CLL

Pesticides have transformed modern agriculture by boosting production yields and helping alleviate food insecurity amid rapid global population growth. However, from a public health perspective, exposure to pesticides has been linked to numerous harmful effects, including neurologic disorders like Parkinson’s disease, weakened immune function, and an increased risk for cancer.

Pesticide exposure has been associated with cancers such as colorectal cancer, lung cancer, leukemia (in children and adults), lymphoma, and pancreatic cancer. But these studies primarily have focused on specific groups of individuals with known exposure to certain pesticides or cancer types, thus offering a limited perspective.

A comprehensive assessment of how pesticide use affects cancer risk across a broader population has yet to be conducted.

A recent population-level study aimed to address this gap by evaluating cancer risks in the US population using a model that accounts for pesticide use and adjusts for various factors. The goal was to identify regional disparities in exposure and contribute to the development of public health policies that protect populations from potential harm.
 

Calculating Cancer Risk

Researchers developed a model using several data sources to estimate the additional cancer risk from agricultural pesticide use. Key data included:

• Pesticide use data from the US Geological Survey in 2019, which covered 69 agricultural pesticides across 3143 counties
• Cancer incidence rates per 100,000 people, which were collected between 2015 and 2019 by the National Institutes of Health and the Centers for Disease Control and Prevention; these data covered various cancers, including bladder, colorectal, leukemia, lung, non-Hodgkin lymphoma, and pancreatic cancers
• Covariates, including smoking prevalence, the Social Vulnerability Index, agricultural land use, and total US population in 2019

Pesticide use profile patterns were developed using latent class analysis, a statistical method used to identify homogeneous subgroups within a heterogeneous population. A generalized linear model then estimated how these pesticide use patterns and the covariates affected cancer incidence.

The model highlighted regions with the highest and lowest “additional” cancer risks linked to pesticide exposure, calculating the estimated increase in cancer cases per year that resulted from variations in agricultural pesticide use.
 

Midwest Most Affected

While this model doesn’t establish causality or assess individual risk, it reveals regional trends in the association between pesticide use patterns and cancer incidence from a population-based perspective.

The Midwest, known for its high corn production, emerged as the region most affected by pesticide use. Compared with regions with the lowest risk, the Midwest faced an additional 154,541 cancer cases annually across all types. For colorectal and pancreatic cancers, the yearly increases were 20,927 and 3835 cases, respectively. Similar trends were observed for leukemia and non-Hodgkin lymphoma.
 

Pesticides vs Smoking

The researchers also estimated the additional cancer risk related to smoking, using the same model. They found that pesticides contributed to a higher risk for cancer than smoking in several cases.

The most significant difference was observed with non-Hodgkin lymphoma, where pesticides were linked to 154.1% more cases than smoking. For all cancers combined, as well as bladder cancer and leukemia, the increases were moderate: 18.7%, 19.3%, and 21.0%, respectively.

This result highlights the importance of considering pesticide exposure alongside smoking when studying cancer risks.
 

Expanding Scope of Research

Some limitations of this study should be noted. Certain counties lacked complete data, and there was heterogeneity in the size and population of the counties studied. The research also did not account for seasonal and migrant workers, who are likely to be heavily exposed. In addition, the data used in the study were not independently validated, and they could not be used to assess individual risk.

The effect of pesticides on human health is a vast and critical field of research, often focusing on a limited range of pesticides or specific cancers. This study stands out by taking a broader, more holistic approach, aiming to highlight regional inequalities and identify less-studied pesticides that could be future research priorities.

Given the significant public health impact, the authors encouraged the authorities to share these findings with the most vulnerable communities to raise awareness.
 

This story was translated from JIM 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.

Pesticides have transformed modern agriculture by boosting production yields and helping alleviate food insecurity amid rapid global population growth. However, from a public health perspective, exposure to pesticides has been linked to numerous harmful effects, including neurologic disorders like Parkinson’s disease, weakened immune function, and an increased risk for cancer.

Pesticide exposure has been associated with cancers such as colorectal cancer, lung cancer, leukemia (in children and adults), lymphoma, and pancreatic cancer. But these studies primarily have focused on specific groups of individuals with known exposure to certain pesticides or cancer types, thus offering a limited perspective.

A comprehensive assessment of how pesticide use affects cancer risk across a broader population has yet to be conducted.

A recent population-level study aimed to address this gap by evaluating cancer risks in the US population using a model that accounts for pesticide use and adjusts for various factors. The goal was to identify regional disparities in exposure and contribute to the development of public health policies that protect populations from potential harm.
 

Calculating Cancer Risk

Researchers developed a model using several data sources to estimate the additional cancer risk from agricultural pesticide use. Key data included:

• Pesticide use data from the US Geological Survey in 2019, which covered 69 agricultural pesticides across 3143 counties
• Cancer incidence rates per 100,000 people, which were collected between 2015 and 2019 by the National Institutes of Health and the Centers for Disease Control and Prevention; these data covered various cancers, including bladder, colorectal, leukemia, lung, non-Hodgkin lymphoma, and pancreatic cancers
• Covariates, including smoking prevalence, the Social Vulnerability Index, agricultural land use, and total US population in 2019

Pesticide use profile patterns were developed using latent class analysis, a statistical method used to identify homogeneous subgroups within a heterogeneous population. A generalized linear model then estimated how these pesticide use patterns and the covariates affected cancer incidence.

The model highlighted regions with the highest and lowest “additional” cancer risks linked to pesticide exposure, calculating the estimated increase in cancer cases per year that resulted from variations in agricultural pesticide use.
 

Midwest Most Affected

While this model doesn’t establish causality or assess individual risk, it reveals regional trends in the association between pesticide use patterns and cancer incidence from a population-based perspective.

The Midwest, known for its high corn production, emerged as the region most affected by pesticide use. Compared with regions with the lowest risk, the Midwest faced an additional 154,541 cancer cases annually across all types. For colorectal and pancreatic cancers, the yearly increases were 20,927 and 3835 cases, respectively. Similar trends were observed for leukemia and non-Hodgkin lymphoma.
 

Pesticides vs Smoking

The researchers also estimated the additional cancer risk related to smoking, using the same model. They found that pesticides contributed to a higher risk for cancer than smoking in several cases.

The most significant difference was observed with non-Hodgkin lymphoma, where pesticides were linked to 154.1% more cases than smoking. For all cancers combined, as well as bladder cancer and leukemia, the increases were moderate: 18.7%, 19.3%, and 21.0%, respectively.

This result highlights the importance of considering pesticide exposure alongside smoking when studying cancer risks.
 

Expanding Scope of Research

Some limitations of this study should be noted. Certain counties lacked complete data, and there was heterogeneity in the size and population of the counties studied. The research also did not account for seasonal and migrant workers, who are likely to be heavily exposed. In addition, the data used in the study were not independently validated, and they could not be used to assess individual risk.

The effect of pesticides on human health is a vast and critical field of research, often focusing on a limited range of pesticides or specific cancers. This study stands out by taking a broader, more holistic approach, aiming to highlight regional inequalities and identify less-studied pesticides that could be future research priorities.

Given the significant public health impact, the authors encouraged the authorities to share these findings with the most vulnerable communities to raise awareness.
 

This story was translated from JIM 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.

Pesticides have transformed modern agriculture by boosting production yields and helping alleviate food insecurity amid rapid global population growth. However, from a public health perspective, exposure to pesticides has been linked to numerous harmful effects, including neurologic disorders like Parkinson’s disease, weakened immune function, and an increased risk for cancer.

Pesticide exposure has been associated with cancers such as colorectal cancer, lung cancer, leukemia (in children and adults), lymphoma, and pancreatic cancer. But these studies primarily have focused on specific groups of individuals with known exposure to certain pesticides or cancer types, thus offering a limited perspective.

A comprehensive assessment of how pesticide use affects cancer risk across a broader population has yet to be conducted.

A recent population-level study aimed to address this gap by evaluating cancer risks in the US population using a model that accounts for pesticide use and adjusts for various factors. The goal was to identify regional disparities in exposure and contribute to the development of public health policies that protect populations from potential harm.
 

Calculating Cancer Risk

Researchers developed a model using several data sources to estimate the additional cancer risk from agricultural pesticide use. Key data included:

• Pesticide use data from the US Geological Survey in 2019, which covered 69 agricultural pesticides across 3143 counties
• Cancer incidence rates per 100,000 people, which were collected between 2015 and 2019 by the National Institutes of Health and the Centers for Disease Control and Prevention; these data covered various cancers, including bladder, colorectal, leukemia, lung, non-Hodgkin lymphoma, and pancreatic cancers
• Covariates, including smoking prevalence, the Social Vulnerability Index, agricultural land use, and total US population in 2019

Pesticide use profile patterns were developed using latent class analysis, a statistical method used to identify homogeneous subgroups within a heterogeneous population. A generalized linear model then estimated how these pesticide use patterns and the covariates affected cancer incidence.

The model highlighted regions with the highest and lowest “additional” cancer risks linked to pesticide exposure, calculating the estimated increase in cancer cases per year that resulted from variations in agricultural pesticide use.
 

Midwest Most Affected

While this model doesn’t establish causality or assess individual risk, it reveals regional trends in the association between pesticide use patterns and cancer incidence from a population-based perspective.

The Midwest, known for its high corn production, emerged as the region most affected by pesticide use. Compared with regions with the lowest risk, the Midwest faced an additional 154,541 cancer cases annually across all types. For colorectal and pancreatic cancers, the yearly increases were 20,927 and 3835 cases, respectively. Similar trends were observed for leukemia and non-Hodgkin lymphoma.
 

Pesticides vs Smoking

The researchers also estimated the additional cancer risk related to smoking, using the same model. They found that pesticides contributed to a higher risk for cancer than smoking in several cases.

The most significant difference was observed with non-Hodgkin lymphoma, where pesticides were linked to 154.1% more cases than smoking. For all cancers combined, as well as bladder cancer and leukemia, the increases were moderate: 18.7%, 19.3%, and 21.0%, respectively.

This result highlights the importance of considering pesticide exposure alongside smoking when studying cancer risks.
 

Expanding Scope of Research

Some limitations of this study should be noted. Certain counties lacked complete data, and there was heterogeneity in the size and population of the counties studied. The research also did not account for seasonal and migrant workers, who are likely to be heavily exposed. In addition, the data used in the study were not independently validated, and they could not be used to assess individual risk.

The effect of pesticides on human health is a vast and critical field of research, often focusing on a limited range of pesticides or specific cancers. This study stands out by taking a broader, more holistic approach, aiming to highlight regional inequalities and identify less-studied pesticides that could be future research priorities.

Given the significant public health impact, the authors encouraged the authorities to share these findings with the most vulnerable communities to raise awareness.
 

This story was translated from JIM 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.

Research offers promising insights into the ideal frontline therapies for mantle cell lymphoma (MCL), but there are continued unmet needs in the relapsed/refractory setting, blood cancer specialists told colleagues. 

In the frontline setting, findings suggest that regimens should differ significantly on the basis of whether patients are older or younger, whereas more data are needed to understand whether treatment can overcome poor prognoses in patients with TP53 mutations, lymphoma specialist Nina Wagner-Johnston, MD, of Johns Hopkins University School of Medicine, Baltimore, said in a presentation at the annual meeting of the Society of Hematologic Oncology (SOHO) 2024 in Houston, Texas.

On the relapsed/refractory front, patients need better options after treatment with Bruton tyrosine kinase inhibitors or chimeric antigen receptor (CAR) T-cell therapy, Krish Patel, MD, a lymphoma specialist with Swedish Cancer Institute in Seattle, said in an adjoining presentation. Fortunately, he said, some treatments are showing early promise.

Here’s a closer look at the presentations by Dr. Wagner-Johnston and Dr. Patel.
 

Frontline MCL: Age Helps Determine Best Approach

“For older and less fit patients, the standard approach has typically been bendamustine (Bendeka, Treanda) and rituximab (Rituxan), and the median progression-free survival is about 4 years, with overall survival not reached at a median 5 years of follow-up,” Dr. Wagner-Johnston said. 

Low doses of the chemotherapy drug cytarabine have been added to the bendamustine-rituximab regimen, with encouraging results, she said. “Certainly there’s more toxicity associated even with lower doses, but those data look fairly promising.”

For younger and fit patients, “the standard of care approach has been to administer intensive chemoimmunotherapy that contains high-dose cytarabine, and then that’s typically followed with an autologous stem cell transplant,” she said. A 2016 study reported median progression-free survival of 8.5 years and median overall survival of 12.7 years.

Now, second-generation Bruton tyrosine kinase inhibitors “look very promising” in the frontline setting, Dr. Wagner-Johnston said.

The road has been rocky, however. The SHINE trial of more than 500 patients aged over 65 found that adding ibrutinib to bendamustine-rituximab improved progression-free survival. “However, progression-free survival did not [connect] to an overall survival benefit, and that’s likely due to the toxicity seen with ibrutinib,” she said. 

“It’s not surprising to many of you that ibrutinib has been removed from the FDA label for mantle cell lymphoma,” she said. However, “second-generation [Bruton tyrosine kinase inhibitors] are known to be associated with less toxicity and potentially increased potency.”

What about Bruton tyrosine kinase inhibitors in younger and fitter patients? The TRIANGLE trial demonstrated their benefit, Dr. Wagner-Johnston said, linking ibrutinib to improvement in progression-free survival. 

However, “it’s really too early to evaluate the statistical significance for overall survival.” And while the study looks at therapy without stem cell transplant, she believes it’s too early to know whether that’s a good option. 

Dr. Wagner-Johnston tackled another topic: Can Bruton tyrosine kinase inhibitors overcome the poor prognosis seen with MCL with TP53 mutation? For now, the limitations of research makes it “hard to know,” she said, although early results of the BOVen trial are promising. 
 

Relapsed/Refractory MCL: Better Options Are Still Needed

In his presentation, Dr. Patel spoke about therapy in patients with MCL and relapsed/refractory disease. “We know that outcomes for patients who progress on covalent [Bruton tyrosine kinase inhibitors] is really dismal,” he said. “This has been shown by multiple groups now across the globe.”

Noncovalent Bruton tyrosine kinase inhibitors are now an option, he noted. “We do understand that they work for some patients, and it can be quite useful, but even noncovalent [Bruton tyrosine kinase inhibitors] themselves are susceptible to resistance mutations. We’ve seen that in the [chronic lymphocytic leukemia] world.”

Dr. Patel asked the audience, “Why not just give everybody CAR T-cells, post-[Bruton tyrosine kinase inhibitors]? You get a CAR T-cell! You get a CAR T-cell! Everybody gets one.”

