Patient & Survivor Care

TOPLINE:

Excess body fat in postmenopausal women is linked to a higher risk for breast cancer, with the Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE) showing a stronger association than body mass index (BMI). Accurate body fat measures are crucial for effective cancer prevention.

METHODOLOGY:

• Researchers conducted a case-control study including 1033 breast cancer cases and 1143 postmenopausal population controls from the MCC-Spain study.
• Participants were aged 20-85 years. BMI was calculated as the ratio of weight to height squared and categorized using World Health Organization standards: < 25, 25-29.9, 30-34.9, and ≥ 35.
• CUN-BAE was calculated using a specific equation and categorized according to the estimated percentage of body fat: < 35%, 35%-39.9%, 40%-44.9%, and ≥ 45%.
• Odds ratios (ORs) were estimated with 95% CIs for both measures (BMI and CUN-BAE) for breast cancer cases using unconditional logistic regression.

TAKEAWAY:

• Excess body weight attributable to the risk for breast cancer was 23% when assessed using a BMI value > 30 and 38% when assessed using a CUN-BAE value > 40% body fat.
• Hormone receptor stratification showed that these differences in population-attributable fractions were only observed in hormone receptor–positive cases, with an estimated burden of 19.9% for BMI and 41.9% for CUN-BAE.
• The highest categories of CUN-BAE showed an increase in the risk for postmenopausal breast cancer (OR, 2.13 for body fat ≥ 45% compared with the reference category < 35%).
• No similar trend was observed for BMI, as the gradient declined after a BMI ≥ 35.

IN PRACTICE:

“The results of our study indicate that excess body fat is a significant risk factor for hormone receptor–positive breast cancer in postmenopausal women. Our findings suggest that the population impact could be underestimated when using traditional BMI estimates, and that more accurate measures of body fat, such as CUN-BAE, should be considered,” the authors of the study wrote.

SOURCE:

This study was led by Verónica Dávila-Batista, University of Las Palmas de Gran Canaria in Las Palmas de Gran Canaria, Spain. It was published online in Journal of Epidemiology and Community Health.

LIMITATIONS:

The case-control design of the study may have limited the ability to establish causal relationships. BMI was self-reported at the time of the interview for controls and 1 year before diagnosis for cancer cases, which may have introduced recall bias. The formula for CUN-BAE was calculated from a sedentary convenience sample, which may not have been representative of the general population. The small sample size of cases that did not express hormone receptors was another limitation. The study’s findings may not be generalizable to non-White populations as non-White participants were excluded.

DISCLOSURES:

Dávila-Batista disclosed receiving grants from the Carlos III Health Institute. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Excess body fat in postmenopausal women is linked to a higher risk for breast cancer, with the Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE) showing a stronger association than body mass index (BMI). Accurate body fat measures are crucial for effective cancer prevention.

METHODOLOGY:

• Researchers conducted a case-control study including 1033 breast cancer cases and 1143 postmenopausal population controls from the MCC-Spain study.
• Participants were aged 20-85 years. BMI was calculated as the ratio of weight to height squared and categorized using World Health Organization standards: < 25, 25-29.9, 30-34.9, and ≥ 35.
• CUN-BAE was calculated using a specific equation and categorized according to the estimated percentage of body fat: < 35%, 35%-39.9%, 40%-44.9%, and ≥ 45%.
• Odds ratios (ORs) were estimated with 95% CIs for both measures (BMI and CUN-BAE) for breast cancer cases using unconditional logistic regression.

TAKEAWAY:

• Excess body weight attributable to the risk for breast cancer was 23% when assessed using a BMI value > 30 and 38% when assessed using a CUN-BAE value > 40% body fat.
• Hormone receptor stratification showed that these differences in population-attributable fractions were only observed in hormone receptor–positive cases, with an estimated burden of 19.9% for BMI and 41.9% for CUN-BAE.
• The highest categories of CUN-BAE showed an increase in the risk for postmenopausal breast cancer (OR, 2.13 for body fat ≥ 45% compared with the reference category < 35%).
• No similar trend was observed for BMI, as the gradient declined after a BMI ≥ 35.

IN PRACTICE:

“The results of our study indicate that excess body fat is a significant risk factor for hormone receptor–positive breast cancer in postmenopausal women. Our findings suggest that the population impact could be underestimated when using traditional BMI estimates, and that more accurate measures of body fat, such as CUN-BAE, should be considered,” the authors of the study wrote.

SOURCE:

This study was led by Verónica Dávila-Batista, University of Las Palmas de Gran Canaria in Las Palmas de Gran Canaria, Spain. It was published online in Journal of Epidemiology and Community Health.

LIMITATIONS:

The case-control design of the study may have limited the ability to establish causal relationships. BMI was self-reported at the time of the interview for controls and 1 year before diagnosis for cancer cases, which may have introduced recall bias. The formula for CUN-BAE was calculated from a sedentary convenience sample, which may not have been representative of the general population. The small sample size of cases that did not express hormone receptors was another limitation. The study’s findings may not be generalizable to non-White populations as non-White participants were excluded.

DISCLOSURES:

Dávila-Batista disclosed receiving grants from the Carlos III Health Institute. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Excess body fat in postmenopausal women is linked to a higher risk for breast cancer, with the Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE) showing a stronger association than body mass index (BMI). Accurate body fat measures are crucial for effective cancer prevention.

METHODOLOGY:

• Researchers conducted a case-control study including 1033 breast cancer cases and 1143 postmenopausal population controls from the MCC-Spain study.
• Participants were aged 20-85 years. BMI was calculated as the ratio of weight to height squared and categorized using World Health Organization standards: < 25, 25-29.9, 30-34.9, and ≥ 35.
• CUN-BAE was calculated using a specific equation and categorized according to the estimated percentage of body fat: < 35%, 35%-39.9%, 40%-44.9%, and ≥ 45%.
• Odds ratios (ORs) were estimated with 95% CIs for both measures (BMI and CUN-BAE) for breast cancer cases using unconditional logistic regression.

TAKEAWAY:

• Excess body weight attributable to the risk for breast cancer was 23% when assessed using a BMI value > 30 and 38% when assessed using a CUN-BAE value > 40% body fat.
• Hormone receptor stratification showed that these differences in population-attributable fractions were only observed in hormone receptor–positive cases, with an estimated burden of 19.9% for BMI and 41.9% for CUN-BAE.
• The highest categories of CUN-BAE showed an increase in the risk for postmenopausal breast cancer (OR, 2.13 for body fat ≥ 45% compared with the reference category < 35%).
• No similar trend was observed for BMI, as the gradient declined after a BMI ≥ 35.

IN PRACTICE:

“The results of our study indicate that excess body fat is a significant risk factor for hormone receptor–positive breast cancer in postmenopausal women. Our findings suggest that the population impact could be underestimated when using traditional BMI estimates, and that more accurate measures of body fat, such as CUN-BAE, should be considered,” the authors of the study wrote.

SOURCE:

This study was led by Verónica Dávila-Batista, University of Las Palmas de Gran Canaria in Las Palmas de Gran Canaria, Spain. It was published online in Journal of Epidemiology and Community Health.

LIMITATIONS:

The case-control design of the study may have limited the ability to establish causal relationships. BMI was self-reported at the time of the interview for controls and 1 year before diagnosis for cancer cases, which may have introduced recall bias. The formula for CUN-BAE was calculated from a sedentary convenience sample, which may not have been representative of the general population. The small sample size of cases that did not express hormone receptors was another limitation. The study’s findings may not be generalizable to non-White populations as non-White participants were excluded.

DISCLOSURES:

Dávila-Batista disclosed receiving grants from the Carlos III Health Institute. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Cancer is becoming more common in younger generations. Data show that people under 50 are experiencing higher rates of cancer than any generation before them. As a genetic counselor, I hoped these upward trends in early-onset malignancies would slow with a better understanding of risk factors and prevention strategies. Unfortunately, the opposite is happening. Recent findings from the American Cancer Society reveal that the incidence of at least 17 of 34 cancer types is rising among GenX and Millennials. 

These statistics are alarming. I appreciate how easy it is for patients to get lost in the headlines about cancer, which may shape how they approach their healthcare. Each year, millions of Americans miss critical cancer screenings, with many citing fear of a positive test result as a leading reason. Others believe, despite the statistics, that cancer is not something they need to worry about until they are older. And then, of course, getting screened is not as easy as it should be. 

In my work, I meet with people from both younger and older generations who have either faced cancer themselves or witnessed a loved one experience the disease. One of the most common sentiments I hear from these patients is the desire to catch cancer earlier. My answer is always this: The first and most important step everyone can take is understanding their risk. 

For some, knowing they are at increased risk for cancer means starting screenings earlier — sometimes as early as age 25 — or getting screened with a more sensitive test. 

This proactive approach is the right one. Early detection can dramatically increase survival rates, sometimes by up to eightfold, depending on the type of cancer. It also significantly reduces the burden of total and cancer-specific healthcare costs. While screening may carry some potential risks, clinicians can minimize these risks by adhering to evidence-based guidelines, such as those from the American Cancer Society, and ensuring there is appropriate discussion of treatment options when a diagnosis is made.
 

Normalizing Cancer Risk Assessment and Screening 

A detailed cancer risk assessment and education about signs and symptoms should be part of every preventive care visit, regardless of someone’s age. Further, that cancer risk assessment should lead to clear recommendations and support for taking the next steps. 

This is where care advocacy and patient navigation come in. Care advocacy can improve outcomes at every stage of the cancer journey, from increasing screening rates to improving quality of life for survivors. I’ve seen first-hand how care advocates help patients overcome hurdles like long wait times for appointments they need, making both screening and diagnostic care easier to access. 

Now, with the finalization of a new rule from the Centers for Medicare & Medicaid Services, providers can bill for oncology navigation services that occur under their supervision. This formal recognition of care navigation affirms the value of these services not just clinically but financially as well. It will be through methods like care navigation, targeted outreach, and engaging educational resources — built into and covered by health plans — that patients will feel more in control over their health and have tools to help minimize the effects of cancer on the rest of their lives. 

These services benefit healthcare providers as well. Care navigation supports clinical care teams, from primary care providers to oncologists, by ensuring patients are seen before their cancer progresses to a more advanced stage. And even if patients follow screening recommendations for the rest of their lives and never get a positive result, they’ve still gained something invaluable: peace of mind, knowing they’ve taken an active role in their health. 
 

Fighting Fear With Routine

Treating cancer as a normal part of young people’s healthcare means helping them envision the disease as a condition that can be treated, much like a diagnosis of diabetes or high cholesterol. This mindset shift means quickly following up on a concerning symptom or screening result and reducing the time to start treatment if needed. And with treatment options and success rates for some cancers being better than ever, survivorship support must be built into every treatment plan from the start. Before treatment begins, healthcare providers should make time to talk about sometimes-overlooked key topics, such as reproductive options for people whose fertility may be affected by their cancer treatment, about plans for returning to work during or after treatment, and finding the right mental health support. 

Where we can’t prevent cancer, both primary care providers and oncologists can work together to help patients receive the right diagnosis and treatment as quickly as possible. Knowing insurance coverage has a direct effect on how early cancer is caught, for example, younger people need support in understanding and accessing benefits and resources that may be available through their existing healthcare channels, like some employer-sponsored health plans. Even if getting treated for cancer is inevitable for some, taking immediate action to get screened when it’s appropriate is the best thing we can do to lessen the impact of these rising cancer incidences across the country. At the end of the day, being afraid of cancer doesn’t decrease the chances of getting sick or dying from it. Proactive screening and early detection do. 
 

Brockman, Genetic Counselor, Color Health, Buffalo, New York, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Cancer is becoming more common in younger generations. Data show that people under 50 are experiencing higher rates of cancer than any generation before them. As a genetic counselor, I hoped these upward trends in early-onset malignancies would slow with a better understanding of risk factors and prevention strategies. Unfortunately, the opposite is happening. Recent findings from the American Cancer Society reveal that the incidence of at least 17 of 34 cancer types is rising among GenX and Millennials. 

These statistics are alarming. I appreciate how easy it is for patients to get lost in the headlines about cancer, which may shape how they approach their healthcare. Each year, millions of Americans miss critical cancer screenings, with many citing fear of a positive test result as a leading reason. Others believe, despite the statistics, that cancer is not something they need to worry about until they are older. And then, of course, getting screened is not as easy as it should be. 

In my work, I meet with people from both younger and older generations who have either faced cancer themselves or witnessed a loved one experience the disease. One of the most common sentiments I hear from these patients is the desire to catch cancer earlier. My answer is always this: The first and most important step everyone can take is understanding their risk. 

For some, knowing they are at increased risk for cancer means starting screenings earlier — sometimes as early as age 25 — or getting screened with a more sensitive test. 

This proactive approach is the right one. Early detection can dramatically increase survival rates, sometimes by up to eightfold, depending on the type of cancer. It also significantly reduces the burden of total and cancer-specific healthcare costs. While screening may carry some potential risks, clinicians can minimize these risks by adhering to evidence-based guidelines, such as those from the American Cancer Society, and ensuring there is appropriate discussion of treatment options when a diagnosis is made.
 

Normalizing Cancer Risk Assessment and Screening 

A detailed cancer risk assessment and education about signs and symptoms should be part of every preventive care visit, regardless of someone’s age. Further, that cancer risk assessment should lead to clear recommendations and support for taking the next steps. 

This is where care advocacy and patient navigation come in. Care advocacy can improve outcomes at every stage of the cancer journey, from increasing screening rates to improving quality of life for survivors. I’ve seen first-hand how care advocates help patients overcome hurdles like long wait times for appointments they need, making both screening and diagnostic care easier to access. 

Now, with the finalization of a new rule from the Centers for Medicare & Medicaid Services, providers can bill for oncology navigation services that occur under their supervision. This formal recognition of care navigation affirms the value of these services not just clinically but financially as well. It will be through methods like care navigation, targeted outreach, and engaging educational resources — built into and covered by health plans — that patients will feel more in control over their health and have tools to help minimize the effects of cancer on the rest of their lives. 

These services benefit healthcare providers as well. Care navigation supports clinical care teams, from primary care providers to oncologists, by ensuring patients are seen before their cancer progresses to a more advanced stage. And even if patients follow screening recommendations for the rest of their lives and never get a positive result, they’ve still gained something invaluable: peace of mind, knowing they’ve taken an active role in their health. 
 

