiology of Serbia in Belgrade, was the discussant on a study that gave an indication on just how useful screening can be for other diseases.

The study, dubbed 4-IN-THE-LUNG-RUN trial (4ITLR), is an ongoing prospective trial in six European countries that is using lung cancer screening scans to also look for coronary artery calcifications, a marker of atherosclerosis.

Usually, coronary calcifications are considered incidental findings on lung cancer screenings and reported to subjects’ physicians for heart disease risk assessment.

The difference in 4ITLR is that investigators are actively looking for the lesions and quantifying the extent of calcifications.

It’s made possible by the artificial intelligence-based software being used to read the scans. In addition to generating reports on lung nodules, it also automatically calculates an Agatston score, a quantification of the degree of coronary artery calcification for each subject.

At the meeting, which was organized by the European Society for Clinical Oncology, 4ITLR investigator Daiwei Han, MD, PhD, a research associate at the Institute for Diagnostic Accuracy in Groningen, the Netherlands, reported outcomes in the first 2487 of the 24,000 planned subjects.

To be eligible for screening, participants had to be 60-79 years old and either current smokers, past smokers who had quit within 10 years, or people with a 35 or more pack-year history. The median age in the study was 68.1 years.

Overall, 53% of subjects had Agatston scores of 100 or more, indicating the need for treatment to prevent active coronary artery disease, Dr. Han said.

Fifteen percent were at high risk for heart disease with scores of 400-999, indicating extensive coronary artery calcification, and 16.2% were at very high risk, with scores of 1000 or higher. The information is being shared with participants’ physicians.

The risk of heart disease was far higher in men, who made up 56% of the study population. While women had a median Agatston score of 61, the median score for men was 211.1.

The findings illustrate the potential of dedicated cardiovascular screening within lung cancer screening programs, Dr. Han said, noting that 4ITLR will also incorporate COPD risk assessment.

The study also shows the increased impact lung cancer screening programs could have if greater use were made of the CT images to look for other diseases, Dr. Spasic said.

4ITLR is funded by the European Union’s Horizon 2020 Program. Dr. Spasic and Dr. Han didn’t have any relevant disclosures.

Screening for lung cancer can detect other health issues, as well.

The reason is because the low-dose CT scans used for screening cover the lower neck down to the upper abdomen, revealing far more anatomy than simply the lungs.

In fact, lung cancer screening can provide information on three of the top 10 causes of death worldwide: ischemic heart disease, chronic obstructive pulmonary disease, and, of course, lung cancer.

With lung cancer screening, “we are basically targeting many birds with one low-dose stone,” explained Jelena Spasic MD, PhD, at the European Lung Cancer Congress (ELCC) 2024.

Dr. Spasic, a medical oncologist at the Institute for Oncology and Radiology of Serbia in Belgrade, was the discussant on a study that gave an indication on just how useful screening can be for other diseases.

The study, dubbed 4-IN-THE-LUNG-RUN trial (4ITLR), is an ongoing prospective trial in six European countries that is using lung cancer screening scans to also look for coronary artery calcifications, a marker of atherosclerosis.

Usually, coronary calcifications are considered incidental findings on lung cancer screenings and reported to subjects’ physicians for heart disease risk assessment.

The difference in 4ITLR is that investigators are actively looking for the lesions and quantifying the extent of calcifications.

It’s made possible by the artificial intelligence-based software being used to read the scans. In addition to generating reports on lung nodules, it also automatically calculates an Agatston score, a quantification of the degree of coronary artery calcification for each subject.

At the meeting, which was organized by the European Society for Clinical Oncology, 4ITLR investigator Daiwei Han, MD, PhD, a research associate at the Institute for Diagnostic Accuracy in Groningen, the Netherlands, reported outcomes in the first 2487 of the 24,000 planned subjects.

To be eligible for screening, participants had to be 60-79 years old and either current smokers, past smokers who had quit within 10 years, or people with a 35 or more pack-year history. The median age in the study was 68.1 years.

