Patient & Survivor Care

TOPLINE:

Aspirin provides greater protection against colorectal cancer (CRC) in people with unhealthy lifestyles, particularly smokers with higher body weight, new data suggest. 

METHODOLOGY:

• Aspirin is an established agent for CRC prevention. Whether individuals with more lifestyle risk factors might derive greater benefit from aspirin remains unclear.
• Researchers analyzed regular aspirin use (defined as taking two or more standard 325-mg tablets per week) using long-term follow-up data from 63,957 women in the Nurses’ Health Study and 43,698 men in the Health Professionals Follow-Up Study.
• They calculated a healthy lifestyle score for each participant based on body mass index (BMI), alcohol intake, physical activity, diet, and smoking, with higher scores corresponding to healthier lifestyles.
• Outcomes included multivariable-adjusted 10-year cumulative incidence of CRC, the absolute risk reduction (ARR) with aspirin use, and number needed to treat associated with regular aspirin use by lifestyle score.

TAKEAWAY:

• During more than 3 million person-years of follow-up, 2544 new cases of CRC were documented.
• The 10-year cumulative incidence of CRC was 1.98% among regular aspirin users compared with 2.95% among nonusers, corresponding to an ARR of 0.97%.
• The ARR associated with aspirin use was greatest among individuals with the unhealthiest lifestyle scores and progressively decreased with healthier lifestyle scores (P < .001 for additive interaction).
• Those with the unhealthiest lifestyle scores (0-1) had a 10-year ARR of 1.28% from aspirin use, whereas those with the healthiest lifestyle scores (4-5) had an ARR of 0.11%.
• The number needed to treat with aspirin for 10 years to prevent one CRC case was 78 for those with the unhealthiest lifestyles, compared with 909 for those with the healthiest lifestyles.
• Among the individual components of the healthy lifestyle score, higher BMI and smoking correlated with greater reductions in CRC risk from aspirin use.

IN PRACTICE:

“These results support the use of lifestyle risk factors to identify individuals who may have a more favorable risk-benefit profile for cancer prevention with aspirin,” the authors wrote. 

SOURCE:

The study, with first author Daniel R. Sikavi, MD, from Massachusetts General Hospital and Harvard Medical School in Boston, was published online in JAMA Oncology.

LIMITATIONS:

The study population consisted of health professionals who were predominantly White, which may limit generalizability of the findings. Lifestyle factors and aspirin use were self-reported, which may introduce measurement errors. The study did not systematically assess adverse outcomes potentially due to aspirin use or the presence of a known hereditary cancer syndrome. 

DISCLOSURES:

The study had no commercial funding. The authors had no relevant conflicts of interest.

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

TOPLINE:

Aspirin provides greater protection against colorectal cancer (CRC) in people with unhealthy lifestyles, particularly smokers with higher body weight, new data suggest. 

METHODOLOGY:

• Aspirin is an established agent for CRC prevention. Whether individuals with more lifestyle risk factors might derive greater benefit from aspirin remains unclear.
• Researchers analyzed regular aspirin use (defined as taking two or more standard 325-mg tablets per week) using long-term follow-up data from 63,957 women in the Nurses’ Health Study and 43,698 men in the Health Professionals Follow-Up Study.
• They calculated a healthy lifestyle score for each participant based on body mass index (BMI), alcohol intake, physical activity, diet, and smoking, with higher scores corresponding to healthier lifestyles.
• Outcomes included multivariable-adjusted 10-year cumulative incidence of CRC, the absolute risk reduction (ARR) with aspirin use, and number needed to treat associated with regular aspirin use by lifestyle score.

TAKEAWAY:

• During more than 3 million person-years of follow-up, 2544 new cases of CRC were documented.
• The 10-year cumulative incidence of CRC was 1.98% among regular aspirin users compared with 2.95% among nonusers, corresponding to an ARR of 0.97%.
• The ARR associated with aspirin use was greatest among individuals with the unhealthiest lifestyle scores and progressively decreased with healthier lifestyle scores (P < .001 for additive interaction).
• Those with the unhealthiest lifestyle scores (0-1) had a 10-year ARR of 1.28% from aspirin use, whereas those with the healthiest lifestyle scores (4-5) had an ARR of 0.11%.
• The number needed to treat with aspirin for 10 years to prevent one CRC case was 78 for those with the unhealthiest lifestyles, compared with 909 for those with the healthiest lifestyles.
• Among the individual components of the healthy lifestyle score, higher BMI and smoking correlated with greater reductions in CRC risk from aspirin use.

IN PRACTICE:

“These results support the use of lifestyle risk factors to identify individuals who may have a more favorable risk-benefit profile for cancer prevention with aspirin,” the authors wrote. 

SOURCE:

The study, with first author Daniel R. Sikavi, MD, from Massachusetts General Hospital and Harvard Medical School in Boston, was published online in JAMA Oncology.

LIMITATIONS:

The study population consisted of health professionals who were predominantly White, which may limit generalizability of the findings. Lifestyle factors and aspirin use were self-reported, which may introduce measurement errors. The study did not systematically assess adverse outcomes potentially due to aspirin use or the presence of a known hereditary cancer syndrome. 

DISCLOSURES:

The study had no commercial funding. The authors had no relevant conflicts of interest.

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

TOPLINE:

Aspirin provides greater protection against colorectal cancer (CRC) in people with unhealthy lifestyles, particularly smokers with higher body weight, new data suggest. 

METHODOLOGY:

• Aspirin is an established agent for CRC prevention. Whether individuals with more lifestyle risk factors might derive greater benefit from aspirin remains unclear.
• Researchers analyzed regular aspirin use (defined as taking two or more standard 325-mg tablets per week) using long-term follow-up data from 63,957 women in the Nurses’ Health Study and 43,698 men in the Health Professionals Follow-Up Study.
• They calculated a healthy lifestyle score for each participant based on body mass index (BMI), alcohol intake, physical activity, diet, and smoking, with higher scores corresponding to healthier lifestyles.
• Outcomes included multivariable-adjusted 10-year cumulative incidence of CRC, the absolute risk reduction (ARR) with aspirin use, and number needed to treat associated with regular aspirin use by lifestyle score.

TAKEAWAY:

• During more than 3 million person-years of follow-up, 2544 new cases of CRC were documented.
• The 10-year cumulative incidence of CRC was 1.98% among regular aspirin users compared with 2.95% among nonusers, corresponding to an ARR of 0.97%.
• The ARR associated with aspirin use was greatest among individuals with the unhealthiest lifestyle scores and progressively decreased with healthier lifestyle scores (P < .001 for additive interaction).
• Those with the unhealthiest lifestyle scores (0-1) had a 10-year ARR of 1.28% from aspirin use, whereas those with the healthiest lifestyle scores (4-5) had an ARR of 0.11%.
• The number needed to treat with aspirin for 10 years to prevent one CRC case was 78 for those with the unhealthiest lifestyles, compared with 909 for those with the healthiest lifestyles.
• Among the individual components of the healthy lifestyle score, higher BMI and smoking correlated with greater reductions in CRC risk from aspirin use.

IN PRACTICE:

“These results support the use of lifestyle risk factors to identify individuals who may have a more favorable risk-benefit profile for cancer prevention with aspirin,” the authors wrote. 

SOURCE:

The study, with first author Daniel R. Sikavi, MD, from Massachusetts General Hospital and Harvard Medical School in Boston, was published online in JAMA Oncology.

LIMITATIONS:

The study population consisted of health professionals who were predominantly White, which may limit generalizability of the findings. Lifestyle factors and aspirin use were self-reported, which may introduce measurement errors. The study did not systematically assess adverse outcomes potentially due to aspirin use or the presence of a known hereditary cancer syndrome. 

DISCLOSURES:

The study had no commercial funding. The authors had no relevant conflicts of interest.

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

TOPLINE:

Spouses of patients with cancer face a significantly higher risk for suicide attempts and deaths, especially within the first year after their spouse is diagnosed with cancer, according to an analysis based in Denmark.

METHODOLOGY:

• A growing body of evidence has revealed higher levels of psychological distress and an increased risk for psychiatric disorders among spouses of patients with cancer, but less is known about suicidal behaviors among spouses.
• In a recent analysis, researchers assessed the risk for suicide attempts and suicide deaths among the spouses of patients with cancer in a nationwide cohort based in Denmark.
• Researchers collected registry-based data from 1986 to 2016, comparing suicide attempts and deaths between individuals with a spouse diagnosed with cancer and those without. Suicide attempts were identified through The Danish National Patient Register and The Danish Psychiatric Central Research Register, and suicide deaths were identified through The Danish Register of Causes of Death.
• A total of 409,338 spouses of patients with cancer (exposed group) were compared with 2,046,682 matched control participants (unexposed group). The participants were followed from cohort entry until a first suicide attempt, suicide death, death from other causes, emigration, or December 31, 2016, whichever came first.

TAKEAWAY:

• Spouses of patients with cancer had an increased risk for suicide attempts (hazard ratio [HR], 1.28) and suicide deaths (HR, 1.47), especially within the first year after a cancer diagnosis (HR for attempts, 1.45; HR for deaths, 2.56).
• The increased risk for suicide attempts was more pronounced among men (HR, 1.42), those with a lower household income (HR, 1.39), and those with a history of cancer themselves (HR, 1.57).
• Among those who attempted suicide, researchers observed positive associations for most, but not all, cancer types and for cancers diagnosed at regional spread or an advanced stage (HR, 1.66) or an unknown stage (HR, 1.28), as well as following the death of the spouse to cancer (HR, 1.57).
• Researchers also observed an increased risk for suicide death for most, but not all, cancer types and greater increases for cancers diagnosed at more advanced stages (HR, 1.61) or unknown stages (HR, 1.52), as well as following the spouse’s death (HR, 1.70).

IN PRACTICE:

“To our knowledge, this nationwide cohort study is the first to show that spouses of patients with cancer have an elevated risk of both suicide attempt and suicide death,” the authors concluded. “These findings suggest a need for clinical and societal awareness to prevent suicidal behaviors among spouses of patients with cancer, particularly during the first year following the cancer diagnosis.” 

In an accompanying editorial, experts noted that “the mental health impacts may well be higher in countries that have more restricted healthcare access,” given that Denmark has universal healthcare. The editorialists also noted the “pressing need to integrate spousal health more fully into cancer survivorship care. 

“Psychosocial distress should no longer be a hidden and unaddressed cause of suffering in spouses of patients with cancer,” they wrote.

SOURCE:

The study, led by Qianwei Liu, MD, PhD, Institute of Environmental Medicine, Karolinska Institutet in Stockholm, Sweden, and the accompanying editorial were published online in JAMA Oncology.

LIMITATIONS:

Residual confounding was one potential limitation, though the researchers tried to control for several important confounders. The result may not be generalizable to other countries with different healthcare systems, cultural contexts, or burdens of cancer and suicidal behaviors.

DISCLOSURES:

One coauthor reported receiving grants from Forte during the conduct of the study. Another coauthor

disclosed receiving grants from the Swedish Cancer Society. Additional disclosures are noted in the original article.

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

TOPLINE:

Spouses of patients with cancer face a significantly higher risk for suicide attempts and deaths, especially within the first year after their spouse is diagnosed with cancer, according to an analysis based in Denmark.

METHODOLOGY:

• A growing body of evidence has revealed higher levels of psychological distress and an increased risk for psychiatric disorders among spouses of patients with cancer, but less is known about suicidal behaviors among spouses.
• In a recent analysis, researchers assessed the risk for suicide attempts and suicide deaths among the spouses of patients with cancer in a nationwide cohort based in Denmark.
• Researchers collected registry-based data from 1986 to 2016, comparing suicide attempts and deaths between individuals with a spouse diagnosed with cancer and those without. Suicide attempts were identified through The Danish National Patient Register and The Danish Psychiatric Central Research Register, and suicide deaths were identified through The Danish Register of Causes of Death.
• A total of 409,338 spouses of patients with cancer (exposed group) were compared with 2,046,682 matched control participants (unexposed group). The participants were followed from cohort entry until a first suicide attempt, suicide death, death from other causes, emigration, or December 31, 2016, whichever came first.

