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Could Baseline MRIs Reshape Prostate Cancer Risk Assessment?
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.
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.
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.
FROM THE JOURNAL OF UROLOGY
Liposomal Irinotecan May Be Effective in Later Lines for Pancreatic Cancer
“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.
“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.
“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.
FROM CANCER
The Next Frontier of Antibiotic Discovery: Inside Your Gut
Scientists at Stanford University and the University of Pennsylvania have discovered a new antibiotic candidate in a surprising place: the human gut.
In mice, the antibiotic — a peptide known as prevotellin-2 — showed antimicrobial potency on par with polymyxin B, an antibiotic medication used to treat multidrug-resistant infections. Meanwhile, the peptide mainly left commensal, or beneficial, bacteria alone. The study, published in Cell, also identified several other potent antibiotic peptides with the potential to combat antimicrobial-resistant infections.
The research is part of a larger quest to find new antibiotics that can fight drug-resistant infections, a critical public health threat with more than 2.8 million cases and 35,000 deaths annually in the United States. That quest is urgent, said study author César de la Fuente, PhD, professor of bioengineering at the University of Pennsylvania, Philadelphia.
“The main pillars that have enabled us to almost double our lifespan in the last 100 years or so have been antibiotics, vaccines, and clean water,” said Dr. de la Fuente. “Imagine taking out one of those. I think it would be pretty dramatic.” (Dr. De la Fuente’s lab has become known for finding antibiotic candidates in unusual places, like ancient genetic information of Neanderthals and woolly mammoths.)
The first widely used antibiotic, penicillin, was discovered in 1928, when a physician studying Staphylococcus bacteria returned to his lab after summer break to find mold growing in one of his petri dishes. But many other antibiotics — like streptomycin, tetracycline, and erythromycin — were discovered from soil bacteria, which produce variations of these substances to compete with other microorganisms.
By looking in the gut microbiome, the researchers hoped to identify peptides that the trillions of microbes use against each other in the fight for limited resources — ideally, peptides that wouldn’t broadly kill off the entire microbiome.
Kill the Bad, Spare the Good
Many traditional antibiotics are small molecules. This means they can wipe out the good bacteria in your body, and because each targets a specific bacterial function, bad bacteria can become resistant to them.
Peptide antibiotics, on the other hand, don’t diffuse into the whole body. If taken orally, they stay in the gut; if taken intravenously, they generally stay in the blood. And because of how they kill bacteria, targeting the membrane, they’re also less prone to bacterial resistance.
The microbiome is like a big reservoir of pathogens, said Ami Bhatt, MD, PhD, hematologist at Stanford University in California and one of the study’s authors. Because many antibiotics kill healthy gut bacteria, “what you have left over,” Dr. Bhatt said, “is this big open niche that gets filled up with multidrug-resistant organisms like E coli [Escherichia coli] or vancomycin-resistant Enterococcus.”
Dr. Bhatt has seen cancer patients undergo successful treatment only to die of a multidrug-resistant infection, because current antibiotics fail against those pathogens. “That’s like winning the battle to lose the war.”
By investigating the microbiome, “we wanted to see if we could identify antimicrobial peptides that might spare key members of our regular microbiome, so that we wouldn’t totally disrupt the microbiome the way we do when we use broad-spectrum, small molecule–based antibiotics,” Dr. Bhatt said.
The researchers used artificial intelligence to sift through 400,000 proteins to predict, based on known antibiotics, which peptide sequences might have antimicrobial properties. From the results, they chose 78 peptides to synthesize and test.
“The application of computational approaches combined with experimental validation is very powerful and exciting,” said Jennifer Geddes-McAlister, PhD, professor of cell biology at the University of Guelph in Ontario, Canada, who was not involved in the study. “The study is robust in its approach to microbiome sampling.”
The Long Journey from Lab to Clinic
More than half of the peptides the team tested effectively inhibited the growth of harmful bacteria, and prevotellin-2 (derived from the bacteria Prevotella copri)stood out as the most powerful.
“The study validates experimental data from the lab using animal models, which moves discoveries closer to the clinic,” said Dr. Geddes-McAlister. “Further testing with clinical trials is needed, but the potential for clinical application is promising.”
Unfortunately, that’s not likely to happen anytime soon, said Dr. de la Fuente. “There is not enough economic incentive” for companies to develop new antibiotics. Ten years is his most hopeful guess for when we might see prevotellin-2, or a similar antibiotic, complete clinical trials.