Fighting Fear With Routine

Treating cancer as a normal part of young people’s healthcare means helping them envision the disease as a condition that can be treated, much like a diagnosis of diabetes or high cholesterol. This mindset shift means quickly following up on a concerning symptom or screening result and reducing the time to start treatment if needed. And with treatment options and success rates for some cancers being better than ever, survivorship support must be built into every treatment plan from the start. Before treatment begins, healthcare providers should make time to talk about sometimes-overlooked key topics, such as reproductive options for people whose fertility may be affected by their cancer treatment, about plans for returning to work during or after treatment, and finding the right mental health support. 

Where we can’t prevent cancer, both primary care providers and oncologists can work together to help patients receive the right diagnosis and treatment as quickly as possible. Knowing insurance coverage has a direct effect on how early cancer is caught, for example, younger people need support in understanding and accessing benefits and resources that may be available through their existing healthcare channels, like some employer-sponsored health plans. Even if getting treated for cancer is inevitable for some, taking immediate action to get screened when it’s appropriate is the best thing we can do to lessen the impact of these rising cancer incidences across the country. At the end of the day, being afraid of cancer doesn’t decrease the chances of getting sick or dying from it. Proactive screening and early detection do. 
 

Brockman, Genetic Counselor, Color Health, Buffalo, New York, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Cancer is becoming more common in younger generations. Data show that people under 50 are experiencing higher rates of cancer than any generation before them. As a genetic counselor, I hoped these upward trends in early-onset malignancies would slow with a better understanding of risk factors and prevention strategies. Unfortunately, the opposite is happening. Recent findings from the American Cancer Society reveal that the incidence of at least 17 of 34 cancer types is rising among GenX and Millennials. 

These statistics are alarming. I appreciate how easy it is for patients to get lost in the headlines about cancer, which may shape how they approach their healthcare. Each year, millions of Americans miss critical cancer screenings, with many citing fear of a positive test result as a leading reason. Others believe, despite the statistics, that cancer is not something they need to worry about until they are older. And then, of course, getting screened is not as easy as it should be. 

In my work, I meet with people from both younger and older generations who have either faced cancer themselves or witnessed a loved one experience the disease. One of the most common sentiments I hear from these patients is the desire to catch cancer earlier. My answer is always this: The first and most important step everyone can take is understanding their risk. 

For some, knowing they are at increased risk for cancer means starting screenings earlier — sometimes as early as age 25 — or getting screened with a more sensitive test. 

This proactive approach is the right one. Early detection can dramatically increase survival rates, sometimes by up to eightfold, depending on the type of cancer. It also significantly reduces the burden of total and cancer-specific healthcare costs. While screening may carry some potential risks, clinicians can minimize these risks by adhering to evidence-based guidelines, such as those from the American Cancer Society, and ensuring there is appropriate discussion of treatment options when a diagnosis is made.
 

Normalizing Cancer Risk Assessment and Screening 

A detailed cancer risk assessment and education about signs and symptoms should be part of every preventive care visit, regardless of someone’s age. Further, that cancer risk assessment should lead to clear recommendations and support for taking the next steps. 

This is where care advocacy and patient navigation come in. Care advocacy can improve outcomes at every stage of the cancer journey, from increasing screening rates to improving quality of life for survivors. I’ve seen first-hand how care advocates help patients overcome hurdles like long wait times for appointments they need, making both screening and diagnostic care easier to access. 

Now, with the finalization of a new rule from the Centers for Medicare & Medicaid Services, providers can bill for oncology navigation services that occur under their supervision. This formal recognition of care navigation affirms the value of these services not just clinically but financially as well. It will be through methods like care navigation, targeted outreach, and engaging educational resources — built into and covered by health plans — that patients will feel more in control over their health and have tools to help minimize the effects of cancer on the rest of their lives. 

These services benefit healthcare providers as well. Care navigation supports clinical care teams, from primary care providers to oncologists, by ensuring patients are seen before their cancer progresses to a more advanced stage. And even if patients follow screening recommendations for the rest of their lives and never get a positive result, they’ve still gained something invaluable: peace of mind, knowing they’ve taken an active role in their health. 
 

Fighting Fear With Routine

Treating cancer as a normal part of young people’s healthcare means helping them envision the disease as a condition that can be treated, much like a diagnosis of diabetes or high cholesterol. This mindset shift means quickly following up on a concerning symptom or screening result and reducing the time to start treatment if needed. And with treatment options and success rates for some cancers being better than ever, survivorship support must be built into every treatment plan from the start. Before treatment begins, healthcare providers should make time to talk about sometimes-overlooked key topics, such as reproductive options for people whose fertility may be affected by their cancer treatment, about plans for returning to work during or after treatment, and finding the right mental health support. 

Where we can’t prevent cancer, both primary care providers and oncologists can work together to help patients receive the right diagnosis and treatment as quickly as possible. Knowing insurance coverage has a direct effect on how early cancer is caught, for example, younger people need support in understanding and accessing benefits and resources that may be available through their existing healthcare channels, like some employer-sponsored health plans. Even if getting treated for cancer is inevitable for some, taking immediate action to get screened when it’s appropriate is the best thing we can do to lessen the impact of these rising cancer incidences across the country. At the end of the day, being afraid of cancer doesn’t decrease the chances of getting sick or dying from it. Proactive screening and early detection do. 
 

Brockman, Genetic Counselor, Color Health, Buffalo, New York, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

About one third of adult survivors of childhood cancer experience a clinically significant or high fear that their primary cancer may recur or that they will develop a subsequent malignancy, according to a recent analysis. The study finds that several factors are associated with a higher risk of experiencing a clinically significant fear of recurrence, including being unemployed or having elevated anxiety or depression.

METHODOLOGY:

• Adult survivors of childhood cancer face a high risk of developing subsequent malignant neoplasms — about a sixfold greater risk than in the general population — and studies indicate that these cancer survivors also fear their cancer will recur. However, data on the prevalence of and risk factors associated with clinically significant fear of recurrence in this population remain limited.
• This cross-sectional study included 229 adult survivors of childhood cancer (mean age at study completion, 39.6 years), recruited from the Childhood Cancer Survivor Study, who completed online surveys between October 2018 and April 2019.
• Fear of cancer recurrence was assessed using the 9-item Fear of Cancer Recurrence Inventory–Short Form, which defines recurrence as the possibility that cancer might return to the same or a different part of the body.
• Chronic pain, symptoms of depression and anxiety, self-perceived health, and intolerance of uncertainty were also evaluated.
• Among the participants, 21 experienced a recurrence of their primary cancer and 17 were diagnosed with a subsequent malignant neoplasm.
•  

TAKEAWAY:

• Overall, 38 (16.6%) adult survivors of childhood cancer reported clinically significant fear that their cancer would recur, and an additional 36 (15.7%) survivors experienced high levels of fear; the remaining 67.7% of participants reported minimal levels of fear.
• Survivors who were unemployed (prevalence ratio [PR], 2.5) were more likely to experience a clinically significant fear of recurrence, as were survivors who had undergone pelvic radiation (PR, 2.9) or limb-sparing or amputation surgery (PR, 2.4).
• Survivors who had elevated anxiety or depression (PR, 2.6) or both (PR, 3.2) were more likely to experience a clinically significant fear of recurrence, as were survivors who had a chronic neurologic health condition (PR, 3.3) or who perceived their health status to be poor or fair vs good to excellent (PR, 3.0).
• Among 94 participants with chronic pain, 25.5% reported clinically significant fear and 13.8% reported high levels of fear. But chronic pain (PR, 1.2; 95% CI, 0.6-2.4) was not significantly associated with a clinically significant fear of recurrence in a multivariable model.
•  

IN PRACTICE:

“These findings underscore the substantial psychological and functional burden of FCR [fear of cancer recurrence] and suggest healthcare professionals should routinely assess FCR as a part of providing comprehensive care to long-term survivors,” the authors wrote.

SOURCE:

The study, led by Alex Pizzo, MSc, Concordia University, Montréal, Québec, Canada, was published online in JAMA Network Open.

LIMITATIONS:

The cross-sectional design limited causal inference. Self-perceived health was assessed with a single item, limiting its measurement. Internet and smartphone access eligibility could have introduced bias. The study also lacked racial and ethnic diversity.

DISCLOSURES:

The study was supported by the Childhood Cancer Survivor Study Career Development Award and a grant from the National Cancer Institute. Additional funding was provided by the Canada Research Chairs Program. Three authors reported receiving grants from various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

About one third of adult survivors of childhood cancer experience a clinically significant or high fear that their primary cancer may recur or that they will develop a subsequent malignancy, according to a recent analysis. The study finds that several factors are associated with a higher risk of experiencing a clinically significant fear of recurrence, including being unemployed or having elevated anxiety or depression.

METHODOLOGY:

• Adult survivors of childhood cancer face a high risk of developing subsequent malignant neoplasms — about a sixfold greater risk than in the general population — and studies indicate that these cancer survivors also fear their cancer will recur. However, data on the prevalence of and risk factors associated with clinically significant fear of recurrence in this population remain limited.
• This cross-sectional study included 229 adult survivors of childhood cancer (mean age at study completion, 39.6 years), recruited from the Childhood Cancer Survivor Study, who completed online surveys between October 2018 and April 2019.
• Fear of cancer recurrence was assessed using the 9-item Fear of Cancer Recurrence Inventory–Short Form, which defines recurrence as the possibility that cancer might return to the same or a different part of the body.
• Chronic pain, symptoms of depression and anxiety, self-perceived health, and intolerance of uncertainty were also evaluated.
• Among the participants, 21 experienced a recurrence of their primary cancer and 17 were diagnosed with a subsequent malignant neoplasm.
•  

TAKEAWAY:

• Overall, 38 (16.6%) adult survivors of childhood cancer reported clinically significant fear that their cancer would recur, and an additional 36 (15.7%) survivors experienced high levels of fear; the remaining 67.7% of participants reported minimal levels of fear.
• Survivors who were unemployed (prevalence ratio [PR], 2.5) were more likely to experience a clinically significant fear of recurrence, as were survivors who had undergone pelvic radiation (PR, 2.9) or limb-sparing or amputation surgery (PR, 2.4).
• Survivors who had elevated anxiety or depression (PR, 2.6) or both (PR, 3.2) were more likely to experience a clinically significant fear of recurrence, as were survivors who had a chronic neurologic health condition (PR, 3.3) or who perceived their health status to be poor or fair vs good to excellent (PR, 3.0).
• Among 94 participants with chronic pain, 25.5% reported clinically significant fear and 13.8% reported high levels of fear. But chronic pain (PR, 1.2; 95% CI, 0.6-2.4) was not significantly associated with a clinically significant fear of recurrence in a multivariable model.
•  

IN PRACTICE:

“These findings underscore the substantial psychological and functional burden of FCR [fear of cancer recurrence] and suggest healthcare professionals should routinely assess FCR as a part of providing comprehensive care to long-term survivors,” the authors wrote.

SOURCE:

The study, led by Alex Pizzo, MSc, Concordia University, Montréal, Québec, Canada, was published online in JAMA Network Open.

LIMITATIONS:

The cross-sectional design limited causal inference. Self-perceived health was assessed with a single item, limiting its measurement. Internet and smartphone access eligibility could have introduced bias. The study also lacked racial and ethnic diversity.

DISCLOSURES:

The study was supported by the Childhood Cancer Survivor Study Career Development Award and a grant from the National Cancer Institute. Additional funding was provided by the Canada Research Chairs Program. Three authors reported receiving grants from various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

About one third of adult survivors of childhood cancer experience a clinically significant or high fear that their primary cancer may recur or that they will develop a subsequent malignancy, according to a recent analysis. The study finds that several factors are associated with a higher risk of experiencing a clinically significant fear of recurrence, including being unemployed or having elevated anxiety or depression.

METHODOLOGY:

• Adult survivors of childhood cancer face a high risk of developing subsequent malignant neoplasms — about a sixfold greater risk than in the general population — and studies indicate that these cancer survivors also fear their cancer will recur. However, data on the prevalence of and risk factors associated with clinically significant fear of recurrence in this population remain limited.
• This cross-sectional study included 229 adult survivors of childhood cancer (mean age at study completion, 39.6 years), recruited from the Childhood Cancer Survivor Study, who completed online surveys between October 2018 and April 2019.
• Fear of cancer recurrence was assessed using the 9-item Fear of Cancer Recurrence Inventory–Short Form, which defines recurrence as the possibility that cancer might return to the same or a different part of the body.
• Chronic pain, symptoms of depression and anxiety, self-perceived health, and intolerance of uncertainty were also evaluated.
• Among the participants, 21 experienced a recurrence of their primary cancer and 17 were diagnosed with a subsequent malignant neoplasm.
•  

TAKEAWAY:

• Overall, 38 (16.6%) adult survivors of childhood cancer reported clinically significant fear that their cancer would recur, and an additional 36 (15.7%) survivors experienced high levels of fear; the remaining 67.7% of participants reported minimal levels of fear.
• Survivors who were unemployed (prevalence ratio [PR], 2.5) were more likely to experience a clinically significant fear of recurrence, as were survivors who had undergone pelvic radiation (PR, 2.9) or limb-sparing or amputation surgery (PR, 2.4).
• Survivors who had elevated anxiety or depression (PR, 2.6) or both (PR, 3.2) were more likely to experience a clinically significant fear of recurrence, as were survivors who had a chronic neurologic health condition (PR, 3.3) or who perceived their health status to be poor or fair vs good to excellent (PR, 3.0).
• Among 94 participants with chronic pain, 25.5% reported clinically significant fear and 13.8% reported high levels of fear. But chronic pain (PR, 1.2; 95% CI, 0.6-2.4) was not significantly associated with a clinically significant fear of recurrence in a multivariable model.
•  

IN PRACTICE:

“These findings underscore the substantial psychological and functional burden of FCR [fear of cancer recurrence] and suggest healthcare professionals should routinely assess FCR as a part of providing comprehensive care to long-term survivors,” the authors wrote.

SOURCE:

The study, led by Alex Pizzo, MSc, Concordia University, Montréal, Québec, Canada, was published online in JAMA Network Open.