TAKEAWAY:

• Spouses of patients with cancer had an increased risk for suicide attempts (hazard ratio [HR], 1.28) and suicide deaths (HR, 1.47), especially within the first year after a cancer diagnosis (HR for attempts, 1.45; HR for deaths, 2.56).
• The increased risk for suicide attempts was more pronounced among men (HR, 1.42), those with a lower household income (HR, 1.39), and those with a history of cancer themselves (HR, 1.57).
• Among those who attempted suicide, researchers observed positive associations for most, but not all, cancer types and for cancers diagnosed at regional spread or an advanced stage (HR, 1.66) or an unknown stage (HR, 1.28), as well as following the death of the spouse to cancer (HR, 1.57).
• Researchers also observed an increased risk for suicide death for most, but not all, cancer types and greater increases for cancers diagnosed at more advanced stages (HR, 1.61) or unknown stages (HR, 1.52), as well as following the spouse’s death (HR, 1.70).

IN PRACTICE:

“To our knowledge, this nationwide cohort study is the first to show that spouses of patients with cancer have an elevated risk of both suicide attempt and suicide death,” the authors concluded. “These findings suggest a need for clinical and societal awareness to prevent suicidal behaviors among spouses of patients with cancer, particularly during the first year following the cancer diagnosis.” 

In an accompanying editorial, experts noted that “the mental health impacts may well be higher in countries that have more restricted healthcare access,” given that Denmark has universal healthcare. The editorialists also noted the “pressing need to integrate spousal health more fully into cancer survivorship care. 

“Psychosocial distress should no longer be a hidden and unaddressed cause of suffering in spouses of patients with cancer,” they wrote.

SOURCE:

The study, led by Qianwei Liu, MD, PhD, Institute of Environmental Medicine, Karolinska Institutet in Stockholm, Sweden, and the accompanying editorial were published online in JAMA Oncology.

LIMITATIONS:

Residual confounding was one potential limitation, though the researchers tried to control for several important confounders. The result may not be generalizable to other countries with different healthcare systems, cultural contexts, or burdens of cancer and suicidal behaviors.

DISCLOSURES:

One coauthor reported receiving grants from Forte during the conduct of the study. Another coauthor

disclosed receiving grants from the Swedish Cancer Society. Additional disclosures are noted in the original article.

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

TOPLINE:

Spouses of patients with cancer face a significantly higher risk for suicide attempts and deaths, especially within the first year after their spouse is diagnosed with cancer, according to an analysis based in Denmark.

METHODOLOGY:

• A growing body of evidence has revealed higher levels of psychological distress and an increased risk for psychiatric disorders among spouses of patients with cancer, but less is known about suicidal behaviors among spouses.
• In a recent analysis, researchers assessed the risk for suicide attempts and suicide deaths among the spouses of patients with cancer in a nationwide cohort based in Denmark.
• Researchers collected registry-based data from 1986 to 2016, comparing suicide attempts and deaths between individuals with a spouse diagnosed with cancer and those without. Suicide attempts were identified through The Danish National Patient Register and The Danish Psychiatric Central Research Register, and suicide deaths were identified through The Danish Register of Causes of Death.
• A total of 409,338 spouses of patients with cancer (exposed group) were compared with 2,046,682 matched control participants (unexposed group). The participants were followed from cohort entry until a first suicide attempt, suicide death, death from other causes, emigration, or December 31, 2016, whichever came first.

TAKEAWAY:

• Spouses of patients with cancer had an increased risk for suicide attempts (hazard ratio [HR], 1.28) and suicide deaths (HR, 1.47), especially within the first year after a cancer diagnosis (HR for attempts, 1.45; HR for deaths, 2.56).
• The increased risk for suicide attempts was more pronounced among men (HR, 1.42), those with a lower household income (HR, 1.39), and those with a history of cancer themselves (HR, 1.57).
• Among those who attempted suicide, researchers observed positive associations for most, but not all, cancer types and for cancers diagnosed at regional spread or an advanced stage (HR, 1.66) or an unknown stage (HR, 1.28), as well as following the death of the spouse to cancer (HR, 1.57).
• Researchers also observed an increased risk for suicide death for most, but not all, cancer types and greater increases for cancers diagnosed at more advanced stages (HR, 1.61) or unknown stages (HR, 1.52), as well as following the spouse’s death (HR, 1.70).

IN PRACTICE:

“To our knowledge, this nationwide cohort study is the first to show that spouses of patients with cancer have an elevated risk of both suicide attempt and suicide death,” the authors concluded. “These findings suggest a need for clinical and societal awareness to prevent suicidal behaviors among spouses of patients with cancer, particularly during the first year following the cancer diagnosis.” 

In an accompanying editorial, experts noted that “the mental health impacts may well be higher in countries that have more restricted healthcare access,” given that Denmark has universal healthcare. The editorialists also noted the “pressing need to integrate spousal health more fully into cancer survivorship care. 

“Psychosocial distress should no longer be a hidden and unaddressed cause of suffering in spouses of patients with cancer,” they wrote.

SOURCE:

The study, led by Qianwei Liu, MD, PhD, Institute of Environmental Medicine, Karolinska Institutet in Stockholm, Sweden, and the accompanying editorial were published online in JAMA Oncology.

LIMITATIONS:

Residual confounding was one potential limitation, though the researchers tried to control for several important confounders. The result may not be generalizable to other countries with different healthcare systems, cultural contexts, or burdens of cancer and suicidal behaviors.

DISCLOSURES:

One coauthor reported receiving grants from Forte during the conduct of the study. Another coauthor

disclosed receiving grants from the Swedish Cancer Society. Additional disclosures are noted in the original article.

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

Adding baseline MRI to conventional prostate cancer risk stratification could improve prognostic accuracy, potentially affecting active surveillance and treatment decisions for some patients, according to the investigators on a new trial.

The multicenter, real-world trial showed that men with low-risk or favorable intermediate-risk disease who had higher Prostate Imaging Reporting and Data System (PI-RADS) scores at baseline were more likely to be reclassified with more aggressive disease on a future biopsy, wrote lead author Kiran R. Nandalur, MD and colleagues. The study was published in The Journal of Urology.

This means that without MRI, some cases of prostate cancer are being labeled as lower-risk than they actually are.

The investigators noted that MRI is increasingly being used to choose patients who are appropriate for active surveillance instead of treatment, but related clinical data are scarce.

Although PI-RADS is the preferred metric for characterizing prostate tumors via MRI, “most previous studies on the prognostic implications of baseline PI-RADS score included smaller populations from academic centers, limited inclusion of clinical and pathologic data into models, and/or [are] ambiguous on the implications of PI-RADS score,” they wrote.

These knowledge gaps prompted the present study.
 

How Were Baseline MRI Findings Related to Prostate Cancer Disease Risk?

The dataset included 1491 men with prostate cancer that was diagnosed at 46 hospital-based, academic, or private practice urology groups. All had low-risk or favorable intermediate-risk disease and had undergone MRI within 6 months before or after initial biopsy, along with enrollment in active surveillance.

“A novel aspect of this study was that the MRIs were not read by dedicated prostate MRI experts at academic institutions, but rather a mix of community and academic radiologists,” Dr. Nandalur, medical director of Corewell Health East Radiology, Royal Oak, Michigan, said in an interview.

After traditional risk factors were accounted for, baseline PI-RADS (four or more lesions) was significantly associated with increased likelihood of biopsy reclassification to high-grade prostate cancer on surveillance biopsy (hazard ratio, 2.3; 95% CI 1.6-3.2; P < .001). 

“These patients with suspicious lesions on their initial MRI were more than twice as likely to have higher-grade disease within 5 years,” Nandalur noted. “This result was not only seen in the low-risk group but also in the favorable intermediate-risk group, which hasn’t been shown before.”

Grade group 2 vs 1 and increasing age were also associated with significantly increased risk for reclassification to a more aggressive cancer type.
 

How Might These Findings Improve Outcomes in Patients With Prostate Cancer?

Currently, 60%-70% of patients with low-risk disease choose active surveillance over immediate treatment, whereas 20% with favorable intermediate-risk disease choose active surveillance, according to Dr. Nandalur.

For low-risk patients, PI-RADS score is unlikely to change this decision, although surveillance intervals could be adjusted in accordance with risk. More notably, those with favorable intermediate-risk disease may benefit from considering PI-RADS score when choosing between active surveillance and immediate treatment.

“Most of the management strategies for prostate cancer are based on just your lab values and your pathology,” Dr. Nandalur said, “but this study shows that maybe we should start taking MRI into account — into the general paradigm of management of prostate cancer.”

Ideally, he added, prospective studies will confirm these findings, although such studies can be challenging to perform and similar data have historically been sufficient to reshape clinical practice.

“We are hoping that [baseline PI-RADS score] will be adopted into the NCCN [National Comprehensive Cancer Network] guidelines,” Dr. Nandalur said.
 

How Likely Are These Findings to Reshape Clinical Practice?

“The study’s large, multicenter cohort and its focus on the prognostic value of baseline MRI in active surveillance make it a crucial contribution to the field, providing evidence that can potentially refine patient management strategies in clinical practice,” Ismail Baris Turkbey, MD, FSAR, head of MRI Section, Molecular Imaging Branch, National Cancer Institute, Rockville, Maryland, said in a written comment.

“The findings from this study are likely to have a significant impact on clinical practice and potentially influence future guidelines in the management of localized prostate cancer, particularly in the context of active surveillance,” Dr. Turkbey said. “MRI, already a commonly used imaging modality in prostate cancer management, may become an even more integral part of the initial assessment and ongoing monitoring of patients with low or favorable-intermediate risk prostate cancer.”

Dr. Turkbey noted several strengths of the study.  

First, the size and the diversity of the cohort, along with the variety of treatment centers, support generalizability of findings. Second, the study pinpoints a “critical aspect” of active surveillance by uncovering the link between baseline MRI findings and later risk reclassification. Finally, the study also showed that increasing age was associated with higher likelihood of risk reclassification, “further emphasizing the need for personalized risk assessment” among these patients.
 

What Were Some Limitations of This Study?

“One important limitation is the lack of inter-reader agreement for PI-RADS evaluations for baseline MRIs,” Dr. Turkbey said. “Variation of PI-RADS is quite known, and centralized evaluations could have made this study stronger. Same applies for centralized quality evaluation of MRIs using The Prostate Imaging Quality (PI-QUAL) score. These items are difficult to do in a multicenter prospective data registry, and maybe authors will consider including these additional analyses in their future work.” 

How Does This New Approach to Prostate Cancer Risk Assessment Compare With Recent Advances in AI-Based Risk Assessment?

Over the past few years, artificial intelligence (AI)–assisted risk assessment in prostate cancer has been gaining increasing attention. Recently, for example, Artera, a self-styled “precision medicine company,” released the first AI tool to help patients choose between active surveillance and active treatment on the basis of analysis of digital pathology images. 

When asked to compare this approach with the methods used in the present study, Dr. Nandalur called the AI model “a step forward” but noted that it still relies on conventional risk criteria.

“Our data show imaging with MRI has independent prognostic information for prostate cancer patients considering active surveillance, over and above these traditional factors,” he said. “Moreover, this predictive ability of MRI was seen in low and favorable intermediate risk groups, so the additive value is broad.”

Still, he predicted that the future will not involve a binary choice, but a combination approach.

“The exciting aspect is that MRI results can eventually be added to this novel AI model and further improve prediction models for patients,” Dr. Nandalur said. “The combination of recent AI models and MRI will likely represent the future paradigm for prostate cancer patients considering active surveillance versus immediate treatment.”

The study was supported by Blue Cross and Blue Shield of Michigan. The investigators and Dr. Turkbey reported no conflicts of interest.

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

Adding baseline MRI to conventional prostate cancer risk stratification could improve prognostic accuracy, potentially affecting active surveillance and treatment decisions for some patients, according to the investigators on a new trial.

The multicenter, real-world trial showed that men with low-risk or favorable intermediate-risk disease who had higher Prostate Imaging Reporting and Data System (PI-RADS) scores at baseline were more likely to be reclassified with more aggressive disease on a future biopsy, wrote lead author Kiran R. Nandalur, MD and colleagues. The study was published in The Journal of Urology.

This means that without MRI, some cases of prostate cancer are being labeled as lower-risk than they actually are.

The investigators noted that MRI is increasingly being used to choose patients who are appropriate for active surveillance instead of treatment, but related clinical data are scarce.

Although PI-RADS is the preferred metric for characterizing prostate tumors via MRI, “most previous studies on the prognostic implications of baseline PI-RADS score included smaller populations from academic centers, limited inclusion of clinical and pathologic data into models, and/or [are] ambiguous on the implications of PI-RADS score,” they wrote.

These knowledge gaps prompted the present study.
 