A version of this article first appeared on Medscape.com.
Scientists at Stanford University and the University of Pennsylvania have discovered a new antibiotic candidate in a surprising place: the human gut.
In mice, the antibiotic — a peptide known as prevotellin-2 — showed antimicrobial potency on par with polymyxin B, an antibiotic medication used to treat multidrug-resistant infections. Meanwhile, the peptide mainly left commensal, or beneficial, bacteria alone. The study, published in Cell, also identified several other potent antibiotic peptides with the potential to combat antimicrobial-resistant infections.
The research is part of a larger quest to find new antibiotics that can fight drug-resistant infections, a critical public health threat with more than 2.8 million cases and 35,000 deaths annually in the United States. That quest is urgent, said study author César de la Fuente, PhD, professor of bioengineering at the University of Pennsylvania, Philadelphia.
“The main pillars that have enabled us to almost double our lifespan in the last 100 years or so have been antibiotics, vaccines, and clean water,” said Dr. de la Fuente. “Imagine taking out one of those. I think it would be pretty dramatic.” (Dr. De la Fuente’s lab has become known for finding antibiotic candidates in unusual places, like ancient genetic information of Neanderthals and woolly mammoths.)
The first widely used antibiotic, penicillin, was discovered in 1928, when a physician studying Staphylococcus bacteria returned to his lab after summer break to find mold growing in one of his petri dishes. But many other antibiotics — like streptomycin, tetracycline, and erythromycin — were discovered from soil bacteria, which produce variations of these substances to compete with other microorganisms.
By looking in the gut microbiome, the researchers hoped to identify peptides that the trillions of microbes use against each other in the fight for limited resources — ideally, peptides that wouldn’t broadly kill off the entire microbiome.
Kill the Bad, Spare the Good
Many traditional antibiotics are small molecules. This means they can wipe out the good bacteria in your body, and because each targets a specific bacterial function, bad bacteria can become resistant to them.
Peptide antibiotics, on the other hand, don’t diffuse into the whole body. If taken orally, they stay in the gut; if taken intravenously, they generally stay in the blood. And because of how they kill bacteria, targeting the membrane, they’re also less prone to bacterial resistance.
The microbiome is like a big reservoir of pathogens, said Ami Bhatt, MD, PhD, hematologist at Stanford University in California and one of the study’s authors. Because many antibiotics kill healthy gut bacteria, “what you have left over,” Dr. Bhatt said, “is this big open niche that gets filled up with multidrug-resistant organisms like E coli [Escherichia coli] or vancomycin-resistant Enterococcus.”
Dr. Bhatt has seen cancer patients undergo successful treatment only to die of a multidrug-resistant infection, because current antibiotics fail against those pathogens. “That’s like winning the battle to lose the war.”
By investigating the microbiome, “we wanted to see if we could identify antimicrobial peptides that might spare key members of our regular microbiome, so that we wouldn’t totally disrupt the microbiome the way we do when we use broad-spectrum, small molecule–based antibiotics,” Dr. Bhatt said.
The researchers used artificial intelligence to sift through 400,000 proteins to predict, based on known antibiotics, which peptide sequences might have antimicrobial properties. From the results, they chose 78 peptides to synthesize and test.
“The application of computational approaches combined with experimental validation is very powerful and exciting,” said Jennifer Geddes-McAlister, PhD, professor of cell biology at the University of Guelph in Ontario, Canada, who was not involved in the study. “The study is robust in its approach to microbiome sampling.”
The Long Journey from Lab to Clinic
More than half of the peptides the team tested effectively inhibited the growth of harmful bacteria, and prevotellin-2 (derived from the bacteria Prevotella copri)stood out as the most powerful.
“The study validates experimental data from the lab using animal models, which moves discoveries closer to the clinic,” said Dr. Geddes-McAlister. “Further testing with clinical trials is needed, but the potential for clinical application is promising.”
Unfortunately, that’s not likely to happen anytime soon, said Dr. de la Fuente. “There is not enough economic incentive” for companies to develop new antibiotics. Ten years is his most hopeful guess for when we might see prevotellin-2, or a similar antibiotic, complete clinical trials.
A version of this article first appeared on Medscape.com.
Scientists at Stanford University and the University of Pennsylvania have discovered a new antibiotic candidate in a surprising place: the human gut.