Overall, 53% of subjects had Agatston scores of 100 or more, indicating the need for treatment to prevent active coronary artery disease, Dr. Han said.

Fifteen percent were at high risk for heart disease with scores of 400-999, indicating extensive coronary artery calcification, and 16.2% were at very high risk, with scores of 1000 or higher. The information is being shared with participants’ physicians.

The risk of heart disease was far higher in men, who made up 56% of the study population. While women had a median Agatston score of 61, the median score for men was 211.1.

The findings illustrate the potential of dedicated cardiovascular screening within lung cancer screening programs, Dr. Han said, noting that 4ITLR will also incorporate COPD risk assessment.

The study also shows the increased impact lung cancer screening programs could have if greater use were made of the CT images to look for other diseases, Dr. Spasic said.

4ITLR is funded by the European Union’s Horizon 2020 Program. Dr. Spasic and Dr. Han didn’t have any relevant disclosures.

Screening for lung cancer can detect other health issues, as well.

The reason is because the low-dose CT scans used for screening cover the lower neck down to the upper abdomen, revealing far more anatomy than simply the lungs.

In fact, lung cancer screening can provide information on three of the top 10 causes of death worldwide: ischemic heart disease, chronic obstructive pulmonary disease, and, of course, lung cancer.

With lung cancer screening, “we are basically targeting many birds with one low-dose stone,” explained Jelena Spasic MD, PhD, at the European Lung Cancer Congress (ELCC) 2024.

Dr. Spasic, a medical oncologist at the Institute for Oncology and Radiology of Serbia in Belgrade, was the discussant on a study that gave an indication on just how useful screening can be for other diseases.

The study, dubbed 4-IN-THE-LUNG-RUN trial (4ITLR), is an ongoing prospective trial in six European countries that is using lung cancer screening scans to also look for coronary artery calcifications, a marker of atherosclerosis.

Usually, coronary calcifications are considered incidental findings on lung cancer screenings and reported to subjects’ physicians for heart disease risk assessment.

The difference in 4ITLR is that investigators are actively looking for the lesions and quantifying the extent of calcifications.

It’s made possible by the artificial intelligence-based software being used to read the scans. In addition to generating reports on lung nodules, it also automatically calculates an Agatston score, a quantification of the degree of coronary artery calcification for each subject.

At the meeting, which was organized by the European Society for Clinical Oncology, 4ITLR investigator Daiwei Han, MD, PhD, a research associate at the Institute for Diagnostic Accuracy in Groningen, the Netherlands, reported outcomes in the first 2487 of the 24,000 planned subjects.

To be eligible for screening, participants had to be 60-79 years old and either current smokers, past smokers who had quit within 10 years, or people with a 35 or more pack-year history. The median age in the study was 68.1 years.

Overall, 53% of subjects had Agatston scores of 100 or more, indicating the need for treatment to prevent active coronary artery disease, Dr. Han said.

Fifteen percent were at high risk for heart disease with scores of 400-999, indicating extensive coronary artery calcification, and 16.2% were at very high risk, with scores of 1000 or higher. The information is being shared with participants’ physicians.

The risk of heart disease was far higher in men, who made up 56% of the study population. While women had a median Agatston score of 61, the median score for men was 211.1.

The findings illustrate the potential of dedicated cardiovascular screening within lung cancer screening programs, Dr. Han said, noting that 4ITLR will also incorporate COPD risk assessment.

The study also shows the increased impact lung cancer screening programs could have if greater use were made of the CT images to look for other diseases, Dr. Spasic said.

4ITLR is funded by the European Union’s Horizon 2020 Program. Dr. Spasic and Dr. Han didn’t have any relevant disclosures.

This transcript has been edited for clarity.

Hello. I’m David Kerr, professor of cancer medicine from University of Oxford. I’d like to talk today about how we communicate with patients.