How Were Baseline MRI Findings Related to Prostate Cancer Disease Risk?

The dataset included 1491 men with prostate cancer that was diagnosed at 46 hospital-based, academic, or private practice urology groups. All had low-risk or favorable intermediate-risk disease and had undergone MRI within 6 months before or after initial biopsy, along with enrollment in active surveillance.

“A novel aspect of this study was that the MRIs were not read by dedicated prostate MRI experts at academic institutions, but rather a mix of community and academic radiologists,” Dr. Nandalur, medical director of Corewell Health East Radiology, Royal Oak, Michigan, said in an interview.

After traditional risk factors were accounted for, baseline PI-RADS (four or more lesions) was significantly associated with increased likelihood of biopsy reclassification to high-grade prostate cancer on surveillance biopsy (hazard ratio, 2.3; 95% CI 1.6-3.2; P < .001). 

“These patients with suspicious lesions on their initial MRI were more than twice as likely to have higher-grade disease within 5 years,” Nandalur noted. “This result was not only seen in the low-risk group but also in the favorable intermediate-risk group, which hasn’t been shown before.”

Grade group 2 vs 1 and increasing age were also associated with significantly increased risk for reclassification to a more aggressive cancer type.
 

How Might These Findings Improve Outcomes in Patients With Prostate Cancer?

Currently, 60%-70% of patients with low-risk disease choose active surveillance over immediate treatment, whereas 20% with favorable intermediate-risk disease choose active surveillance, according to Dr. Nandalur.

For low-risk patients, PI-RADS score is unlikely to change this decision, although surveillance intervals could be adjusted in accordance with risk. More notably, those with favorable intermediate-risk disease may benefit from considering PI-RADS score when choosing between active surveillance and immediate treatment.

“Most of the management strategies for prostate cancer are based on just your lab values and your pathology,” Dr. Nandalur said, “but this study shows that maybe we should start taking MRI into account — into the general paradigm of management of prostate cancer.”

Ideally, he added, prospective studies will confirm these findings, although such studies can be challenging to perform and similar data have historically been sufficient to reshape clinical practice.

“We are hoping that [baseline PI-RADS score] will be adopted into the NCCN [National Comprehensive Cancer Network] guidelines,” Dr. Nandalur said.
 

How Likely Are These Findings to Reshape Clinical Practice?

“The study’s large, multicenter cohort and its focus on the prognostic value of baseline MRI in active surveillance make it a crucial contribution to the field, providing evidence that can potentially refine patient management strategies in clinical practice,” Ismail Baris Turkbey, MD, FSAR, head of MRI Section, Molecular Imaging Branch, National Cancer Institute, Rockville, Maryland, said in a written comment.

“The findings from this study are likely to have a significant impact on clinical practice and potentially influence future guidelines in the management of localized prostate cancer, particularly in the context of active surveillance,” Dr. Turkbey said. “MRI, already a commonly used imaging modality in prostate cancer management, may become an even more integral part of the initial assessment and ongoing monitoring of patients with low or favorable-intermediate risk prostate cancer.”

Dr. Turkbey noted several strengths of the study.  

First, the size and the diversity of the cohort, along with the variety of treatment centers, support generalizability of findings. Second, the study pinpoints a “critical aspect” of active surveillance by uncovering the link between baseline MRI findings and later risk reclassification. Finally, the study also showed that increasing age was associated with higher likelihood of risk reclassification, “further emphasizing the need for personalized risk assessment” among these patients.
 

What Were Some Limitations of This Study?

“One important limitation is the lack of inter-reader agreement for PI-RADS evaluations for baseline MRIs,” Dr. Turkbey said. “Variation of PI-RADS is quite known, and centralized evaluations could have made this study stronger. Same applies for centralized quality evaluation of MRIs using The Prostate Imaging Quality (PI-QUAL) score. These items are difficult to do in a multicenter prospective data registry, and maybe authors will consider including these additional analyses in their future work.” 

How Does This New Approach to Prostate Cancer Risk Assessment Compare With Recent Advances in AI-Based Risk Assessment?

Over the past few years, artificial intelligence (AI)–assisted risk assessment in prostate cancer has been gaining increasing attention. Recently, for example, Artera, a self-styled “precision medicine company,” released the first AI tool to help patients choose between active surveillance and active treatment on the basis of analysis of digital pathology images. 

When asked to compare this approach with the methods used in the present study, Dr. Nandalur called the AI model “a step forward” but noted that it still relies on conventional risk criteria.

“Our data show imaging with MRI has independent prognostic information for prostate cancer patients considering active surveillance, over and above these traditional factors,” he said. “Moreover, this predictive ability of MRI was seen in low and favorable intermediate risk groups, so the additive value is broad.”

Still, he predicted that the future will not involve a binary choice, but a combination approach.

“The exciting aspect is that MRI results can eventually be added to this novel AI model and further improve prediction models for patients,” Dr. Nandalur said. “The combination of recent AI models and MRI will likely represent the future paradigm for prostate cancer patients considering active surveillance versus immediate treatment.”

The study was supported by Blue Cross and Blue Shield of Michigan. The investigators and Dr. Turkbey reported no conflicts of interest.

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

Adding baseline MRI to conventional prostate cancer risk stratification could improve prognostic accuracy, potentially affecting active surveillance and treatment decisions for some patients, according to the investigators on a new trial.

The multicenter, real-world trial showed that men with low-risk or favorable intermediate-risk disease who had higher Prostate Imaging Reporting and Data System (PI-RADS) scores at baseline were more likely to be reclassified with more aggressive disease on a future biopsy, wrote lead author Kiran R. Nandalur, MD and colleagues. The study was published in The Journal of Urology.

This means that without MRI, some cases of prostate cancer are being labeled as lower-risk than they actually are.

The investigators noted that MRI is increasingly being used to choose patients who are appropriate for active surveillance instead of treatment, but related clinical data are scarce.

Although PI-RADS is the preferred metric for characterizing prostate tumors via MRI, “most previous studies on the prognostic implications of baseline PI-RADS score included smaller populations from academic centers, limited inclusion of clinical and pathologic data into models, and/or [are] ambiguous on the implications of PI-RADS score,” they wrote.

These knowledge gaps prompted the present study.
 

How Were Baseline MRI Findings Related to Prostate Cancer Disease Risk?

The dataset included 1491 men with prostate cancer that was diagnosed at 46 hospital-based, academic, or private practice urology groups. All had low-risk or favorable intermediate-risk disease and had undergone MRI within 6 months before or after initial biopsy, along with enrollment in active surveillance.

“A novel aspect of this study was that the MRIs were not read by dedicated prostate MRI experts at academic institutions, but rather a mix of community and academic radiologists,” Dr. Nandalur, medical director of Corewell Health East Radiology, Royal Oak, Michigan, said in an interview.

After traditional risk factors were accounted for, baseline PI-RADS (four or more lesions) was significantly associated with increased likelihood of biopsy reclassification to high-grade prostate cancer on surveillance biopsy (hazard ratio, 2.3; 95% CI 1.6-3.2; P < .001). 

“These patients with suspicious lesions on their initial MRI were more than twice as likely to have higher-grade disease within 5 years,” Nandalur noted. “This result was not only seen in the low-risk group but also in the favorable intermediate-risk group, which hasn’t been shown before.”

Grade group 2 vs 1 and increasing age were also associated with significantly increased risk for reclassification to a more aggressive cancer type.
 

How Might These Findings Improve Outcomes in Patients With Prostate Cancer?

Currently, 60%-70% of patients with low-risk disease choose active surveillance over immediate treatment, whereas 20% with favorable intermediate-risk disease choose active surveillance, according to Dr. Nandalur.

For low-risk patients, PI-RADS score is unlikely to change this decision, although surveillance intervals could be adjusted in accordance with risk. More notably, those with favorable intermediate-risk disease may benefit from considering PI-RADS score when choosing between active surveillance and immediate treatment.

“Most of the management strategies for prostate cancer are based on just your lab values and your pathology,” Dr. Nandalur said, “but this study shows that maybe we should start taking MRI into account — into the general paradigm of management of prostate cancer.”

Ideally, he added, prospective studies will confirm these findings, although such studies can be challenging to perform and similar data have historically been sufficient to reshape clinical practice.

“We are hoping that [baseline PI-RADS score] will be adopted into the NCCN [National Comprehensive Cancer Network] guidelines,” Dr. Nandalur said.
 

How Likely Are These Findings to Reshape Clinical Practice?

“The study’s large, multicenter cohort and its focus on the prognostic value of baseline MRI in active surveillance make it a crucial contribution to the field, providing evidence that can potentially refine patient management strategies in clinical practice,” Ismail Baris Turkbey, MD, FSAR, head of MRI Section, Molecular Imaging Branch, National Cancer Institute, Rockville, Maryland, said in a written comment.

“The findings from this study are likely to have a significant impact on clinical practice and potentially influence future guidelines in the management of localized prostate cancer, particularly in the context of active surveillance,” Dr. Turkbey said. “MRI, already a commonly used imaging modality in prostate cancer management, may become an even more integral part of the initial assessment and ongoing monitoring of patients with low or favorable-intermediate risk prostate cancer.”

Dr. Turkbey noted several strengths of the study.  

First, the size and the diversity of the cohort, along with the variety of treatment centers, support generalizability of findings. Second, the study pinpoints a “critical aspect” of active surveillance by uncovering the link between baseline MRI findings and later risk reclassification. Finally, the study also showed that increasing age was associated with higher likelihood of risk reclassification, “further emphasizing the need for personalized risk assessment” among these patients.
 

What Were Some Limitations of This Study?

“One important limitation is the lack of inter-reader agreement for PI-RADS evaluations for baseline MRIs,” Dr. Turkbey said. “Variation of PI-RADS is quite known, and centralized evaluations could have made this study stronger. Same applies for centralized quality evaluation of MRIs using The Prostate Imaging Quality (PI-QUAL) score. These items are difficult to do in a multicenter prospective data registry, and maybe authors will consider including these additional analyses in their future work.” 

How Does This New Approach to Prostate Cancer Risk Assessment Compare With Recent Advances in AI-Based Risk Assessment?

Over the past few years, artificial intelligence (AI)–assisted risk assessment in prostate cancer has been gaining increasing attention. Recently, for example, Artera, a self-styled “precision medicine company,” released the first AI tool to help patients choose between active surveillance and active treatment on the basis of analysis of digital pathology images. 

When asked to compare this approach with the methods used in the present study, Dr. Nandalur called the AI model “a step forward” but noted that it still relies on conventional risk criteria.

“Our data show imaging with MRI has independent prognostic information for prostate cancer patients considering active surveillance, over and above these traditional factors,” he said. “Moreover, this predictive ability of MRI was seen in low and favorable intermediate risk groups, so the additive value is broad.”

Still, he predicted that the future will not involve a binary choice, but a combination approach.

“The exciting aspect is that MRI results can eventually be added to this novel AI model and further improve prediction models for patients,” Dr. Nandalur said. “The combination of recent AI models and MRI will likely represent the future paradigm for prostate cancer patients considering active surveillance versus immediate treatment.”

The study was supported by Blue Cross and Blue Shield of Michigan. The investigators and Dr. Turkbey reported no conflicts of interest.

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

Prior exposure to conventional irinotecan does not affect survival in patients with advanced pancreatic ductal adenocarcinoma (PDAC) who are subsequently treated with the liposomal formulation nanoliposomal irinotecan (nal‐IRI), according to a meta-analysis of real-world studies.

“The selection of later lines of chemotherapy regimens should be based on the differential safety profile, patient status, the cost of treatment, and health‐related quality of life,” reported lead author Amol Gupta, MD, from the Sidney Kimmel Comprehensive Cancer Center at the Johns Hopkins Hospital in Baltimore.

The findings, published in Cancer on July 10, 2024, are “noteworthy with respect to calling attention to this important situation and the role of a new drug in the PDAC pharmacologic armamentarium,” Vincent J. Picozzi, MD from the Division of Hematology‐Oncology, Virginia Mason Medical Center, Seattle, wrote in an accompanying editorial.

Treatment of PDAC remains a challenge, the authors noted, as most diagnoses occur at a metastatic or locally advanced stage at which treatments provide only modest benefits and significant toxicities.