In mice, the antibiotic — a peptide known as prevotellin-2 — showed antimicrobial potency on par with polymyxin B, an antibiotic medication used to treat multidrug-resistant infections. Meanwhile, the peptide mainly left commensal, or beneficial, bacteria alone. The study, published in Cell, also identified several other potent antibiotic peptides with the potential to combat antimicrobial-resistant infections.
The research is part of a larger quest to find new antibiotics that can fight drug-resistant infections, a critical public health threat with more than 2.8 million cases and 35,000 deaths annually in the United States. That quest is urgent, said study author César de la Fuente, PhD, professor of bioengineering at the University of Pennsylvania, Philadelphia.
“The main pillars that have enabled us to almost double our lifespan in the last 100 years or so have been antibiotics, vaccines, and clean water,” said Dr. de la Fuente. “Imagine taking out one of those. I think it would be pretty dramatic.” (Dr. De la Fuente’s lab has become known for finding antibiotic candidates in unusual places, like ancient genetic information of Neanderthals and woolly mammoths.)
The first widely used antibiotic, penicillin, was discovered in 1928, when a physician studying Staphylococcus bacteria returned to his lab after summer break to find mold growing in one of his petri dishes. But many other antibiotics — like streptomycin, tetracycline, and erythromycin — were discovered from soil bacteria, which produce variations of these substances to compete with other microorganisms.
By looking in the gut microbiome, the researchers hoped to identify peptides that the trillions of microbes use against each other in the fight for limited resources — ideally, peptides that wouldn’t broadly kill off the entire microbiome.
Kill the Bad, Spare the Good
Many traditional antibiotics are small molecules. This means they can wipe out the good bacteria in your body, and because each targets a specific bacterial function, bad bacteria can become resistant to them.
Peptide antibiotics, on the other hand, don’t diffuse into the whole body. If taken orally, they stay in the gut; if taken intravenously, they generally stay in the blood. And because of how they kill bacteria, targeting the membrane, they’re also less prone to bacterial resistance.
The microbiome is like a big reservoir of pathogens, said Ami Bhatt, MD, PhD, hematologist at Stanford University in California and one of the study’s authors. Because many antibiotics kill healthy gut bacteria, “what you have left over,” Dr. Bhatt said, “is this big open niche that gets filled up with multidrug-resistant organisms like E coli [Escherichia coli] or vancomycin-resistant Enterococcus.”
Dr. Bhatt has seen cancer patients undergo successful treatment only to die of a multidrug-resistant infection, because current antibiotics fail against those pathogens. “That’s like winning the battle to lose the war.”
By investigating the microbiome, “we wanted to see if we could identify antimicrobial peptides that might spare key members of our regular microbiome, so that we wouldn’t totally disrupt the microbiome the way we do when we use broad-spectrum, small molecule–based antibiotics,” Dr. Bhatt said.
The researchers used artificial intelligence to sift through 400,000 proteins to predict, based on known antibiotics, which peptide sequences might have antimicrobial properties. From the results, they chose 78 peptides to synthesize and test.
“The application of computational approaches combined with experimental validation is very powerful and exciting,” said Jennifer Geddes-McAlister, PhD, professor of cell biology at the University of Guelph in Ontario, Canada, who was not involved in the study. “The study is robust in its approach to microbiome sampling.”
The Long Journey from Lab to Clinic
More than half of the peptides the team tested effectively inhibited the growth of harmful bacteria, and prevotellin-2 (derived from the bacteria Prevotella copri)stood out as the most powerful.
“The study validates experimental data from the lab using animal models, which moves discoveries closer to the clinic,” said Dr. Geddes-McAlister. “Further testing with clinical trials is needed, but the potential for clinical application is promising.”
Unfortunately, that’s not likely to happen anytime soon, said Dr. de la Fuente. “There is not enough economic incentive” for companies to develop new antibiotics. Ten years is his most hopeful guess for when we might see prevotellin-2, or a similar antibiotic, complete clinical trials.
A version of this article first appeared on Medscape.com.
FROM CELL
Physicians Lament Over Reliance on Relative Value Units: Survey
Most physicians oppose the way standardized relative value units (RVUs) are used to determine performance and compensation, according to Medscape’s 2024 Physicians and RVUs Report. About 6 in 10 survey respondents were unhappy with how RVUs affected them financially, while 7 in 10 said RVUs were poor measures of productivity.