However, he noted, “Unfortunately, mantle cell lymphoma patients experience the worst high-grade toxicity when receiving CD19[-targeted] CAR T-cells.” 

Are there better options? At the moment, “really, really early data” suggest benefits from molecular glues and degraders, novel inhibitors, antibody-drug conjugates, novel CAR T-cells, and bispecific antibodies, Dr. Patel said.

“All of these tools are in clinical trials, and hopefully some of them will help,” he said.

Disclosures were not provided. Dr. Wagner-Johnston recently disclosed advisory committee/board of directors’ relationships with ADC Therapeutics, Regeneron, Calibr, and Verastem. Dr. Patel recently disclosed ties with a long list of pharmaceutical companies, including AbbVie, AstraZeneca, BeiGene, Bristol Myers Squibb, Genentech, Janssen, Merck, and others.
 

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

Research offers promising insights into the ideal frontline therapies for mantle cell lymphoma (MCL), but there are continued unmet needs in the relapsed/refractory setting, blood cancer specialists told colleagues. 

In the frontline setting, findings suggest that regimens should differ significantly on the basis of whether patients are older or younger, whereas more data are needed to understand whether treatment can overcome poor prognoses in patients with TP53 mutations, lymphoma specialist Nina Wagner-Johnston, MD, of Johns Hopkins University School of Medicine, Baltimore, said in a presentation at the annual meeting of the Society of Hematologic Oncology (SOHO) 2024 in Houston, Texas.

On the relapsed/refractory front, patients need better options after treatment with Bruton tyrosine kinase inhibitors or chimeric antigen receptor (CAR) T-cell therapy, Krish Patel, MD, a lymphoma specialist with Swedish Cancer Institute in Seattle, said in an adjoining presentation. Fortunately, he said, some treatments are showing early promise.

Here’s a closer look at the presentations by Dr. Wagner-Johnston and Dr. Patel.
 

Frontline MCL: Age Helps Determine Best Approach

“For older and less fit patients, the standard approach has typically been bendamustine (Bendeka, Treanda) and rituximab (Rituxan), and the median progression-free survival is about 4 years, with overall survival not reached at a median 5 years of follow-up,” Dr. Wagner-Johnston said. 

Low doses of the chemotherapy drug cytarabine have been added to the bendamustine-rituximab regimen, with encouraging results, she said. “Certainly there’s more toxicity associated even with lower doses, but those data look fairly promising.”

For younger and fit patients, “the standard of care approach has been to administer intensive chemoimmunotherapy that contains high-dose cytarabine, and then that’s typically followed with an autologous stem cell transplant,” she said. A 2016 study reported median progression-free survival of 8.5 years and median overall survival of 12.7 years.

Now, second-generation Bruton tyrosine kinase inhibitors “look very promising” in the frontline setting, Dr. Wagner-Johnston said.

The road has been rocky, however. The SHINE trial of more than 500 patients aged over 65 found that adding ibrutinib to bendamustine-rituximab improved progression-free survival. “However, progression-free survival did not [connect] to an overall survival benefit, and that’s likely due to the toxicity seen with ibrutinib,” she said. 

“It’s not surprising to many of you that ibrutinib has been removed from the FDA label for mantle cell lymphoma,” she said. However, “second-generation [Bruton tyrosine kinase inhibitors] are known to be associated with less toxicity and potentially increased potency.”

What about Bruton tyrosine kinase inhibitors in younger and fitter patients? The TRIANGLE trial demonstrated their benefit, Dr. Wagner-Johnston said, linking ibrutinib to improvement in progression-free survival. 

However, “it’s really too early to evaluate the statistical significance for overall survival.” And while the study looks at therapy without stem cell transplant, she believes it’s too early to know whether that’s a good option. 

Dr. Wagner-Johnston tackled another topic: Can Bruton tyrosine kinase inhibitors overcome the poor prognosis seen with MCL with TP53 mutation? For now, the limitations of research makes it “hard to know,” she said, although early results of the BOVen trial are promising. 
 

Relapsed/Refractory MCL: Better Options Are Still Needed

In his presentation, Dr. Patel spoke about therapy in patients with MCL and relapsed/refractory disease. “We know that outcomes for patients who progress on covalent [Bruton tyrosine kinase inhibitors] is really dismal,” he said. “This has been shown by multiple groups now across the globe.”

Noncovalent Bruton tyrosine kinase inhibitors are now an option, he noted. “We do understand that they work for some patients, and it can be quite useful, but even noncovalent [Bruton tyrosine kinase inhibitors] themselves are susceptible to resistance mutations. We’ve seen that in the [chronic lymphocytic leukemia] world.”

Dr. Patel asked the audience, “Why not just give everybody CAR T-cells, post-[Bruton tyrosine kinase inhibitors]? You get a CAR T-cell! You get a CAR T-cell! Everybody gets one.”

However, he noted, “Unfortunately, mantle cell lymphoma patients experience the worst high-grade toxicity when receiving CD19[-targeted] CAR T-cells.” 

Are there better options? At the moment, “really, really early data” suggest benefits from molecular glues and degraders, novel inhibitors, antibody-drug conjugates, novel CAR T-cells, and bispecific antibodies, Dr. Patel said.

“All of these tools are in clinical trials, and hopefully some of them will help,” he said.

Disclosures were not provided. Dr. Wagner-Johnston recently disclosed advisory committee/board of directors’ relationships with ADC Therapeutics, Regeneron, Calibr, and Verastem. Dr. Patel recently disclosed ties with a long list of pharmaceutical companies, including AbbVie, AstraZeneca, BeiGene, Bristol Myers Squibb, Genentech, Janssen, Merck, and others.
 

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

Research offers promising insights into the ideal frontline therapies for mantle cell lymphoma (MCL), but there are continued unmet needs in the relapsed/refractory setting, blood cancer specialists told colleagues. 

In the frontline setting, findings suggest that regimens should differ significantly on the basis of whether patients are older or younger, whereas more data are needed to understand whether treatment can overcome poor prognoses in patients with TP53 mutations, lymphoma specialist Nina Wagner-Johnston, MD, of Johns Hopkins University School of Medicine, Baltimore, said in a presentation at the annual meeting of the Society of Hematologic Oncology (SOHO) 2024 in Houston, Texas.

On the relapsed/refractory front, patients need better options after treatment with Bruton tyrosine kinase inhibitors or chimeric antigen receptor (CAR) T-cell therapy, Krish Patel, MD, a lymphoma specialist with Swedish Cancer Institute in Seattle, said in an adjoining presentation. Fortunately, he said, some treatments are showing early promise.

Here’s a closer look at the presentations by Dr. Wagner-Johnston and Dr. Patel.
 

Frontline MCL: Age Helps Determine Best Approach

“For older and less fit patients, the standard approach has typically been bendamustine (Bendeka, Treanda) and rituximab (Rituxan), and the median progression-free survival is about 4 years, with overall survival not reached at a median 5 years of follow-up,” Dr. Wagner-Johnston said. 

Low doses of the chemotherapy drug cytarabine have been added to the bendamustine-rituximab regimen, with encouraging results, she said. “Certainly there’s more toxicity associated even with lower doses, but those data look fairly promising.”

For younger and fit patients, “the standard of care approach has been to administer intensive chemoimmunotherapy that contains high-dose cytarabine, and then that’s typically followed with an autologous stem cell transplant,” she said. A 2016 study reported median progression-free survival of 8.5 years and median overall survival of 12.7 years.

Now, second-generation Bruton tyrosine kinase inhibitors “look very promising” in the frontline setting, Dr. Wagner-Johnston said.

The road has been rocky, however. The SHINE trial of more than 500 patients aged over 65 found that adding ibrutinib to bendamustine-rituximab improved progression-free survival. “However, progression-free survival did not [connect] to an overall survival benefit, and that’s likely due to the toxicity seen with ibrutinib,” she said. 

“It’s not surprising to many of you that ibrutinib has been removed from the FDA label for mantle cell lymphoma,” she said. However, “second-generation [Bruton tyrosine kinase inhibitors] are known to be associated with less toxicity and potentially increased potency.”

What about Bruton tyrosine kinase inhibitors in younger and fitter patients? The TRIANGLE trial demonstrated their benefit, Dr. Wagner-Johnston said, linking ibrutinib to improvement in progression-free survival. 

However, “it’s really too early to evaluate the statistical significance for overall survival.” And while the study looks at therapy without stem cell transplant, she believes it’s too early to know whether that’s a good option. 

Dr. Wagner-Johnston tackled another topic: Can Bruton tyrosine kinase inhibitors overcome the poor prognosis seen with MCL with TP53 mutation? For now, the limitations of research makes it “hard to know,” she said, although early results of the BOVen trial are promising. 
 

Relapsed/Refractory MCL: Better Options Are Still Needed

In his presentation, Dr. Patel spoke about therapy in patients with MCL and relapsed/refractory disease. “We know that outcomes for patients who progress on covalent [Bruton tyrosine kinase inhibitors] is really dismal,” he said. “This has been shown by multiple groups now across the globe.”

Noncovalent Bruton tyrosine kinase inhibitors are now an option, he noted. “We do understand that they work for some patients, and it can be quite useful, but even noncovalent [Bruton tyrosine kinase inhibitors] themselves are susceptible to resistance mutations. We’ve seen that in the [chronic lymphocytic leukemia] world.”

Dr. Patel asked the audience, “Why not just give everybody CAR T-cells, post-[Bruton tyrosine kinase inhibitors]? You get a CAR T-cell! You get a CAR T-cell! Everybody gets one.”

However, he noted, “Unfortunately, mantle cell lymphoma patients experience the worst high-grade toxicity when receiving CD19[-targeted] CAR T-cells.” 

Are there better options? At the moment, “really, really early data” suggest benefits from molecular glues and degraders, novel inhibitors, antibody-drug conjugates, novel CAR T-cells, and bispecific antibodies, Dr. Patel said.

“All of these tools are in clinical trials, and hopefully some of them will help,” he said.

Disclosures were not provided. Dr. Wagner-Johnston recently disclosed advisory committee/board of directors’ relationships with ADC Therapeutics, Regeneron, Calibr, and Verastem. Dr. Patel recently disclosed ties with a long list of pharmaceutical companies, including AbbVie, AstraZeneca, BeiGene, Bristol Myers Squibb, Genentech, Janssen, Merck, and others.
 

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

Bruton’s tyrosine kinase inhibitors such as ibrutinib, acalabrutinib, and zanubrutinib have revolutionized the treatment of chronic lymphocytic leukemia (CLL). But should patients take a break from them?

At the annual meeting of the Society of Hematologic Oncology, two hematologist-oncologists — Inhye Ahn, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts, and Kerry A. Rogers, MD, of Ohio State University in Columbus — faced off in a debate. Ahn said the drugs can indeed be discontinued, while Rogers argued against stopping the medications.

“When I talk to my own patient about standard of care options in CLL, I use the analogy of a marathon and a sprint,” Dr. Ahn said. A marathon refers to continuous treatment with Bruton’s kinase inhibitors given daily for years, while the sprint refers to the combination of venetoclax with an anti-CD20 monoclonal antibody given over 12 cycles for the frontline regimen and 2 years for refractory CLL.

“I tell them these are both considered very efficacious regimens and well tolerated, one is by IV [the venetoclax regimen] and the other isn’t [Bruton’s kinase inhibitors], and they have different toxicity profile. I ask them what would you do? The most common question that I get from my patient is, ‘why would anyone do a marathon?’ ”

It’s not solely the length of treatment that’s important, Dr. Ahn said, as toxicities from the long-term use of Bruton’s kinase inhibitors build up over time and can lead to hypertension, arrhythmia, and sudden cardiac death.

In addition, she said, infections can occur, as well as hampered vaccine response, an important risk in the era of the COVID-19 pandemic. The cost of the drugs is high and adds up over time, and continuous use can boost resistance.

Is there a way to turn the marathon of Bruton’s kinase inhibitor use into a sprint without hurting patients? The answer is yes, through temporary discontinuation, Dr. Ahn said, although she cautioned that early cessation could lead to disease flare. “We dipped into our own database of 84 CLL patients treated with ibrutinib, and our conclusion was that temporary dose interruption or dose reduction did not impact progression-free survival”

Moving forward, she said, “more research is needed to define the optimal regimen that would lead to treatment cessation, the optimal patient population, who would benefit most from the cessation strategy, treatment duration, and how we define success.” For her part, Dr. Rogers argued that the continuous use of Bruton’s kinase inhibitors is “really the most effective treatment we have in CLL.”

It’s clear that “responses deepen with continued treatment,” Dr. Rogers said, noting that remission times grow over years of treatment. She highlighted a 2022 study of patients with CLL who took ibrutinib that found complete remission or complete remission with incomplete hematologic recovery was 7% at 12 months and 34% at 7 years. When patients quit taking the drugs, “you don’t get to maximize your patient’s response to this treatment.”

Dr. Rogers also noted that the RESONATE-2 trial found that ibrutinib is linked to the longest median progression-free survival of any CLL treatment at 8.9 years. “That really struck me a very effective initial therapy.”

Indeed, “when you’re offering someone initial therapy with a Bruton’s kinase inhibitor as a continuous treatment strategy, you can tell people that they can expect a normal lifespan with this approach. That’s extremely important when you’re talking to patients about whether they might want to alter their leukemia treatment.”

Finally, she noted that discontinuation of ibrutinib was linked to shorter survival in early research. “This was the first suggestion that discontinuation is not good.”

Dr. Rogers said that discontinuing the drugs is sometimes necessary because of adverse events, but patients can “certainly switch to a more tolerable Bruton’s kinase inhibitor. With the options available today, that should be a strategy that’s considered.”

Audience members at the debate were invited to respond to a live online survey about whether Bruton’s kinase inhibitors can be discontinued. Among 49 respondents, most (52.3%) said no, 42.8% said yes, and the rest were undecided/other.

Disclosures for the speakers were not provided. Dr. Ahn disclosed consulting for BeiGene and AstraZeneca. Dr. Rogers disclosed receiving research funding from Genentech, AbbVie, Janssen, and Novartis; consulting for AstraZeneca, BeiGene, Janssen, Pharmacyclics, AbbVie, Genentech, and LOXO@Lilly; and receiving travel funding from AstraZeneca.

A version of this article appeared on Medscape.com.

Bruton’s tyrosine kinase inhibitors such as ibrutinib, acalabrutinib, and zanubrutinib have revolutionized the treatment of chronic lymphocytic leukemia (CLL). But should patients take a break from them?