The introduction of the first‐line FOLFIRINOX regimen (fluorouracil [5‐FU], leucovorin [LV], irinotecan [IRI], and oxaliplatin) and gemcitabine plus nanoparticle albumin‐bound (nab)‐paclitaxel “has improved the survival of patients with advanced PDAC and increased the number of patients eligible for subsequent therapies” beyond the first-line setting, according to the authors. But survival benefits with FOLFIRINOX and gemcitabine‐based therapy remain poor, with median overall survival (OS) of 6 and 7.6 months, respectively, they noted.
 

Timing Liposomal Irinotecan

The liposomal formulation of IRI has resulted in improved pharmacokinetics and decreased toxicity, but use of this new formulation in later lines of therapy is sometimes limited by concerns that prior exposure to conventional IRI in FOLFIRINOX might produce cross-resistance and reduce the benefit of nal-IRI, the authors explained.

To examine this question, the researchers included eight retrospective chart reviews published up until April 2023 that included a total of 1368 patients who were treated with nal-IRI for locally advanced or metastatic PDAC (five studies) or locally advanced or metastatic PDAC (three studies). Patients ranged in age from 57.8 to 65 years, with the proportion of male patients ranging from 45.7% to 68.6%. The sample sizes of the studies ranged from 29 to 675 patients, with a follow-up range of 6-12.9 months.

Between 84.5% and 100% of patients had received two or more prior lines of therapy, with prior IRI exposure ranging from 20.9% to 100%. In total, 499 patients had prior IRI exposure, mostly in the first-line setting. When reported, most patients gave the reason for IRI discontinuation as disease progression.

Across all patients, the pooled progression-free survival (PFS) and OS were 2.02 months and 4.26 months, respectively, with comparable outcomes in patients with prior IRI exposure compared with those without: PFS (hazard ratio [HR], 1.17; 95% CI, 0.94-1.47; P = .17) and OS (HR, 1.16; 95% CI, 0.95-1.42; P = .16), respectively. This held true regardless of whether patients had experienced progressive disease on conventional IRI. Specifically, the PFS and OS of patients who discontinued conventional IRI because of progressive disease were comparable (HR, 1.50 and HR, 1.70) with those of patients who did not have progressive disease.

The authors reported there was substantial variation in predictors of nal-IRI outcomes among the studies examined. One study reported a numerical but not statistically significant better PFS and OS associated with longer IRI exposure and a higher cumulative dose of prior IRI. Two studies suggested worse PFS and OS associated with later treatment lines of nal-IRI, although adjusted HR did not reflect this. Sequence of treatment was a significant predictor of outcome, as were surgery and metastatic disease, bone and liver metastases, serum albumin < 40 g/L, a neutrophil‐to-lymphocyte ratio > 5, and an elevated baseline carbohydrate antigen 19‐9 level.

“There are several reasons to consider why nal‐IRI may be effective after standard IRI has failed to be so,” said Dr. Picozzi, suggesting pharmacokinetics or an improved tumor tissue/normal tissue exposure ratio as possible explanations. “However, as the authors point out, the results from this pooled, retrospective review could also simply be the result of methodological bias (eg, selection bias) or patient selection,” he added.

“Perhaps the best way of considering the results of the analysis (remembering that the median PFS was essentially the same as the first restaging visit) is that nal‐IRI may be just another in a list of suboptimal treatment options in this situation, he wrote. “If its inherent activity is very low in third‐line treatment (like all other agents to date), the use and response to prior standard IRI may be largely irrelevant.”

Consequently, he concurs with the authors that the selection of third-line treatment options and beyond for advanced APDAC should not be influenced by prior IRI exposure.
 

First-Line Liposomal Irinotecan Approved

In February, the US Food and Drug Administration (FDA) approved nal-IRI (Onivyde) as part of a new first-line regimen for first-line metastatic PDAC. In the new regimen (NALIRIFOX), nal-IRI is substituted for the conventional IRI found in FOLFIRINOX, boosting the cost more than 15-fold from around $500-$7800 per cycle.

The FDA approval was based on the results of the NAPOLI-3 study, which did not compare outcomes of NALIRIFOX with FOLFIRINOX, but rather, compared first-line nal-IRI with the combination of nab‐paclitaxel and gemcitabine. The study showed longer OS (HR, 0.83; 95% CI, 0.70-0.99; P = .04) and PFS (HR, 0.69; 95% CI, 0.58-0.83; P < .001), with first-line nal-IRI.

The absence of a head-to-head comparison has some oncologists debating whether the new regimen is a potential new standard first-line treatment or whether the cost outweighs the potential benefits.

One study author reported grants/contracts from AbbVie, Bristol Myers Squibb, Curegenix, Medivir, Merck, and Nouscom; personal/consulting fees from Bayer, Catenion, G1 Therapeutics, Janssen Pharmaceuticals, Merck, Merus, Nouscom, Regeneron, Sirtex Medical Inc., Tango Therapeutics, and Tavotek Biotherapeutics; and support for other professional activities from Bristol Myers Squibb and Merck outside the submitted work. Another study author reported personal/consulting fees from Astellas Pharma, AstraZeneca, IDEAYA Biosciences, Merck, Merus, Moderna, RenovoRx, Seattle Genetics, and TriSalus Life Sciences outside the submitted work. The remaining authors and Picozzi disclosed no conflicts of interest.
 

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

Prior exposure to conventional irinotecan does not affect survival in patients with advanced pancreatic ductal adenocarcinoma (PDAC) who are subsequently treated with the liposomal formulation nanoliposomal irinotecan (nal‐IRI), according to a meta-analysis of real-world studies.

“The selection of later lines of chemotherapy regimens should be based on the differential safety profile, patient status, the cost of treatment, and health‐related quality of life,” reported lead author Amol Gupta, MD, from the Sidney Kimmel Comprehensive Cancer Center at the Johns Hopkins Hospital in Baltimore.

The findings, published in Cancer on July 10, 2024, are “noteworthy with respect to calling attention to this important situation and the role of a new drug in the PDAC pharmacologic armamentarium,” Vincent J. Picozzi, MD from the Division of Hematology‐Oncology, Virginia Mason Medical Center, Seattle, wrote in an accompanying editorial.

Treatment of PDAC remains a challenge, the authors noted, as most diagnoses occur at a metastatic or locally advanced stage at which treatments provide only modest benefits and significant toxicities.

The introduction of the first‐line FOLFIRINOX regimen (fluorouracil [5‐FU], leucovorin [LV], irinotecan [IRI], and oxaliplatin) and gemcitabine plus nanoparticle albumin‐bound (nab)‐paclitaxel “has improved the survival of patients with advanced PDAC and increased the number of patients eligible for subsequent therapies” beyond the first-line setting, according to the authors. But survival benefits with FOLFIRINOX and gemcitabine‐based therapy remain poor, with median overall survival (OS) of 6 and 7.6 months, respectively, they noted.
 

Timing Liposomal Irinotecan

The liposomal formulation of IRI has resulted in improved pharmacokinetics and decreased toxicity, but use of this new formulation in later lines of therapy is sometimes limited by concerns that prior exposure to conventional IRI in FOLFIRINOX might produce cross-resistance and reduce the benefit of nal-IRI, the authors explained.

To examine this question, the researchers included eight retrospective chart reviews published up until April 2023 that included a total of 1368 patients who were treated with nal-IRI for locally advanced or metastatic PDAC (five studies) or locally advanced or metastatic PDAC (three studies). Patients ranged in age from 57.8 to 65 years, with the proportion of male patients ranging from 45.7% to 68.6%. The sample sizes of the studies ranged from 29 to 675 patients, with a follow-up range of 6-12.9 months.

Between 84.5% and 100% of patients had received two or more prior lines of therapy, with prior IRI exposure ranging from 20.9% to 100%. In total, 499 patients had prior IRI exposure, mostly in the first-line setting. When reported, most patients gave the reason for IRI discontinuation as disease progression.

Across all patients, the pooled progression-free survival (PFS) and OS were 2.02 months and 4.26 months, respectively, with comparable outcomes in patients with prior IRI exposure compared with those without: PFS (hazard ratio [HR], 1.17; 95% CI, 0.94-1.47; P = .17) and OS (HR, 1.16; 95% CI, 0.95-1.42; P = .16), respectively. This held true regardless of whether patients had experienced progressive disease on conventional IRI. Specifically, the PFS and OS of patients who discontinued conventional IRI because of progressive disease were comparable (HR, 1.50 and HR, 1.70) with those of patients who did not have progressive disease.

The authors reported there was substantial variation in predictors of nal-IRI outcomes among the studies examined. One study reported a numerical but not statistically significant better PFS and OS associated with longer IRI exposure and a higher cumulative dose of prior IRI. Two studies suggested worse PFS and OS associated with later treatment lines of nal-IRI, although adjusted HR did not reflect this. Sequence of treatment was a significant predictor of outcome, as were surgery and metastatic disease, bone and liver metastases, serum albumin < 40 g/L, a neutrophil‐to-lymphocyte ratio > 5, and an elevated baseline carbohydrate antigen 19‐9 level.

“There are several reasons to consider why nal‐IRI may be effective after standard IRI has failed to be so,” said Dr. Picozzi, suggesting pharmacokinetics or an improved tumor tissue/normal tissue exposure ratio as possible explanations. “However, as the authors point out, the results from this pooled, retrospective review could also simply be the result of methodological bias (eg, selection bias) or patient selection,” he added.

“Perhaps the best way of considering the results of the analysis (remembering that the median PFS was essentially the same as the first restaging visit) is that nal‐IRI may be just another in a list of suboptimal treatment options in this situation, he wrote. “If its inherent activity is very low in third‐line treatment (like all other agents to date), the use and response to prior standard IRI may be largely irrelevant.”

Consequently, he concurs with the authors that the selection of third-line treatment options and beyond for advanced APDAC should not be influenced by prior IRI exposure.
 

First-Line Liposomal Irinotecan Approved

In February, the US Food and Drug Administration (FDA) approved nal-IRI (Onivyde) as part of a new first-line regimen for first-line metastatic PDAC. In the new regimen (NALIRIFOX), nal-IRI is substituted for the conventional IRI found in FOLFIRINOX, boosting the cost more than 15-fold from around $500-$7800 per cycle.

The FDA approval was based on the results of the NAPOLI-3 study, which did not compare outcomes of NALIRIFOX with FOLFIRINOX, but rather, compared first-line nal-IRI with the combination of nab‐paclitaxel and gemcitabine. The study showed longer OS (HR, 0.83; 95% CI, 0.70-0.99; P = .04) and PFS (HR, 0.69; 95% CI, 0.58-0.83; P < .001), with first-line nal-IRI.

The absence of a head-to-head comparison has some oncologists debating whether the new regimen is a potential new standard first-line treatment or whether the cost outweighs the potential benefits.

One study author reported grants/contracts from AbbVie, Bristol Myers Squibb, Curegenix, Medivir, Merck, and Nouscom; personal/consulting fees from Bayer, Catenion, G1 Therapeutics, Janssen Pharmaceuticals, Merck, Merus, Nouscom, Regeneron, Sirtex Medical Inc., Tango Therapeutics, and Tavotek Biotherapeutics; and support for other professional activities from Bristol Myers Squibb and Merck outside the submitted work. Another study author reported personal/consulting fees from Astellas Pharma, AstraZeneca, IDEAYA Biosciences, Merck, Merus, Moderna, RenovoRx, Seattle Genetics, and TriSalus Life Sciences outside the submitted work. The remaining authors and Picozzi disclosed no conflicts of interest.
 

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

Prior exposure to conventional irinotecan does not affect survival in patients with advanced pancreatic ductal adenocarcinoma (PDAC) who are subsequently treated with the liposomal formulation nanoliposomal irinotecan (nal‐IRI), according to a meta-analysis of real-world studies.

“The selection of later lines of chemotherapy regimens should be based on the differential safety profile, patient status, the cost of treatment, and health‐related quality of life,” reported lead author Amol Gupta, MD, from the Sidney Kimmel Comprehensive Cancer Center at the Johns Hopkins Hospital in Baltimore.

The findings, published in Cancer on July 10, 2024, are “noteworthy with respect to calling attention to this important situation and the role of a new drug in the PDAC pharmacologic armamentarium,” Vincent J. Picozzi, MD from the Division of Hematology‐Oncology, Virginia Mason Medical Center, Seattle, wrote in an accompanying editorial.

Treatment of PDAC remains a challenge, the authors noted, as most diagnoses occur at a metastatic or locally advanced stage at which treatments provide only modest benefits and significant toxicities.