This is current on my mind because on Friday after clinic, I popped around to see a couple of patients who were in our local hospice. They were there for end-of-life care, being wonderfully well looked after. These were patients I have looked after for 3, 4, or 5 years, patients whom I cared for, and patients of whom I was fond. I think that relationship was reciprocated by them.

I found myself in the hospice, standing at the patients’ bedside, towering above them, effectively saying goodbye. The dynamics of that setting just made me think about how odd it seemed. We know that any effective communication between patients and doctors is absolutely critical and fundamental to the delivery of patient-centered care. It’s really hard to measure and challenging to attain in the dynamic, often noisy environment of a busy ward or even in the relative peace and quiet of a hospice.

We know that specific behavior by doctors can make a real difference to how they’re perceived by the patient, including their communicative skills and so on. I’ve been a doctor for more than 40 years, but sophisticated communicator though I think I am, there I was, standing by the bedside. It’s really interesting and odd, actually, when you stop and think about it.

There’s an increasing body of evidence that suggests that if the physician sits at the patient’s bedside, establishes better, more direct eye-to-eye contact and so on, then the quality of communication and patient satisfaction is improved.

I picked up on a recent study published just a few days ago in The BMJ; the title of the study is “Effect of Chair Placement on Physicians’ Behavior and Patients’ Satisfaction: Randomized Deception Trial.”

It was done in a single center and there were 125 separate physician interactions. In half of them, the chair in the patient’s room was in its conventional place back against the wall, round a corner, not particularly accessible. The randomization, or the active intervention, if you like, was to have a chair placed less than 3 feet from the patient’s bed and at the patient’s eye level.

What was really interesting was that of these randomized interventions in the setting in which the chair placement was close to the patient’s bed — it was accessible, less than 3 feet — 38 of the 60 physicians sat down in the chair and engaged with the patient from that level.

In the other setting, in which the chair wasn’t immediately adjacent to the bedside (it was back against the wall, out of the way), only in 5 of 60 did the physician retrieve the chair and move it to the right position. Otherwise, they stood and talked to the patient in that way.

The patient satisfaction scores that were measured using a conventional tool were much better for those seated physicians rather than those who stood and towered above.

This is an interesting study with statistically significant findings. It didn’t mean that the physicians who sat spent more time with the patient. It was the same in both settings, at about 10 or 11 minutes. It didn’t alter the physician’s perception of how long they spent with the patient — they guessed it was about 10 minutes, equally on both sides — or indeed the patient’s interpretation of how long the physician stayed.

It wasn’t a temporal thing but just the quality of communication. The patient satisfaction was much better, just simply by sitting at the patient’s bedside and engaging with them. It’s a tiny thing to do that made for a significant qualitative improvement. I’ve learned that lesson. No more towering above. No more standing at the bottom of the patient’s bedside, as I was taught and as I’ve always done.

I’m going to nudge my behavior. I’m going to use the psychology of that small study to nudge myself, the junior doctors that I train, and perhaps even my consultant colleagues, to do the same. It’s a small but effective step forward in improving patient-centered communication.

I’d be delighted to see what you think. How many of you stand? Being old-school, I would have thought that that’s most of us. How many of you make the effort to drag the chair over to sit at the patient’s bedside and to engage more fully? I’d be really interested in any comments that you’ve got.

For the time being, over and out. Ahoy. Thanks for listening.

Dr. Kerr disclosed the following relevant financial relationships Served as a director, officer, partner, employee, advisor, consultant, or trustee for Celleron Therapeutics and Oxford Cancer Biomarkers (board of directors); Afrox (charity; trustee); and GlaxoSmithKline and Bayer HealthCare Pharmaceuticals (consultant). Serve(d) as a speaker or a member of a speakers bureau for Genomic Health and Merck Serono. Received research grant from Roche. Has a 5% or greater equity interest in Celleron Therapeutics and Oxford Cancer Biomarkers.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Hello. I’m David Kerr, professor of cancer medicine from University of Oxford. I’d like to talk today about how we communicate with patients.