At the annual meeting of the Society of Hematologic Oncology, two hematologist-oncologists — Inhye Ahn, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts, and Kerry A. Rogers, MD, of Ohio State University in Columbus — faced off in a debate. Ahn said the drugs can indeed be discontinued, while Rogers argued against stopping the medications.

“When I talk to my own patient about standard of care options in CLL, I use the analogy of a marathon and a sprint,” Dr. Ahn said. A marathon refers to continuous treatment with Bruton’s kinase inhibitors given daily for years, while the sprint refers to the combination of venetoclax with an anti-CD20 monoclonal antibody given over 12 cycles for the frontline regimen and 2 years for refractory CLL.

“I tell them these are both considered very efficacious regimens and well tolerated, one is by IV [the venetoclax regimen] and the other isn’t [Bruton’s kinase inhibitors], and they have different toxicity profile. I ask them what would you do? The most common question that I get from my patient is, ‘why would anyone do a marathon?’ ”

It’s not solely the length of treatment that’s important, Dr. Ahn said, as toxicities from the long-term use of Bruton’s kinase inhibitors build up over time and can lead to hypertension, arrhythmia, and sudden cardiac death.

In addition, she said, infections can occur, as well as hampered vaccine response, an important risk in the era of the COVID-19 pandemic. The cost of the drugs is high and adds up over time, and continuous use can boost resistance.

Is there a way to turn the marathon of Bruton’s kinase inhibitor use into a sprint without hurting patients? The answer is yes, through temporary discontinuation, Dr. Ahn said, although she cautioned that early cessation could lead to disease flare. “We dipped into our own database of 84 CLL patients treated with ibrutinib, and our conclusion was that temporary dose interruption or dose reduction did not impact progression-free survival”

Moving forward, she said, “more research is needed to define the optimal regimen that would lead to treatment cessation, the optimal patient population, who would benefit most from the cessation strategy, treatment duration, and how we define success.” For her part, Dr. Rogers argued that the continuous use of Bruton’s kinase inhibitors is “really the most effective treatment we have in CLL.”

It’s clear that “responses deepen with continued treatment,” Dr. Rogers said, noting that remission times grow over years of treatment. She highlighted a 2022 study of patients with CLL who took ibrutinib that found complete remission or complete remission with incomplete hematologic recovery was 7% at 12 months and 34% at 7 years. When patients quit taking the drugs, “you don’t get to maximize your patient’s response to this treatment.”

Dr. Rogers also noted that the RESONATE-2 trial found that ibrutinib is linked to the longest median progression-free survival of any CLL treatment at 8.9 years. “That really struck me a very effective initial therapy.”

Indeed, “when you’re offering someone initial therapy with a Bruton’s kinase inhibitor as a continuous treatment strategy, you can tell people that they can expect a normal lifespan with this approach. That’s extremely important when you’re talking to patients about whether they might want to alter their leukemia treatment.”

Finally, she noted that discontinuation of ibrutinib was linked to shorter survival in early research. “This was the first suggestion that discontinuation is not good.”

Dr. Rogers said that discontinuing the drugs is sometimes necessary because of adverse events, but patients can “certainly switch to a more tolerable Bruton’s kinase inhibitor. With the options available today, that should be a strategy that’s considered.”

Audience members at the debate were invited to respond to a live online survey about whether Bruton’s kinase inhibitors can be discontinued. Among 49 respondents, most (52.3%) said no, 42.8% said yes, and the rest were undecided/other.

Disclosures for the speakers were not provided. Dr. Ahn disclosed consulting for BeiGene and AstraZeneca. Dr. Rogers disclosed receiving research funding from Genentech, AbbVie, Janssen, and Novartis; consulting for AstraZeneca, BeiGene, Janssen, Pharmacyclics, AbbVie, Genentech, and LOXO@Lilly; and receiving travel funding from AstraZeneca.

A version of this article appeared on Medscape.com.

Bruton’s tyrosine kinase inhibitors such as ibrutinib, acalabrutinib, and zanubrutinib have revolutionized the treatment of chronic lymphocytic leukemia (CLL). But should patients take a break from them?

At the annual meeting of the Society of Hematologic Oncology, two hematologist-oncologists — Inhye Ahn, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts, and Kerry A. Rogers, MD, of Ohio State University in Columbus — faced off in a debate. Ahn said the drugs can indeed be discontinued, while Rogers argued against stopping the medications.

“When I talk to my own patient about standard of care options in CLL, I use the analogy of a marathon and a sprint,” Dr. Ahn said. A marathon refers to continuous treatment with Bruton’s kinase inhibitors given daily for years, while the sprint refers to the combination of venetoclax with an anti-CD20 monoclonal antibody given over 12 cycles for the frontline regimen and 2 years for refractory CLL.

“I tell them these are both considered very efficacious regimens and well tolerated, one is by IV [the venetoclax regimen] and the other isn’t [Bruton’s kinase inhibitors], and they have different toxicity profile. I ask them what would you do? The most common question that I get from my patient is, ‘why would anyone do a marathon?’ ”

It’s not solely the length of treatment that’s important, Dr. Ahn said, as toxicities from the long-term use of Bruton’s kinase inhibitors build up over time and can lead to hypertension, arrhythmia, and sudden cardiac death.

In addition, she said, infections can occur, as well as hampered vaccine response, an important risk in the era of the COVID-19 pandemic. The cost of the drugs is high and adds up over time, and continuous use can boost resistance.

Is there a way to turn the marathon of Bruton’s kinase inhibitor use into a sprint without hurting patients? The answer is yes, through temporary discontinuation, Dr. Ahn said, although she cautioned that early cessation could lead to disease flare. “We dipped into our own database of 84 CLL patients treated with ibrutinib, and our conclusion was that temporary dose interruption or dose reduction did not impact progression-free survival”

Moving forward, she said, “more research is needed to define the optimal regimen that would lead to treatment cessation, the optimal patient population, who would benefit most from the cessation strategy, treatment duration, and how we define success.” For her part, Dr. Rogers argued that the continuous use of Bruton’s kinase inhibitors is “really the most effective treatment we have in CLL.”

It’s clear that “responses deepen with continued treatment,” Dr. Rogers said, noting that remission times grow over years of treatment. She highlighted a 2022 study of patients with CLL who took ibrutinib that found complete remission or complete remission with incomplete hematologic recovery was 7% at 12 months and 34% at 7 years. When patients quit taking the drugs, “you don’t get to maximize your patient’s response to this treatment.”

Dr. Rogers also noted that the RESONATE-2 trial found that ibrutinib is linked to the longest median progression-free survival of any CLL treatment at 8.9 years. “That really struck me a very effective initial therapy.”

Indeed, “when you’re offering someone initial therapy with a Bruton’s kinase inhibitor as a continuous treatment strategy, you can tell people that they can expect a normal lifespan with this approach. That’s extremely important when you’re talking to patients about whether they might want to alter their leukemia treatment.”

Finally, she noted that discontinuation of ibrutinib was linked to shorter survival in early research. “This was the first suggestion that discontinuation is not good.”

Dr. Rogers said that discontinuing the drugs is sometimes necessary because of adverse events, but patients can “certainly switch to a more tolerable Bruton’s kinase inhibitor. With the options available today, that should be a strategy that’s considered.”

Audience members at the debate were invited to respond to a live online survey about whether Bruton’s kinase inhibitors can be discontinued. Among 49 respondents, most (52.3%) said no, 42.8% said yes, and the rest were undecided/other.

Disclosures for the speakers were not provided. Dr. Ahn disclosed consulting for BeiGene and AstraZeneca. Dr. Rogers disclosed receiving research funding from Genentech, AbbVie, Janssen, and Novartis; consulting for AstraZeneca, BeiGene, Janssen, Pharmacyclics, AbbVie, Genentech, and LOXO@Lilly; and receiving travel funding from AstraZeneca.

A version of this article appeared on Medscape.com.

When it comes to selecting a cost-effective, first-line tyrosine kinase inhibitor (TKI) for the treatment of chronic myeloid leukemia (CML), consider the treatment goal.

For survival, generic imatinib remains the gold standard, Elias Jabbour, MD, said during a session at the annual meeting of the Society of Hematologic Oncology in Houston.

For treatment-free remission, generic dasatinib or another generic second-generation TKI is needed, but not yet available in the United States, so generic imatinib is the best current choice, said Dr. Jabbour, a professor of medicine in the Department of Leukemia at the University of Texas MD Anderson Cancer Center, Houston.

Prior to the availability of generic imatinib, that wasn’t the case, he noted, explaining that second-generation TKIs met the cost-efficacy criteria, but now — at about $35 per month or about $400 per year — imatinib is far less expensive than the approximately $250,000 per year that brand-name second- and third-generation TKIs can currently cost.

To have treatment value, any new TKI should cost $40,000-$50,000 per quality-adjusted life-year, which is defined as the quality and duration of life after a novel TKI vs with the existing standard of care, Dr. Jabbour said.

And to qualify as a frontline therapy for CML, any new TKI should show efficacy superior to second-generation TKIs, in addition to meeting the cost-effectiveness criteria.

“It is hard to show survival benefit anymore, but we need to improve on the rate of durable deep molecular remission,” he said.

An equivalent or better long-term safety profile over at least 7-8 years is also needed.

Based on the current literature, none of the TKIs currently being evaluated has met that standard, although some trials are ongoing.

In a recent editorial, Dr. Jabbour and colleagues outlined treatment recommendations based on the currently available data. They suggested using lower-than-approved doses of TKIs in both frontline and later therapies to reduce toxicity, improve treatment compliance, and reduce costs.

They also suggested that the absence of an early molecular response might not warrant changing the TKI, especially when a second-generation TKI was used first line. 

When treatment-free remission is not a therapeutic goal or is unlikely, changing the TKI to improve the depth of molecular response, which has been shown to improve the likelihood of treatment-free remission, could do more harm than good, they argued. 

Instead, consider reducing the dose to manage reversible side effects, they suggested, noting that generic imatinib, and eventually generic dasatinib and possibly other generic second-generation TKIs, will likely offer 90% of patients with CML an effective, safe, and affordable treatment that normalizes life expectancy and leads to treatment-free remission in 30%-50% of patients over time.

Dr. Jabbour disclosed ties with AbbVie, Almoosa Specialist Hospital, Amgen, Ascentage Pharma, Biologix FZ, Hikma Pharmaceuticals, Kite, Takeda, and Terns.

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

When it comes to selecting a cost-effective, first-line tyrosine kinase inhibitor (TKI) for the treatment of chronic myeloid leukemia (CML), consider the treatment goal.

For survival, generic imatinib remains the gold standard, Elias Jabbour, MD, said during a session at the annual meeting of the Society of Hematologic Oncology in Houston.

For treatment-free remission, generic dasatinib or another generic second-generation TKI is needed, but not yet available in the United States, so generic imatinib is the best current choice, said Dr. Jabbour, a professor of medicine in the Department of Leukemia at the University of Texas MD Anderson Cancer Center, Houston.

Prior to the availability of generic imatinib, that wasn’t the case, he noted, explaining that second-generation TKIs met the cost-efficacy criteria, but now — at about $35 per month or about $400 per year — imatinib is far less expensive than the approximately $250,000 per year that brand-name second- and third-generation TKIs can currently cost.

To have treatment value, any new TKI should cost $40,000-$50,000 per quality-adjusted life-year, which is defined as the quality and duration of life after a novel TKI vs with the existing standard of care, Dr. Jabbour said.

And to qualify as a frontline therapy for CML, any new TKI should show efficacy superior to second-generation TKIs, in addition to meeting the cost-effectiveness criteria.

“It is hard to show survival benefit anymore, but we need to improve on the rate of durable deep molecular remission,” he said.

An equivalent or better long-term safety profile over at least 7-8 years is also needed.

Based on the current literature, none of the TKIs currently being evaluated has met that standard, although some trials are ongoing.

In a recent editorial, Dr. Jabbour and colleagues outlined treatment recommendations based on the currently available data. They suggested using lower-than-approved doses of TKIs in both frontline and later therapies to reduce toxicity, improve treatment compliance, and reduce costs.

They also suggested that the absence of an early molecular response might not warrant changing the TKI, especially when a second-generation TKI was used first line. 

When treatment-free remission is not a therapeutic goal or is unlikely, changing the TKI to improve the depth of molecular response, which has been shown to improve the likelihood of treatment-free remission, could do more harm than good, they argued. 

Instead, consider reducing the dose to manage reversible side effects, they suggested, noting that generic imatinib, and eventually generic dasatinib and possibly other generic second-generation TKIs, will likely offer 90% of patients with CML an effective, safe, and affordable treatment that normalizes life expectancy and leads to treatment-free remission in 30%-50% of patients over time.

Dr. Jabbour disclosed ties with AbbVie, Almoosa Specialist Hospital, Amgen, Ascentage Pharma, Biologix FZ, Hikma Pharmaceuticals, Kite, Takeda, and Terns.

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

When it comes to selecting a cost-effective, first-line tyrosine kinase inhibitor (TKI) for the treatment of chronic myeloid leukemia (CML), consider the treatment goal.

For survival, generic imatinib remains the gold standard, Elias Jabbour, MD, said during a session at the annual meeting of the Society of Hematologic Oncology in Houston.

For treatment-free remission, generic dasatinib or another generic second-generation TKI is needed, but not yet available in the United States, so generic imatinib is the best current choice, said Dr. Jabbour, a professor of medicine in the Department of Leukemia at the University of Texas MD Anderson Cancer Center, Houston.

Prior to the availability of generic imatinib, that wasn’t the case, he noted, explaining that second-generation TKIs met the cost-efficacy criteria, but now — at about $35 per month or about $400 per year — imatinib is far less expensive than the approximately $250,000 per year that brand-name second- and third-generation TKIs can currently cost.

To have treatment value, any new TKI should cost $40,000-$50,000 per quality-adjusted life-year, which is defined as the quality and duration of life after a novel TKI vs with the existing standard of care, Dr. Jabbour said.

And to qualify as a frontline therapy for CML, any new TKI should show efficacy superior to second-generation TKIs, in addition to meeting the cost-effectiveness criteria.

“It is hard to show survival benefit anymore, but we need to improve on the rate of durable deep molecular remission,” he said.

An equivalent or better long-term safety profile over at least 7-8 years is also needed.

Based on the current literature, none of the TKIs currently being evaluated has met that standard, although some trials are ongoing.