The introduction of the first‐line FOLFIRINOX regimen (fluorouracil [5‐FU], leucovorin [LV], irinotecan [IRI], and oxaliplatin) and gemcitabine plus nanoparticle albumin‐bound (nab)‐paclitaxel “has improved the survival of patients with advanced PDAC and increased the number of patients eligible for subsequent therapies” beyond the first-line setting, according to the authors. But survival benefits with FOLFIRINOX and gemcitabine‐based therapy remain poor, with median overall survival (OS) of 6 and 7.6 months, respectively, they noted.
 

Timing Liposomal Irinotecan

The liposomal formulation of IRI has resulted in improved pharmacokinetics and decreased toxicity, but use of this new formulation in later lines of therapy is sometimes limited by concerns that prior exposure to conventional IRI in FOLFIRINOX might produce cross-resistance and reduce the benefit of nal-IRI, the authors explained.

To examine this question, the researchers included eight retrospective chart reviews published up until April 2023 that included a total of 1368 patients who were treated with nal-IRI for locally advanced or metastatic PDAC (five studies) or locally advanced or metastatic PDAC (three studies). Patients ranged in age from 57.8 to 65 years, with the proportion of male patients ranging from 45.7% to 68.6%. The sample sizes of the studies ranged from 29 to 675 patients, with a follow-up range of 6-12.9 months.

Between 84.5% and 100% of patients had received two or more prior lines of therapy, with prior IRI exposure ranging from 20.9% to 100%. In total, 499 patients had prior IRI exposure, mostly in the first-line setting. When reported, most patients gave the reason for IRI discontinuation as disease progression.

Across all patients, the pooled progression-free survival (PFS) and OS were 2.02 months and 4.26 months, respectively, with comparable outcomes in patients with prior IRI exposure compared with those without: PFS (hazard ratio [HR], 1.17; 95% CI, 0.94-1.47; P = .17) and OS (HR, 1.16; 95% CI, 0.95-1.42; P = .16), respectively. This held true regardless of whether patients had experienced progressive disease on conventional IRI. Specifically, the PFS and OS of patients who discontinued conventional IRI because of progressive disease were comparable (HR, 1.50 and HR, 1.70) with those of patients who did not have progressive disease.

The authors reported there was substantial variation in predictors of nal-IRI outcomes among the studies examined. One study reported a numerical but not statistically significant better PFS and OS associated with longer IRI exposure and a higher cumulative dose of prior IRI. Two studies suggested worse PFS and OS associated with later treatment lines of nal-IRI, although adjusted HR did not reflect this. Sequence of treatment was a significant predictor of outcome, as were surgery and metastatic disease, bone and liver metastases, serum albumin < 40 g/L, a neutrophil‐to-lymphocyte ratio > 5, and an elevated baseline carbohydrate antigen 19‐9 level.

“There are several reasons to consider why nal‐IRI may be effective after standard IRI has failed to be so,” said Dr. Picozzi, suggesting pharmacokinetics or an improved tumor tissue/normal tissue exposure ratio as possible explanations. “However, as the authors point out, the results from this pooled, retrospective review could also simply be the result of methodological bias (eg, selection bias) or patient selection,” he added.

“Perhaps the best way of considering the results of the analysis (remembering that the median PFS was essentially the same as the first restaging visit) is that nal‐IRI may be just another in a list of suboptimal treatment options in this situation, he wrote. “If its inherent activity is very low in third‐line treatment (like all other agents to date), the use and response to prior standard IRI may be largely irrelevant.”

Consequently, he concurs with the authors that the selection of third-line treatment options and beyond for advanced APDAC should not be influenced by prior IRI exposure.
 

First-Line Liposomal Irinotecan Approved

In February, the US Food and Drug Administration (FDA) approved nal-IRI (Onivyde) as part of a new first-line regimen for first-line metastatic PDAC. In the new regimen (NALIRIFOX), nal-IRI is substituted for the conventional IRI found in FOLFIRINOX, boosting the cost more than 15-fold from around $500-$7800 per cycle.

The FDA approval was based on the results of the NAPOLI-3 study, which did not compare outcomes of NALIRIFOX with FOLFIRINOX, but rather, compared first-line nal-IRI with the combination of nab‐paclitaxel and gemcitabine. The study showed longer OS (HR, 0.83; 95% CI, 0.70-0.99; P = .04) and PFS (HR, 0.69; 95% CI, 0.58-0.83; P < .001), with first-line nal-IRI.

The absence of a head-to-head comparison has some oncologists debating whether the new regimen is a potential new standard first-line treatment or whether the cost outweighs the potential benefits.

One study author reported grants/contracts from AbbVie, Bristol Myers Squibb, Curegenix, Medivir, Merck, and Nouscom; personal/consulting fees from Bayer, Catenion, G1 Therapeutics, Janssen Pharmaceuticals, Merck, Merus, Nouscom, Regeneron, Sirtex Medical Inc., Tango Therapeutics, and Tavotek Biotherapeutics; and support for other professional activities from Bristol Myers Squibb and Merck outside the submitted work. Another study author reported personal/consulting fees from Astellas Pharma, AstraZeneca, IDEAYA Biosciences, Merck, Merus, Moderna, RenovoRx, Seattle Genetics, and TriSalus Life Sciences outside the submitted work. The remaining authors and Picozzi disclosed no conflicts of interest.
 

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.

TOPLINE: 

Belzutifan demonstrated a significant benefit over everolimus in progression-free survival and objective response rates in advanced renal cell carcinoma. At 18 months, 24% of participants on belzutifan were alive and progression free, compared with 8.3% on everolimus.
 

METHODOLOGY:

• The phase 3, multicenter, open-label, randomized, active-controlled LITESPARK-005 trial was conducted at 147 sites in six regions.
• The trial aimed to compare the efficacy and safety of belzutifan with everolimus in 746 participants with advanced clear cell renal cell carcinoma who had disease progression after receiving immune checkpoint and antiangiogenic therapies. 
• Patients were randomly assigned to receive either 120 mg of belzutifan or 10 mg of everolimus orally once daily and were followed for a median of 18.4 months at the first interim analysis and of 25.7 months at the second interim analysis.
• The dual primary endpoints were progression-free survival and overall survival, with the key secondary endpoint having been a confirmed objective response, defined as a complete or partial response.
• Dose modifications were allowed to manage adverse events, with belzutifan doses reduced to 80 mg and then to 40 mg daily if needed.

TAKEAWAY:

• Belzutifan showed a significant benefit over everolimus in progression-free survival, with 24% of participants on belzutifan alive and progression free at 18 months, compared with 8.3% on everolimus (P = .002).
• The objective response rate was significantly higher in the belzutifan group (21.9%) compared with the everolimus group (3.5%) (P < .001).
• The median overall survival was 21.4 months for belzutifan and 18.1 months for everolimus, with a hazard ratio for death of 0.88 (95% CI, 0.73-1.07; P = .20).
• Grade 3 or higher adverse events occurred in 61.8% of participants in the belzutifan group and in 62.5% in the everolimus group, with adverse events leading to treatment discontinuation in 5.9% and 14.7% of participants, respectively.

IN PRACTICE:

“The LITESPARK-005 trial introduced [hypoxia-Inducible factor 2 alpha] inhibition as an active therapeutic mechanism and established belzutifan as a treatment option in patients with advanced renal-cell carcinoma after both immune checkpoint and antiangiogenic therapies,” the authors wrote.
 

SOURCE:

Corresponding author Toni K. Choueiri, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, was one of four authors who contributed equally to the article, which was published on August 21 in The New England Journal of Medicine.
 

LIMITATIONS: 

The study’s limitations include the open-label design, which may introduce bias. The trial did not include a placebo group, and the follow-up period may not be sufficient to capture long-term outcomes. In addition, the study population was heavily pretreated, which may limit the generalizability of the findings to broader patient populations.
 

DISCLOSURES:

Dr. Choueiri disclosed receiving consultancy fees from Merck, the sponsor of the study, and other pharmaceutical companies. Additional disclosures are noted in the original article.

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

TOPLINE: 

Belzutifan demonstrated a significant benefit over everolimus in progression-free survival and objective response rates in advanced renal cell carcinoma. At 18 months, 24% of participants on belzutifan were alive and progression free, compared with 8.3% on everolimus.
 

METHODOLOGY:

• The phase 3, multicenter, open-label, randomized, active-controlled LITESPARK-005 trial was conducted at 147 sites in six regions.
• The trial aimed to compare the efficacy and safety of belzutifan with everolimus in 746 participants with advanced clear cell renal cell carcinoma who had disease progression after receiving immune checkpoint and antiangiogenic therapies. 
• Patients were randomly assigned to receive either 120 mg of belzutifan or 10 mg of everolimus orally once daily and were followed for a median of 18.4 months at the first interim analysis and of 25.7 months at the second interim analysis.
• The dual primary endpoints were progression-free survival and overall survival, with the key secondary endpoint having been a confirmed objective response, defined as a complete or partial response.
• Dose modifications were allowed to manage adverse events, with belzutifan doses reduced to 80 mg and then to 40 mg daily if needed.

TAKEAWAY:

• Belzutifan showed a significant benefit over everolimus in progression-free survival, with 24% of participants on belzutifan alive and progression free at 18 months, compared with 8.3% on everolimus (P = .002).
• The objective response rate was significantly higher in the belzutifan group (21.9%) compared with the everolimus group (3.5%) (P < .001).
• The median overall survival was 21.4 months for belzutifan and 18.1 months for everolimus, with a hazard ratio for death of 0.88 (95% CI, 0.73-1.07; P = .20).
• Grade 3 or higher adverse events occurred in 61.8% of participants in the belzutifan group and in 62.5% in the everolimus group, with adverse events leading to treatment discontinuation in 5.9% and 14.7% of participants, respectively.

IN PRACTICE:

“The LITESPARK-005 trial introduced [hypoxia-Inducible factor 2 alpha] inhibition as an active therapeutic mechanism and established belzutifan as a treatment option in patients with advanced renal-cell carcinoma after both immune checkpoint and antiangiogenic therapies,” the authors wrote.
 

SOURCE:

Corresponding author Toni K. Choueiri, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, was one of four authors who contributed equally to the article, which was published on August 21 in The New England Journal of Medicine.
 

LIMITATIONS: 

The study’s limitations include the open-label design, which may introduce bias. The trial did not include a placebo group, and the follow-up period may not be sufficient to capture long-term outcomes. In addition, the study population was heavily pretreated, which may limit the generalizability of the findings to broader patient populations.
 

DISCLOSURES:

Dr. Choueiri disclosed receiving consultancy fees from Merck, the sponsor of the study, and other pharmaceutical companies. Additional disclosures are noted in the original article.

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

TOPLINE: 

Belzutifan demonstrated a significant benefit over everolimus in progression-free survival and objective response rates in advanced renal cell carcinoma. At 18 months, 24% of participants on belzutifan were alive and progression free, compared with 8.3% on everolimus.
 

METHODOLOGY:

• The phase 3, multicenter, open-label, randomized, active-controlled LITESPARK-005 trial was conducted at 147 sites in six regions.
• The trial aimed to compare the efficacy and safety of belzutifan with everolimus in 746 participants with advanced clear cell renal cell carcinoma who had disease progression after receiving immune checkpoint and antiangiogenic therapies. 
• Patients were randomly assigned to receive either 120 mg of belzutifan or 10 mg of everolimus orally once daily and were followed for a median of 18.4 months at the first interim analysis and of 25.7 months at the second interim analysis.
• The dual primary endpoints were progression-free survival and overall survival, with the key secondary endpoint having been a confirmed objective response, defined as a complete or partial response.
• Dose modifications were allowed to manage adverse events, with belzutifan doses reduced to 80 mg and then to 40 mg daily if needed.

TAKEAWAY:

• Belzutifan showed a significant benefit over everolimus in progression-free survival, with 24% of participants on belzutifan alive and progression free at 18 months, compared with 8.3% on everolimus (P = .002).
• The objective response rate was significantly higher in the belzutifan group (21.9%) compared with the everolimus group (3.5%) (P < .001).
• The median overall survival was 21.4 months for belzutifan and 18.1 months for everolimus, with a hazard ratio for death of 0.88 (95% CI, 0.73-1.07; P = .20).
• Grade 3 or higher adverse events occurred in 61.8% of participants in the belzutifan group and in 62.5% in the everolimus group, with adverse events leading to treatment discontinuation in 5.9% and 14.7% of participants, respectively.