This is current on my mind because on Friday after clinic, I popped around to see a couple of patients who were in our local hospice. They were there for end-of-life care, being wonderfully well looked after. These were patients I have looked after for 3, 4, or 5 years, patients whom I cared for, and patients of whom I was fond. I think that relationship was reciprocated by them.

I found myself in the hospice, standing at the patients’ bedside, towering above them, effectively saying goodbye. The dynamics of that setting just made me think about how odd it seemed. We know that any effective communication between patients and doctors is absolutely critical and fundamental to the delivery of patient-centered care. It’s really hard to measure and challenging to attain in the dynamic, often noisy environment of a busy ward or even in the relative peace and quiet of a hospice.

We know that specific behavior by doctors can make a real difference to how they’re perceived by the patient, including their communicative skills and so on. I’ve been a doctor for more than 40 years, but sophisticated communicator though I think I am, there I was, standing by the bedside. It’s really interesting and odd, actually, when you stop and think about it.

There’s an increasing body of evidence that suggests that if the physician sits at the patient’s bedside, establishes better, more direct eye-to-eye contact and so on, then the quality of communication and patient satisfaction is improved.

I picked up on a recent study published just a few days ago in The BMJ; the title of the study is “Effect of Chair Placement on Physicians’ Behavior and Patients’ Satisfaction: Randomized Deception Trial.”

It was done in a single center and there were 125 separate physician interactions. In half of them, the chair in the patient’s room was in its conventional place back against the wall, round a corner, not particularly accessible. The randomization, or the active intervention, if you like, was to have a chair placed less than 3 feet from the patient’s bed and at the patient’s eye level.

What was really interesting was that of these randomized interventions in the setting in which the chair placement was close to the patient’s bed — it was accessible, less than 3 feet — 38 of the 60 physicians sat down in the chair and engaged with the patient from that level.

In the other setting, in which the chair wasn’t immediately adjacent to the bedside (it was back against the wall, out of the way), only in 5 of 60 did the physician retrieve the chair and move it to the right position. Otherwise, they stood and talked to the patient in that way.

The patient satisfaction scores that were measured using a conventional tool were much better for those seated physicians rather than those who stood and towered above.

This is an interesting study with statistically significant findings. It didn’t mean that the physicians who sat spent more time with the patient. It was the same in both settings, at about 10 or 11 minutes. It didn’t alter the physician’s perception of how long they spent with the patient — they guessed it was about 10 minutes, equally on both sides — or indeed the patient’s interpretation of how long the physician stayed.

It wasn’t a temporal thing but just the quality of communication. The patient satisfaction was much better, just simply by sitting at the patient’s bedside and engaging with them. It’s a tiny thing to do that made for a significant qualitative improvement. I’ve learned that lesson. No more towering above. No more standing at the bottom of the patient’s bedside, as I was taught and as I’ve always done.

I’m going to nudge my behavior. I’m going to use the psychology of that small study to nudge myself, the junior doctors that I train, and perhaps even my consultant colleagues, to do the same. It’s a small but effective step forward in improving patient-centered communication.

I’d be delighted to see what you think. How many of you stand? Being old-school, I would have thought that that’s most of us. How many of you make the effort to drag the chair over to sit at the patient’s bedside and to engage more fully? I’d be really interested in any comments that you’ve got.

For the time being, over and out. Ahoy. Thanks for listening.

Dr. Kerr disclosed the following relevant financial relationships Served as a director, officer, partner, employee, advisor, consultant, or trustee for Celleron Therapeutics and Oxford Cancer Biomarkers (board of directors); Afrox (charity; trustee); and GlaxoSmithKline and Bayer HealthCare Pharmaceuticals (consultant). Serve(d) as a speaker or a member of a speakers bureau for Genomic Health and Merck Serono. Received research grant from Roche. Has a 5% or greater equity interest in Celleron Therapeutics and Oxford Cancer Biomarkers.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Hello. I’m David Kerr, professor of cancer medicine from University of Oxford. I’d like to talk today about how we communicate with patients.