In a recent editorial, Dr. Jabbour and colleagues outlined treatment recommendations based on the currently available data. They suggested using lower-than-approved doses of TKIs in both frontline and later therapies to reduce toxicity, improve treatment compliance, and reduce costs.

They also suggested that the absence of an early molecular response might not warrant changing the TKI, especially when a second-generation TKI was used first line. 

When treatment-free remission is not a therapeutic goal or is unlikely, changing the TKI to improve the depth of molecular response, which has been shown to improve the likelihood of treatment-free remission, could do more harm than good, they argued. 

Instead, consider reducing the dose to manage reversible side effects, they suggested, noting that generic imatinib, and eventually generic dasatinib and possibly other generic second-generation TKIs, will likely offer 90% of patients with CML an effective, safe, and affordable treatment that normalizes life expectancy and leads to treatment-free remission in 30%-50% of patients over time.

Dr. Jabbour disclosed ties with AbbVie, Almoosa Specialist Hospital, Amgen, Ascentage Pharma, Biologix FZ, Hikma Pharmaceuticals, Kite, Takeda, and Terns.

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

Clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) are associated with an increased risk for breast cancer, and CHIP is associated with increased mortality in patients with colon cancer, according to the authors of new research.

These findings, drawn from almost 11,000 patients in the Women’s Health Initiative (WHI) study, add further evidence that CHIP and mCA drive solid tumor risk, alongside known associations with hematologic malignancies, reported lead author Pinkal Desai, MD, associate professor of medicine and clinical director of molecular aging at Englander Institute for Precision Medicine, Weill Cornell Medical College, New York City, and colleagues.
 

How This Study Differs From Others of Breast Cancer Risk Factors

“The independent effect of CHIP and mCA on risk and mortality from solid tumors has not been elucidated due to lack of detailed data on mortality outcomes and risk factors,” the investigators wrote in Cancer, although some previous studies have suggested a link.

In particular, the investigators highlighted a 2022 UK Biobank study, which reported an association between CHIP and lung cancer and a borderline association with breast cancer that did not quite reach statistical significance.

But the UK Biobank study was confined to a UK population, Dr. Desai noted in an interview, and the data were less detailed than those in the present investigation.

“In terms of risk, the part that was lacking in previous studies was a comprehensive assessment of risk factors that increase risk for all these cancers,” Dr. Desai said. “For example, for breast cancer, we had very detailed data on [participants’] Gail risk score, which is known to impact breast cancer risk. We also had mammogram data and colonoscopy data.”

In an accompanying editorial, Koichi Takahashi, MD, PhD , and Nehali Shah, BS, of The University of Texas MD Anderson Cancer Center, Houston, Texas, pointed out the same UK Biobank findings, then noted that CHIP has also been linked with worse overall survival in unselected cancer patients. Still, they wrote, “the impact of CH on cancer risk and mortality remains controversial due to conflicting data and context‐dependent effects,” necessitating studies like this one by Dr. Desai and colleagues.
 

How Was the Relationship Between CHIP, MCA, and Solid Tumor Risk Assessed?

To explore possible associations between CHIP, mCA, and solid tumors, the investigators analyzed whole genome sequencing data from 10,866 women in the WHI, a multi-study program that began in 1992 and involved 161,808 women in both observational and clinical trial cohorts.

In 2002, the first big data release from the WHI suggested that hormone replacement therapy (HRT) increased breast cancer risk, leading to widespread reduction in HRT use.

More recent reports continue to shape our understanding of these risks, suggesting differences across cancer types. For breast cancer, the WHI data suggested that HRT-associated risk was largely driven by formulations involving progesterone and estrogen, whereas estrogen-only formulations, now more common, are generally considered to present an acceptable risk profile for suitable patients.

The new study accounted for this potential HRT-associated risk, including by adjusting for patients who received HRT, type of HRT received, and duration of HRT received. According to Desai, this approach is commonly used when analyzing data from the WHI, nullifying concerns about the potentially deleterious effects of the hormones used in the study.

“Our question was not ‘does HRT cause cancer?’ ” Dr. Desai said in an interview. “But HRT can be linked to breast cancer risk and has a potential to be a confounder, and hence the above methodology.

“So I can say that the confounding/effect modification that HRT would have contributed to in the relationship between exposure (CH and mCA) and outcome (cancer) is well adjusted for as described above. This is standard in WHI analyses,” she continued.

“Every Women’s Health Initiative analysis that comes out — not just for our study — uses a standard method ... where you account for hormonal therapy,” Dr. Desai added, again noting that many other potential risk factors were considered, enabling a “detailed, robust” analysis.

Dr. Takahashi and Ms. Shah agreed. “A notable strength of this study is its adjustment for many confounding factors,” they wrote. “The cohort’s well‐annotated data on other known cancer risk factors allowed for a robust assessment of CH’s independent risk.”
 

How Do Findings Compare With Those of the UK Biobank Study?

CHIP was associated with a 30% increased risk for breast cancer (hazard ratio [HR], 1.30; 95% CI, 1.03-1.64; P = .02), strengthening the borderline association reported by the UK Biobank study.

In contrast with the UK Biobank study, CHIP was not associated with lung cancer risk, although this may have been caused by fewer cases of lung cancer and a lack of male patients, Dr. Desai suggested.

“The discrepancy between the studies lies in the risk of lung cancer, although the point estimate in the current study suggested a positive association,” wrote Dr. Takahashi and Ms. Shah.

As in the UK Biobank study, CHIP was not associated with increased risk of developing colorectal cancer.

Mortality analysis, however, which was not conducted in the UK Biobank study, offered a new insight: Patients with existing colorectal cancer and CHIP had a significantly higher mortality risk than those without CHIP. Before stage adjustment, risk for mortality among those with colorectal cancer and CHIP was fourfold higher than those without CHIP (HR, 3.99; 95% CI, 2.41-6.62; P < .001). After stage adjustment, CHIP was still associated with a twofold higher mortality risk (HR, 2.50; 95% CI, 1.32-4.72; P = .004).

The investigators’ first mCA analyses, which employed a cell fraction cutoff greater than 3%, were unfruitful. But raising the cell fraction threshold to 5% in an exploratory analysis showed that autosomal mCA was associated with a 39% increased risk for breast cancer (HR, 1.39; 95% CI, 1.06-1.83; P = .01). No such associations were found between mCA and colorectal or lung cancer, regardless of cell fraction threshold.

The original 3% cell fraction threshold was selected on the basis of previous studies reporting a link between mCA and hematologic malignancies at this cutoff, Dr. Desai said.

She and her colleagues said a higher 5% cutoff might be needed, as they suspected that the link between mCA and solid tumors may not be causal, requiring a higher mutation rate.
 

Why Do Results Differ Between These Types of Studies?

Dr. Takahashi and Ms. Shah suggested that one possible limitation of the new study, and an obstacle to comparing results with the UK Biobank study and others like it, goes beyond population heterogeneity; incongruent findings could also be explained by differences in whole genome sequencing (WGS) technique.

“Although WGS allows sensitive detection of mCA through broad genomic coverage, it is less effective at detecting CHIP with low variant allele frequency (VAF) due to its relatively shallow depth (30x),” they wrote. “Consequently, the prevalence of mCA (18.8%) was much higher than that of CHIP (8.3%) in this cohort, contrasting with other studies using deeper sequencing.” As a result, the present study may have underestimated CHIP prevalence because of shallow sequencing depth.

“This inconsistency is a common challenge in CH population studies due to the lack of standardized methodologies and the frequent reliance on preexisting data not originally intended for CH detection,” Dr. Takahashi and Ms. Shah said.

Even so, despite the “heavily context-dependent” nature of these reported risks, the body of evidence to date now offers a convincing biological rationale linking CH with cancer development and outcomes, they added.
 

How Do the CHIP- and mCA-associated Risks Differ Between Solid Tumors and Blood Cancers?

“[These solid tumor risks are] not causal in the way CHIP mutations are causal for blood cancers,” Dr. Desai said. “Here we are talking about solid tumor risk, and it’s kind of scattered. It’s not just breast cancer ... there’s also increased colon cancer mortality. So I feel these mutations are doing something different ... they are sort of an added factor.”

Specific mechanisms remain unclear, Dr. Desai said, although she speculated about possible impacts on the inflammatory state or alterations to the tumor microenvironment.

“These are blood cells, right?” Dr. Desai asked. “They’re everywhere, and they’re changing something inherently in these tumors.”
 

Future research and therapeutic development

Siddhartha Jaiswal, MD, PhD, assistant professor in the Department of Pathology at Stanford University in California, whose lab focuses on clonal hematopoiesis, said the causality question is central to future research.

“The key question is, are these mutations acting because they alter the function of blood cells in some way to promote cancer risk, or is it reflective of some sort of shared etiology that’s not causal?” Dr. Jaiswal said in an interview.

Available data support both possibilities.

On one side, “reasonable evidence” supports the noncausal view, Dr. Jaiswal noted, because telomere length is one of the most common genetic risk factors for clonal hematopoiesis and also for solid tumors, suggesting a shared genetic factor. On the other hand, CHIP and mCA could be directly protumorigenic via conferred disturbances of immune cell function.

When asked if both causal and noncausal factors could be at play, Dr. Jaiswal said, “yeah, absolutely.”

The presence of a causal association could be promising from a therapeutic standpoint.

“If it turns out that this association is driven by a direct causal effect of the mutations, perhaps related to immune cell function or dysfunction, then targeting that dysfunction could be a therapeutic path to improve outcomes in people, and there’s a lot of interest in this,” Dr. Jaiswal said. He went on to explain how a trial exploring this approach via interleukin-8 inhibition in lung cancer fell short.

Yet earlier intervention may still hold promise, according to experts.

“[This study] provokes the hypothesis that CH‐targeted interventions could potentially reduce cancer risk in the future,” Dr. Takahashi and Ms. Shah said in their editorial.

The WHI program is funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; and the Department of Health & Human Services. The investigators disclosed relationships with Eli Lilly, AbbVie, Celgene, and others. Dr. Jaiswal reported stock equity in a company that has an interest in clonal hematopoiesis.

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

Clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) are associated with an increased risk for breast cancer, and CHIP is associated with increased mortality in patients with colon cancer, according to the authors of new research.

These findings, drawn from almost 11,000 patients in the Women’s Health Initiative (WHI) study, add further evidence that CHIP and mCA drive solid tumor risk, alongside known associations with hematologic malignancies, reported lead author Pinkal Desai, MD, associate professor of medicine and clinical director of molecular aging at Englander Institute for Precision Medicine, Weill Cornell Medical College, New York City, and colleagues.
 

How This Study Differs From Others of Breast Cancer Risk Factors

“The independent effect of CHIP and mCA on risk and mortality from solid tumors has not been elucidated due to lack of detailed data on mortality outcomes and risk factors,” the investigators wrote in Cancer, although some previous studies have suggested a link.

In particular, the investigators highlighted a 2022 UK Biobank study, which reported an association between CHIP and lung cancer and a borderline association with breast cancer that did not quite reach statistical significance.

But the UK Biobank study was confined to a UK population, Dr. Desai noted in an interview, and the data were less detailed than those in the present investigation.

“In terms of risk, the part that was lacking in previous studies was a comprehensive assessment of risk factors that increase risk for all these cancers,” Dr. Desai said. “For example, for breast cancer, we had very detailed data on [participants’] Gail risk score, which is known to impact breast cancer risk. We also had mammogram data and colonoscopy data.”

In an accompanying editorial, Koichi Takahashi, MD, PhD , and Nehali Shah, BS, of The University of Texas MD Anderson Cancer Center, Houston, Texas, pointed out the same UK Biobank findings, then noted that CHIP has also been linked with worse overall survival in unselected cancer patients. Still, they wrote, “the impact of CH on cancer risk and mortality remains controversial due to conflicting data and context‐dependent effects,” necessitating studies like this one by Dr. Desai and colleagues.
 

How Was the Relationship Between CHIP, MCA, and Solid Tumor Risk Assessed?

To explore possible associations between CHIP, mCA, and solid tumors, the investigators analyzed whole genome sequencing data from 10,866 women in the WHI, a multi-study program that began in 1992 and involved 161,808 women in both observational and clinical trial cohorts.

In 2002, the first big data release from the WHI suggested that hormone replacement therapy (HRT) increased breast cancer risk, leading to widespread reduction in HRT use.

More recent reports continue to shape our understanding of these risks, suggesting differences across cancer types. For breast cancer, the WHI data suggested that HRT-associated risk was largely driven by formulations involving progesterone and estrogen, whereas estrogen-only formulations, now more common, are generally considered to present an acceptable risk profile for suitable patients.

The new study accounted for this potential HRT-associated risk, including by adjusting for patients who received HRT, type of HRT received, and duration of HRT received. According to Desai, this approach is commonly used when analyzing data from the WHI, nullifying concerns about the potentially deleterious effects of the hormones used in the study.

“Our question was not ‘does HRT cause cancer?’ ” Dr. Desai said in an interview. “But HRT can be linked to breast cancer risk and has a potential to be a confounder, and hence the above methodology.

“So I can say that the confounding/effect modification that HRT would have contributed to in the relationship between exposure (CH and mCA) and outcome (cancer) is well adjusted for as described above. This is standard in WHI analyses,” she continued.

“Every Women’s Health Initiative analysis that comes out — not just for our study — uses a standard method ... where you account for hormonal therapy,” Dr. Desai added, again noting that many other potential risk factors were considered, enabling a “detailed, robust” analysis.

Dr. Takahashi and Ms. Shah agreed. “A notable strength of this study is its adjustment for many confounding factors,” they wrote. “The cohort’s well‐annotated data on other known cancer risk factors allowed for a robust assessment of CH’s independent risk.”
 

How Do Findings Compare With Those of the UK Biobank Study?

CHIP was associated with a 30% increased risk for breast cancer (hazard ratio [HR], 1.30; 95% CI, 1.03-1.64; P = .02), strengthening the borderline association reported by the UK Biobank study.

In contrast with the UK Biobank study, CHIP was not associated with lung cancer risk, although this may have been caused by fewer cases of lung cancer and a lack of male patients, Dr. Desai suggested.

“The discrepancy between the studies lies in the risk of lung cancer, although the point estimate in the current study suggested a positive association,” wrote Dr. Takahashi and Ms. Shah.

As in the UK Biobank study, CHIP was not associated with increased risk of developing colorectal cancer.

Mortality analysis, however, which was not conducted in the UK Biobank study, offered a new insight: Patients with existing colorectal cancer and CHIP had a significantly higher mortality risk than those without CHIP. Before stage adjustment, risk for mortality among those with colorectal cancer and CHIP was fourfold higher than those without CHIP (HR, 3.99; 95% CI, 2.41-6.62; P < .001). After stage adjustment, CHIP was still associated with a twofold higher mortality risk (HR, 2.50; 95% CI, 1.32-4.72; P = .004).