LIMITATIONS:

The cross-sectional design limited causal inference. Self-perceived health was assessed with a single item, limiting its measurement. Internet and smartphone access eligibility could have introduced bias. The study also lacked racial and ethnic diversity.

DISCLOSURES:

The study was supported by the Childhood Cancer Survivor Study Career Development Award and a grant from the National Cancer Institute. Additional funding was provided by the Canada Research Chairs Program. Three authors reported receiving grants from various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Physicians who treat patients are potentially exposed to two opposing psychological processes: A positive feeling related to the experience of helping someone in need and, on the other hand, the adverse experience of seeing someone’s suffering and being frustrated about their inability to help. The ability to share the feelings of others is often referred to as empathy, while the ability to care for and show interest in others is the key aspect of compassion. Empathy makes it possible to share the positive and negative feelings of others in the same way: We can therefore feel happy when we indirectly share others’ joy and sad when we indirectly share others’ suffering.

Empathy in healthcare professionals is associated with patient satisfaction, diagnostic accuracy, adherence to treatment recommendations, clinical outcomes, clinical expertise, and physician retention. However, evidence indicates a tendency for empathy to decline during physicians’ training and specialization.
 

Estimating Empathy

Empathy studies are primarily based on observational data that include physician self-assessment or patient-perceived empathy. External evaluation of empathy by the recipient or observer is not the dominant approach, and a systematic review of the topic showed that, in 331 of the 470 studies examined (70.4%), individuals self-reported their level of empathy. The self-assessment system, particularly for doctors, is more likely to measure the doctor’s attitudes about empathy than empathy itself. The lack of correlation between physician and patient empathy assessments made it clear that patients cannot be disregarded when assessing physician empathy.

Consultation and Relational Empathy (CARE) is the primary assessment tool available to patients to measure physician empathy. It is a reliable and consistent system, particularly in primary care scenarios.

The CARE measure captures even small nuances of patient interactions with the physician and has been confirmed as a valuable tool in assessing the relational components of empathy.
 

Doctor-Patient Relationship

Communication with the physician is generally considered an important element of chronic pain care because it affects patient engagement and decision-making. A collaborative approach involving the patient and clinician in clinical decisions was associated with adherence to pain treatment and improved outcomes among patients with chronic lower back pain. The study conducted in a primary care setting of 1352 participants showed findings regarding physician empathy that did not necessarily involve a therapeutic alliance with the patient based on collaborative communication or expectation of a therapeutic effect of pharmacotherapy. Physician empathy remained the strongest factor associated with patient satisfaction, even after considering various potential confounders, including communication with the physician. In addition, ongoing empathy, especially when reported by patients with a long-term relationship with the physician, supported the hypothesis of a possible lasting effect on patient satisfaction.

Treating Chronic Pain

Empathy is an aspect of the doctor-patient relationship that may be particularly important in patients with chronic pain. A cohort study of 1470 patients with chronic low back pain analyzed whether and how it correlated with chronic pain outcomes. Patients reported their physician’s empathy at the time of enrollment using the CARE measure, which included 10 items on physician’s empathy characteristics during meetings. Physicians whose scores were 30 or higher (ie, rated as good, very good, or excellent in most items) were classified as very empathetic physicians (VEPs), while those whose scores were 29 or lower (ie, rated as poor or passable in most items) were classified as slightly empathetic physicians (SEPs).

Pain intensity was measured with a numerical rating scale (0-10) for the typical pain level within 7 days before each encounter. The long-term stability of CARE scores was assessed in patients who maintained the same physician for more than 24 months. The study showed the following results:

• The CARE score was inversely associated with pain intensity (P < .001).
• Pain intensity was lower in patients in the VEP group than those in the SEP group (6.3 vs 6.7; P < .001).
• The likelihood of having a more empathetic physician generally increased with the decrease in the cut point of the CARE score for greater or less empathy of the physician.
• The extent of the physician’s empathy effects exceeded that reported for nonpharmacological treatments, current opioid use, and lumbar spine surgery.
• The effects of the interaction of empathy with time tended to favor the VEP group with regard to pain but were not statistically significant.

Empathy is an essential aspect of the patient-physician relationship (particularly in delivering care), and these findings demonstrate its relevance in pain therapy. Empathy has high therapeutic value, compared with many pain treatments that are often recommended in clinical practice.

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Physicians who treat patients are potentially exposed to two opposing psychological processes: A positive feeling related to the experience of helping someone in need and, on the other hand, the adverse experience of seeing someone’s suffering and being frustrated about their inability to help. The ability to share the feelings of others is often referred to as empathy, while the ability to care for and show interest in others is the key aspect of compassion. Empathy makes it possible to share the positive and negative feelings of others in the same way: We can therefore feel happy when we indirectly share others’ joy and sad when we indirectly share others’ suffering.

Empathy in healthcare professionals is associated with patient satisfaction, diagnostic accuracy, adherence to treatment recommendations, clinical outcomes, clinical expertise, and physician retention. However, evidence indicates a tendency for empathy to decline during physicians’ training and specialization.
 

Estimating Empathy

Empathy studies are primarily based on observational data that include physician self-assessment or patient-perceived empathy. External evaluation of empathy by the recipient or observer is not the dominant approach, and a systematic review of the topic showed that, in 331 of the 470 studies examined (70.4%), individuals self-reported their level of empathy. The self-assessment system, particularly for doctors, is more likely to measure the doctor’s attitudes about empathy than empathy itself. The lack of correlation between physician and patient empathy assessments made it clear that patients cannot be disregarded when assessing physician empathy.

Consultation and Relational Empathy (CARE) is the primary assessment tool available to patients to measure physician empathy. It is a reliable and consistent system, particularly in primary care scenarios.

The CARE measure captures even small nuances of patient interactions with the physician and has been confirmed as a valuable tool in assessing the relational components of empathy.
 

Doctor-Patient Relationship

Communication with the physician is generally considered an important element of chronic pain care because it affects patient engagement and decision-making. A collaborative approach involving the patient and clinician in clinical decisions was associated with adherence to pain treatment and improved outcomes among patients with chronic lower back pain. The study conducted in a primary care setting of 1352 participants showed findings regarding physician empathy that did not necessarily involve a therapeutic alliance with the patient based on collaborative communication or expectation of a therapeutic effect of pharmacotherapy. Physician empathy remained the strongest factor associated with patient satisfaction, even after considering various potential confounders, including communication with the physician. In addition, ongoing empathy, especially when reported by patients with a long-term relationship with the physician, supported the hypothesis of a possible lasting effect on patient satisfaction.

Treating Chronic Pain

Empathy is an aspect of the doctor-patient relationship that may be particularly important in patients with chronic pain. A cohort study of 1470 patients with chronic low back pain analyzed whether and how it correlated with chronic pain outcomes. Patients reported their physician’s empathy at the time of enrollment using the CARE measure, which included 10 items on physician’s empathy characteristics during meetings. Physicians whose scores were 30 or higher (ie, rated as good, very good, or excellent in most items) were classified as very empathetic physicians (VEPs), while those whose scores were 29 or lower (ie, rated as poor or passable in most items) were classified as slightly empathetic physicians (SEPs).

Pain intensity was measured with a numerical rating scale (0-10) for the typical pain level within 7 days before each encounter. The long-term stability of CARE scores was assessed in patients who maintained the same physician for more than 24 months. The study showed the following results:

• The CARE score was inversely associated with pain intensity (P < .001).
• Pain intensity was lower in patients in the VEP group than those in the SEP group (6.3 vs 6.7; P < .001).
• The likelihood of having a more empathetic physician generally increased with the decrease in the cut point of the CARE score for greater or less empathy of the physician.
• The extent of the physician’s empathy effects exceeded that reported for nonpharmacological treatments, current opioid use, and lumbar spine surgery.
• The effects of the interaction of empathy with time tended to favor the VEP group with regard to pain but were not statistically significant.

Empathy is an essential aspect of the patient-physician relationship (particularly in delivering care), and these findings demonstrate its relevance in pain therapy. Empathy has high therapeutic value, compared with many pain treatments that are often recommended in clinical practice.

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Physicians who treat patients are potentially exposed to two opposing psychological processes: A positive feeling related to the experience of helping someone in need and, on the other hand, the adverse experience of seeing someone’s suffering and being frustrated about their inability to help. The ability to share the feelings of others is often referred to as empathy, while the ability to care for and show interest in others is the key aspect of compassion. Empathy makes it possible to share the positive and negative feelings of others in the same way: We can therefore feel happy when we indirectly share others’ joy and sad when we indirectly share others’ suffering.

Empathy in healthcare professionals is associated with patient satisfaction, diagnostic accuracy, adherence to treatment recommendations, clinical outcomes, clinical expertise, and physician retention. However, evidence indicates a tendency for empathy to decline during physicians’ training and specialization.
 

Estimating Empathy

Empathy studies are primarily based on observational data that include physician self-assessment or patient-perceived empathy. External evaluation of empathy by the recipient or observer is not the dominant approach, and a systematic review of the topic showed that, in 331 of the 470 studies examined (70.4%), individuals self-reported their level of empathy. The self-assessment system, particularly for doctors, is more likely to measure the doctor’s attitudes about empathy than empathy itself. The lack of correlation between physician and patient empathy assessments made it clear that patients cannot be disregarded when assessing physician empathy.

Consultation and Relational Empathy (CARE) is the primary assessment tool available to patients to measure physician empathy. It is a reliable and consistent system, particularly in primary care scenarios.

The CARE measure captures even small nuances of patient interactions with the physician and has been confirmed as a valuable tool in assessing the relational components of empathy.
 

Doctor-Patient Relationship

Communication with the physician is generally considered an important element of chronic pain care because it affects patient engagement and decision-making. A collaborative approach involving the patient and clinician in clinical decisions was associated with adherence to pain treatment and improved outcomes among patients with chronic lower back pain. The study conducted in a primary care setting of 1352 participants showed findings regarding physician empathy that did not necessarily involve a therapeutic alliance with the patient based on collaborative communication or expectation of a therapeutic effect of pharmacotherapy. Physician empathy remained the strongest factor associated with patient satisfaction, even after considering various potential confounders, including communication with the physician. In addition, ongoing empathy, especially when reported by patients with a long-term relationship with the physician, supported the hypothesis of a possible lasting effect on patient satisfaction.

Treating Chronic Pain

Empathy is an aspect of the doctor-patient relationship that may be particularly important in patients with chronic pain. A cohort study of 1470 patients with chronic low back pain analyzed whether and how it correlated with chronic pain outcomes. Patients reported their physician’s empathy at the time of enrollment using the CARE measure, which included 10 items on physician’s empathy characteristics during meetings. Physicians whose scores were 30 or higher (ie, rated as good, very good, or excellent in most items) were classified as very empathetic physicians (VEPs), while those whose scores were 29 or lower (ie, rated as poor or passable in most items) were classified as slightly empathetic physicians (SEPs).

Pain intensity was measured with a numerical rating scale (0-10) for the typical pain level within 7 days before each encounter. The long-term stability of CARE scores was assessed in patients who maintained the same physician for more than 24 months. The study showed the following results:

• The CARE score was inversely associated with pain intensity (P < .001).
• Pain intensity was lower in patients in the VEP group than those in the SEP group (6.3 vs 6.7; P < .001).
• The likelihood of having a more empathetic physician generally increased with the decrease in the cut point of the CARE score for greater or less empathy of the physician.
• The extent of the physician’s empathy effects exceeded that reported for nonpharmacological treatments, current opioid use, and lumbar spine surgery.
• The effects of the interaction of empathy with time tended to favor the VEP group with regard to pain but were not statistically significant.

Empathy is an essential aspect of the patient-physician relationship (particularly in delivering care), and these findings demonstrate its relevance in pain therapy. Empathy has high therapeutic value, compared with many pain treatments that are often recommended in clinical practice.

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Cancer survivors who had overweight or obesity at the time of their initial cancer diagnosis have a higher risk for a second primary cancer, particularly an obesity-related cancer, a new analysis found.

METHODOLOGY:

• Cancer survivors have an increased risk for another primary cancer. Studies suggest that lifestyle factors, such as excess body weight, may contribute to the risk for a second cancer; however, prospective long-term data on this association remain limited.
• Researchers evaluated 26,894 participants (mean age at first cancer diagnosis, 72.2 years; 97.6% White) from the Cancer Prevention Study II Nutrition cohort, who were diagnosed with a first nonmetastatic primary cancer between 1992 and 2015.
• Body mass index (BMI) was calculated from self-reported data at the time of the first primary cancer diagnosis; 10,713 participants had a normal BMI (18.5 to < 25.0), 11,497 had overweight (25.0 to < 30.0), and 4684 had obesity (≥ 30.0). Participants were followed through 2017.
• The study outcomes were the incidences of any second primary cancer and obesity-related second cancers.
• The most common first primary cancers were prostate (35.0%), breast (19.1%), and colorectal (9.5%) cancers; almost 40% of all first primary cancers were related to obesity.

TAKEAWAY:

• Overall, 13.9% participants (3749 of 26,894) were diagnosed with a second cancer over a median of 7.9 years; 33.2% of these cancers were related to obesity.
• Compared with participants with a normal BMI, those who had overweight had a 15% higher risk for any second cancer (adjusted hazard ratio [aHR], 1.15) and a 40% higher risk for an obesity-related second cancer (aHR, 1.40). Additionally, those with obesity had a 34% higher risk for any second cancer and a 78% higher risk for an obesity-related second cancer.
• For every 5-unit increase in BMI, the risk for an obesity-related cancer (aHR, 1.28) was considerably higher than the risk for any second cancer (aHR, 1.13).
• Among all survivors, every 5-unit increase in BMI was associated with a 42% increased risk for colorectal cancer as a second cancer (aHR, 1.42) and a 70% higher risk for kidney cancer as a second cancer (aHR, 1.70).

IN PRACTICE:

“In this cohort study of older survivors of nonmetastatic cancer, those who had overweight or obesity at the time of their first cancer diagnosis were at higher risk of developing a second cancer, especially obesity-related cancers,” the authors wrote. “These findings have important public health implications and may inform evidence-based survivorship guidelines to reduce the risk of second primary cancers among cancer survivors.”

SOURCE:

This study, led by Clara Bodelon, PhD, MS, American Cancer Society, Atlanta, was published online in JAMA Network Open.