IN PRACTICE:

“The LITESPARK-005 trial introduced [hypoxia-Inducible factor 2 alpha] inhibition as an active therapeutic mechanism and established belzutifan as a treatment option in patients with advanced renal-cell carcinoma after both immune checkpoint and antiangiogenic therapies,” the authors wrote.
 

SOURCE:

Corresponding author Toni K. Choueiri, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, was one of four authors who contributed equally to the article, which was published on August 21 in The New England Journal of Medicine.
 

LIMITATIONS: 

The study’s limitations include the open-label design, which may introduce bias. The trial did not include a placebo group, and the follow-up period may not be sufficient to capture long-term outcomes. In addition, the study population was heavily pretreated, which may limit the generalizability of the findings to broader patient populations.
 

DISCLOSURES:

Dr. Choueiri disclosed receiving consultancy fees from Merck, the sponsor of the study, and other pharmaceutical companies. Additional disclosures are noted in the original article.

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

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.

TOPLINE:

Liver transplant improved progression-free survival (PFS) in carefully selected patients with unresectable colorectal liver metastasis; however, the overall survival and recurrence rate benefits did not reach statistical significance.

METHODOLOGY:

• Research has shown promising results for well-selected patients with unresectable colorectal liver metastasis undergoing liver transplant; however, the absence of a suitable comparison group makes it difficult to evaluate the overall effectiveness of this treatment method. 
• Researchers evaluated 33 patients with colorectal cancer and unresectable liver metastasis (mean age, 43.5 years; 52% women) who were eligible for liver transplants, according to validated selection criteria. 
• Of these, 20 patients (61%) underwent a liver transplant, while 13 (39%) declined transplantation and received alternative therapy. 
• Patients who received liver transplants did not undergo regular chemotherapy until recurrence, whereas those in the alternative therapy group continued systemic chemotherapy, with hepatic artery infusion pump placement (n = 5), liver resections (n = 6), and locoregional therapies (n = 6). 
• The main outcomes of the study were overall survival and PFS. 

TAKEAWAY:

• The median follow-up duration was 986 days in the liver transplant group and 657 days in the alternative therapy group. 
• Patients who underwent liver transplant showed higher PFS rates at 1 year (90.0% vs 41.7%), 2 years (72.7% vs 10.4%), and 3 years (36.4% vs 10.4%). The PFS gains were statistically significant (P < .01). 
• Overall survival was also higher in the transplant group — 100% vs 83.9% at 1 year, and 90.0% vs 73.4% at both 2 and 3 years. The differences, however, did not reach significance (P = .12). 
• Liver transplant was associated with a lower recurrence rate (5% vs 23%), which also did not reach significance (P = .28) possibly because of the small patient population. 

IN PRACTICE:

“This study represents the best available data for evaluating alternatives to [liver transplant],” the authors wrote, adding that the patients should be “referred for multidisciplinary evaluation to transplant oncology centers with strict criteria.”

SOURCE:

The study was led by Matthew M. Byrne, MD, Department of Surgery, University of Rochester Medical Center, Rochester, New York, and was published online in JAMA Surgery.

LIMITATIONS:

The patient population was small, making it difficult to interpret statistical significance. The inclusion of patients with financial and social support might limit generalizability. The survival was calculated from the date of transplant or dropout. Additionally, the study did not explore sex-based differences in treatment choice.

DISCLOSURES:

The authors did not disclose any funding information. One author reported holding shares with HistoSonics, not related to the submitted work.

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

TOPLINE:

Liver transplant improved progression-free survival (PFS) in carefully selected patients with unresectable colorectal liver metastasis; however, the overall survival and recurrence rate benefits did not reach statistical significance.

METHODOLOGY:

• Research has shown promising results for well-selected patients with unresectable colorectal liver metastasis undergoing liver transplant; however, the absence of a suitable comparison group makes it difficult to evaluate the overall effectiveness of this treatment method. 
• Researchers evaluated 33 patients with colorectal cancer and unresectable liver metastasis (mean age, 43.5 years; 52% women) who were eligible for liver transplants, according to validated selection criteria. 
• Of these, 20 patients (61%) underwent a liver transplant, while 13 (39%) declined transplantation and received alternative therapy. 
• Patients who received liver transplants did not undergo regular chemotherapy until recurrence, whereas those in the alternative therapy group continued systemic chemotherapy, with hepatic artery infusion pump placement (n = 5), liver resections (n = 6), and locoregional therapies (n = 6). 
• The main outcomes of the study were overall survival and PFS. 

TAKEAWAY:

• The median follow-up duration was 986 days in the liver transplant group and 657 days in the alternative therapy group. 
• Patients who underwent liver transplant showed higher PFS rates at 1 year (90.0% vs 41.7%), 2 years (72.7% vs 10.4%), and 3 years (36.4% vs 10.4%). The PFS gains were statistically significant (P < .01). 
• Overall survival was also higher in the transplant group — 100% vs 83.9% at 1 year, and 90.0% vs 73.4% at both 2 and 3 years. The differences, however, did not reach significance (P = .12). 
• Liver transplant was associated with a lower recurrence rate (5% vs 23%), which also did not reach significance (P = .28) possibly because of the small patient population. 

IN PRACTICE:

“This study represents the best available data for evaluating alternatives to [liver transplant],” the authors wrote, adding that the patients should be “referred for multidisciplinary evaluation to transplant oncology centers with strict criteria.”

SOURCE:

The study was led by Matthew M. Byrne, MD, Department of Surgery, University of Rochester Medical Center, Rochester, New York, and was published online in JAMA Surgery.

LIMITATIONS:

The patient population was small, making it difficult to interpret statistical significance. The inclusion of patients with financial and social support might limit generalizability. The survival was calculated from the date of transplant or dropout. Additionally, the study did not explore sex-based differences in treatment choice.

DISCLOSURES:

The authors did not disclose any funding information. One author reported holding shares with HistoSonics, not related to the submitted work.

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

TOPLINE:

Liver transplant improved progression-free survival (PFS) in carefully selected patients with unresectable colorectal liver metastasis; however, the overall survival and recurrence rate benefits did not reach statistical significance.

METHODOLOGY:

• Research has shown promising results for well-selected patients with unresectable colorectal liver metastasis undergoing liver transplant; however, the absence of a suitable comparison group makes it difficult to evaluate the overall effectiveness of this treatment method. 
• Researchers evaluated 33 patients with colorectal cancer and unresectable liver metastasis (mean age, 43.5 years; 52% women) who were eligible for liver transplants, according to validated selection criteria. 
• Of these, 20 patients (61%) underwent a liver transplant, while 13 (39%) declined transplantation and received alternative therapy. 
• Patients who received liver transplants did not undergo regular chemotherapy until recurrence, whereas those in the alternative therapy group continued systemic chemotherapy, with hepatic artery infusion pump placement (n = 5), liver resections (n = 6), and locoregional therapies (n = 6). 
• The main outcomes of the study were overall survival and PFS. 

TAKEAWAY:

• The median follow-up duration was 986 days in the liver transplant group and 657 days in the alternative therapy group. 
• Patients who underwent liver transplant showed higher PFS rates at 1 year (90.0% vs 41.7%), 2 years (72.7% vs 10.4%), and 3 years (36.4% vs 10.4%). The PFS gains were statistically significant (P < .01). 
• Overall survival was also higher in the transplant group — 100% vs 83.9% at 1 year, and 90.0% vs 73.4% at both 2 and 3 years. The differences, however, did not reach significance (P = .12). 
• Liver transplant was associated with a lower recurrence rate (5% vs 23%), which also did not reach significance (P = .28) possibly because of the small patient population. 

IN PRACTICE:

“This study represents the best available data for evaluating alternatives to [liver transplant],” the authors wrote, adding that the patients should be “referred for multidisciplinary evaluation to transplant oncology centers with strict criteria.”

SOURCE:

The study was led by Matthew M. Byrne, MD, Department of Surgery, University of Rochester Medical Center, Rochester, New York, and was published online in JAMA Surgery.

LIMITATIONS:

The patient population was small, making it difficult to interpret statistical significance. The inclusion of patients with financial and social support might limit generalizability. The survival was calculated from the date of transplant or dropout. Additionally, the study did not explore sex-based differences in treatment choice.

DISCLOSURES:

The authors did not disclose any funding information. One author reported holding shares with HistoSonics, not related to the submitted work.

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

In the 18 months after Francine Milano was diagnosed with a recurrence of the ovarian cancer she thought she’d beaten 20 years ago, she traveled twice from her home in Pennsylvania to Vermont. She went not to ski, hike, or leaf-peep, but to arrange to die.

“I really wanted to take control over how I left this world,” said the 61-year-old who lives in Lancaster. “I decided that this was an option for me.”

Dying with medical assistance wasn’t an option when Ms. Milano learned in early 2023 that her disease was incurable. At that point, she would have had to travel to Switzerland — or live in the District of Columbia or one of the 10 states where medical aid in dying was legal.

But Vermont lifted its residency requirement in May 2023, followed by Oregon two months later. (Montana effectively allows aid in dying through a 2009 court decision, but that ruling doesn’t spell out rules around residency. And though New York and California recently considered legislation that would allow out-of-staters to secure aid in dying, neither provision passed.)

Despite the limited options and the challenges — such as finding doctors in a new state, figuring out where to die, and traveling when too sick to walk to the next room, let alone climb into a car — dozens have made the trek to the two states that have opened their doors to terminally ill nonresidents seeking aid in dying.

At least 26 people have traveled to Vermont to die, representing nearly 25% of the reported assisted deaths in the state from May 2023 through this June, according to the Vermont Department of Health. In Oregon, 23 out-of-state residents died using medical assistance in 2023, just over 6% of the state total, according to the Oregon Health Authority.

Oncologist Charles Blanke, MD, whose clinic in Portland is devoted to end-of-life care, said he thinks that Oregon’s total is likely an undercount and he expects the numbers to grow. Over the past year, he said, he’s seen two to four out-of-state patients a week — about one-quarter of his practice — and fielded calls from across the U.S., including New York, the Carolinas, Florida, and “tons from Texas.” But just because patients are willing to travel doesn’t mean it’s easy or that they get their desired outcome.

“The law is pretty strict about what has to be done,” Dr. Blanke said.

As in other states that allow what some call physician-assisted death or assisted suicide, Oregon and Vermont require patients to be assessed by two doctors. Patients must have less than six months to live, be mentally and cognitively sound, and be physically able to ingest the drugs to end their lives. Charts and records must be reviewed in the state; neglecting to do so constitutes practicing medicine out of state, which violates medical licensing requirements. For the same reason, the patients must be in the state for the initial exam, when they request the drugs, and when they ingest them.

State legislatures impose those restrictions as safeguards — to balance the rights of patients seeking aid in dying with a legislative imperative not to pass laws that are harmful to anyone, said Peg Sandeen, CEO of the group Death With Dignity. Like many aid-in-dying advocates, however, she said such rules create undue burdens for people who are already suffering.

Diana Barnard, MD, a Vermont palliative care physician, said some patients cannot even come for their appointments. “They end up being sick or not feeling like traveling, so there’s rescheduling involved,” she said. “It’s asking people to use a significant part of their energy to come here when they really deserve to have the option closer to home.”

Those opposed to aid in dying include religious groups that say taking a life is immoral, and medical practitioners who argue their job is to make people more comfortable at the end of life, not to end the life itself.

Anthropologist Anita Hannig, who interviewed dozens of terminally ill patients while researching her 2022 book, “The Day I Die: The Untold Story of Assisted Dying in America,” said she doesn’t expect federal legislation to settle the issue anytime soon. As the Supreme Court did with abortion in 2022, it ruled assisted dying to be a states’ rights issue in 1997.

During the 2023-24 legislative sessions, 19 states (including Ms. Milano’s home state of Pennsylvania) considered aid-in-dying legislation, according to the advocacy group Compassion & Choices. Delaware was the sole state to pass it, but the governor has yet to act on it.

Ms. Sandeen said that many states initially pass restrictive laws — requiring 21-day wait times and psychiatric evaluations, for instance — only to eventually repeal provisions that prove unduly onerous. That makes her optimistic that more states will eventually follow Vermont and Oregon, she said.

Ms. Milano would have preferred to travel to neighboring New Jersey, where aid in dying has been legal since 2019, but its residency requirement made that a nonstarter. And though Oregon has more providers than the largely rural state of Vermont, Ms. Milano opted for the 9-hour car ride to Burlington because it was less physically and financially draining than a cross-country trip.