The investigators’ first mCA analyses, which employed a cell fraction cutoff greater than 3%, were unfruitful. But raising the cell fraction threshold to 5% in an exploratory analysis showed that autosomal mCA was associated with a 39% increased risk for breast cancer (HR, 1.39; 95% CI, 1.06-1.83; P = .01). No such associations were found between mCA and colorectal or lung cancer, regardless of cell fraction threshold.

The original 3% cell fraction threshold was selected on the basis of previous studies reporting a link between mCA and hematologic malignancies at this cutoff, Dr. Desai said.

She and her colleagues said a higher 5% cutoff might be needed, as they suspected that the link between mCA and solid tumors may not be causal, requiring a higher mutation rate.
 

Why Do Results Differ Between These Types of Studies?

Dr. Takahashi and Ms. Shah suggested that one possible limitation of the new study, and an obstacle to comparing results with the UK Biobank study and others like it, goes beyond population heterogeneity; incongruent findings could also be explained by differences in whole genome sequencing (WGS) technique.

“Although WGS allows sensitive detection of mCA through broad genomic coverage, it is less effective at detecting CHIP with low variant allele frequency (VAF) due to its relatively shallow depth (30x),” they wrote. “Consequently, the prevalence of mCA (18.8%) was much higher than that of CHIP (8.3%) in this cohort, contrasting with other studies using deeper sequencing.” As a result, the present study may have underestimated CHIP prevalence because of shallow sequencing depth.

“This inconsistency is a common challenge in CH population studies due to the lack of standardized methodologies and the frequent reliance on preexisting data not originally intended for CH detection,” Dr. Takahashi and Ms. Shah said.

Even so, despite the “heavily context-dependent” nature of these reported risks, the body of evidence to date now offers a convincing biological rationale linking CH with cancer development and outcomes, they added.
 

How Do the CHIP- and mCA-associated Risks Differ Between Solid Tumors and Blood Cancers?

“[These solid tumor risks are] not causal in the way CHIP mutations are causal for blood cancers,” Dr. Desai said. “Here we are talking about solid tumor risk, and it’s kind of scattered. It’s not just breast cancer ... there’s also increased colon cancer mortality. So I feel these mutations are doing something different ... they are sort of an added factor.”

Specific mechanisms remain unclear, Dr. Desai said, although she speculated about possible impacts on the inflammatory state or alterations to the tumor microenvironment.

“These are blood cells, right?” Dr. Desai asked. “They’re everywhere, and they’re changing something inherently in these tumors.”
 

Future research and therapeutic development

Siddhartha Jaiswal, MD, PhD, assistant professor in the Department of Pathology at Stanford University in California, whose lab focuses on clonal hematopoiesis, said the causality question is central to future research.

“The key question is, are these mutations acting because they alter the function of blood cells in some way to promote cancer risk, or is it reflective of some sort of shared etiology that’s not causal?” Dr. Jaiswal said in an interview.

Available data support both possibilities.

On one side, “reasonable evidence” supports the noncausal view, Dr. Jaiswal noted, because telomere length is one of the most common genetic risk factors for clonal hematopoiesis and also for solid tumors, suggesting a shared genetic factor. On the other hand, CHIP and mCA could be directly protumorigenic via conferred disturbances of immune cell function.

When asked if both causal and noncausal factors could be at play, Dr. Jaiswal said, “yeah, absolutely.”

The presence of a causal association could be promising from a therapeutic standpoint.

“If it turns out that this association is driven by a direct causal effect of the mutations, perhaps related to immune cell function or dysfunction, then targeting that dysfunction could be a therapeutic path to improve outcomes in people, and there’s a lot of interest in this,” Dr. Jaiswal said. He went on to explain how a trial exploring this approach via interleukin-8 inhibition in lung cancer fell short.

Yet earlier intervention may still hold promise, according to experts.

“[This study] provokes the hypothesis that CH‐targeted interventions could potentially reduce cancer risk in the future,” Dr. Takahashi and Ms. Shah said in their editorial.

The WHI program is funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; and the Department of Health & Human Services. The investigators disclosed relationships with Eli Lilly, AbbVie, Celgene, and others. Dr. Jaiswal reported stock equity in a company that has an interest in clonal hematopoiesis.

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

Clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) are associated with an increased risk for breast cancer, and CHIP is associated with increased mortality in patients with colon cancer, according to the authors of new research.

These findings, drawn from almost 11,000 patients in the Women’s Health Initiative (WHI) study, add further evidence that CHIP and mCA drive solid tumor risk, alongside known associations with hematologic malignancies, reported lead author Pinkal Desai, MD, associate professor of medicine and clinical director of molecular aging at Englander Institute for Precision Medicine, Weill Cornell Medical College, New York City, and colleagues.
 

How This Study Differs From Others of Breast Cancer Risk Factors

“The independent effect of CHIP and mCA on risk and mortality from solid tumors has not been elucidated due to lack of detailed data on mortality outcomes and risk factors,” the investigators wrote in Cancer, although some previous studies have suggested a link.

In particular, the investigators highlighted a 2022 UK Biobank study, which reported an association between CHIP and lung cancer and a borderline association with breast cancer that did not quite reach statistical significance.

But the UK Biobank study was confined to a UK population, Dr. Desai noted in an interview, and the data were less detailed than those in the present investigation.

“In terms of risk, the part that was lacking in previous studies was a comprehensive assessment of risk factors that increase risk for all these cancers,” Dr. Desai said. “For example, for breast cancer, we had very detailed data on [participants’] Gail risk score, which is known to impact breast cancer risk. We also had mammogram data and colonoscopy data.”

In an accompanying editorial, Koichi Takahashi, MD, PhD , and Nehali Shah, BS, of The University of Texas MD Anderson Cancer Center, Houston, Texas, pointed out the same UK Biobank findings, then noted that CHIP has also been linked with worse overall survival in unselected cancer patients. Still, they wrote, “the impact of CH on cancer risk and mortality remains controversial due to conflicting data and context‐dependent effects,” necessitating studies like this one by Dr. Desai and colleagues.
 

How Was the Relationship Between CHIP, MCA, and Solid Tumor Risk Assessed?

To explore possible associations between CHIP, mCA, and solid tumors, the investigators analyzed whole genome sequencing data from 10,866 women in the WHI, a multi-study program that began in 1992 and involved 161,808 women in both observational and clinical trial cohorts.

In 2002, the first big data release from the WHI suggested that hormone replacement therapy (HRT) increased breast cancer risk, leading to widespread reduction in HRT use.

More recent reports continue to shape our understanding of these risks, suggesting differences across cancer types. For breast cancer, the WHI data suggested that HRT-associated risk was largely driven by formulations involving progesterone and estrogen, whereas estrogen-only formulations, now more common, are generally considered to present an acceptable risk profile for suitable patients.

The new study accounted for this potential HRT-associated risk, including by adjusting for patients who received HRT, type of HRT received, and duration of HRT received. According to Desai, this approach is commonly used when analyzing data from the WHI, nullifying concerns about the potentially deleterious effects of the hormones used in the study.

“Our question was not ‘does HRT cause cancer?’ ” Dr. Desai said in an interview. “But HRT can be linked to breast cancer risk and has a potential to be a confounder, and hence the above methodology.

“So I can say that the confounding/effect modification that HRT would have contributed to in the relationship between exposure (CH and mCA) and outcome (cancer) is well adjusted for as described above. This is standard in WHI analyses,” she continued.

“Every Women’s Health Initiative analysis that comes out — not just for our study — uses a standard method ... where you account for hormonal therapy,” Dr. Desai added, again noting that many other potential risk factors were considered, enabling a “detailed, robust” analysis.

Dr. Takahashi and Ms. Shah agreed. “A notable strength of this study is its adjustment for many confounding factors,” they wrote. “The cohort’s well‐annotated data on other known cancer risk factors allowed for a robust assessment of CH’s independent risk.”
 

How Do Findings Compare With Those of the UK Biobank Study?

CHIP was associated with a 30% increased risk for breast cancer (hazard ratio [HR], 1.30; 95% CI, 1.03-1.64; P = .02), strengthening the borderline association reported by the UK Biobank study.

In contrast with the UK Biobank study, CHIP was not associated with lung cancer risk, although this may have been caused by fewer cases of lung cancer and a lack of male patients, Dr. Desai suggested.

“The discrepancy between the studies lies in the risk of lung cancer, although the point estimate in the current study suggested a positive association,” wrote Dr. Takahashi and Ms. Shah.

As in the UK Biobank study, CHIP was not associated with increased risk of developing colorectal cancer.

Mortality analysis, however, which was not conducted in the UK Biobank study, offered a new insight: Patients with existing colorectal cancer and CHIP had a significantly higher mortality risk than those without CHIP. Before stage adjustment, risk for mortality among those with colorectal cancer and CHIP was fourfold higher than those without CHIP (HR, 3.99; 95% CI, 2.41-6.62; P < .001). After stage adjustment, CHIP was still associated with a twofold higher mortality risk (HR, 2.50; 95% CI, 1.32-4.72; P = .004).

The investigators’ first mCA analyses, which employed a cell fraction cutoff greater than 3%, were unfruitful. But raising the cell fraction threshold to 5% in an exploratory analysis showed that autosomal mCA was associated with a 39% increased risk for breast cancer (HR, 1.39; 95% CI, 1.06-1.83; P = .01). No such associations were found between mCA and colorectal or lung cancer, regardless of cell fraction threshold.

The original 3% cell fraction threshold was selected on the basis of previous studies reporting a link between mCA and hematologic malignancies at this cutoff, Dr. Desai said.

She and her colleagues said a higher 5% cutoff might be needed, as they suspected that the link between mCA and solid tumors may not be causal, requiring a higher mutation rate.
 

Why Do Results Differ Between These Types of Studies?

Dr. Takahashi and Ms. Shah suggested that one possible limitation of the new study, and an obstacle to comparing results with the UK Biobank study and others like it, goes beyond population heterogeneity; incongruent findings could also be explained by differences in whole genome sequencing (WGS) technique.

“Although WGS allows sensitive detection of mCA through broad genomic coverage, it is less effective at detecting CHIP with low variant allele frequency (VAF) due to its relatively shallow depth (30x),” they wrote. “Consequently, the prevalence of mCA (18.8%) was much higher than that of CHIP (8.3%) in this cohort, contrasting with other studies using deeper sequencing.” As a result, the present study may have underestimated CHIP prevalence because of shallow sequencing depth.

“This inconsistency is a common challenge in CH population studies due to the lack of standardized methodologies and the frequent reliance on preexisting data not originally intended for CH detection,” Dr. Takahashi and Ms. Shah said.

Even so, despite the “heavily context-dependent” nature of these reported risks, the body of evidence to date now offers a convincing biological rationale linking CH with cancer development and outcomes, they added.
 

How Do the CHIP- and mCA-associated Risks Differ Between Solid Tumors and Blood Cancers?

“[These solid tumor risks are] not causal in the way CHIP mutations are causal for blood cancers,” Dr. Desai said. “Here we are talking about solid tumor risk, and it’s kind of scattered. It’s not just breast cancer ... there’s also increased colon cancer mortality. So I feel these mutations are doing something different ... they are sort of an added factor.”

Specific mechanisms remain unclear, Dr. Desai said, although she speculated about possible impacts on the inflammatory state or alterations to the tumor microenvironment.

“These are blood cells, right?” Dr. Desai asked. “They’re everywhere, and they’re changing something inherently in these tumors.”
 

Future research and therapeutic development

Siddhartha Jaiswal, MD, PhD, assistant professor in the Department of Pathology at Stanford University in California, whose lab focuses on clonal hematopoiesis, said the causality question is central to future research.

“The key question is, are these mutations acting because they alter the function of blood cells in some way to promote cancer risk, or is it reflective of some sort of shared etiology that’s not causal?” Dr. Jaiswal said in an interview.

Available data support both possibilities.

On one side, “reasonable evidence” supports the noncausal view, Dr. Jaiswal noted, because telomere length is one of the most common genetic risk factors for clonal hematopoiesis and also for solid tumors, suggesting a shared genetic factor. On the other hand, CHIP and mCA could be directly protumorigenic via conferred disturbances of immune cell function.

When asked if both causal and noncausal factors could be at play, Dr. Jaiswal said, “yeah, absolutely.”

The presence of a causal association could be promising from a therapeutic standpoint.

“If it turns out that this association is driven by a direct causal effect of the mutations, perhaps related to immune cell function or dysfunction, then targeting that dysfunction could be a therapeutic path to improve outcomes in people, and there’s a lot of interest in this,” Dr. Jaiswal said. He went on to explain how a trial exploring this approach via interleukin-8 inhibition in lung cancer fell short.

Yet earlier intervention may still hold promise, according to experts.

“[This study] provokes the hypothesis that CH‐targeted interventions could potentially reduce cancer risk in the future,” Dr. Takahashi and Ms. Shah said in their editorial.

The WHI program is funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; and the Department of Health & Human Services. The investigators disclosed relationships with Eli Lilly, AbbVie, Celgene, and others. Dr. Jaiswal reported stock equity in a company that has an interest in clonal hematopoiesis.

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

Each year in the United States, approximately 1.7 million Americans are diagnosed with a potentially lethal malignancy. Typical therapies of choice include surgery, radiation, and occasionally, toxic chemotherapy (chemo) — approaches that eliminate the cancer in about 1,000,000 of these cases. The remaining 700,000 or so often proceed to chemotherapy either immediately or upon cancer recurrence, spread, or newly recognized metastases. “Cures” after that point are rare.

I’m speaking in generalities, understanding that each cancer and each patient is unique.
 

Chemotherapy

Chemotherapy alone can cure a small number of cancer types. When added to radiation or surgery, chemotherapy can help to cure a wider range of cancer types. As an add-on, chemotherapy can extend the length and quality of life for many patients with cancer. Since chemotherapy is by definition “toxic,” it can also shorten the duration or harm the quality of life and provide false hope. The Table summarizes what chemotherapy can and cannot achieve in selected cancer types.

• Lack of response (the tumor failed to shrink).
• Progression (the cancer may have grown or spread further).
• Adverse side effects were too severe to continue.