LIMITATIONS:

The exclusion of multiple primary cancers in the same site could have underestimated the magnitude of the association of excess body weight with the risk for second primary cancers. BMI was used as a measure of excess body fat in this study, which does not differentiate between fat and lean mass. Unmeasured or residual confounding factors might be present.

DISCLOSURES:

The study was supported by grants from the Centers for Disease Control and Prevention’s National Program of Cancer Registries and cancer registries supported by the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program. No relevant conflicts of interest were disclosed by the authors.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Cancer survivors who had overweight or obesity at the time of their initial cancer diagnosis have a higher risk for a second primary cancer, particularly an obesity-related cancer, a new analysis found.

METHODOLOGY:

• Cancer survivors have an increased risk for another primary cancer. Studies suggest that lifestyle factors, such as excess body weight, may contribute to the risk for a second cancer; however, prospective long-term data on this association remain limited.
• Researchers evaluated 26,894 participants (mean age at first cancer diagnosis, 72.2 years; 97.6% White) from the Cancer Prevention Study II Nutrition cohort, who were diagnosed with a first nonmetastatic primary cancer between 1992 and 2015.
• Body mass index (BMI) was calculated from self-reported data at the time of the first primary cancer diagnosis; 10,713 participants had a normal BMI (18.5 to < 25.0), 11,497 had overweight (25.0 to < 30.0), and 4684 had obesity (≥ 30.0). Participants were followed through 2017.
• The study outcomes were the incidences of any second primary cancer and obesity-related second cancers.
• The most common first primary cancers were prostate (35.0%), breast (19.1%), and colorectal (9.5%) cancers; almost 40% of all first primary cancers were related to obesity.

TAKEAWAY:

• Overall, 13.9% participants (3749 of 26,894) were diagnosed with a second cancer over a median of 7.9 years; 33.2% of these cancers were related to obesity.
• Compared with participants with a normal BMI, those who had overweight had a 15% higher risk for any second cancer (adjusted hazard ratio [aHR], 1.15) and a 40% higher risk for an obesity-related second cancer (aHR, 1.40). Additionally, those with obesity had a 34% higher risk for any second cancer and a 78% higher risk for an obesity-related second cancer.
• For every 5-unit increase in BMI, the risk for an obesity-related cancer (aHR, 1.28) was considerably higher than the risk for any second cancer (aHR, 1.13).
• Among all survivors, every 5-unit increase in BMI was associated with a 42% increased risk for colorectal cancer as a second cancer (aHR, 1.42) and a 70% higher risk for kidney cancer as a second cancer (aHR, 1.70).

IN PRACTICE:

“In this cohort study of older survivors of nonmetastatic cancer, those who had overweight or obesity at the time of their first cancer diagnosis were at higher risk of developing a second cancer, especially obesity-related cancers,” the authors wrote. “These findings have important public health implications and may inform evidence-based survivorship guidelines to reduce the risk of second primary cancers among cancer survivors.”

SOURCE:

This study, led by Clara Bodelon, PhD, MS, American Cancer Society, Atlanta, was published online in JAMA Network Open.

LIMITATIONS:

The exclusion of multiple primary cancers in the same site could have underestimated the magnitude of the association of excess body weight with the risk for second primary cancers. BMI was used as a measure of excess body fat in this study, which does not differentiate between fat and lean mass. Unmeasured or residual confounding factors might be present.

DISCLOSURES:

The study was supported by grants from the Centers for Disease Control and Prevention’s National Program of Cancer Registries and cancer registries supported by the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program. No relevant conflicts of interest were disclosed by the authors.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Cancer survivors who had overweight or obesity at the time of their initial cancer diagnosis have a higher risk for a second primary cancer, particularly an obesity-related cancer, a new analysis found.

METHODOLOGY:

• Cancer survivors have an increased risk for another primary cancer. Studies suggest that lifestyle factors, such as excess body weight, may contribute to the risk for a second cancer; however, prospective long-term data on this association remain limited.
• Researchers evaluated 26,894 participants (mean age at first cancer diagnosis, 72.2 years; 97.6% White) from the Cancer Prevention Study II Nutrition cohort, who were diagnosed with a first nonmetastatic primary cancer between 1992 and 2015.
• Body mass index (BMI) was calculated from self-reported data at the time of the first primary cancer diagnosis; 10,713 participants had a normal BMI (18.5 to < 25.0), 11,497 had overweight (25.0 to < 30.0), and 4684 had obesity (≥ 30.0). Participants were followed through 2017.
• The study outcomes were the incidences of any second primary cancer and obesity-related second cancers.
• The most common first primary cancers were prostate (35.0%), breast (19.1%), and colorectal (9.5%) cancers; almost 40% of all first primary cancers were related to obesity.

TAKEAWAY:

• Overall, 13.9% participants (3749 of 26,894) were diagnosed with a second cancer over a median of 7.9 years; 33.2% of these cancers were related to obesity.
• Compared with participants with a normal BMI, those who had overweight had a 15% higher risk for any second cancer (adjusted hazard ratio [aHR], 1.15) and a 40% higher risk for an obesity-related second cancer (aHR, 1.40). Additionally, those with obesity had a 34% higher risk for any second cancer and a 78% higher risk for an obesity-related second cancer.
• For every 5-unit increase in BMI, the risk for an obesity-related cancer (aHR, 1.28) was considerably higher than the risk for any second cancer (aHR, 1.13).
• Among all survivors, every 5-unit increase in BMI was associated with a 42% increased risk for colorectal cancer as a second cancer (aHR, 1.42) and a 70% higher risk for kidney cancer as a second cancer (aHR, 1.70).

IN PRACTICE:

“In this cohort study of older survivors of nonmetastatic cancer, those who had overweight or obesity at the time of their first cancer diagnosis were at higher risk of developing a second cancer, especially obesity-related cancers,” the authors wrote. “These findings have important public health implications and may inform evidence-based survivorship guidelines to reduce the risk of second primary cancers among cancer survivors.”

SOURCE:

This study, led by Clara Bodelon, PhD, MS, American Cancer Society, Atlanta, was published online in JAMA Network Open.

LIMITATIONS:

The exclusion of multiple primary cancers in the same site could have underestimated the magnitude of the association of excess body weight with the risk for second primary cancers. BMI was used as a measure of excess body fat in this study, which does not differentiate between fat and lean mass. Unmeasured or residual confounding factors might be present.

DISCLOSURES:

The study was supported by grants from the Centers for Disease Control and Prevention’s National Program of Cancer Registries and cancer registries supported by the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program. No relevant conflicts of interest were disclosed by the authors.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Many patients ask us to request a prostate-specific antigen (PSA) test. According to the Brazilian Ministry of Health, prostate cancer is the second most common type of cancer in the male population in all regions of our country. It is the second-leading cause of cancer death in the male population, reaffirming its epidemiologic importance in Brazil. On the other hand, a Ministry of Health technical paper recommends against population-based screening for prostate cancer. So, what should we do?

First, it is important to distinguish early diagnosis from screening. Early diagnosis is the identification of cancer in early stages in people with signs and symptoms. Screening is characterized by the systematic application of exams — digital rectal exam and PSA test — in asymptomatic people, with the aim of identifying cancer in an early stage.

Studies show that screening significantly increases the diagnosis of prostate cancer, without a significant reduction in specific mortality and with significant health damage to men. A recent European epidemiologic study reinforced this thesis and helps guide us.

The study included men aged 35-84 years from 26 European countries. Data on cancer incidence and mortality were collected between 1980 and 2017. The data suggested overdiagnosis of prostate cancer, which varied over time and among populations. The findings supported previous recommendations that any implementation of prostate cancer screening should be carefully designed, with an emphasis on minimizing the harms of overdiagnosis.

The clinical evolution of prostate cancer is still not well understood. Increasing age is associated with increased mortality. Many men with less aggressive disease tend to die with cancer rather than die of cancer. However, it is not always possible at the time of diagnosis to determine which tumors will be aggressive and which will grow slowly.

On the other hand, with screening, many of these indolent cancers are unnecessarily detected, generating excessive exams and treatments with negative repercussions (eg, pain, bleeding, infections, stress, and urinary and sexual dysfunction).

So, how should we as clinicians proceed regarding screening?

We should request the PSA test and emphasize the importance of digital rectal exam by a urologist for those at high risk for prostatic neoplasia (ie, those with family history) or those with urinary symptoms that may be associated with prostate cancer.

In general, we should draw attention to the possible risks and benefits of testing and adopt a shared decision-making approach with asymptomatic men or those at low risk who wish to have the screening exam. But achieving a shared decision is not a simple task.

I always have a thorough conversation with patients, but I confess that I request the exam in most cases.

Dr. Wajngarten is a professor of cardiology, Faculty of Medicine, at the University of São Paulo in Brazil. Dr. Wajngarten reported no conflicts of interest.

This story was translated from the Medscape Portuguese edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Many patients ask us to request a prostate-specific antigen (PSA) test. According to the Brazilian Ministry of Health, prostate cancer is the second most common type of cancer in the male population in all regions of our country. It is the second-leading cause of cancer death in the male population, reaffirming its epidemiologic importance in Brazil. On the other hand, a Ministry of Health technical paper recommends against population-based screening for prostate cancer. So, what should we do?

First, it is important to distinguish early diagnosis from screening. Early diagnosis is the identification of cancer in early stages in people with signs and symptoms. Screening is characterized by the systematic application of exams — digital rectal exam and PSA test — in asymptomatic people, with the aim of identifying cancer in an early stage.

Studies show that screening significantly increases the diagnosis of prostate cancer, without a significant reduction in specific mortality and with significant health damage to men. A recent European epidemiologic study reinforced this thesis and helps guide us.

The study included men aged 35-84 years from 26 European countries. Data on cancer incidence and mortality were collected between 1980 and 2017. The data suggested overdiagnosis of prostate cancer, which varied over time and among populations. The findings supported previous recommendations that any implementation of prostate cancer screening should be carefully designed, with an emphasis on minimizing the harms of overdiagnosis.

The clinical evolution of prostate cancer is still not well understood. Increasing age is associated with increased mortality. Many men with less aggressive disease tend to die with cancer rather than die of cancer. However, it is not always possible at the time of diagnosis to determine which tumors will be aggressive and which will grow slowly.

On the other hand, with screening, many of these indolent cancers are unnecessarily detected, generating excessive exams and treatments with negative repercussions (eg, pain, bleeding, infections, stress, and urinary and sexual dysfunction).

So, how should we as clinicians proceed regarding screening?

We should request the PSA test and emphasize the importance of digital rectal exam by a urologist for those at high risk for prostatic neoplasia (ie, those with family history) or those with urinary symptoms that may be associated with prostate cancer.

In general, we should draw attention to the possible risks and benefits of testing and adopt a shared decision-making approach with asymptomatic men or those at low risk who wish to have the screening exam. But achieving a shared decision is not a simple task.

I always have a thorough conversation with patients, but I confess that I request the exam in most cases.

Dr. Wajngarten is a professor of cardiology, Faculty of Medicine, at the University of São Paulo in Brazil. Dr. Wajngarten reported no conflicts of interest.

This story was translated from the Medscape Portuguese edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Many patients ask us to request a prostate-specific antigen (PSA) test. According to the Brazilian Ministry of Health, prostate cancer is the second most common type of cancer in the male population in all regions of our country. It is the second-leading cause of cancer death in the male population, reaffirming its epidemiologic importance in Brazil. On the other hand, a Ministry of Health technical paper recommends against population-based screening for prostate cancer. So, what should we do?

First, it is important to distinguish early diagnosis from screening. Early diagnosis is the identification of cancer in early stages in people with signs and symptoms. Screening is characterized by the systematic application of exams — digital rectal exam and PSA test — in asymptomatic people, with the aim of identifying cancer in an early stage.

Studies show that screening significantly increases the diagnosis of prostate cancer, without a significant reduction in specific mortality and with significant health damage to men. A recent European epidemiologic study reinforced this thesis and helps guide us.

The study included men aged 35-84 years from 26 European countries. Data on cancer incidence and mortality were collected between 1980 and 2017. The data suggested overdiagnosis of prostate cancer, which varied over time and among populations. The findings supported previous recommendations that any implementation of prostate cancer screening should be carefully designed, with an emphasis on minimizing the harms of overdiagnosis.

The clinical evolution of prostate cancer is still not well understood. Increasing age is associated with increased mortality. Many men with less aggressive disease tend to die with cancer rather than die of cancer. However, it is not always possible at the time of diagnosis to determine which tumors will be aggressive and which will grow slowly.

On the other hand, with screening, many of these indolent cancers are unnecessarily detected, generating excessive exams and treatments with negative repercussions (eg, pain, bleeding, infections, stress, and urinary and sexual dysfunction).

So, how should we as clinicians proceed regarding screening?

We should request the PSA test and emphasize the importance of digital rectal exam by a urologist for those at high risk for prostatic neoplasia (ie, those with family history) or those with urinary symptoms that may be associated with prostate cancer.

In general, we should draw attention to the possible risks and benefits of testing and adopt a shared decision-making approach with asymptomatic men or those at low risk who wish to have the screening exam. But achieving a shared decision is not a simple task.

I always have a thorough conversation with patients, but I confess that I request the exam in most cases.

Dr. Wajngarten is a professor of cardiology, Faculty of Medicine, at the University of São Paulo in Brazil. Dr. Wajngarten reported no conflicts of interest.

This story was translated from the Medscape Portuguese edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Testing for mismatch repair (MMR) and microsatellite instability (MSI) among patients with colorectal cancer (CRC) increased from 22.7% in 2012 to 71.5% in 2021, but variations in access remain, with testing rates differing by cancer stage, individual hospital, patient sex, race, and insurance status.

METHODOLOGY:

• In 2017, the National Comprehensive Cancer Network (NCCN) recommended universal testing for MMR and MSI among patients with CRC, but studies suggest that testing may still be underused.
• To assess trends and factors associated with MMR/MSI testing in the United States, researchers evaluated 834,797 patients diagnosed with stage I-IV CRC between 2012 and 2021 across 1366 Commission on Cancer–accredited hospitals in the National Cancer Database.
• The variability in MMR/MSI testing was assessed in relation to both patient and hospital-level factors.
• Overall, 70.7% patients had colon cancer, 7.3% had rectosigmoid cancer, and 22.0% had rectal cancer. The median patient age was 66 years; just over half (53%) were men, 81.8% were White, and 11.9% were Black.