The logistics were key because Ms. Milano knew she’d have to return. When she traveled to Vermont in May 2023 with her husband and her brother, she wasn’t near death. She figured that the next time she was in Vermont, it would be to request the medication. Then she’d have to wait 15 days to receive it.

The waiting period is standard to ensure that a person has what Dr. Barnard calls “thoughtful time to contemplate the decision,” although she said most have done that long before. Some states have shortened the period or, like Oregon, have a waiver option.

That waiting period can be hard on patients, on top of being away from their health care team, home, and family. Blanke said he has seen as many as 25 relatives attend the death of an Oregon resident, but out-of-staters usually bring only one person. And while finding a place to die can be a problem for Oregonians who are in care homes or hospitals that prohibit aid in dying, it’s especially challenging for nonresidents.

When Oregon lifted its residency requirement, Dr. Blanke advertised on Craigslist and used the results to compile a list of short-term accommodations, including Airbnbs, willing to allow patients to die there. Nonprofits in states with aid-in-dying laws also maintain such lists, Ms. Sandeen said.

Ms. Milano hasn’t gotten to the point where she needs to find a place to take the meds and end her life. In fact, because she had a relatively healthy year after her first trip to Vermont, she let her 6-month approval period lapse.

In June, though, she headed back to open another 6-month window. This time, she went with a girlfriend who has a camper van. They drove 6 hours to cross the state border, stopping at a playground and gift shop before sitting in a parking lot where Ms. Milano had a Zoom appointment with her doctors rather than driving 3 more hours to Burlington to meet in person.

“I don’t know if they do GPS tracking or IP address kind of stuff, but I would have been afraid not to be honest,” she said.

That’s not all that scares her. She worries she’ll be too sick to return to Vermont when she is ready to die. And, even if she can get there, she wonders whether she’ll have the courage to take the medication. About one-third of people approved for assisted death don’t follow through, Dr. Blanke said. For them, it’s often enough to know they have the meds — the control — to end their lives when they want.

Ms. Milano said she is grateful she has that power now while she’s still healthy enough to travel and enjoy life. “I just wish more people had the option,” she said.
 

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

In the 18 months after Francine Milano was diagnosed with a recurrence of the ovarian cancer she thought she’d beaten 20 years ago, she traveled twice from her home in Pennsylvania to Vermont. She went not to ski, hike, or leaf-peep, but to arrange to die.

“I really wanted to take control over how I left this world,” said the 61-year-old who lives in Lancaster. “I decided that this was an option for me.”

Dying with medical assistance wasn’t an option when Ms. Milano learned in early 2023 that her disease was incurable. At that point, she would have had to travel to Switzerland — or live in the District of Columbia or one of the 10 states where medical aid in dying was legal.

But Vermont lifted its residency requirement in May 2023, followed by Oregon two months later. (Montana effectively allows aid in dying through a 2009 court decision, but that ruling doesn’t spell out rules around residency. And though New York and California recently considered legislation that would allow out-of-staters to secure aid in dying, neither provision passed.)

Despite the limited options and the challenges — such as finding doctors in a new state, figuring out where to die, and traveling when too sick to walk to the next room, let alone climb into a car — dozens have made the trek to the two states that have opened their doors to terminally ill nonresidents seeking aid in dying.

At least 26 people have traveled to Vermont to die, representing nearly 25% of the reported assisted deaths in the state from May 2023 through this June, according to the Vermont Department of Health. In Oregon, 23 out-of-state residents died using medical assistance in 2023, just over 6% of the state total, according to the Oregon Health Authority.

Oncologist Charles Blanke, MD, whose clinic in Portland is devoted to end-of-life care, said he thinks that Oregon’s total is likely an undercount and he expects the numbers to grow. Over the past year, he said, he’s seen two to four out-of-state patients a week — about one-quarter of his practice — and fielded calls from across the U.S., including New York, the Carolinas, Florida, and “tons from Texas.” But just because patients are willing to travel doesn’t mean it’s easy or that they get their desired outcome.

“The law is pretty strict about what has to be done,” Dr. Blanke said.

As in other states that allow what some call physician-assisted death or assisted suicide, Oregon and Vermont require patients to be assessed by two doctors. Patients must have less than six months to live, be mentally and cognitively sound, and be physically able to ingest the drugs to end their lives. Charts and records must be reviewed in the state; neglecting to do so constitutes practicing medicine out of state, which violates medical licensing requirements. For the same reason, the patients must be in the state for the initial exam, when they request the drugs, and when they ingest them.

State legislatures impose those restrictions as safeguards — to balance the rights of patients seeking aid in dying with a legislative imperative not to pass laws that are harmful to anyone, said Peg Sandeen, CEO of the group Death With Dignity. Like many aid-in-dying advocates, however, she said such rules create undue burdens for people who are already suffering.

Diana Barnard, MD, a Vermont palliative care physician, said some patients cannot even come for their appointments. “They end up being sick or not feeling like traveling, so there’s rescheduling involved,” she said. “It’s asking people to use a significant part of their energy to come here when they really deserve to have the option closer to home.”

Those opposed to aid in dying include religious groups that say taking a life is immoral, and medical practitioners who argue their job is to make people more comfortable at the end of life, not to end the life itself.

Anthropologist Anita Hannig, who interviewed dozens of terminally ill patients while researching her 2022 book, “The Day I Die: The Untold Story of Assisted Dying in America,” said she doesn’t expect federal legislation to settle the issue anytime soon. As the Supreme Court did with abortion in 2022, it ruled assisted dying to be a states’ rights issue in 1997.

During the 2023-24 legislative sessions, 19 states (including Ms. Milano’s home state of Pennsylvania) considered aid-in-dying legislation, according to the advocacy group Compassion & Choices. Delaware was the sole state to pass it, but the governor has yet to act on it.

Ms. Sandeen said that many states initially pass restrictive laws — requiring 21-day wait times and psychiatric evaluations, for instance — only to eventually repeal provisions that prove unduly onerous. That makes her optimistic that more states will eventually follow Vermont and Oregon, she said.

Ms. Milano would have preferred to travel to neighboring New Jersey, where aid in dying has been legal since 2019, but its residency requirement made that a nonstarter. And though Oregon has more providers than the largely rural state of Vermont, Ms. Milano opted for the 9-hour car ride to Burlington because it was less physically and financially draining than a cross-country trip.

The logistics were key because Ms. Milano knew she’d have to return. When she traveled to Vermont in May 2023 with her husband and her brother, she wasn’t near death. She figured that the next time she was in Vermont, it would be to request the medication. Then she’d have to wait 15 days to receive it.

The waiting period is standard to ensure that a person has what Dr. Barnard calls “thoughtful time to contemplate the decision,” although she said most have done that long before. Some states have shortened the period or, like Oregon, have a waiver option.

That waiting period can be hard on patients, on top of being away from their health care team, home, and family. Blanke said he has seen as many as 25 relatives attend the death of an Oregon resident, but out-of-staters usually bring only one person. And while finding a place to die can be a problem for Oregonians who are in care homes or hospitals that prohibit aid in dying, it’s especially challenging for nonresidents.

When Oregon lifted its residency requirement, Dr. Blanke advertised on Craigslist and used the results to compile a list of short-term accommodations, including Airbnbs, willing to allow patients to die there. Nonprofits in states with aid-in-dying laws also maintain such lists, Ms. Sandeen said.

Ms. Milano hasn’t gotten to the point where she needs to find a place to take the meds and end her life. In fact, because she had a relatively healthy year after her first trip to Vermont, she let her 6-month approval period lapse.

In June, though, she headed back to open another 6-month window. This time, she went with a girlfriend who has a camper van. They drove 6 hours to cross the state border, stopping at a playground and gift shop before sitting in a parking lot where Ms. Milano had a Zoom appointment with her doctors rather than driving 3 more hours to Burlington to meet in person.

“I don’t know if they do GPS tracking or IP address kind of stuff, but I would have been afraid not to be honest,” she said.

That’s not all that scares her. She worries she’ll be too sick to return to Vermont when she is ready to die. And, even if she can get there, she wonders whether she’ll have the courage to take the medication. About one-third of people approved for assisted death don’t follow through, Dr. Blanke said. For them, it’s often enough to know they have the meds — the control — to end their lives when they want.

Ms. Milano said she is grateful she has that power now while she’s still healthy enough to travel and enjoy life. “I just wish more people had the option,” she said.
 

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

In the 18 months after Francine Milano was diagnosed with a recurrence of the ovarian cancer she thought she’d beaten 20 years ago, she traveled twice from her home in Pennsylvania to Vermont. She went not to ski, hike, or leaf-peep, but to arrange to die.

“I really wanted to take control over how I left this world,” said the 61-year-old who lives in Lancaster. “I decided that this was an option for me.”

Dying with medical assistance wasn’t an option when Ms. Milano learned in early 2023 that her disease was incurable. At that point, she would have had to travel to Switzerland — or live in the District of Columbia or one of the 10 states where medical aid in dying was legal.

But Vermont lifted its residency requirement in May 2023, followed by Oregon two months later. (Montana effectively allows aid in dying through a 2009 court decision, but that ruling doesn’t spell out rules around residency. And though New York and California recently considered legislation that would allow out-of-staters to secure aid in dying, neither provision passed.)

Despite the limited options and the challenges — such as finding doctors in a new state, figuring out where to die, and traveling when too sick to walk to the next room, let alone climb into a car — dozens have made the trek to the two states that have opened their doors to terminally ill nonresidents seeking aid in dying.

At least 26 people have traveled to Vermont to die, representing nearly 25% of the reported assisted deaths in the state from May 2023 through this June, according to the Vermont Department of Health. In Oregon, 23 out-of-state residents died using medical assistance in 2023, just over 6% of the state total, according to the Oregon Health Authority.

Oncologist Charles Blanke, MD, whose clinic in Portland is devoted to end-of-life care, said he thinks that Oregon’s total is likely an undercount and he expects the numbers to grow. Over the past year, he said, he’s seen two to four out-of-state patients a week — about one-quarter of his practice — and fielded calls from across the U.S., including New York, the Carolinas, Florida, and “tons from Texas.” But just because patients are willing to travel doesn’t mean it’s easy or that they get their desired outcome.

“The law is pretty strict about what has to be done,” Dr. Blanke said.

As in other states that allow what some call physician-assisted death or assisted suicide, Oregon and Vermont require patients to be assessed by two doctors. Patients must have less than six months to live, be mentally and cognitively sound, and be physically able to ingest the drugs to end their lives. Charts and records must be reviewed in the state; neglecting to do so constitutes practicing medicine out of state, which violates medical licensing requirements. For the same reason, the patients must be in the state for the initial exam, when they request the drugs, and when they ingest them.

State legislatures impose those restrictions as safeguards — to balance the rights of patients seeking aid in dying with a legislative imperative not to pass laws that are harmful to anyone, said Peg Sandeen, CEO of the group Death With Dignity. Like many aid-in-dying advocates, however, she said such rules create undue burdens for people who are already suffering.

Diana Barnard, MD, a Vermont palliative care physician, said some patients cannot even come for their appointments. “They end up being sick or not feeling like traveling, so there’s rescheduling involved,” she said. “It’s asking people to use a significant part of their energy to come here when they really deserve to have the option closer to home.”

Those opposed to aid in dying include religious groups that say taking a life is immoral, and medical practitioners who argue their job is to make people more comfortable at the end of life, not to end the life itself.

Anthropologist Anita Hannig, who interviewed dozens of terminally ill patients while researching her 2022 book, “The Day I Die: The Untold Story of Assisted Dying in America,” said she doesn’t expect federal legislation to settle the issue anytime soon. As the Supreme Court did with abortion in 2022, it ruled assisted dying to be a states’ rights issue in 1997.

During the 2023-24 legislative sessions, 19 states (including Ms. Milano’s home state of Pennsylvania) considered aid-in-dying legislation, according to the advocacy group Compassion & Choices. Delaware was the sole state to pass it, but the governor has yet to act on it.

Ms. Sandeen said that many states initially pass restrictive laws — requiring 21-day wait times and psychiatric evaluations, for instance — only to eventually repeal provisions that prove unduly onerous. That makes her optimistic that more states will eventually follow Vermont and Oregon, she said.

Ms. Milano would have preferred to travel to neighboring New Jersey, where aid in dying has been legal since 2019, but its residency requirement made that a nonstarter. And though Oregon has more providers than the largely rural state of Vermont, Ms. Milano opted for the 9-hour car ride to Burlington because it was less physically and financially draining than a cross-country trip.