The drugs used in second-line chemo will typically be different from those used in first line, sometimes because cancer cells can develop resistance to chemotherapy drugs over time. Moreover, the goal of second-line chemo may differ from that of first-line therapy. Rather than chiefly aiming for a cure, second-line treatment might focus on slowing cancer growth, managing symptoms, or improving quality of life. Unfortunately, not every type of cancer has a readily available second-line option.

Third-line treatment. Third-line options come into play when both the initial course of chemo (first line) and the subsequent treatment (second line) have failed to achieve remission or control the cancer’s spread. Owing to the progressive nature of advanced cancers, patients might not be eligible or healthy enough for third-line therapy. Depending on cancer type, the patient’s general health, and response to previous treatments, third-line options could include:

• New or different chemotherapy drugs compared with prior lines.
• Surgery to debulk the tumor.
• Radiation for symptom control.
• Targeted therapy: drugs designed to target specific vulnerabilities in cancer cells.
• Immunotherapy: agents that help the body’s immune system fight cancer cells.
• Clinical trials testing new or investigational treatments, which may be applicable at any time, depending on the questions being addressed.

The goals of third-line therapy may shift from aiming for a cure to managing symptoms, improving quality of life, and potentially slowing cancer growth. The decision to pursue third-line therapy involves careful consideration by the doctor and patient, weighing the potential benefits and risks of treatment considering the individual’s overall health and specific situation.

It’s important to have realistic expectations about the potential outcomes of third-line therapy. Although remission may be unlikely, third-line therapy can still play a role in managing the disease.

Navigating advanced cancer treatment is very complex. The patient and physician must together consider detailed explanations and clarifications to set expectations and make informed decisions about care.
 

Interventions to Consider Earlier

In traditional clinical oncology practice, other interventions are possible, but these may not be offered until treatment has reached the third line:

• Molecular testing.
• Palliation.
• Clinical trials.
• Innovative testing to guide targeted therapy by ascertaining which agents are most likely (or not likely at all) to be effective.

I would argue that the patient’s interests are better served by considering and offering these other interventions much earlier, even before starting first-line chemotherapy.

Molecular testing. The best time for molecular testing of a new malignant tumor is typically at the time of diagnosis. Here’s why:

• Molecular testing helps identify specific genetic mutations in the cancer cells. This information can be crucial for selecting targeted therapies that are most effective against those specific mutations. Early detection allows for the most treatment options. For example, for non–small cell lung cancer, early is best because treatment and outcomes may well be changed by test results.
• Knowing the tumor’s molecular makeup can help determine whether a patient qualifies for clinical trials of new drugs designed for specific mutations.
• Some molecular markers can offer information about the tumor’s aggressiveness and potential for metastasis so that prognosis can be informed.

Molecular testing can be a valuable tool throughout a cancer patient’s journey. With genetically diverse tumors, the initial biopsy might not capture the full picture. Molecular testing of circulating tumor DNA can be used to monitor a patient’s response to treatment and detect potential mutations that might arise during treatment resistance. Retesting after metastasis can provide additional information that can aid in treatment decisions.

Palliative care. The ideal time to discuss palliative care with a patient with cancer is early in the diagnosis and treatment process. Palliative care is not the same as hospice care; it isn’t just about end-of-life. Palliative care focuses on improving a patient’s quality of life throughout cancer treatment. Palliative care specialists can address a wide range of symptoms a patient might experience from cancer or its treatment, including pain, fatigue, nausea, and anxiety.

Early discussions allow for a more comprehensive care plan. Open communication about all treatment options, including palliative care, empowers patients to make informed decisions about their care goals and preferences.

Specific situations where discussing palliative care might be appropriate are:

• Soon after a cancer diagnosis.
• If the patient experiences significant side effects from cancer treatment.
• When considering different treatment options, palliative care can complement those treatments.
• In advanced stages of cancer, to focus on comfort and quality of life.

Clinical trials. Participation in a clinical trial to explore new or investigational treatments should always be considered.

In theory, clinical trials should be an option at any time in the patient’s course. But the organized clinical trial experience may not be available or appropriate. Then, the individual becomes a de facto “clinical trial with an n of 1.” Read this brief open-access blog post at Cancer Commons to learn more about that circumstance.

Innovative testing. The best choice of chemotherapeutic or targeted therapies is often unclear. The clinician is likely to follow published guidelines, often from the National Comprehensive Cancer Network.

These are evidence based and driven by consensus of experts. But guideline-recommended therapy is not always effective, and weeks or months can pass before this ineffectiveness becomes apparent. Thus, many researchers and companies are seeking methods of testing each patient’s specific cancer to determine in advance, or very quickly, whether a particular drug is likely to be effective.

Read more about these leading innovations:

SAGE Oncotest: Entering the Next Generation of Tailored Cancer Treatment

Alibrex: A New Blood Test to Reveal Whether a Cancer Treatment is Working

PARIS Test Uses Lab-Grown Mini-Tumors to Find a Patient’s Best Treatment

Using Live Cells from Patients to Find the Right Cancer Drug

Other innovative therapies under investigation could even be agnostic to cancer type:

Treating Pancreatic Cancer: Could Metabolism — Not Genomics — Be the Key?

High-Energy Blue Light Powers a Promising New Treatment to Destroy Cancer Cells

All-Clear Follow-Up: Hydrogen Peroxide Appears to Treat Oral and Skin Lesions

Cancer is a tough nut to crack. Many people and organizations are trying very hard. So much is being learned. Some approaches will be effective. We can all hope.

Dr. Lundberg, editor in chief, Cancer Commons, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Each year in the United States, approximately 1.7 million Americans are diagnosed with a potentially lethal malignancy. Typical therapies of choice include surgery, radiation, and occasionally, toxic chemotherapy (chemo) — approaches that eliminate the cancer in about 1,000,000 of these cases. The remaining 700,000 or so often proceed to chemotherapy either immediately or upon cancer recurrence, spread, or newly recognized metastases. “Cures” after that point are rare.

I’m speaking in generalities, understanding that each cancer and each patient is unique.
 

Chemotherapy

Chemotherapy alone can cure a small number of cancer types. When added to radiation or surgery, chemotherapy can help to cure a wider range of cancer types. As an add-on, chemotherapy can extend the length and quality of life for many patients with cancer. Since chemotherapy is by definition “toxic,” it can also shorten the duration or harm the quality of life and provide false hope. The Table summarizes what chemotherapy can and cannot achieve in selected cancer types.

• Lack of response (the tumor failed to shrink).
• Progression (the cancer may have grown or spread further).
• Adverse side effects were too severe to continue.

The drugs used in second-line chemo will typically be different from those used in first line, sometimes because cancer cells can develop resistance to chemotherapy drugs over time. Moreover, the goal of second-line chemo may differ from that of first-line therapy. Rather than chiefly aiming for a cure, second-line treatment might focus on slowing cancer growth, managing symptoms, or improving quality of life. Unfortunately, not every type of cancer has a readily available second-line option.

Third-line treatment. Third-line options come into play when both the initial course of chemo (first line) and the subsequent treatment (second line) have failed to achieve remission or control the cancer’s spread. Owing to the progressive nature of advanced cancers, patients might not be eligible or healthy enough for third-line therapy. Depending on cancer type, the patient’s general health, and response to previous treatments, third-line options could include:

• New or different chemotherapy drugs compared with prior lines.
• Surgery to debulk the tumor.
• Radiation for symptom control.
• Targeted therapy: drugs designed to target specific vulnerabilities in cancer cells.
• Immunotherapy: agents that help the body’s immune system fight cancer cells.
• Clinical trials testing new or investigational treatments, which may be applicable at any time, depending on the questions being addressed.

The goals of third-line therapy may shift from aiming for a cure to managing symptoms, improving quality of life, and potentially slowing cancer growth. The decision to pursue third-line therapy involves careful consideration by the doctor and patient, weighing the potential benefits and risks of treatment considering the individual’s overall health and specific situation.

It’s important to have realistic expectations about the potential outcomes of third-line therapy. Although remission may be unlikely, third-line therapy can still play a role in managing the disease.

Navigating advanced cancer treatment is very complex. The patient and physician must together consider detailed explanations and clarifications to set expectations and make informed decisions about care.
 

Interventions to Consider Earlier

In traditional clinical oncology practice, other interventions are possible, but these may not be offered until treatment has reached the third line:

• Molecular testing.
• Palliation.
• Clinical trials.
• Innovative testing to guide targeted therapy by ascertaining which agents are most likely (or not likely at all) to be effective.

I would argue that the patient’s interests are better served by considering and offering these other interventions much earlier, even before starting first-line chemotherapy.

Molecular testing. The best time for molecular testing of a new malignant tumor is typically at the time of diagnosis. Here’s why:

• Molecular testing helps identify specific genetic mutations in the cancer cells. This information can be crucial for selecting targeted therapies that are most effective against those specific mutations. Early detection allows for the most treatment options. For example, for non–small cell lung cancer, early is best because treatment and outcomes may well be changed by test results.
• Knowing the tumor’s molecular makeup can help determine whether a patient qualifies for clinical trials of new drugs designed for specific mutations.
• Some molecular markers can offer information about the tumor’s aggressiveness and potential for metastasis so that prognosis can be informed.

Molecular testing can be a valuable tool throughout a cancer patient’s journey. With genetically diverse tumors, the initial biopsy might not capture the full picture. Molecular testing of circulating tumor DNA can be used to monitor a patient’s response to treatment and detect potential mutations that might arise during treatment resistance. Retesting after metastasis can provide additional information that can aid in treatment decisions.

Palliative care. The ideal time to discuss palliative care with a patient with cancer is early in the diagnosis and treatment process. Palliative care is not the same as hospice care; it isn’t just about end-of-life. Palliative care focuses on improving a patient’s quality of life throughout cancer treatment. Palliative care specialists can address a wide range of symptoms a patient might experience from cancer or its treatment, including pain, fatigue, nausea, and anxiety.

Early discussions allow for a more comprehensive care plan. Open communication about all treatment options, including palliative care, empowers patients to make informed decisions about their care goals and preferences.

Specific situations where discussing palliative care might be appropriate are:

• Soon after a cancer diagnosis.
• If the patient experiences significant side effects from cancer treatment.
• When considering different treatment options, palliative care can complement those treatments.
• In advanced stages of cancer, to focus on comfort and quality of life.

Clinical trials. Participation in a clinical trial to explore new or investigational treatments should always be considered.

In theory, clinical trials should be an option at any time in the patient’s course. But the organized clinical trial experience may not be available or appropriate. Then, the individual becomes a de facto “clinical trial with an n of 1.” Read this brief open-access blog post at Cancer Commons to learn more about that circumstance.

Innovative testing. The best choice of chemotherapeutic or targeted therapies is often unclear. The clinician is likely to follow published guidelines, often from the National Comprehensive Cancer Network.

These are evidence based and driven by consensus of experts. But guideline-recommended therapy is not always effective, and weeks or months can pass before this ineffectiveness becomes apparent. Thus, many researchers and companies are seeking methods of testing each patient’s specific cancer to determine in advance, or very quickly, whether a particular drug is likely to be effective.

Read more about these leading innovations:

SAGE Oncotest: Entering the Next Generation of Tailored Cancer Treatment

Alibrex: A New Blood Test to Reveal Whether a Cancer Treatment is Working

PARIS Test Uses Lab-Grown Mini-Tumors to Find a Patient’s Best Treatment

Using Live Cells from Patients to Find the Right Cancer Drug

Other innovative therapies under investigation could even be agnostic to cancer type:

Treating Pancreatic Cancer: Could Metabolism — Not Genomics — Be the Key?

High-Energy Blue Light Powers a Promising New Treatment to Destroy Cancer Cells

All-Clear Follow-Up: Hydrogen Peroxide Appears to Treat Oral and Skin Lesions

Cancer is a tough nut to crack. Many people and organizations are trying very hard. So much is being learned. Some approaches will be effective. We can all hope.

Dr. Lundberg, editor in chief, Cancer Commons, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Each year in the United States, approximately 1.7 million Americans are diagnosed with a potentially lethal malignancy. Typical therapies of choice include surgery, radiation, and occasionally, toxic chemotherapy (chemo) — approaches that eliminate the cancer in about 1,000,000 of these cases. The remaining 700,000 or so often proceed to chemotherapy either immediately or upon cancer recurrence, spread, or newly recognized metastases. “Cures” after that point are rare.

I’m speaking in generalities, understanding that each cancer and each patient is unique.
 

Chemotherapy

Chemotherapy alone can cure a small number of cancer types. When added to radiation or surgery, chemotherapy can help to cure a wider range of cancer types. As an add-on, chemotherapy can extend the length and quality of life for many patients with cancer. Since chemotherapy is by definition “toxic,” it can also shorten the duration or harm the quality of life and provide false hope. The Table summarizes what chemotherapy can and cannot achieve in selected cancer types.

• Lack of response (the tumor failed to shrink).
• Progression (the cancer may have grown or spread further).
• Adverse side effects were too severe to continue.

The drugs used in second-line chemo will typically be different from those used in first line, sometimes because cancer cells can develop resistance to chemotherapy drugs over time. Moreover, the goal of second-line chemo may differ from that of first-line therapy. Rather than chiefly aiming for a cure, second-line treatment might focus on slowing cancer growth, managing symptoms, or improving quality of life. Unfortunately, not every type of cancer has a readily available second-line option.

Third-line treatment. Third-line options come into play when both the initial course of chemo (first line) and the subsequent treatment (second line) have failed to achieve remission or control the cancer’s spread. Owing to the progressive nature of advanced cancers, patients might not be eligible or healthy enough for third-line therapy. Depending on cancer type, the patient’s general health, and response to previous treatments, third-line options could include:

• New or different chemotherapy drugs compared with prior lines.
• Surgery to debulk the tumor.
• Radiation for symptom control.
• Targeted therapy: drugs designed to target specific vulnerabilities in cancer cells.
• Immunotherapy: agents that help the body’s immune system fight cancer cells.
• Clinical trials testing new or investigational treatments, which may be applicable at any time, depending on the questions being addressed.

The goals of third-line therapy may shift from aiming for a cure to managing symptoms, improving quality of life, and potentially slowing cancer growth. The decision to pursue third-line therapy involves careful consideration by the doctor and patient, weighing the potential benefits and risks of treatment considering the individual’s overall health and specific situation.

It’s important to have realistic expectations about the potential outcomes of third-line therapy. Although remission may be unlikely, third-line therapy can still play a role in managing the disease.

Navigating advanced cancer treatment is very complex. The patient and physician must together consider detailed explanations and clarifications to set expectations and make informed decisions about care.
 