TAKEAWAY:

• Overall, 43.9% patients underwent MMR/MSI testing, but testing rates increased more than threefold between 2012 and 2021 — from 22.7% to 71.5%. Still, testing rates varied depending on a range of factors.
• About 22% variability in MMR/MSI testing was attributed to hospital-level variations, with the best vs worst performing hospitals reporting testing rates of 90% vs 2%. This hospital-level variation may be caused by testing protocol differences at individual institutions, the authors said.
• The likelihood of undergoing MMR/MSI testing was lower in patients with stage IV vs stage I disease (adjusted odds ratio [aOR], 0.78) but higher in those with stage II (aOR, 1.53) and III (aOR, 1.40) disease.
• The likelihood of undergoing MMR/MSI testing was slightly lower for men than for women (aOR, 0.98) and for Black patients than for White patients (aOR, 0.97). Having a lower household income, public or no insurance (vs private insurance), or living a longer distance (more than 5 miles) from the treatment facility was also associated with lower odds of testing.

IN PRACTICE:

“This cohort study indicated that MMR/MSI testing increased markedly, suggesting increased NCCN guideline adherence,” the authors said. However, variations still exist by cancer stage, hospital, and patient factors. Implementing “widespread institution-level reflexive testing for every initial diagnostic biopsy” can improve testing rates and reduce disparities, the authors suggested.

SOURCE:

This study, led by Totadri Dhimal, MD, University of Rochester Medical Center in New York, was published online in JAMA Oncology.

LIMITATIONS:

The study lacked clinical granularity, and potential coding inaccuracies and incomplete data could have affected the interpretation and generalizability of the findings.

DISCLOSURES:

No funding information was provided for the study. One author reported receiving author royalties from UpToDate outside the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Testing for mismatch repair (MMR) and microsatellite instability (MSI) among patients with colorectal cancer (CRC) increased from 22.7% in 2012 to 71.5% in 2021, but variations in access remain, with testing rates differing by cancer stage, individual hospital, patient sex, race, and insurance status.

METHODOLOGY:

• In 2017, the National Comprehensive Cancer Network (NCCN) recommended universal testing for MMR and MSI among patients with CRC, but studies suggest that testing may still be underused.
• To assess trends and factors associated with MMR/MSI testing in the United States, researchers evaluated 834,797 patients diagnosed with stage I-IV CRC between 2012 and 2021 across 1366 Commission on Cancer–accredited hospitals in the National Cancer Database.
• The variability in MMR/MSI testing was assessed in relation to both patient and hospital-level factors.
• Overall, 70.7% patients had colon cancer, 7.3% had rectosigmoid cancer, and 22.0% had rectal cancer. The median patient age was 66 years; just over half (53%) were men, 81.8% were White, and 11.9% were Black.

TAKEAWAY:

• Overall, 43.9% patients underwent MMR/MSI testing, but testing rates increased more than threefold between 2012 and 2021 — from 22.7% to 71.5%. Still, testing rates varied depending on a range of factors.
• About 22% variability in MMR/MSI testing was attributed to hospital-level variations, with the best vs worst performing hospitals reporting testing rates of 90% vs 2%. This hospital-level variation may be caused by testing protocol differences at individual institutions, the authors said.
• The likelihood of undergoing MMR/MSI testing was lower in patients with stage IV vs stage I disease (adjusted odds ratio [aOR], 0.78) but higher in those with stage II (aOR, 1.53) and III (aOR, 1.40) disease.
• The likelihood of undergoing MMR/MSI testing was slightly lower for men than for women (aOR, 0.98) and for Black patients than for White patients (aOR, 0.97). Having a lower household income, public or no insurance (vs private insurance), or living a longer distance (more than 5 miles) from the treatment facility was also associated with lower odds of testing.

IN PRACTICE:

“This cohort study indicated that MMR/MSI testing increased markedly, suggesting increased NCCN guideline adherence,” the authors said. However, variations still exist by cancer stage, hospital, and patient factors. Implementing “widespread institution-level reflexive testing for every initial diagnostic biopsy” can improve testing rates and reduce disparities, the authors suggested.

SOURCE:

This study, led by Totadri Dhimal, MD, University of Rochester Medical Center in New York, was published online in JAMA Oncology.

LIMITATIONS:

The study lacked clinical granularity, and potential coding inaccuracies and incomplete data could have affected the interpretation and generalizability of the findings.

DISCLOSURES:

No funding information was provided for the study. One author reported receiving author royalties from UpToDate outside the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Testing for mismatch repair (MMR) and microsatellite instability (MSI) among patients with colorectal cancer (CRC) increased from 22.7% in 2012 to 71.5% in 2021, but variations in access remain, with testing rates differing by cancer stage, individual hospital, patient sex, race, and insurance status.

METHODOLOGY:

• In 2017, the National Comprehensive Cancer Network (NCCN) recommended universal testing for MMR and MSI among patients with CRC, but studies suggest that testing may still be underused.
• To assess trends and factors associated with MMR/MSI testing in the United States, researchers evaluated 834,797 patients diagnosed with stage I-IV CRC between 2012 and 2021 across 1366 Commission on Cancer–accredited hospitals in the National Cancer Database.
• The variability in MMR/MSI testing was assessed in relation to both patient and hospital-level factors.
• Overall, 70.7% patients had colon cancer, 7.3% had rectosigmoid cancer, and 22.0% had rectal cancer. The median patient age was 66 years; just over half (53%) were men, 81.8% were White, and 11.9% were Black.

TAKEAWAY:

• Overall, 43.9% patients underwent MMR/MSI testing, but testing rates increased more than threefold between 2012 and 2021 — from 22.7% to 71.5%. Still, testing rates varied depending on a range of factors.
• About 22% variability in MMR/MSI testing was attributed to hospital-level variations, with the best vs worst performing hospitals reporting testing rates of 90% vs 2%. This hospital-level variation may be caused by testing protocol differences at individual institutions, the authors said.
• The likelihood of undergoing MMR/MSI testing was lower in patients with stage IV vs stage I disease (adjusted odds ratio [aOR], 0.78) but higher in those with stage II (aOR, 1.53) and III (aOR, 1.40) disease.
• The likelihood of undergoing MMR/MSI testing was slightly lower for men than for women (aOR, 0.98) and for Black patients than for White patients (aOR, 0.97). Having a lower household income, public or no insurance (vs private insurance), or living a longer distance (more than 5 miles) from the treatment facility was also associated with lower odds of testing.

IN PRACTICE:

“This cohort study indicated that MMR/MSI testing increased markedly, suggesting increased NCCN guideline adherence,” the authors said. However, variations still exist by cancer stage, hospital, and patient factors. Implementing “widespread institution-level reflexive testing for every initial diagnostic biopsy” can improve testing rates and reduce disparities, the authors suggested.

SOURCE:

This study, led by Totadri Dhimal, MD, University of Rochester Medical Center in New York, was published online in JAMA Oncology.

LIMITATIONS:

The study lacked clinical granularity, and potential coding inaccuracies and incomplete data could have affected the interpretation and generalizability of the findings.

DISCLOSURES:

No funding information was provided for the study. One author reported receiving author royalties from UpToDate outside the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

SAN DIEGO — Chimeric antigen receptor (CAR) T-cell therapies offer the tantalizing prospect of dramatically altering the outcome of lung cancers, but there are many hurdles to treating patients with them, according to experts.

These hurdles include finding the right targets, minimizing the risks of the treatment, and reducing the enormous burdens getting these therapies places on patients.

“Precision immunotherapy,” or unleashing the immune system in a highly specific manner, “is obviously, in a way, a holy grail” in lung cancer, said Martin Forster, MD, PhD, who cochaired a session on the topic at the World Conference on Lung Cancer (WCLC) 2024.

He underlined, however, that “immunology is very complex, as is cancer biology,” and consequently, there are different avenues being explored, including CAR T-cell therapies, T-cell receptor therapies, and tumor-infiltrating lymphocytes, among others.

Antibody technology is also being harnessed to target chemotherapy, via antibody-drug conjugates, noted Forster, who is clinical lead of the early phase clinical trials programme at University College London in England.

Moreover, investigators are looking at combining various therapies, such as immune checkpoint inhibitors with T cell–engaging approaches.

He highlighted, however, that the ideal target for these approaches is something that is recognized by the immune system as being foreign, but is found within the cancer, “and you also want it ideally to be in all of the cancer cells.”

A good example is a clonal change, meaning an early evolutionary genetic alteration in the tumor that is present in all the cells, Forster said.
 

Identifying the Right Target

“One of the big challenges in all forms of targeted immunotherapy is around selecting the target and developing the right product for the right target,” Forster emphasized.

“This concept works really well in hematological malignancies” but is “proving to be more challenging to deliver within solid malignancies,” he added.

“The reason why so many lung tumors are resistant to immunotherapy is because they ‘re immunologically cold,” Roy Herbst, MD, PhD, Department of Medical Oncology, Yale Comprehensive Cancer Center, New Haven, Connecticut, said in an interview.

“There are no T cells in the tumor,” he explained, so it “doesn’t really matter how much you block checkpoint inhibitors, you still have to have a T cell in there in order to have effect.”

To overcome this problem CAR T-cell therapies are engineered to target a tumor, Herbst continued, but that “is a little hard in lung cancer because you need to have a unique antigen that’s on a lung tumor that’s not present on normal cells.”

Charu Aggarwal, MD, MPH, Leslye M. Heisler Associate Professor for Lung Cancer Excellence, Penn Medicine, Philadelphia, Pennsylvania, agreed, saying that there is “a lot of excitement with CAR T-cell therapies, and the promise of cure,” but “the biology is not as simple as we think.”

“For example, it’s not as simple as CD20 or CD19 targeting,” she said in an interview. “Most of the antigens that are being targeted in the solid tumor world, unfortunately, are also expressed on normal tissue. So there is always this potential for toxicity.”
 

A Question of Time

Another aspect of CAR T-cell therapy that is proving difficult is its delivery.

Forster outlined that the process involves first leukapheresis, in which T cells are obtained from a blood draw. These are then genetically modified to express chimeric antigen receptors before being multiplied in the laboratory and introduced to the patient.

This process can take several weeks, during which patients may require bridging treatment, such as chemotherapy or radiotherapy, to keep their cancer under control. “Sometimes, patients with solid tumors who are in later lines of therapy may not have the luxury of time to be able to wait for all of these steps,” Aggarwal said.

There is also the question of whether a bespoke treatment can be scaled up so that it can be delivered to more patients in a more timely manner.

“There are certainly lessons to be learned from use of off-the-shelf CAR T-cell products” in hematologic malignancies, she noted, “but we’re just not there yet in lung cancer.”
 

Life-Threatening Toxicities

To improve the chances of engraftment when the CAR T cells are introduced, patients will require prior lymphodepletion with chemotherapy.

This, Forster said, is a “relatively intensive part of treatment.” However, “if you just give immune cells to somebody, when the host body is already full of immune cells,” the CAR T cells are unlikely to engraft, and “so you need to create space for those cells to develop.”

“What you want is not an immediate effect” but rather an immune “memory” that will give an ongoing benefit, he underscored.

Many patients will need to stay in the hospital one or more nights “because when you bring T cells to a tumor, you get cytokine release syndrome [CRS],” Herbst said. This can cause hypotension, fever, and chills, similar to a viral response.

“So patients can get sick,” which in turn requires treatment and follow-up. That puts a “big burden on the health system” and is a major issue, Herbst said.

Patients are also at a risk for “significant neurotoxicity,” said session cochair Amy Moore, PhD, vice president of Global Engagement and Patient Partnerships, LUNGevity Foundation, Chicago. This, alongside CRS, “can be life threatening for our patients.”

Lengthy hospital stays also have a psychosocial impact on the patient and their quality of life, she emphasized, especially when they are treated in a center far away from family and loved ones.

“We’ve also heard anecdotally some reports recently of secondary malignancies” with CAR T cell and other therapies, and that’s something that needs to be monitored as more patients go on these treatments, she said.
 

‘At What Cost’ to Patients?

The difficulties faced by patients in receiving CAR T-cell therapy go far beyond the practicalities of generating the cells or the risks associated with lymphodepletion, however.

“These therapies are extraordinarily expensive,” although that has to be weighed against the cost of years of ongoing treatment with immunotherapy, Moore said.

Moreover, as CAR T-cell therapies are a “last resort” option, patients have to “exhaust all other treatments” before being eligible, she continued. There’s significant prior authorization challenges, which means patients “have to go through many hurdles before they can qualify for treatment with these therapies.”

This typically involves having numerous laboratory tests, which can add up to out-of-pocket expenses for patients often reaching tens of thousands of dollars, Moore said.

Another issue is that they must be administered in certified treatment centers, and there are a limited number of those in the United States, she added.

This increases the risk of heightening disparities, as patients are “forced to travel, seek lodging, and have meal expenses,” and the costs “are not trivial,” Moore underlined. “It can rack up quickly and mount to $10,000 or more.”

For physicians, there are difficulties in terms of the logistics of following up with those patients who need to be treated at centers on the other side of the country, uncertainties around reimbursement, and restrictions in terms of staff time and resources, among others.

“I’m as excited as you are at the science,” but it is the implementation that is at issue, Moore said. In other words, there is the offer of a cure with CAR T-cell therapy, but “at what cost?”

“For patients, these considerations are real and they’re significant” and “we have to ensure that what we’re doing is in service of people with cancer,” she emphasized.

No funding was declared. Aggarwal declared relationships with Genentech, Celgene, AstraZeneca, Daiichi Sankyo, Turning Point, Janssen, Pfizer, Lilly, Merck, Regeneron/Sanofi, Eisai, BeiGene, Boehringer Ingelheim, Blueprint Genetics, and Shionogi. Forster declared relationships with AstraZeneca, Boehringer Ingelheim, Merck, MSD, Achilles, Amgen, Bayer, Bristol-Myers Squibb, Celgene, EQRx, GSK, Immutep, Janssen, Merck, Oxford Vacmedix, PharmaMar, Roche, Takeda, Syncorp, Transgene, and Ultrahuman. Moore declared no relevant financial relationships.