The report analyzed 2024 survey data from 1005 practicing physicians who earn RVUs.
“I’m already mad that the medical field is controlled by health insurers and what they pay and authorize,” said an anesthesiologist in New York. “Then [that approach] is transferred to medical offices and hospitals, where physicians are paid by RVUs.”
Most physicians surveyed produced between 4000 and 8000 RVUs per year. Roughly one in six were high RVU generators, generating more than 10,000 annually.
In most cases, the metric influences earning potential — 42% of doctors surveyed said RVUs affect their salaries to some degree. One quarter said their salary was based entirely on RVUs. More than three fourths of physicians who received performance bonuses said they must meet RVU targets to do so.
“The current RVU system encourages unnecessary procedures, hurting patients,” said an orthopedic surgeon in Maine.
Nearly three fourths of practitioners surveyed said they occasionally to frequently felt pressure to take on more patients as a result of this system.
“I know numerous primary care doctors and specialists who have been forced to increase patient volume to meet RVU goals, and none is happy about it,” said Alok Patel, MD, a pediatric hospitalist with Stanford Hospital in Palo Alto, California. “Plus, patients are definitely not happy about being rushed.”
More than half of respondents said they occasionally or frequently felt compelled by their employer to use higher-level coding, which interferes with a physician’s ethical responsibility to the patient, said Arthur L. Caplan, PhD, a bioethicist at NYU Langone Medical Center in New York City.
“Rather than rewarding excellence or good outcomes, you’re kind of rewarding procedures and volume,” said Dr. Caplan. “It’s more than pressure; it’s expected.”
Nearly 6 in 10 physicians said that the method for calculating reimbursements was unfair. Almost half said that they weren’t happy with how their workplace uses RVUs.
A few respondents said that their RVU model, which is often based on what Dr. Patel called an “overly complicated algorithm,” did not account for the time spent on tasks or the fact that some patients miss appointments. RVUs also rely on factors outside the control of a physician, such as location and patient volume, said one doctor.
The model can also lower the level of care patients receive, Dr. Patel said.
“I know primary care doctors who work in RVU-based systems and simply cannot take the necessary time — even if it’s 30-45 minutes — to thoroughly assess a patient, when the model forces them to take on 15-minute encounters.”
Finally, over half of clinicians said alternatives to the RVU system would be more effective, and 77% suggested including qualitative data. One respondent recommended incorporating time spent doing paperwork and communicating with patients, complexity of conditions, and medication management.
A version of this article first appeared on Medscape.com.
Most physicians oppose the way standardized relative value units (RVUs) are used to determine performance and compensation, according to Medscape’s 2024 Physicians and RVUs Report. About 6 in 10 survey respondents were unhappy with how RVUs affected them financially, while 7 in 10 said RVUs were poor measures of productivity.
The report analyzed 2024 survey data from 1005 practicing physicians who earn RVUs.
“I’m already mad that the medical field is controlled by health insurers and what they pay and authorize,” said an anesthesiologist in New York. “Then [that approach] is transferred to medical offices and hospitals, where physicians are paid by RVUs.”
Most physicians surveyed produced between 4000 and 8000 RVUs per year. Roughly one in six were high RVU generators, generating more than 10,000 annually.
In most cases, the metric influences earning potential — 42% of doctors surveyed said RVUs affect their salaries to some degree. One quarter said their salary was based entirely on RVUs. More than three fourths of physicians who received performance bonuses said they must meet RVU targets to do so.
“The current RVU system encourages unnecessary procedures, hurting patients,” said an orthopedic surgeon in Maine.
Nearly three fourths of practitioners surveyed said they occasionally to frequently felt pressure to take on more patients as a result of this system.
“I know numerous primary care doctors and specialists who have been forced to increase patient volume to meet RVU goals, and none is happy about it,” said Alok Patel, MD, a pediatric hospitalist with Stanford Hospital in Palo Alto, California. “Plus, patients are definitely not happy about being rushed.”
More than half of respondents said they occasionally or frequently felt compelled by their employer to use higher-level coding, which interferes with a physician’s ethical responsibility to the patient, said Arthur L. Caplan, PhD, a bioethicist at NYU Langone Medical Center in New York City.
“Rather than rewarding excellence or good outcomes, you’re kind of rewarding procedures and volume,” said Dr. Caplan. “It’s more than pressure; it’s expected.”