The logistics were key because Ms. Milano knew she’d have to return. When she traveled to Vermont in May 2023 with her husband and her brother, she wasn’t near death. She figured that the next time she was in Vermont, it would be to request the medication. Then she’d have to wait 15 days to receive it.

The waiting period is standard to ensure that a person has what Dr. Barnard calls “thoughtful time to contemplate the decision,” although she said most have done that long before. Some states have shortened the period or, like Oregon, have a waiver option.

That waiting period can be hard on patients, on top of being away from their health care team, home, and family. Blanke said he has seen as many as 25 relatives attend the death of an Oregon resident, but out-of-staters usually bring only one person. And while finding a place to die can be a problem for Oregonians who are in care homes or hospitals that prohibit aid in dying, it’s especially challenging for nonresidents.

When Oregon lifted its residency requirement, Dr. Blanke advertised on Craigslist and used the results to compile a list of short-term accommodations, including Airbnbs, willing to allow patients to die there. Nonprofits in states with aid-in-dying laws also maintain such lists, Ms. Sandeen said.

Ms. Milano hasn’t gotten to the point where she needs to find a place to take the meds and end her life. In fact, because she had a relatively healthy year after her first trip to Vermont, she let her 6-month approval period lapse.

In June, though, she headed back to open another 6-month window. This time, she went with a girlfriend who has a camper van. They drove 6 hours to cross the state border, stopping at a playground and gift shop before sitting in a parking lot where Ms. Milano had a Zoom appointment with her doctors rather than driving 3 more hours to Burlington to meet in person.

“I don’t know if they do GPS tracking or IP address kind of stuff, but I would have been afraid not to be honest,” she said.

That’s not all that scares her. She worries she’ll be too sick to return to Vermont when she is ready to die. And, even if she can get there, she wonders whether she’ll have the courage to take the medication. About one-third of people approved for assisted death don’t follow through, Dr. Blanke said. For them, it’s often enough to know they have the meds — the control — to end their lives when they want.

Ms. Milano said she is grateful she has that power now while she’s still healthy enough to travel and enjoy life. “I just wish more people had the option,” she said.
 

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

TOPLINE: 

The Breast Cancer Index (BCI) can predict which premenopausal women with hormone receptor–positive breast cancer benefit from ovarian function suppression (OFS) therapy. Women with BCI HOXB13/IL17BR ratio (BCI[H/I])–low tumors showed significant benefit from OFS, whereas those with BCI(H/I)-high tumors did not.

METHODOLOGY:

• Researchers conducted a prospective-retrospective translational study using tumor tissue samples from 1,718 premenopausal women with hormone receptor–positive early-stage breast cancer.
• Participants were randomly assigned to receive 5 years of tamoxifen alone, tamoxifen plus OFS, or exemestane plus OFS.
• BCI testing was performed on RNA extracted from formalin-fixed paraffin-embedded tumor specimens, blinded to clinical data and outcomes.
• The primary endpoints were breast cancer–free interval (BCFI) and distant recurrence-free interval (DRFI), with a median follow-up time of 12 years.
• Settings spanned multiple centers internationally, and data were collected from December 2003 to April 2021, analyzed from May 2022 to October 2022.

TAKEAWAY:

• According to the authors, patients with BCI(H/I)-low tumors exhibited a 12-year absolute benefit in BCFI of 11.6% from exemestane plus OFS (hazard ratio [HR], 0.48; 95% CI, 0.33-0.71) and 7.3% from tamoxifen plus OFS (HR, 0.69; 95% CI, 0.48-0.97), relative to tamoxifen alone.
• Patients with BCI(H/I)-high tumors did not derive significant benefit from either exemestane plus OFS (absolute benefit, -0.4%; HR, 1.03; 95% CI, 0.70-1.53) or tamoxifen plus OFS (absolute benefit, -1.2%; HR, 1.05; 95% CI, 0.72-1.54), compared with tamoxifen alone.
• In the ERBB2-negative subgroup, patients with BCI(H/I)-low tumors experienced a 12-year absolute benefit of 13.2% in BCFI from exemestane plus OFS (HR, 0.39; 95% CI, 0.25-0.60) and 7.4% from tamoxifen plus OFS (HR, 0.64; 95% CI, 0.44-0.93), compared with tamoxifen alone.
• BCI continuous index was significantly prognostic in the subgroup for DRFI (n = 1110; P =.004), with 12-year DRFI of 95.9%, 90.8%, and 86.3% in BCI low-risk, intermediate-risk, and high-risk cases of cancer than had not spread to nearly lymph nodes (N0 cancers), respectively.

IN PRACTICE:

“This investigation suggests a potential clinical use of BCI(H/I) results, adding to their use to identify patients most likely to benefit from extended endocrine therapy, as proven in multiple studies, although in the extended endocrine validation studies, it was the BCI(H/I)-high group that derived the greatest benefit,” wrote the authors of the study.

SOURCE:

The study was led by Ruth M. O’Regan, MD, University of Rochester Department of Medicine in Rochester, New York. It was published online on August 15, in JAMA Oncology.

LIMITATIONS: 

The study’s retrospective nature may introduce biases despite the prospective statistical analysis plan. The sample size for certain clinical subgroups might be too small to definitively confirm the predictive value of BCI(H/I) for OFS benefit. The generalizability of the findings may be limited due to the specific population studied. Further validation in other patient cohorts is necessary to confirm these findings.

DISCLOSURES:

Dr. O’Regan disclosed receiving personal fees from Pfizer and Gilead DSMB, grants from Puma, and nonfinancial support from Novartis. Additional disclosures are noted in the original article.

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

TOPLINE: 

The Breast Cancer Index (BCI) can predict which premenopausal women with hormone receptor–positive breast cancer benefit from ovarian function suppression (OFS) therapy. Women with BCI HOXB13/IL17BR ratio (BCI[H/I])–low tumors showed significant benefit from OFS, whereas those with BCI(H/I)-high tumors did not.

METHODOLOGY:

• Researchers conducted a prospective-retrospective translational study using tumor tissue samples from 1,718 premenopausal women with hormone receptor–positive early-stage breast cancer.
• Participants were randomly assigned to receive 5 years of tamoxifen alone, tamoxifen plus OFS, or exemestane plus OFS.
• BCI testing was performed on RNA extracted from formalin-fixed paraffin-embedded tumor specimens, blinded to clinical data and outcomes.
• The primary endpoints were breast cancer–free interval (BCFI) and distant recurrence-free interval (DRFI), with a median follow-up time of 12 years.
• Settings spanned multiple centers internationally, and data were collected from December 2003 to April 2021, analyzed from May 2022 to October 2022.

TAKEAWAY:

• According to the authors, patients with BCI(H/I)-low tumors exhibited a 12-year absolute benefit in BCFI of 11.6% from exemestane plus OFS (hazard ratio [HR], 0.48; 95% CI, 0.33-0.71) and 7.3% from tamoxifen plus OFS (HR, 0.69; 95% CI, 0.48-0.97), relative to tamoxifen alone.
• Patients with BCI(H/I)-high tumors did not derive significant benefit from either exemestane plus OFS (absolute benefit, -0.4%; HR, 1.03; 95% CI, 0.70-1.53) or tamoxifen plus OFS (absolute benefit, -1.2%; HR, 1.05; 95% CI, 0.72-1.54), compared with tamoxifen alone.
• In the ERBB2-negative subgroup, patients with BCI(H/I)-low tumors experienced a 12-year absolute benefit of 13.2% in BCFI from exemestane plus OFS (HR, 0.39; 95% CI, 0.25-0.60) and 7.4% from tamoxifen plus OFS (HR, 0.64; 95% CI, 0.44-0.93), compared with tamoxifen alone.
• BCI continuous index was significantly prognostic in the subgroup for DRFI (n = 1110; P =.004), with 12-year DRFI of 95.9%, 90.8%, and 86.3% in BCI low-risk, intermediate-risk, and high-risk cases of cancer than had not spread to nearly lymph nodes (N0 cancers), respectively.

IN PRACTICE:

“This investigation suggests a potential clinical use of BCI(H/I) results, adding to their use to identify patients most likely to benefit from extended endocrine therapy, as proven in multiple studies, although in the extended endocrine validation studies, it was the BCI(H/I)-high group that derived the greatest benefit,” wrote the authors of the study.

SOURCE:

The study was led by Ruth M. O’Regan, MD, University of Rochester Department of Medicine in Rochester, New York. It was published online on August 15, in JAMA Oncology.

LIMITATIONS: 

The study’s retrospective nature may introduce biases despite the prospective statistical analysis plan. The sample size for certain clinical subgroups might be too small to definitively confirm the predictive value of BCI(H/I) for OFS benefit. The generalizability of the findings may be limited due to the specific population studied. Further validation in other patient cohorts is necessary to confirm these findings.

DISCLOSURES:

Dr. O’Regan disclosed receiving personal fees from Pfizer and Gilead DSMB, grants from Puma, and nonfinancial support from Novartis. Additional disclosures are noted in the original article.

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

TOPLINE: 

The Breast Cancer Index (BCI) can predict which premenopausal women with hormone receptor–positive breast cancer benefit from ovarian function suppression (OFS) therapy. Women with BCI HOXB13/IL17BR ratio (BCI[H/I])–low tumors showed significant benefit from OFS, whereas those with BCI(H/I)-high tumors did not.

METHODOLOGY:

• Researchers conducted a prospective-retrospective translational study using tumor tissue samples from 1,718 premenopausal women with hormone receptor–positive early-stage breast cancer.
• Participants were randomly assigned to receive 5 years of tamoxifen alone, tamoxifen plus OFS, or exemestane plus OFS.
• BCI testing was performed on RNA extracted from formalin-fixed paraffin-embedded tumor specimens, blinded to clinical data and outcomes.
• The primary endpoints were breast cancer–free interval (BCFI) and distant recurrence-free interval (DRFI), with a median follow-up time of 12 years.
• Settings spanned multiple centers internationally, and data were collected from December 2003 to April 2021, analyzed from May 2022 to October 2022.

TAKEAWAY:

• According to the authors, patients with BCI(H/I)-low tumors exhibited a 12-year absolute benefit in BCFI of 11.6% from exemestane plus OFS (hazard ratio [HR], 0.48; 95% CI, 0.33-0.71) and 7.3% from tamoxifen plus OFS (HR, 0.69; 95% CI, 0.48-0.97), relative to tamoxifen alone.
• Patients with BCI(H/I)-high tumors did not derive significant benefit from either exemestane plus OFS (absolute benefit, -0.4%; HR, 1.03; 95% CI, 0.70-1.53) or tamoxifen plus OFS (absolute benefit, -1.2%; HR, 1.05; 95% CI, 0.72-1.54), compared with tamoxifen alone.
• In the ERBB2-negative subgroup, patients with BCI(H/I)-low tumors experienced a 12-year absolute benefit of 13.2% in BCFI from exemestane plus OFS (HR, 0.39; 95% CI, 0.25-0.60) and 7.4% from tamoxifen plus OFS (HR, 0.64; 95% CI, 0.44-0.93), compared with tamoxifen alone.
• BCI continuous index was significantly prognostic in the subgroup for DRFI (n = 1110; P =.004), with 12-year DRFI of 95.9%, 90.8%, and 86.3% in BCI low-risk, intermediate-risk, and high-risk cases of cancer than had not spread to nearly lymph nodes (N0 cancers), respectively.

IN PRACTICE:

“This investigation suggests a potential clinical use of BCI(H/I) results, adding to their use to identify patients most likely to benefit from extended endocrine therapy, as proven in multiple studies, although in the extended endocrine validation studies, it was the BCI(H/I)-high group that derived the greatest benefit,” wrote the authors of the study.

SOURCE:

The study was led by Ruth M. O’Regan, MD, University of Rochester Department of Medicine in Rochester, New York. It was published online on August 15, in JAMA Oncology.

LIMITATIONS: 

The study’s retrospective nature may introduce biases despite the prospective statistical analysis plan. The sample size for certain clinical subgroups might be too small to definitively confirm the predictive value of BCI(H/I) for OFS benefit. The generalizability of the findings may be limited due to the specific population studied. Further validation in other patient cohorts is necessary to confirm these findings.

DISCLOSURES:

Dr. O’Regan disclosed receiving personal fees from Pfizer and Gilead DSMB, grants from Puma, and nonfinancial support from Novartis. Additional disclosures are noted in the original article.

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