Interventions to Consider Earlier

In traditional clinical oncology practice, other interventions are possible, but these may not be offered until treatment has reached the third line:

• Molecular testing.
• Palliation.
• Clinical trials.
• Innovative testing to guide targeted therapy by ascertaining which agents are most likely (or not likely at all) to be effective.

I would argue that the patient’s interests are better served by considering and offering these other interventions much earlier, even before starting first-line chemotherapy.

Molecular testing. The best time for molecular testing of a new malignant tumor is typically at the time of diagnosis. Here’s why:

• Molecular testing helps identify specific genetic mutations in the cancer cells. This information can be crucial for selecting targeted therapies that are most effective against those specific mutations. Early detection allows for the most treatment options. For example, for non–small cell lung cancer, early is best because treatment and outcomes may well be changed by test results.
• Knowing the tumor’s molecular makeup can help determine whether a patient qualifies for clinical trials of new drugs designed for specific mutations.
• Some molecular markers can offer information about the tumor’s aggressiveness and potential for metastasis so that prognosis can be informed.

Molecular testing can be a valuable tool throughout a cancer patient’s journey. With genetically diverse tumors, the initial biopsy might not capture the full picture. Molecular testing of circulating tumor DNA can be used to monitor a patient’s response to treatment and detect potential mutations that might arise during treatment resistance. Retesting after metastasis can provide additional information that can aid in treatment decisions.

Palliative care. The ideal time to discuss palliative care with a patient with cancer is early in the diagnosis and treatment process. Palliative care is not the same as hospice care; it isn’t just about end-of-life. Palliative care focuses on improving a patient’s quality of life throughout cancer treatment. Palliative care specialists can address a wide range of symptoms a patient might experience from cancer or its treatment, including pain, fatigue, nausea, and anxiety.

Early discussions allow for a more comprehensive care plan. Open communication about all treatment options, including palliative care, empowers patients to make informed decisions about their care goals and preferences.

Specific situations where discussing palliative care might be appropriate are:

• Soon after a cancer diagnosis.
• If the patient experiences significant side effects from cancer treatment.
• When considering different treatment options, palliative care can complement those treatments.
• In advanced stages of cancer, to focus on comfort and quality of life.

Clinical trials. Participation in a clinical trial to explore new or investigational treatments should always be considered.

In theory, clinical trials should be an option at any time in the patient’s course. But the organized clinical trial experience may not be available or appropriate. Then, the individual becomes a de facto “clinical trial with an n of 1.” Read this brief open-access blog post at Cancer Commons to learn more about that circumstance.

Innovative testing. The best choice of chemotherapeutic or targeted therapies is often unclear. The clinician is likely to follow published guidelines, often from the National Comprehensive Cancer Network.

These are evidence based and driven by consensus of experts. But guideline-recommended therapy is not always effective, and weeks or months can pass before this ineffectiveness becomes apparent. Thus, many researchers and companies are seeking methods of testing each patient’s specific cancer to determine in advance, or very quickly, whether a particular drug is likely to be effective.

Read more about these leading innovations:

SAGE Oncotest: Entering the Next Generation of Tailored Cancer Treatment

Alibrex: A New Blood Test to Reveal Whether a Cancer Treatment is Working

PARIS Test Uses Lab-Grown Mini-Tumors to Find a Patient’s Best Treatment

Using Live Cells from Patients to Find the Right Cancer Drug

Other innovative therapies under investigation could even be agnostic to cancer type:

Treating Pancreatic Cancer: Could Metabolism — Not Genomics — Be the Key?

High-Energy Blue Light Powers a Promising New Treatment to Destroy Cancer Cells

All-Clear Follow-Up: Hydrogen Peroxide Appears to Treat Oral and Skin Lesions

Cancer is a tough nut to crack. Many people and organizations are trying very hard. So much is being learned. Some approaches will be effective. We can all hope.

Dr. Lundberg, editor in chief, Cancer Commons, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Childhood cancers represent a diverse group of neoplasms, and thanks to advances in treatment, survival rates have improved significantly. Today, more than 80%-85% of children diagnosed with cancer in developed countries survive into adulthood.

This increase in survival has brought new challenges, however. Compared with the general population, childhood cancer survivors (CCS) are at a notably higher risk for early mortality, developing secondary cancers, and experiencing various long-term clinical and psychosocial issues stemming from their disease or its treatment.

Long-term follow-up care for CCS is a complex and evolving field. Despite ongoing efforts to establish global and national guidelines, current evidence indicates that the care and management of these patients remain suboptimal.

Sexual dysfunction is a common and significant late effect among CCS. The disruptions caused by cancer and its treatment can interfere with normal physiological and psychological development, leading to issues with sexual function. This aspect of health is critical as it influences not just physical well-being but also psychosocial, developmental, and emotional health.
 

Characteristics and Mechanisms

Sexual functioning encompasses the physiological and psychological aspects of sexual behavior, including desire, arousal, orgasm, sexual pleasure, and overall satisfaction.

As CCS reach adolescence or adulthood, they often face sexual and reproductive issues, particularly as they enter romantic relationships.

Sexual functioning is a complex process that relies on the interaction of various factors, including physiological health, psychosexual development, romantic relationships, body image, and desire.

Despite its importance, the impact of childhood cancer on sexual function is often overlooked, even though cancer and its treatments can have lifelong effects. 
 

Sexual Function in CCS

A recent review aimed to summarize the existing research on sexual function among CCS, highlighting assessment tools, key stages of psychosexual development, common sexual problems, and the prevalence of sexual dysfunction.

The review study included 22 studies published between 2000 and 2022, comprising two qualitative, six cohort, and 14 cross-sectional studies.

Most CCS reached all key stages of psychosexual development at an average age of 29.8 years. Although some milestones were achieved later than is typical, many survivors felt they reached these stages at the appropriate time. Sexual initiation was less common among those who had undergone intensive neurotoxic treatments, such as those diagnosed with brain tumors or leukemia in childhood.

In a cross-sectional study of CCS aged 17-39 years, about one third had never engaged in sexual intercourse, 41.4% reported never experiencing sexual attraction, 44.8% were dissatisfied with their sex lives, and many rarely felt sexually attractive to others. Another study found that common issues among CCS included a lack of interest in sex (30%), difficulty enjoying sex (24%), and difficulty becoming aroused (23%). However, comparing and analyzing these problems was challenging due to the lack of standardized assessment criteria.

The prevalence of sexual dysfunction among CCS ranged from 12.3% to 46.5%. For males, the prevalence ranged from 12.3% to 54.0%, while for females, it ranged from 19.9% to 57.0%.
 

Factors Influencing Sexual Function

The review identified the following four categories of factors influencing sexual function in CCS: Demographic, treatment-related, psychological, and physiological.

Demographic factors: Gender, age, education level, relationship status, income level, and race all play roles in sexual function.

Female survivors reported more severe sexual dysfunction and poorer sexual health than did male survivors. Age at cancer diagnosis, age at evaluation, and the time since diagnosis were closely linked to sexual experiences. Patients diagnosed with cancer during childhood tended to report better sexual function than those diagnosed during adolescence.

Treatment-related factors: The type of cancer and intensity of treatment, along with surgical history, were significant factors. Surgeries involving the spinal cord or sympathetic nerves, as well as a history of prostate or pelvic surgery, were strongly associated with erectile dysfunction in men. In women, pelvic surgeries and treatments to the pelvic area were commonly linked to sexual dysfunction.

The association between treatment intensity and sexual function was noted across several studies, although the results were not always consistent. For example, testicular radiation above 10 Gy was positively correlated with sexual dysfunction. Women who underwent more intensive treatments were more likely to report issues in multiple areas of sexual function, while men in this group were less likely to have children.

Among female CCS, certain types of cancer, such as germ cell tumors, renal tumors, and leukemia, present a higher risk for sexual dysfunction. Women who had CNS tumors in childhood frequently reported problems like difficulty in sexual arousal, low sexual satisfaction, infrequent sexual activity, and fewer sexual partners, compared with survivors of other cancers. Survivors of acute lymphoblastic leukemia and those who underwent hematopoietic stem cell transplantation (HSCT) also showed varying degrees of impaired sexual function, compared with the general population. The HSCT group showed significant testicular damage, including reduced testicular volumes, low testosterone levels, and low sperm counts.

Psychological factors: These factors, such as emotional distress, play a significant role in sexual dysfunction among CCS. Symptoms like anxiety, nervousness during sexual activity, and depression are commonly reported by those with sexual dysfunction. The connection between body image and sexual function is complex. Many CCS with sexual dysfunction express concern about how others, particularly their partners, perceived their altered body image due to cancer and its treatment.

Physiological factors: In male CCS, low serum testosterone levels and low lean muscle mass are linked to an increased risk for sexual dysfunction. Treatments involving alkylating agents or testicular radiation, and surgery or radiotherapy targeting the genitourinary organs or the hypothalamic-pituitary region, can lead to various physiological and endocrine disorders, contributing to sexual dysfunction. Despite these risks, there is a lack of research evaluating sexual function through the lens of the hypothalamic-pituitary-gonadal axis and neuroendocrine pathways.
 

This story was translated from Univadis Italy 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.

Childhood cancers represent a diverse group of neoplasms, and thanks to advances in treatment, survival rates have improved significantly. Today, more than 80%-85% of children diagnosed with cancer in developed countries survive into adulthood.

This increase in survival has brought new challenges, however. Compared with the general population, childhood cancer survivors (CCS) are at a notably higher risk for early mortality, developing secondary cancers, and experiencing various long-term clinical and psychosocial issues stemming from their disease or its treatment.

Long-term follow-up care for CCS is a complex and evolving field. Despite ongoing efforts to establish global and national guidelines, current evidence indicates that the care and management of these patients remain suboptimal.

Sexual dysfunction is a common and significant late effect among CCS. The disruptions caused by cancer and its treatment can interfere with normal physiological and psychological development, leading to issues with sexual function. This aspect of health is critical as it influences not just physical well-being but also psychosocial, developmental, and emotional health.
 

Characteristics and Mechanisms

Sexual functioning encompasses the physiological and psychological aspects of sexual behavior, including desire, arousal, orgasm, sexual pleasure, and overall satisfaction.

As CCS reach adolescence or adulthood, they often face sexual and reproductive issues, particularly as they enter romantic relationships.

Sexual functioning is a complex process that relies on the interaction of various factors, including physiological health, psychosexual development, romantic relationships, body image, and desire.

Despite its importance, the impact of childhood cancer on sexual function is often overlooked, even though cancer and its treatments can have lifelong effects. 
 

Sexual Function in CCS

A recent review aimed to summarize the existing research on sexual function among CCS, highlighting assessment tools, key stages of psychosexual development, common sexual problems, and the prevalence of sexual dysfunction.

The review study included 22 studies published between 2000 and 2022, comprising two qualitative, six cohort, and 14 cross-sectional studies.

Most CCS reached all key stages of psychosexual development at an average age of 29.8 years. Although some milestones were achieved later than is typical, many survivors felt they reached these stages at the appropriate time. Sexual initiation was less common among those who had undergone intensive neurotoxic treatments, such as those diagnosed with brain tumors or leukemia in childhood.

In a cross-sectional study of CCS aged 17-39 years, about one third had never engaged in sexual intercourse, 41.4% reported never experiencing sexual attraction, 44.8% were dissatisfied with their sex lives, and many rarely felt sexually attractive to others. Another study found that common issues among CCS included a lack of interest in sex (30%), difficulty enjoying sex (24%), and difficulty becoming aroused (23%). However, comparing and analyzing these problems was challenging due to the lack of standardized assessment criteria.

The prevalence of sexual dysfunction among CCS ranged from 12.3% to 46.5%. For males, the prevalence ranged from 12.3% to 54.0%, while for females, it ranged from 19.9% to 57.0%.
 

Factors Influencing Sexual Function

The review identified the following four categories of factors influencing sexual function in CCS: Demographic, treatment-related, psychological, and physiological.

Demographic factors: Gender, age, education level, relationship status, income level, and race all play roles in sexual function.

Female survivors reported more severe sexual dysfunction and poorer sexual health than did male survivors. Age at cancer diagnosis, age at evaluation, and the time since diagnosis were closely linked to sexual experiences. Patients diagnosed with cancer during childhood tended to report better sexual function than those diagnosed during adolescence.

Treatment-related factors: The type of cancer and intensity of treatment, along with surgical history, were significant factors. Surgeries involving the spinal cord or sympathetic nerves, as well as a history of prostate or pelvic surgery, were strongly associated with erectile dysfunction in men. In women, pelvic surgeries and treatments to the pelvic area were commonly linked to sexual dysfunction.

The association between treatment intensity and sexual function was noted across several studies, although the results were not always consistent. For example, testicular radiation above 10 Gy was positively correlated with sexual dysfunction. Women who underwent more intensive treatments were more likely to report issues in multiple areas of sexual function, while men in this group were less likely to have children.

Among female CCS, certain types of cancer, such as germ cell tumors, renal tumors, and leukemia, present a higher risk for sexual dysfunction. Women who had CNS tumors in childhood frequently reported problems like difficulty in sexual arousal, low sexual satisfaction, infrequent sexual activity, and fewer sexual partners, compared with survivors of other cancers. Survivors of acute lymphoblastic leukemia and those who underwent hematopoietic stem cell transplantation (HSCT) also showed varying degrees of impaired sexual function, compared with the general population. The HSCT group showed significant testicular damage, including reduced testicular volumes, low testosterone levels, and low sperm counts.

Psychological factors: These factors, such as emotional distress, play a significant role in sexual dysfunction among CCS. Symptoms like anxiety, nervousness during sexual activity, and depression are commonly reported by those with sexual dysfunction. The connection between body image and sexual function is complex. Many CCS with sexual dysfunction express concern about how others, particularly their partners, perceived their altered body image due to cancer and its treatment.

Physiological factors: In male CCS, low serum testosterone levels and low lean muscle mass are linked to an increased risk for sexual dysfunction. Treatments involving alkylating agents or testicular radiation, and surgery or radiotherapy targeting the genitourinary organs or the hypothalamic-pituitary region, can lead to various physiological and endocrine disorders, contributing to sexual dysfunction. Despite these risks, there is a lack of research evaluating sexual function through the lens of the hypothalamic-pituitary-gonadal axis and neuroendocrine pathways.
 

This story was translated from Univadis Italy 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.

Childhood cancers represent a diverse group of neoplasms, and thanks to advances in treatment, survival rates have improved significantly. Today, more than 80%-85% of children diagnosed with cancer in developed countries survive into adulthood.