A version of this article appeared on Medscape.com.

SAN DIEGO — Chimeric antigen receptor (CAR) T-cell therapies offer the tantalizing prospect of dramatically altering the outcome of lung cancers, but there are many hurdles to treating patients with them, according to experts.

These hurdles include finding the right targets, minimizing the risks of the treatment, and reducing the enormous burdens getting these therapies places on patients.

“Precision immunotherapy,” or unleashing the immune system in a highly specific manner, “is obviously, in a way, a holy grail” in lung cancer, said Martin Forster, MD, PhD, who cochaired a session on the topic at the World Conference on Lung Cancer (WCLC) 2024.

He underlined, however, that “immunology is very complex, as is cancer biology,” and consequently, there are different avenues being explored, including CAR T-cell therapies, T-cell receptor therapies, and tumor-infiltrating lymphocytes, among others.

Antibody technology is also being harnessed to target chemotherapy, via antibody-drug conjugates, noted Forster, who is clinical lead of the early phase clinical trials programme at University College London in England.

Moreover, investigators are looking at combining various therapies, such as immune checkpoint inhibitors with T cell–engaging approaches.

He highlighted, however, that the ideal target for these approaches is something that is recognized by the immune system as being foreign, but is found within the cancer, “and you also want it ideally to be in all of the cancer cells.”

A good example is a clonal change, meaning an early evolutionary genetic alteration in the tumor that is present in all the cells, Forster said.
 

Identifying the Right Target

“One of the big challenges in all forms of targeted immunotherapy is around selecting the target and developing the right product for the right target,” Forster emphasized.

“This concept works really well in hematological malignancies” but is “proving to be more challenging to deliver within solid malignancies,” he added.

“The reason why so many lung tumors are resistant to immunotherapy is because they ‘re immunologically cold,” Roy Herbst, MD, PhD, Department of Medical Oncology, Yale Comprehensive Cancer Center, New Haven, Connecticut, said in an interview.

“There are no T cells in the tumor,” he explained, so it “doesn’t really matter how much you block checkpoint inhibitors, you still have to have a T cell in there in order to have effect.”

To overcome this problem CAR T-cell therapies are engineered to target a tumor, Herbst continued, but that “is a little hard in lung cancer because you need to have a unique antigen that’s on a lung tumor that’s not present on normal cells.”

Charu Aggarwal, MD, MPH, Leslye M. Heisler Associate Professor for Lung Cancer Excellence, Penn Medicine, Philadelphia, Pennsylvania, agreed, saying that there is “a lot of excitement with CAR T-cell therapies, and the promise of cure,” but “the biology is not as simple as we think.”

“For example, it’s not as simple as CD20 or CD19 targeting,” she said in an interview. “Most of the antigens that are being targeted in the solid tumor world, unfortunately, are also expressed on normal tissue. So there is always this potential for toxicity.”
 

A Question of Time

Another aspect of CAR T-cell therapy that is proving difficult is its delivery.

Forster outlined that the process involves first leukapheresis, in which T cells are obtained from a blood draw. These are then genetically modified to express chimeric antigen receptors before being multiplied in the laboratory and introduced to the patient.

This process can take several weeks, during which patients may require bridging treatment, such as chemotherapy or radiotherapy, to keep their cancer under control. “Sometimes, patients with solid tumors who are in later lines of therapy may not have the luxury of time to be able to wait for all of these steps,” Aggarwal said.

There is also the question of whether a bespoke treatment can be scaled up so that it can be delivered to more patients in a more timely manner.

“There are certainly lessons to be learned from use of off-the-shelf CAR T-cell products” in hematologic malignancies, she noted, “but we’re just not there yet in lung cancer.”
 

Life-Threatening Toxicities

To improve the chances of engraftment when the CAR T cells are introduced, patients will require prior lymphodepletion with chemotherapy.

This, Forster said, is a “relatively intensive part of treatment.” However, “if you just give immune cells to somebody, when the host body is already full of immune cells,” the CAR T cells are unlikely to engraft, and “so you need to create space for those cells to develop.”

“What you want is not an immediate effect” but rather an immune “memory” that will give an ongoing benefit, he underscored.

Many patients will need to stay in the hospital one or more nights “because when you bring T cells to a tumor, you get cytokine release syndrome [CRS],” Herbst said. This can cause hypotension, fever, and chills, similar to a viral response.

“So patients can get sick,” which in turn requires treatment and follow-up. That puts a “big burden on the health system” and is a major issue, Herbst said.

Patients are also at a risk for “significant neurotoxicity,” said session cochair Amy Moore, PhD, vice president of Global Engagement and Patient Partnerships, LUNGevity Foundation, Chicago. This, alongside CRS, “can be life threatening for our patients.”

Lengthy hospital stays also have a psychosocial impact on the patient and their quality of life, she emphasized, especially when they are treated in a center far away from family and loved ones.

“We’ve also heard anecdotally some reports recently of secondary malignancies” with CAR T cell and other therapies, and that’s something that needs to be monitored as more patients go on these treatments, she said.
 

‘At What Cost’ to Patients?

The difficulties faced by patients in receiving CAR T-cell therapy go far beyond the practicalities of generating the cells or the risks associated with lymphodepletion, however.

“These therapies are extraordinarily expensive,” although that has to be weighed against the cost of years of ongoing treatment with immunotherapy, Moore said.

Moreover, as CAR T-cell therapies are a “last resort” option, patients have to “exhaust all other treatments” before being eligible, she continued. There’s significant prior authorization challenges, which means patients “have to go through many hurdles before they can qualify for treatment with these therapies.”

This typically involves having numerous laboratory tests, which can add up to out-of-pocket expenses for patients often reaching tens of thousands of dollars, Moore said.

Another issue is that they must be administered in certified treatment centers, and there are a limited number of those in the United States, she added.

This increases the risk of heightening disparities, as patients are “forced to travel, seek lodging, and have meal expenses,” and the costs “are not trivial,” Moore underlined. “It can rack up quickly and mount to $10,000 or more.”

For physicians, there are difficulties in terms of the logistics of following up with those patients who need to be treated at centers on the other side of the country, uncertainties around reimbursement, and restrictions in terms of staff time and resources, among others.

“I’m as excited as you are at the science,” but it is the implementation that is at issue, Moore said. In other words, there is the offer of a cure with CAR T-cell therapy, but “at what cost?”

“For patients, these considerations are real and they’re significant” and “we have to ensure that what we’re doing is in service of people with cancer,” she emphasized.

No funding was declared. Aggarwal declared relationships with Genentech, Celgene, AstraZeneca, Daiichi Sankyo, Turning Point, Janssen, Pfizer, Lilly, Merck, Regeneron/Sanofi, Eisai, BeiGene, Boehringer Ingelheim, Blueprint Genetics, and Shionogi. Forster declared relationships with AstraZeneca, Boehringer Ingelheim, Merck, MSD, Achilles, Amgen, Bayer, Bristol-Myers Squibb, Celgene, EQRx, GSK, Immutep, Janssen, Merck, Oxford Vacmedix, PharmaMar, Roche, Takeda, Syncorp, Transgene, and Ultrahuman. Moore declared no relevant financial relationships.

A version of this article appeared on Medscape.com.

SAN DIEGO — Chimeric antigen receptor (CAR) T-cell therapies offer the tantalizing prospect of dramatically altering the outcome of lung cancers, but there are many hurdles to treating patients with them, according to experts.

These hurdles include finding the right targets, minimizing the risks of the treatment, and reducing the enormous burdens getting these therapies places on patients.

“Precision immunotherapy,” or unleashing the immune system in a highly specific manner, “is obviously, in a way, a holy grail” in lung cancer, said Martin Forster, MD, PhD, who cochaired a session on the topic at the World Conference on Lung Cancer (WCLC) 2024.

He underlined, however, that “immunology is very complex, as is cancer biology,” and consequently, there are different avenues being explored, including CAR T-cell therapies, T-cell receptor therapies, and tumor-infiltrating lymphocytes, among others.

Antibody technology is also being harnessed to target chemotherapy, via antibody-drug conjugates, noted Forster, who is clinical lead of the early phase clinical trials programme at University College London in England.

Moreover, investigators are looking at combining various therapies, such as immune checkpoint inhibitors with T cell–engaging approaches.

He highlighted, however, that the ideal target for these approaches is something that is recognized by the immune system as being foreign, but is found within the cancer, “and you also want it ideally to be in all of the cancer cells.”

A good example is a clonal change, meaning an early evolutionary genetic alteration in the tumor that is present in all the cells, Forster said.
 

Identifying the Right Target

“One of the big challenges in all forms of targeted immunotherapy is around selecting the target and developing the right product for the right target,” Forster emphasized.

“This concept works really well in hematological malignancies” but is “proving to be more challenging to deliver within solid malignancies,” he added.

“The reason why so many lung tumors are resistant to immunotherapy is because they ‘re immunologically cold,” Roy Herbst, MD, PhD, Department of Medical Oncology, Yale Comprehensive Cancer Center, New Haven, Connecticut, said in an interview.

“There are no T cells in the tumor,” he explained, so it “doesn’t really matter how much you block checkpoint inhibitors, you still have to have a T cell in there in order to have effect.”

To overcome this problem CAR T-cell therapies are engineered to target a tumor, Herbst continued, but that “is a little hard in lung cancer because you need to have a unique antigen that’s on a lung tumor that’s not present on normal cells.”

Charu Aggarwal, MD, MPH, Leslye M. Heisler Associate Professor for Lung Cancer Excellence, Penn Medicine, Philadelphia, Pennsylvania, agreed, saying that there is “a lot of excitement with CAR T-cell therapies, and the promise of cure,” but “the biology is not as simple as we think.”

“For example, it’s not as simple as CD20 or CD19 targeting,” she said in an interview. “Most of the antigens that are being targeted in the solid tumor world, unfortunately, are also expressed on normal tissue. So there is always this potential for toxicity.”
 

A Question of Time

Another aspect of CAR T-cell therapy that is proving difficult is its delivery.

Forster outlined that the process involves first leukapheresis, in which T cells are obtained from a blood draw. These are then genetically modified to express chimeric antigen receptors before being multiplied in the laboratory and introduced to the patient.

This process can take several weeks, during which patients may require bridging treatment, such as chemotherapy or radiotherapy, to keep their cancer under control. “Sometimes, patients with solid tumors who are in later lines of therapy may not have the luxury of time to be able to wait for all of these steps,” Aggarwal said.

There is also the question of whether a bespoke treatment can be scaled up so that it can be delivered to more patients in a more timely manner.

“There are certainly lessons to be learned from use of off-the-shelf CAR T-cell products” in hematologic malignancies, she noted, “but we’re just not there yet in lung cancer.”
 

Life-Threatening Toxicities

To improve the chances of engraftment when the CAR T cells are introduced, patients will require prior lymphodepletion with chemotherapy.

This, Forster said, is a “relatively intensive part of treatment.” However, “if you just give immune cells to somebody, when the host body is already full of immune cells,” the CAR T cells are unlikely to engraft, and “so you need to create space for those cells to develop.”

“What you want is not an immediate effect” but rather an immune “memory” that will give an ongoing benefit, he underscored.

Many patients will need to stay in the hospital one or more nights “because when you bring T cells to a tumor, you get cytokine release syndrome [CRS],” Herbst said. This can cause hypotension, fever, and chills, similar to a viral response.

“So patients can get sick,” which in turn requires treatment and follow-up. That puts a “big burden on the health system” and is a major issue, Herbst said.

Patients are also at a risk for “significant neurotoxicity,” said session cochair Amy Moore, PhD, vice president of Global Engagement and Patient Partnerships, LUNGevity Foundation, Chicago. This, alongside CRS, “can be life threatening for our patients.”

Lengthy hospital stays also have a psychosocial impact on the patient and their quality of life, she emphasized, especially when they are treated in a center far away from family and loved ones.

“We’ve also heard anecdotally some reports recently of secondary malignancies” with CAR T cell and other therapies, and that’s something that needs to be monitored as more patients go on these treatments, she said.
 

‘At What Cost’ to Patients?

The difficulties faced by patients in receiving CAR T-cell therapy go far beyond the practicalities of generating the cells or the risks associated with lymphodepletion, however.

“These therapies are extraordinarily expensive,” although that has to be weighed against the cost of years of ongoing treatment with immunotherapy, Moore said.

Moreover, as CAR T-cell therapies are a “last resort” option, patients have to “exhaust all other treatments” before being eligible, she continued. There’s significant prior authorization challenges, which means patients “have to go through many hurdles before they can qualify for treatment with these therapies.”

This typically involves having numerous laboratory tests, which can add up to out-of-pocket expenses for patients often reaching tens of thousands of dollars, Moore said.

Another issue is that they must be administered in certified treatment centers, and there are a limited number of those in the United States, she added.

This increases the risk of heightening disparities, as patients are “forced to travel, seek lodging, and have meal expenses,” and the costs “are not trivial,” Moore underlined. “It can rack up quickly and mount to $10,000 or more.”

For physicians, there are difficulties in terms of the logistics of following up with those patients who need to be treated at centers on the other side of the country, uncertainties around reimbursement, and restrictions in terms of staff time and resources, among others.

“I’m as excited as you are at the science,” but it is the implementation that is at issue, Moore said. In other words, there is the offer of a cure with CAR T-cell therapy, but “at what cost?”

“For patients, these considerations are real and they’re significant” and “we have to ensure that what we’re doing is in service of people with cancer,” she emphasized.

No funding was declared. Aggarwal declared relationships with Genentech, Celgene, AstraZeneca, Daiichi Sankyo, Turning Point, Janssen, Pfizer, Lilly, Merck, Regeneron/Sanofi, Eisai, BeiGene, Boehringer Ingelheim, Blueprint Genetics, and Shionogi. Forster declared relationships with AstraZeneca, Boehringer Ingelheim, Merck, MSD, Achilles, Amgen, Bayer, Bristol-Myers Squibb, Celgene, EQRx, GSK, Immutep, Janssen, Merck, Oxford Vacmedix, PharmaMar, Roche, Takeda, Syncorp, Transgene, and Ultrahuman. Moore declared no relevant financial relationships.

A version of this article appeared on Medscape.com.