This is current on my mind because on Friday after clinic, I popped around to see a couple of patients who were in our local hospice. They were there for end-of-life care, being wonderfully well looked after. These were patients I have looked after for 3, 4, or 5 years, patients whom I cared for, and patients of whom I was fond. I think that relationship was reciprocated by them.

I found myself in the hospice, standing at the patients’ bedside, towering above them, effectively saying goodbye. The dynamics of that setting just made me think about how odd it seemed. We know that any effective communication between patients and doctors is absolutely critical and fundamental to the delivery of patient-centered care. It’s really hard to measure and challenging to attain in the dynamic, often noisy environment of a busy ward or even in the relative peace and quiet of a hospice.

We know that specific behavior by doctors can make a real difference to how they’re perceived by the patient, including their communicative skills and so on. I’ve been a doctor for more than 40 years, but sophisticated communicator though I think I am, there I was, standing by the bedside. It’s really interesting and odd, actually, when you stop and think about it.

There’s an increasing body of evidence that suggests that if the physician sits at the patient’s bedside, establishes better, more direct eye-to-eye contact and so on, then the quality of communication and patient satisfaction is improved.

I picked up on a recent study published just a few days ago in The BMJ; the title of the study is “Effect of Chair Placement on Physicians’ Behavior and Patients’ Satisfaction: Randomized Deception Trial.”

It was done in a single center and there were 125 separate physician interactions. In half of them, the chair in the patient’s room was in its conventional place back against the wall, round a corner, not particularly accessible. The randomization, or the active intervention, if you like, was to have a chair placed less than 3 feet from the patient’s bed and at the patient’s eye level.

What was really interesting was that of these randomized interventions in the setting in which the chair placement was close to the patient’s bed — it was accessible, less than 3 feet — 38 of the 60 physicians sat down in the chair and engaged with the patient from that level.

In the other setting, in which the chair wasn’t immediately adjacent to the bedside (it was back against the wall, out of the way), only in 5 of 60 did the physician retrieve the chair and move it to the right position. Otherwise, they stood and talked to the patient in that way.

The patient satisfaction scores that were measured using a conventional tool were much better for those seated physicians rather than those who stood and towered above.

This is an interesting study with statistically significant findings. It didn’t mean that the physicians who sat spent more time with the patient. It was the same in both settings, at about 10 or 11 minutes. It didn’t alter the physician’s perception of how long they spent with the patient — they guessed it was about 10 minutes, equally on both sides — or indeed the patient’s interpretation of how long the physician stayed.

It wasn’t a temporal thing but just the quality of communication. The patient satisfaction was much better, just simply by sitting at the patient’s bedside and engaging with them. It’s a tiny thing to do that made for a significant qualitative improvement. I’ve learned that lesson. No more towering above. No more standing at the bottom of the patient’s bedside, as I was taught and as I’ve always done.

I’m going to nudge my behavior. I’m going to use the psychology of that small study to nudge myself, the junior doctors that I train, and perhaps even my consultant colleagues, to do the same. It’s a small but effective step forward in improving patient-centered communication.

I’d be delighted to see what you think. How many of you stand? Being old-school, I would have thought that that’s most of us. How many of you make the effort to drag the chair over to sit at the patient’s bedside and to engage more fully? I’d be really interested in any comments that you’ve got.

For the time being, over and out. Ahoy. Thanks for listening.

Dr. Kerr disclosed the following relevant financial relationships Served as a director, officer, partner, employee, advisor, consultant, or trustee for Celleron Therapeutics and Oxford Cancer Biomarkers (board of directors); Afrox (charity; trustee); and GlaxoSmithKline and Bayer HealthCare Pharmaceuticals (consultant). Serve(d) as a speaker or a member of a speakers bureau for Genomic Health and Merck Serono. Received research grant from Roche. Has a 5% or greater equity interest in Celleron Therapeutics and Oxford Cancer Biomarkers.

A version of this article appeared on Medscape.com.