Nearly 6 in 10 physicians said that the method for calculating reimbursements was unfair. Almost half said that they weren’t happy with how their workplace uses RVUs.
A few respondents said that their RVU model, which is often based on what Dr. Patel called an “overly complicated algorithm,” did not account for the time spent on tasks or the fact that some patients miss appointments. RVUs also rely on factors outside the control of a physician, such as location and patient volume, said one doctor.
The model can also lower the level of care patients receive, Dr. Patel said.
“I know primary care doctors who work in RVU-based systems and simply cannot take the necessary time — even if it’s 30-45 minutes — to thoroughly assess a patient, when the model forces them to take on 15-minute encounters.”
Finally, over half of clinicians said alternatives to the RVU system would be more effective, and 77% suggested including qualitative data. One respondent recommended incorporating time spent doing paperwork and communicating with patients, complexity of conditions, and medication management.
A version of this article first appeared on Medscape.com.
Most physicians oppose the way standardized relative value units (RVUs) are used to determine performance and compensation, according to Medscape’s 2024 Physicians and RVUs Report. About 6 in 10 survey respondents were unhappy with how RVUs affected them financially, while 7 in 10 said RVUs were poor measures of productivity.
The report analyzed 2024 survey data from 1005 practicing physicians who earn RVUs.
“I’m already mad that the medical field is controlled by health insurers and what they pay and authorize,” said an anesthesiologist in New York. “Then [that approach] is transferred to medical offices and hospitals, where physicians are paid by RVUs.”
Most physicians surveyed produced between 4000 and 8000 RVUs per year. Roughly one in six were high RVU generators, generating more than 10,000 annually.
In most cases, the metric influences earning potential — 42% of doctors surveyed said RVUs affect their salaries to some degree. One quarter said their salary was based entirely on RVUs. More than three fourths of physicians who received performance bonuses said they must meet RVU targets to do so.
“The current RVU system encourages unnecessary procedures, hurting patients,” said an orthopedic surgeon in Maine.
Nearly three fourths of practitioners surveyed said they occasionally to frequently felt pressure to take on more patients as a result of this system.
“I know numerous primary care doctors and specialists who have been forced to increase patient volume to meet RVU goals, and none is happy about it,” said Alok Patel, MD, a pediatric hospitalist with Stanford Hospital in Palo Alto, California. “Plus, patients are definitely not happy about being rushed.”
More than half of respondents said they occasionally or frequently felt compelled by their employer to use higher-level coding, which interferes with a physician’s ethical responsibility to the patient, said Arthur L. Caplan, PhD, a bioethicist at NYU Langone Medical Center in New York City.
“Rather than rewarding excellence or good outcomes, you’re kind of rewarding procedures and volume,” said Dr. Caplan. “It’s more than pressure; it’s expected.”
Nearly 6 in 10 physicians said that the method for calculating reimbursements was unfair. Almost half said that they weren’t happy with how their workplace uses RVUs.
A few respondents said that their RVU model, which is often based on what Dr. Patel called an “overly complicated algorithm,” did not account for the time spent on tasks or the fact that some patients miss appointments. RVUs also rely on factors outside the control of a physician, such as location and patient volume, said one doctor.
The model can also lower the level of care patients receive, Dr. Patel said.
“I know primary care doctors who work in RVU-based systems and simply cannot take the necessary time — even if it’s 30-45 minutes — to thoroughly assess a patient, when the model forces them to take on 15-minute encounters.”
Finally, over half of clinicians said alternatives to the RVU system would be more effective, and 77% suggested including qualitative data. One respondent recommended incorporating time spent doing paperwork and communicating with patients, complexity of conditions, and medication management.
A version of this article first appeared on Medscape.com.
Hearing Loss, Hearing Aids, and Dementia Risk: What to Tell Your Patients
In addition, some studies suggest that wearing hearing aids may help prevent dementia, though one study was recently voluntarily retracted due to methodological errors.
Given the overall evidence, how robust are these associations? And what guidance should clinicians provide to their patients?
Frank Lin, MD, PhD, a clinician and professor of otolaryngology and epidemiology at Johns Hopkins University School of Medicine, Baltimore, emphasized that the evidence from the past 10-15 years strongly links hearing loss to cognitive decline.
While quantifying the exact increase in risk is challenging, Dr. Lin said, “there’s no doubt about it; it’s not trivial.”