Thanks to the continuously improving treatment options for cancer, the number of cancer survivors is increasing, and a large proportion of survivors is confronted with the long-term effects of cancer treatment. Especially for young patients, the question of the impact of therapy on fertility arises.

Dose adjustment or modification of the treatment regimen can achieve a lot. But experts at the congress of the European Society for Medical Oncology (ESMO) 2024 noted that knowledge about newer treatment options like immunotherapies is still insufficient.
 

Therapy Selection

The question of preserving fertility must be considered when deciding on the appropriate treatment, said Matteo Lambertini, MD, PhD, medical oncology consultant at the University of Genoa in Genoa, Italy. A patient’s age, the type of therapy, and the dose are crucial in determining whether or how much fertility is affected. “Preserving fertility is also an aim of cancer therapy,” he said.

Lambertini, who is also a member of the ESMO Guideline Group on fertility preservation in cancer patients, referred to the 2020 ESMO guidelines, which list the gonadotoxicity of a substance depending on the treatment regimen and the patient’s age.

Isabelle Demeestere, MD, PhD, director of the research lab for human reproduction at the Erasmus Hospital of the Free University of Brussels in Brussels, Belgium, pointed out the limitations of general guidelines. “Therapies change over time, and a classification must be updated regularly.”

Knowledge gaps related to well-known therapies and many novel options persist. “For many FDA-approved medications, there are either no fertility data or only preclinical data available,” she added.
 

Chemotherapies and Immunotherapies

Chemotherapies with alkylating or platinum-containing substances are known for their effects on oocytes, follicle maturation, and spermatogenesis, said Demeestere.

Chemotherapy is gonadotoxic and leads to a temporary decrease in sperm quality or temporary azoospermia in men.

These effects, however, can lead to permanent azoospermia and endocrine disorders, depending on the dose, duration, or combination with radiation, said Demeestere.

Cryopreservation of sperm should always be performed before starting treatment. For high-risk patients who are prepubertal, samples of testicular tissue are taken.

In women, chemotherapy affects primordial follicles and follicle maturation through DNA damage. This process results in severe or temporary amenorrhea, a temporary or permanent decrease in egg reserve, and ultimately premature egg insufficiency.

Novel immunotherapies also influence fertility, presumably through interactions of the immune system with the reproductive organs. But insufficient data are available, according to Lambertini, who emphasized that “these data are urgently needed, especially for young patients with cancer.”

In a mouse model, immune checkpoint inhibitors affected ovarian function, and the inflammatory reaction in humans can affect fertility. No long-term data are available for women yet, however, explained Demeestere. The effects of other therapeutics such as PARP, CDK4/6, or tyrosine kinase inhibitors, as well as monoclonal antibodies like trastuzumab, are only seen sporadically.

In the PENELOPE-B phase 3 study, the CDK4/6 inhibitor palbociclib did not affect ovarian function, even though the cyclin-dependent kinases play an important role in mitotic arrest, said Demeestere.
 

Adjusting the Regimen

In a PET-guided approach, Demeestere’s research team investigated the effects of dose reduction or adjustment of the treatment regimen of procarbazine and cyclophosphamide on the fertility of patients younger than 45 years with advanced Hodgkin lymphoma.

By regularly controlling tumor growth with PET, the treatment could be adjusted so that the effect on egg reserve or spermatogenesis was significantly reduced and loss of fertility could be prevented.

During the 5-year follow-up period, the ovarian function of participating women was assessed by the serum concentration of follicle-stimulating hormone (FSH), estradiol, and anti-Müllerian hormone (AMH) to evaluate egg reserve. In men, testicular function was assessed at the beginning of the study. At the end of treatment, sperm analysis and FSH and testosterone levels were checked.

Demeestere and colleagues demonstrated that dose reduction or altering the treatment regimen for patients who responded early to treatment (determined by PET-guided monitoring) reduced the risk for gonadotoxicity from 46% to 14.5%. That is, the risk was reduced by more than half.

FSH and AMH correlated with the patient’s age and the dose of the alkylating agent. In men, sperm parameters recovered after dose or agent adjustment compared with the unchanged treatment regimen.

Newer results from the PHERGain study in women with early human epidermal growth factor receptor 2–positive breast cancer also provided hope, according to Demeestere. Under PET-guided control, chemotherapy could be reduced.
 

More Data Needed

The new treatment options pose a challenge to preserving fertility during cancer treatment, said Demeestere.

For new targeted therapies, uniform recommendations cannot be issued because of the lack of data and varying treatment durations. Still, the new therapies are safer than chemotherapy.

The need to collect data on fertility and long-term effects in cancer survivors in clinical studies is also reflected in the literature, according to Demeestere. “There are more review articles on this topic than clinical studies.”
 

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Thanks to the continuously improving treatment options for cancer, the number of cancer survivors is increasing, and a large proportion of survivors is confronted with the long-term effects of cancer treatment. Especially for young patients, the question of the impact of therapy on fertility arises.

Dose adjustment or modification of the treatment regimen can achieve a lot. But experts at the congress of the European Society for Medical Oncology (ESMO) 2024 noted that knowledge about newer treatment options like immunotherapies is still insufficient.
 

Therapy Selection

The question of preserving fertility must be considered when deciding on the appropriate treatment, said Matteo Lambertini, MD, PhD, medical oncology consultant at the University of Genoa in Genoa, Italy. A patient’s age, the type of therapy, and the dose are crucial in determining whether or how much fertility is affected. “Preserving fertility is also an aim of cancer therapy,” he said.

Lambertini, who is also a member of the ESMO Guideline Group on fertility preservation in cancer patients, referred to the 2020 ESMO guidelines, which list the gonadotoxicity of a substance depending on the treatment regimen and the patient’s age.

Isabelle Demeestere, MD, PhD, director of the research lab for human reproduction at the Erasmus Hospital of the Free University of Brussels in Brussels, Belgium, pointed out the limitations of general guidelines. “Therapies change over time, and a classification must be updated regularly.”

Knowledge gaps related to well-known therapies and many novel options persist. “For many FDA-approved medications, there are either no fertility data or only preclinical data available,” she added.
 

Chemotherapies and Immunotherapies

Chemotherapies with alkylating or platinum-containing substances are known for their effects on oocytes, follicle maturation, and spermatogenesis, said Demeestere.

Chemotherapy is gonadotoxic and leads to a temporary decrease in sperm quality or temporary azoospermia in men.

These effects, however, can lead to permanent azoospermia and endocrine disorders, depending on the dose, duration, or combination with radiation, said Demeestere.

Cryopreservation of sperm should always be performed before starting treatment. For high-risk patients who are prepubertal, samples of testicular tissue are taken.

In women, chemotherapy affects primordial follicles and follicle maturation through DNA damage. This process results in severe or temporary amenorrhea, a temporary or permanent decrease in egg reserve, and ultimately premature egg insufficiency.

Novel immunotherapies also influence fertility, presumably through interactions of the immune system with the reproductive organs. But insufficient data are available, according to Lambertini, who emphasized that “these data are urgently needed, especially for young patients with cancer.”

In a mouse model, immune checkpoint inhibitors affected ovarian function, and the inflammatory reaction in humans can affect fertility. No long-term data are available for women yet, however, explained Demeestere. The effects of other therapeutics such as PARP, CDK4/6, or tyrosine kinase inhibitors, as well as monoclonal antibodies like trastuzumab, are only seen sporadically.

In the PENELOPE-B phase 3 study, the CDK4/6 inhibitor palbociclib did not affect ovarian function, even though the cyclin-dependent kinases play an important role in mitotic arrest, said Demeestere.
 

Adjusting the Regimen

In a PET-guided approach, Demeestere’s research team investigated the effects of dose reduction or adjustment of the treatment regimen of procarbazine and cyclophosphamide on the fertility of patients younger than 45 years with advanced Hodgkin lymphoma.

By regularly controlling tumor growth with PET, the treatment could be adjusted so that the effect on egg reserve or spermatogenesis was significantly reduced and loss of fertility could be prevented.

During the 5-year follow-up period, the ovarian function of participating women was assessed by the serum concentration of follicle-stimulating hormone (FSH), estradiol, and anti-Müllerian hormone (AMH) to evaluate egg reserve. In men, testicular function was assessed at the beginning of the study. At the end of treatment, sperm analysis and FSH and testosterone levels were checked.

Demeestere and colleagues demonstrated that dose reduction or altering the treatment regimen for patients who responded early to treatment (determined by PET-guided monitoring) reduced the risk for gonadotoxicity from 46% to 14.5%. That is, the risk was reduced by more than half.

FSH and AMH correlated with the patient’s age and the dose of the alkylating agent. In men, sperm parameters recovered after dose or agent adjustment compared with the unchanged treatment regimen.

Newer results from the PHERGain study in women with early human epidermal growth factor receptor 2–positive breast cancer also provided hope, according to Demeestere. Under PET-guided control, chemotherapy could be reduced.
 

More Data Needed

The new treatment options pose a challenge to preserving fertility during cancer treatment, said Demeestere.

For new targeted therapies, uniform recommendations cannot be issued because of the lack of data and varying treatment durations. Still, the new therapies are safer than chemotherapy.

The need to collect data on fertility and long-term effects in cancer survivors in clinical studies is also reflected in the literature, according to Demeestere. “There are more review articles on this topic than clinical studies.”
 

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Thanks to the continuously improving treatment options for cancer, the number of cancer survivors is increasing, and a large proportion of survivors is confronted with the long-term effects of cancer treatment. Especially for young patients, the question of the impact of therapy on fertility arises.

Dose adjustment or modification of the treatment regimen can achieve a lot. But experts at the congress of the European Society for Medical Oncology (ESMO) 2024 noted that knowledge about newer treatment options like immunotherapies is still insufficient.
 

Therapy Selection

The question of preserving fertility must be considered when deciding on the appropriate treatment, said Matteo Lambertini, MD, PhD, medical oncology consultant at the University of Genoa in Genoa, Italy. A patient’s age, the type of therapy, and the dose are crucial in determining whether or how much fertility is affected. “Preserving fertility is also an aim of cancer therapy,” he said.

Lambertini, who is also a member of the ESMO Guideline Group on fertility preservation in cancer patients, referred to the 2020 ESMO guidelines, which list the gonadotoxicity of a substance depending on the treatment regimen and the patient’s age.

Isabelle Demeestere, MD, PhD, director of the research lab for human reproduction at the Erasmus Hospital of the Free University of Brussels in Brussels, Belgium, pointed out the limitations of general guidelines. “Therapies change over time, and a classification must be updated regularly.”

Knowledge gaps related to well-known therapies and many novel options persist. “For many FDA-approved medications, there are either no fertility data or only preclinical data available,” she added.
 

Chemotherapies and Immunotherapies

Chemotherapies with alkylating or platinum-containing substances are known for their effects on oocytes, follicle maturation, and spermatogenesis, said Demeestere.

Chemotherapy is gonadotoxic and leads to a temporary decrease in sperm quality or temporary azoospermia in men.

These effects, however, can lead to permanent azoospermia and endocrine disorders, depending on the dose, duration, or combination with radiation, said Demeestere.

Cryopreservation of sperm should always be performed before starting treatment. For high-risk patients who are prepubertal, samples of testicular tissue are taken.

In women, chemotherapy affects primordial follicles and follicle maturation through DNA damage. This process results in severe or temporary amenorrhea, a temporary or permanent decrease in egg reserve, and ultimately premature egg insufficiency.

Novel immunotherapies also influence fertility, presumably through interactions of the immune system with the reproductive organs. But insufficient data are available, according to Lambertini, who emphasized that “these data are urgently needed, especially for young patients with cancer.”

In a mouse model, immune checkpoint inhibitors affected ovarian function, and the inflammatory reaction in humans can affect fertility. No long-term data are available for women yet, however, explained Demeestere. The effects of other therapeutics such as PARP, CDK4/6, or tyrosine kinase inhibitors, as well as monoclonal antibodies like trastuzumab, are only seen sporadically.

In the PENELOPE-B phase 3 study, the CDK4/6 inhibitor palbociclib did not affect ovarian function, even though the cyclin-dependent kinases play an important role in mitotic arrest, said Demeestere.
 

Adjusting the Regimen

In a PET-guided approach, Demeestere’s research team investigated the effects of dose reduction or adjustment of the treatment regimen of procarbazine and cyclophosphamide on the fertility of patients younger than 45 years with advanced Hodgkin lymphoma.

By regularly controlling tumor growth with PET, the treatment could be adjusted so that the effect on egg reserve or spermatogenesis was significantly reduced and loss of fertility could be prevented.

During the 5-year follow-up period, the ovarian function of participating women was assessed by the serum concentration of follicle-stimulating hormone (FSH), estradiol, and anti-Müllerian hormone (AMH) to evaluate egg reserve. In men, testicular function was assessed at the beginning of the study. At the end of treatment, sperm analysis and FSH and testosterone levels were checked.

Demeestere and colleagues demonstrated that dose reduction or altering the treatment regimen for patients who responded early to treatment (determined by PET-guided monitoring) reduced the risk for gonadotoxicity from 46% to 14.5%. That is, the risk was reduced by more than half.

FSH and AMH correlated with the patient’s age and the dose of the alkylating agent. In men, sperm parameters recovered after dose or agent adjustment compared with the unchanged treatment regimen.

Newer results from the PHERGain study in women with early human epidermal growth factor receptor 2–positive breast cancer also provided hope, according to Demeestere. Under PET-guided control, chemotherapy could be reduced.
 

More Data Needed

The new treatment options pose a challenge to preserving fertility during cancer treatment, said Demeestere.

For new targeted therapies, uniform recommendations cannot be issued because of the lack of data and varying treatment durations. Still, the new therapies are safer than chemotherapy.

The need to collect data on fertility and long-term effects in cancer survivors in clinical studies is also reflected in the literature, according to Demeestere. “There are more review articles on this topic than clinical studies.”
 

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Some breast cancer types are more likely than others to recur. Researchers have known this for more than a decade.

But they have long wondered why.

“How did those tumor types arise?” said Christina Curtis, PhD, a professor of medicine, genetics and biomedical data science at Stanford University in California. “They’re all breast cancers. They’re all estrogen receptor positive. But these groups are different. When did they become different, and how is that determined?”