This increase in survival has brought new challenges, however. Compared with the general population, childhood cancer survivors (CCS) are at a notably higher risk for early mortality, developing secondary cancers, and experiencing various long-term clinical and psychosocial issues stemming from their disease or its treatment.

Long-term follow-up care for CCS is a complex and evolving field. Despite ongoing efforts to establish global and national guidelines, current evidence indicates that the care and management of these patients remain suboptimal.

Sexual dysfunction is a common and significant late effect among CCS. The disruptions caused by cancer and its treatment can interfere with normal physiological and psychological development, leading to issues with sexual function. This aspect of health is critical as it influences not just physical well-being but also psychosocial, developmental, and emotional health.
 

Characteristics and Mechanisms

Sexual functioning encompasses the physiological and psychological aspects of sexual behavior, including desire, arousal, orgasm, sexual pleasure, and overall satisfaction.

As CCS reach adolescence or adulthood, they often face sexual and reproductive issues, particularly as they enter romantic relationships.

Sexual functioning is a complex process that relies on the interaction of various factors, including physiological health, psychosexual development, romantic relationships, body image, and desire.

Despite its importance, the impact of childhood cancer on sexual function is often overlooked, even though cancer and its treatments can have lifelong effects. 
 

Sexual Function in CCS

A recent review aimed to summarize the existing research on sexual function among CCS, highlighting assessment tools, key stages of psychosexual development, common sexual problems, and the prevalence of sexual dysfunction.

The review study included 22 studies published between 2000 and 2022, comprising two qualitative, six cohort, and 14 cross-sectional studies.

Most CCS reached all key stages of psychosexual development at an average age of 29.8 years. Although some milestones were achieved later than is typical, many survivors felt they reached these stages at the appropriate time. Sexual initiation was less common among those who had undergone intensive neurotoxic treatments, such as those diagnosed with brain tumors or leukemia in childhood.

In a cross-sectional study of CCS aged 17-39 years, about one third had never engaged in sexual intercourse, 41.4% reported never experiencing sexual attraction, 44.8% were dissatisfied with their sex lives, and many rarely felt sexually attractive to others. Another study found that common issues among CCS included a lack of interest in sex (30%), difficulty enjoying sex (24%), and difficulty becoming aroused (23%). However, comparing and analyzing these problems was challenging due to the lack of standardized assessment criteria.

The prevalence of sexual dysfunction among CCS ranged from 12.3% to 46.5%. For males, the prevalence ranged from 12.3% to 54.0%, while for females, it ranged from 19.9% to 57.0%.
 

Factors Influencing Sexual Function

The review identified the following four categories of factors influencing sexual function in CCS: Demographic, treatment-related, psychological, and physiological.

Demographic factors: Gender, age, education level, relationship status, income level, and race all play roles in sexual function.

Female survivors reported more severe sexual dysfunction and poorer sexual health than did male survivors. Age at cancer diagnosis, age at evaluation, and the time since diagnosis were closely linked to sexual experiences. Patients diagnosed with cancer during childhood tended to report better sexual function than those diagnosed during adolescence.

Treatment-related factors: The type of cancer and intensity of treatment, along with surgical history, were significant factors. Surgeries involving the spinal cord or sympathetic nerves, as well as a history of prostate or pelvic surgery, were strongly associated with erectile dysfunction in men. In women, pelvic surgeries and treatments to the pelvic area were commonly linked to sexual dysfunction.

The association between treatment intensity and sexual function was noted across several studies, although the results were not always consistent. For example, testicular radiation above 10 Gy was positively correlated with sexual dysfunction. Women who underwent more intensive treatments were more likely to report issues in multiple areas of sexual function, while men in this group were less likely to have children.

Among female CCS, certain types of cancer, such as germ cell tumors, renal tumors, and leukemia, present a higher risk for sexual dysfunction. Women who had CNS tumors in childhood frequently reported problems like difficulty in sexual arousal, low sexual satisfaction, infrequent sexual activity, and fewer sexual partners, compared with survivors of other cancers. Survivors of acute lymphoblastic leukemia and those who underwent hematopoietic stem cell transplantation (HSCT) also showed varying degrees of impaired sexual function, compared with the general population. The HSCT group showed significant testicular damage, including reduced testicular volumes, low testosterone levels, and low sperm counts.

Psychological factors: These factors, such as emotional distress, play a significant role in sexual dysfunction among CCS. Symptoms like anxiety, nervousness during sexual activity, and depression are commonly reported by those with sexual dysfunction. The connection between body image and sexual function is complex. Many CCS with sexual dysfunction express concern about how others, particularly their partners, perceived their altered body image due to cancer and its treatment.

Physiological factors: In male CCS, low serum testosterone levels and low lean muscle mass are linked to an increased risk for sexual dysfunction. Treatments involving alkylating agents or testicular radiation, and surgery or radiotherapy targeting the genitourinary organs or the hypothalamic-pituitary region, can lead to various physiological and endocrine disorders, contributing to sexual dysfunction. Despite these risks, there is a lack of research evaluating sexual function through the lens of the hypothalamic-pituitary-gonadal axis and neuroendocrine pathways.
 

This story was translated from Univadis Italy 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.

The US Food and Drug Administration (FDA) has approved axatilimab (Niktimvo, Incyte Corporation and Syndax) for the treatment of adult and pediatric patients with chronic graft versus host disease (GVHD) who have not responded to at least two prior lines of systemic therapy and who weigh ≥ 40 kg.

Chronic GVHD is a potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation that develops in about 50% of transplant recipients.

The first-in-class treatment for chronic GVHD is a monoclonal antibody that targets the colony-stimulating factor 1 (CSF-1) receptor. Approval for axatilimab followed priority review of Incyte’s Biologic License Application and was based on findings from the open-label phase 2 AGAVE-201 trial. 

Study participants had chronic GVHD after allogeneic hematopoietic stem cell transplantation and had failed to respond to at least two prior lines of systemic therapy (median, four lines of therapy). Prior therapies included ruxolitinib, belumosudil, and ibrutinib in 74%, 23%, and 31% of patients, respectively. Overall, 239 patients were enrolled at 121 study sites and were randomly assigned 1:1:1 to three doses.

The FDA recommended dose of axatilimab is 0.3 mg/kg (to a maximum of 35 mg) as an intravenous infusion over 30 minutes every 2 weeks until disease progression or unacceptable toxicity. Other doses tested in the AGAVE-201 trial were 1 mg/kg every 2 weeks and 3 mg/kg every 4 weeks. 

The trial measured overall response rate over the first six cycles (24 weeks). In the 79 patients who received the recommended 0.3-mg/kg dose, the overall response rate was 75%, and the median time to first response was 1.5 months (range, 0.9-5.1). The median duration of response — measured from first response to progression, death, or switch to a new systemic therapy for chronic GVHD — was 1.9 months. 

In those who responded to the therapy, there were no deaths or new therapies required in 60% of patients.

The most common adverse reactions, occurring in 15% or more patients, included increased aspartate aminotransferase, infection (pathogen unspecified), increased alanine aminotransferase, decreased phosphate, decreased hemoglobin, musculoskeletal pain, increased lipase, fatigue, increased amylase, increased calcium, increased creatine phosphokinase, nausea, headache, diarrhea, cough, pyrexia, and dyspnea. 

In the AGAVE-201 trial results, researchers noted that drug discontinuation from treatment-emergent adverse events occurred in 6% of patients in the 0.3-mg/kg cohort, in 22% in the 1-mg/kg cohort, and in 18% in the 3-mg/kg cohort. Fatal treatment-emergent adverse events occurred in 1.3% of patients in the 0.3-mg/kg cohort. 

“Advanced chronic GVHD is characterized by the development of fibrotic tissue across multiple organ systems, including most commonly the skin and mucosa, and can be extremely difficult to treat, leading to high rates of morbidity and mortality,” lead study author Daniel Wolff, MD, PhD, head of the GVHD Center at the University Hospital Regensburg, Germany, said in a company press release. “I am excited that Niktimvo is designed to specifically target key drivers of inflammation and fibrosis in chronic GVHD, and I am highly encouraged by the robust responses observed across all organs and patient subgroups within the heavily pretreated population enrolled in the AGAVE-201 trial. I look forward to having a new and differentiated treatment option for my patients who need additional therapies to address this very difficult to manage, debilitating, disease.”

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

The US Food and Drug Administration (FDA) has approved axatilimab (Niktimvo, Incyte Corporation and Syndax) for the treatment of adult and pediatric patients with chronic graft versus host disease (GVHD) who have not responded to at least two prior lines of systemic therapy and who weigh ≥ 40 kg.

Chronic GVHD is a potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation that develops in about 50% of transplant recipients.

The first-in-class treatment for chronic GVHD is a monoclonal antibody that targets the colony-stimulating factor 1 (CSF-1) receptor. Approval for axatilimab followed priority review of Incyte’s Biologic License Application and was based on findings from the open-label phase 2 AGAVE-201 trial. 

Study participants had chronic GVHD after allogeneic hematopoietic stem cell transplantation and had failed to respond to at least two prior lines of systemic therapy (median, four lines of therapy). Prior therapies included ruxolitinib, belumosudil, and ibrutinib in 74%, 23%, and 31% of patients, respectively. Overall, 239 patients were enrolled at 121 study sites and were randomly assigned 1:1:1 to three doses.

The FDA recommended dose of axatilimab is 0.3 mg/kg (to a maximum of 35 mg) as an intravenous infusion over 30 minutes every 2 weeks until disease progression or unacceptable toxicity. Other doses tested in the AGAVE-201 trial were 1 mg/kg every 2 weeks and 3 mg/kg every 4 weeks. 

The trial measured overall response rate over the first six cycles (24 weeks). In the 79 patients who received the recommended 0.3-mg/kg dose, the overall response rate was 75%, and the median time to first response was 1.5 months (range, 0.9-5.1). The median duration of response — measured from first response to progression, death, or switch to a new systemic therapy for chronic GVHD — was 1.9 months. 

In those who responded to the therapy, there were no deaths or new therapies required in 60% of patients.

The most common adverse reactions, occurring in 15% or more patients, included increased aspartate aminotransferase, infection (pathogen unspecified), increased alanine aminotransferase, decreased phosphate, decreased hemoglobin, musculoskeletal pain, increased lipase, fatigue, increased amylase, increased calcium, increased creatine phosphokinase, nausea, headache, diarrhea, cough, pyrexia, and dyspnea. 

In the AGAVE-201 trial results, researchers noted that drug discontinuation from treatment-emergent adverse events occurred in 6% of patients in the 0.3-mg/kg cohort, in 22% in the 1-mg/kg cohort, and in 18% in the 3-mg/kg cohort. Fatal treatment-emergent adverse events occurred in 1.3% of patients in the 0.3-mg/kg cohort. 

“Advanced chronic GVHD is characterized by the development of fibrotic tissue across multiple organ systems, including most commonly the skin and mucosa, and can be extremely difficult to treat, leading to high rates of morbidity and mortality,” lead study author Daniel Wolff, MD, PhD, head of the GVHD Center at the University Hospital Regensburg, Germany, said in a company press release. “I am excited that Niktimvo is designed to specifically target key drivers of inflammation and fibrosis in chronic GVHD, and I am highly encouraged by the robust responses observed across all organs and patient subgroups within the heavily pretreated population enrolled in the AGAVE-201 trial. I look forward to having a new and differentiated treatment option for my patients who need additional therapies to address this very difficult to manage, debilitating, disease.”

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

The US Food and Drug Administration (FDA) has approved axatilimab (Niktimvo, Incyte Corporation and Syndax) for the treatment of adult and pediatric patients with chronic graft versus host disease (GVHD) who have not responded to at least two prior lines of systemic therapy and who weigh ≥ 40 kg.

Chronic GVHD is a potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation that develops in about 50% of transplant recipients.

The first-in-class treatment for chronic GVHD is a monoclonal antibody that targets the colony-stimulating factor 1 (CSF-1) receptor. Approval for axatilimab followed priority review of Incyte’s Biologic License Application and was based on findings from the open-label phase 2 AGAVE-201 trial. 

Study participants had chronic GVHD after allogeneic hematopoietic stem cell transplantation and had failed to respond to at least two prior lines of systemic therapy (median, four lines of therapy). Prior therapies included ruxolitinib, belumosudil, and ibrutinib in 74%, 23%, and 31% of patients, respectively. Overall, 239 patients were enrolled at 121 study sites and were randomly assigned 1:1:1 to three doses.

The FDA recommended dose of axatilimab is 0.3 mg/kg (to a maximum of 35 mg) as an intravenous infusion over 30 minutes every 2 weeks until disease progression or unacceptable toxicity. Other doses tested in the AGAVE-201 trial were 1 mg/kg every 2 weeks and 3 mg/kg every 4 weeks. 

The trial measured overall response rate over the first six cycles (24 weeks). In the 79 patients who received the recommended 0.3-mg/kg dose, the overall response rate was 75%, and the median time to first response was 1.5 months (range, 0.9-5.1). The median duration of response — measured from first response to progression, death, or switch to a new systemic therapy for chronic GVHD — was 1.9 months. 

In those who responded to the therapy, there were no deaths or new therapies required in 60% of patients.

The most common adverse reactions, occurring in 15% or more patients, included increased aspartate aminotransferase, infection (pathogen unspecified), increased alanine aminotransferase, decreased phosphate, decreased hemoglobin, musculoskeletal pain, increased lipase, fatigue, increased amylase, increased calcium, increased creatine phosphokinase, nausea, headache, diarrhea, cough, pyrexia, and dyspnea. 

In the AGAVE-201 trial results, researchers noted that drug discontinuation from treatment-emergent adverse events occurred in 6% of patients in the 0.3-mg/kg cohort, in 22% in the 1-mg/kg cohort, and in 18% in the 3-mg/kg cohort. Fatal treatment-emergent adverse events occurred in 1.3% of patients in the 0.3-mg/kg cohort. 

“Advanced chronic GVHD is characterized by the development of fibrotic tissue across multiple organ systems, including most commonly the skin and mucosa, and can be extremely difficult to treat, leading to high rates of morbidity and mortality,” lead study author Daniel Wolff, MD, PhD, head of the GVHD Center at the University Hospital Regensburg, Germany, said in a company press release. “I am excited that Niktimvo is designed to specifically target key drivers of inflammation and fibrosis in chronic GVHD, and I am highly encouraged by the robust responses observed across all organs and patient subgroups within the heavily pretreated population enrolled in the AGAVE-201 trial. I look forward to having a new and differentiated treatment option for my patients who need additional therapies to address this very difficult to manage, debilitating, disease.”

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