With respect to the potential link between hearing aids and dementia prevention, Dr. Lin is involved in the ongoing ACHIEVE randomized trial. Results presented at the 2023 Alzheimer’s Association International Conference and simultaneously published in The Lancet revealed participants who used hearing aids experienced a significant slowing of cognitive decline compared with those who received health education.
“It’s a no-risk intervention that can benefit social function, and for people at risk for cognitive decline, it can actually benefit cognitive health,” Dr. Lin said.
Potential Mechanisms
Dr. Lin pointed out that the Lancet Commission on Dementia identifies hearing impairment as one of the most significant risk factors for dementia. Overall, the consensus from most studies is that hearing loss definitely increases the risk for cognitive decline and dementia, he said.
Several hypotheses may explain this connection, and Dr. Lin believes that a combination of three key mechanisms is likely to be central to understanding this link.
The first theory focuses on cognitive load. As people experience age-related hearing changes, “the inner ear is no longer sending signals clearly to the brain,” Dr. Lin explained. This forces the brain to work harder, increasing its cognitive load as it reallocates resources to assist with hearing.
Dr. Lin emphasized that this is a hypothesis and does not prove hearing loss directly causes cognitive decline or dementia. Rather, it suggests that hearing loss accelerates the “unmasking” of cognitive issues. Brain resources that might otherwise buffer against dementia’s pathologic triggers are consumed earlier due to the demands of managing hearing loss.
The second potential mechanism suggests that hearing loss may have detrimental effects on brain structure and function over time — a theory supported by several recent studies.
These studies show that individuals with more severe hearing loss experience faster rates of brain atrophy. The reduced stimulation from poor auditory signals accelerates brain atrophy, Dr. Lin explained.
The third hypothesis focuses on social isolation. Individuals with hearing loss may engage less in social activities, reducing cognitive stimulation and overall social interaction. It’s well-known that social engagement and cognitive stimulation are crucial for maintaining cognitive health over time, Dr. Lin said.
Overall, Dr. Lin believes that the association between hearing loss and an increased risk for cognitive decline likely involves a combination of all three potential mechanisms. It’s not a matter of one theory being right and the others being wrong, he said.
The Role of Hearing Aids
However, the jury is out on the role of hearing aids in preventing dementia.
A large observational study published in 2023 in Lancet Public Health was hailed by its investigators as providing “the best evidence to date” that hearing aids could mitigate the impact of hearing loss on dementia (Lancet Public Health. 2023 May;8[5]:e329-e338. doi: 10.1016/S2468-2667[23]00048-8). However, the authors voluntarily retracted the paper in December 2023 due to a coding error.
Despite this, a large meta-analysis published in JAMA Neurology suggested that hearing aids might reduce cognitive decline and dementia risk and even enhance short-term cognitive function.
Additionally, the ACHIEVE study, the first randomized trial to investigate these issues, included nearly 1000 older participants from two populations — those from the ARIC study and healthy volunteers. Participants were randomly assigned to receive either a hearing intervention or education on healthy aging.
Although the primary endpoint of change in standardized neurocognitive scores at year 3 showed no significant difference between the hearing intervention and health education groups, the ARIC cohort experienced a notable 48% reduction in cognitive decline with hearing aids compared with education.
Dr. Lin explained that, due to the study’s design, the control group was healthier than the ARIC cohort, which was at higher risk for cognitive decline due to factors such as age and diabetes. This is where they observed a strong effect of hearing intervention in reducing cognitive decline within just 3 years, Dr. Lin said.
Conversely, the hearing aids had minimal impact on the healthy controls, likely because they had not experienced cognitive decline to begin with. Essentially, the benefits of hearing aids were more apparent once cognitive issues were already present.
“It seems sort of obvious. In a group of people who aren’t at risk for cognitive decline, a hearing intervention isn’t going to benefit their cognition” in the short term, Dr. Lin noted. That said, the investigators are continuing to follow the healthy controls to determine whether hearing aids lower dementia risk over the long term.
Which Comes First?
Some experts have questioned the directionality of the link between hearing aids and dementia — do hearing aids reduce dementia risk or are individuals with dementia simply less likely to use them?
Dr. Lin noted that observational studies often have confounders. For instance, people who use hearing aids are often healthier and better educated. This makes it difficult to distinguish the effect of the intervention from the factors that led people to use it, he said.
In contrast, the ACHIEVE trial, a randomized study, was designed to separate these factors from the hearing intervention, Dr. Lin explained.