Dr. Curtis and colleagues are finally starting to answer these questions. They recently broke new ground in a study linking differences in cancer-related genes to disease subtype and aggressiveness.

Dr. Curtis and colleagues found that, like fingers molding clay, the genes you’re born with can coax the immune system into shape. DNA inherited from our parents is known as the germline genome. It affects whether the immune system attacks or retreats when confronted with variations that may lead to breast cancer.

“It turns out, the germline genome sculpts tumor evolution,” said Dr. Curtis.

The study is part of a growing effort to understand “precancer” — the critical period after cells have started to grow abnormally but before they’ve developed into cancer — a research trend that could trigger a decisive shift in how cancer treatments are realized. Therapeutics could be designed on the basis of the biology of these precancerous cells.

While biotech start-ups push new tests to catch cancer early, researchers like Dr. Curtis hope to stop cancer before it even starts.

“This is a really exciting area of research,” said Susan Domchek, MD, executive director of the Basser Center for BRCA at the University of Pennsylvania, Philadelphia, who was not involved in the study. “What we hope for is that, over time, we’re going to have more and more biologically driven interception.”
 

‘We’re Basically Unearthing the Dark Matter of the Human Genome’

Of course, we already have mechanical ways of heading off cancer, like having a precancerous polyp removed. But for the Stanford researchers, biologic interception is the goal. They hope to figure out how to use the immune system to stop the cancer.

In their study, they looked at DNA variabilities known as somatic aberrations or single-nucleotide protein sequences (SNPs). The HER2 gene, for example, can contain SNPs — possibly affecting how the HER2 protein regulates breast cell growth and division.

“There’s been a huge effort through genomewide association studies to link SNPs to cancer outcomes and risk,” Dr. Curtis said.

Focusing on people with a genetic predisposition for breast cancer, Dr. Curtis used machine learning to show that these variabilities can occur in specific epitopes (protein features that can trigger an immune response).

They also found that heightened variability can show up in a region of the genome called the human leukocyte antigen (HLA). Each HLA molecule can contain many epitopes.

“We developed a whole new algorithm to compute this ‘germline epitope burden,’ ” Dr. Curtis said. “We’re basically unearthing the dark matter of the human genome to ask about the interplay between SNPs and HLA class one presentation.”

These aberration-rich regions can grab the immune system’s attention. Sometimes the immune system identifies and eradicates those epitopes.

In that case: “I have immunosurveillance. I’ve cured my cancer,” said Nora Disis, PhD, director of the Cancer Vaccine Institute and a professor of medicine at the University of Washington, Seattle. Dr. Disis was not involved in the study.

But other times, the immune system finds a way around the high “epitope burden,” and the tumors become more aggressive and immunosuppressive. That’s when cancer forms.

This suggests a “critical juncture between preinvasive and invasive disease,” Dr. Curtis said.

And that “critical juncture” may very well be the optimal time for intervention.
 

The Precancer Push

Stanford’s findings add information to prior biomarkers and may provide a way to identify “bad-acting tumors” from a simple blood draw measuring germline epitope burden, Dr. Curtis said. Looking further ahead, “this also reveals a new source of epitopes that might be immunogenic and might be informative for the development of vaccines.”

Many labs are trying to understand the biology of precancer and exploring possible vaccines.

The National Cancer Institute’s Human Tumor Atlas Network is building three-dimensional models of the evolution from precancerous to advanced disease. And researchers at the Cancer Vaccine Institute at the University of Washington are developing a vaccine for a precancerous lesion linked to many ovarian cancers.

Dr. Domchek’s research explores whether breast cancers caused by mutations in the BRCA 1 and 2 genes can be intercepted at very early stages. In a clinical trial of healthy people with those mutations, Dr. Domchek and colleagues are attempting to “rev up the immune system to tackle telomerase,” an enzyme that’s over-expressed in 95% of cancers. The hope is for this experimental vaccine to lower their risk of developing cancer.

At the Fred Hutch Cancer Center, Seattle, Ming Yu, PhD, is studying how senescent cells affect immune cells in precancer. As cells age and stop dividing, she said, they can accumulate and create a “tumor-promoting microenvironment” in older people.

Dr. Yu has found that the antiaging drug rapamycin can eliminate those “zombie cells” in mice. She’s studying whether the “cleanup” can help prevent cancer and expects results in a few months.

In the years and decades to come, all of this could lead to a new era in cancer treatment.

“Most drug development starts with people with advanced cancer and then goes into the earlier and earlier spaces,” said Dr. Domchek. “But it may be that we’re thinking about it all wrong and that you really have to understand the unique biology of early lesions to go after them.”

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

Some breast cancer types are more likely than others to recur. Researchers have known this for more than a decade.

But they have long wondered why.

“How did those tumor types arise?” said Christina Curtis, PhD, a professor of medicine, genetics and biomedical data science at Stanford University in California. “They’re all breast cancers. They’re all estrogen receptor positive. But these groups are different. When did they become different, and how is that determined?”

Dr. Curtis and colleagues are finally starting to answer these questions. They recently broke new ground in a study linking differences in cancer-related genes to disease subtype and aggressiveness.

Dr. Curtis and colleagues found that, like fingers molding clay, the genes you’re born with can coax the immune system into shape. DNA inherited from our parents is known as the germline genome. It affects whether the immune system attacks or retreats when confronted with variations that may lead to breast cancer.

“It turns out, the germline genome sculpts tumor evolution,” said Dr. Curtis.

The study is part of a growing effort to understand “precancer” — the critical period after cells have started to grow abnormally but before they’ve developed into cancer — a research trend that could trigger a decisive shift in how cancer treatments are realized. Therapeutics could be designed on the basis of the biology of these precancerous cells.

While biotech start-ups push new tests to catch cancer early, researchers like Dr. Curtis hope to stop cancer before it even starts.

“This is a really exciting area of research,” said Susan Domchek, MD, executive director of the Basser Center for BRCA at the University of Pennsylvania, Philadelphia, who was not involved in the study. “What we hope for is that, over time, we’re going to have more and more biologically driven interception.”
 

‘We’re Basically Unearthing the Dark Matter of the Human Genome’

Of course, we already have mechanical ways of heading off cancer, like having a precancerous polyp removed. But for the Stanford researchers, biologic interception is the goal. They hope to figure out how to use the immune system to stop the cancer.

In their study, they looked at DNA variabilities known as somatic aberrations or single-nucleotide protein sequences (SNPs). The HER2 gene, for example, can contain SNPs — possibly affecting how the HER2 protein regulates breast cell growth and division.

“There’s been a huge effort through genomewide association studies to link SNPs to cancer outcomes and risk,” Dr. Curtis said.

Focusing on people with a genetic predisposition for breast cancer, Dr. Curtis used machine learning to show that these variabilities can occur in specific epitopes (protein features that can trigger an immune response).

They also found that heightened variability can show up in a region of the genome called the human leukocyte antigen (HLA). Each HLA molecule can contain many epitopes.

“We developed a whole new algorithm to compute this ‘germline epitope burden,’ ” Dr. Curtis said. “We’re basically unearthing the dark matter of the human genome to ask about the interplay between SNPs and HLA class one presentation.”

These aberration-rich regions can grab the immune system’s attention. Sometimes the immune system identifies and eradicates those epitopes.

In that case: “I have immunosurveillance. I’ve cured my cancer,” said Nora Disis, PhD, director of the Cancer Vaccine Institute and a professor of medicine at the University of Washington, Seattle. Dr. Disis was not involved in the study.

But other times, the immune system finds a way around the high “epitope burden,” and the tumors become more aggressive and immunosuppressive. That’s when cancer forms.

This suggests a “critical juncture between preinvasive and invasive disease,” Dr. Curtis said.

And that “critical juncture” may very well be the optimal time for intervention.
 

The Precancer Push

Stanford’s findings add information to prior biomarkers and may provide a way to identify “bad-acting tumors” from a simple blood draw measuring germline epitope burden, Dr. Curtis said. Looking further ahead, “this also reveals a new source of epitopes that might be immunogenic and might be informative for the development of vaccines.”

Many labs are trying to understand the biology of precancer and exploring possible vaccines.

The National Cancer Institute’s Human Tumor Atlas Network is building three-dimensional models of the evolution from precancerous to advanced disease. And researchers at the Cancer Vaccine Institute at the University of Washington are developing a vaccine for a precancerous lesion linked to many ovarian cancers.

Dr. Domchek’s research explores whether breast cancers caused by mutations in the BRCA 1 and 2 genes can be intercepted at very early stages. In a clinical trial of healthy people with those mutations, Dr. Domchek and colleagues are attempting to “rev up the immune system to tackle telomerase,” an enzyme that’s over-expressed in 95% of cancers. The hope is for this experimental vaccine to lower their risk of developing cancer.

At the Fred Hutch Cancer Center, Seattle, Ming Yu, PhD, is studying how senescent cells affect immune cells in precancer. As cells age and stop dividing, she said, they can accumulate and create a “tumor-promoting microenvironment” in older people.

Dr. Yu has found that the antiaging drug rapamycin can eliminate those “zombie cells” in mice. She’s studying whether the “cleanup” can help prevent cancer and expects results in a few months.

In the years and decades to come, all of this could lead to a new era in cancer treatment.

“Most drug development starts with people with advanced cancer and then goes into the earlier and earlier spaces,” said Dr. Domchek. “But it may be that we’re thinking about it all wrong and that you really have to understand the unique biology of early lesions to go after them.”

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

Some breast cancer types are more likely than others to recur. Researchers have known this for more than a decade.

But they have long wondered why.

“How did those tumor types arise?” said Christina Curtis, PhD, a professor of medicine, genetics and biomedical data science at Stanford University in California. “They’re all breast cancers. They’re all estrogen receptor positive. But these groups are different. When did they become different, and how is that determined?”

Dr. Curtis and colleagues are finally starting to answer these questions. They recently broke new ground in a study linking differences in cancer-related genes to disease subtype and aggressiveness.

Dr. Curtis and colleagues found that, like fingers molding clay, the genes you’re born with can coax the immune system into shape. DNA inherited from our parents is known as the germline genome. It affects whether the immune system attacks or retreats when confronted with variations that may lead to breast cancer.

“It turns out, the germline genome sculpts tumor evolution,” said Dr. Curtis.

The study is part of a growing effort to understand “precancer” — the critical period after cells have started to grow abnormally but before they’ve developed into cancer — a research trend that could trigger a decisive shift in how cancer treatments are realized. Therapeutics could be designed on the basis of the biology of these precancerous cells.

While biotech start-ups push new tests to catch cancer early, researchers like Dr. Curtis hope to stop cancer before it even starts.

“This is a really exciting area of research,” said Susan Domchek, MD, executive director of the Basser Center for BRCA at the University of Pennsylvania, Philadelphia, who was not involved in the study. “What we hope for is that, over time, we’re going to have more and more biologically driven interception.”
 

‘We’re Basically Unearthing the Dark Matter of the Human Genome’

Of course, we already have mechanical ways of heading off cancer, like having a precancerous polyp removed. But for the Stanford researchers, biologic interception is the goal. They hope to figure out how to use the immune system to stop the cancer.

In their study, they looked at DNA variabilities known as somatic aberrations or single-nucleotide protein sequences (SNPs). The HER2 gene, for example, can contain SNPs — possibly affecting how the HER2 protein regulates breast cell growth and division.

“There’s been a huge effort through genomewide association studies to link SNPs to cancer outcomes and risk,” Dr. Curtis said.

Focusing on people with a genetic predisposition for breast cancer, Dr. Curtis used machine learning to show that these variabilities can occur in specific epitopes (protein features that can trigger an immune response).

They also found that heightened variability can show up in a region of the genome called the human leukocyte antigen (HLA). Each HLA molecule can contain many epitopes.

“We developed a whole new algorithm to compute this ‘germline epitope burden,’ ” Dr. Curtis said. “We’re basically unearthing the dark matter of the human genome to ask about the interplay between SNPs and HLA class one presentation.”

These aberration-rich regions can grab the immune system’s attention. Sometimes the immune system identifies and eradicates those epitopes.

In that case: “I have immunosurveillance. I’ve cured my cancer,” said Nora Disis, PhD, director of the Cancer Vaccine Institute and a professor of medicine at the University of Washington, Seattle. Dr. Disis was not involved in the study.

But other times, the immune system finds a way around the high “epitope burden,” and the tumors become more aggressive and immunosuppressive. That’s when cancer forms.

This suggests a “critical juncture between preinvasive and invasive disease,” Dr. Curtis said.

And that “critical juncture” may very well be the optimal time for intervention.
 

The Precancer Push

Stanford’s findings add information to prior biomarkers and may provide a way to identify “bad-acting tumors” from a simple blood draw measuring germline epitope burden, Dr. Curtis said. Looking further ahead, “this also reveals a new source of epitopes that might be immunogenic and might be informative for the development of vaccines.”

Many labs are trying to understand the biology of precancer and exploring possible vaccines.

The National Cancer Institute’s Human Tumor Atlas Network is building three-dimensional models of the evolution from precancerous to advanced disease. And researchers at the Cancer Vaccine Institute at the University of Washington are developing a vaccine for a precancerous lesion linked to many ovarian cancers.

Dr. Domchek’s research explores whether breast cancers caused by mutations in the BRCA 1 and 2 genes can be intercepted at very early stages. In a clinical trial of healthy people with those mutations, Dr. Domchek and colleagues are attempting to “rev up the immune system to tackle telomerase,” an enzyme that’s over-expressed in 95% of cancers. The hope is for this experimental vaccine to lower their risk of developing cancer.

At the Fred Hutch Cancer Center, Seattle, Ming Yu, PhD, is studying how senescent cells affect immune cells in precancer. As cells age and stop dividing, she said, they can accumulate and create a “tumor-promoting microenvironment” in older people.

Dr. Yu has found that the antiaging drug rapamycin can eliminate those “zombie cells” in mice. She’s studying whether the “cleanup” can help prevent cancer and expects results in a few months.

In the years and decades to come, all of this could lead to a new era in cancer treatment.

“Most drug development starts with people with advanced cancer and then goes into the earlier and earlier spaces,” said Dr. Domchek. “But it may be that we’re thinking about it all wrong and that you really have to understand the unique biology of early lesions to go after them.”

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