However, he added that ACHIEVE was not specifically powered to assess dementia development, focusing instead on cognitive decline. The investigators plan long-term follow-up of participants to evaluate the impact on dementia in the future.
So, given the current evidence, what should clinicians tell their patients?
Because all people experience some degree of hearing changes as they age, which can gradually affect communication and social engagement, it’s important for everyone to be aware of their hearing health, Dr. Lin said.
He noted there are apps available that allow individuals to measure their hearing with their phones, including determining their “hearing number.”
With respect to hearing aids, Dr. Lin noted that if individuals have trouble participating in everyday activities, addressing hearing issues and considering a hearing intervention is crucial.
There’s no medical risk associated with hearing aids, he said. Even if they only improve social activities and engagement, that’s a benefit. If they also have potential positive effects on cognitive health, “even better,” he added.
Dr. Lin noted that as of 2022, hearing aids are now available over the counter, a move that has improved accessibility. In addition, new technologies, such as stylish “hearing aid glasses,” are being developed to offer more appealing options and reduce the stigma associated with traditional devices.
People often view hearing loss as a significant life event and are reluctant to admit they need hearing aids. However, focusing on “what’s your hearing?” as a neutral tracking metric could make it easier to adopt new technologies in the future, Lin said.
Alzheimer’s Association Weighs in
Heather Snyder, PhD, vice president, Medical & Scientific Relations at the Alzheimer’s Association, echoed Dr. Lin, noting that there has been substantial research showing a link between hearing loss and cognitive decline.
“This association is something that we have seen repeated and replicated in a number of different studies. What we don’t know is the cause and effect,” Dr. Snyder said.
She noted it is unknown whether there is a causal link between hearing loss and cognitive decline and/or whether cognitive decline may contribute to hearing loss. These are some of the “big questions” that remain, said Dr. Snyder.
Still, she noted that hearing health is an important part of quality of life and overall brain health and “should be part of the conversation” between clinicians and their patients.
Discussing the results of the ACHIEVE study, Dr. Snyder highlighted that while the subgroup at higher risk for cognitive decline did experience significant improvement, the overall population did not show a benefit from the intervention.
The brain “is complex,” and it’s unlikely that a single intervention or target will provide all the benefits, Dr. Snyder said.
She emphasized that addressing hearing loss with hearing aids, combined with managing other modifiable risk factors — such as heart and metabolic health, physical activity, and a balanced diet — appears to offer the greatest potential for synergy and preserving cognition.
Drs. Lin and Snyder reported no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
In addition, some studies suggest that wearing hearing aids may help prevent dementia, though one study was recently voluntarily retracted due to methodological errors.
Given the overall evidence, how robust are these associations? And what guidance should clinicians provide to their patients?
Frank Lin, MD, PhD, a clinician and professor of otolaryngology and epidemiology at Johns Hopkins University School of Medicine, Baltimore, emphasized that the evidence from the past 10-15 years strongly links hearing loss to cognitive decline.
While quantifying the exact increase in risk is challenging, Dr. Lin said, “there’s no doubt about it; it’s not trivial.”
With respect to the potential link between hearing aids and dementia prevention, Dr. Lin is involved in the ongoing ACHIEVE randomized trial. Results presented at the 2023 Alzheimer’s Association International Conference and simultaneously published in The Lancet revealed participants who used hearing aids experienced a significant slowing of cognitive decline compared with those who received health education.
“It’s a no-risk intervention that can benefit social function, and for people at risk for cognitive decline, it can actually benefit cognitive health,” Dr. Lin said.
Potential Mechanisms
Dr. Lin pointed out that the Lancet Commission on Dementia identifies hearing impairment as one of the most significant risk factors for dementia. Overall, the consensus from most studies is that hearing loss definitely increases the risk for cognitive decline and dementia, he said.
Several hypotheses may explain this connection, and Dr. Lin believes that a combination of three key mechanisms is likely to be central to understanding this link.
The first theory focuses on cognitive load. As people experience age-related hearing changes, “the inner ear is no longer sending signals clearly to the brain,” Dr. Lin explained. This forces the brain to work harder, increasing its cognitive load as it reallocates resources to assist with hearing.
Dr. Lin emphasized that this is a hypothesis and does not prove hearing loss directly causes cognitive decline or dementia. Rather, it suggests that hearing loss accelerates the “unmasking” of cognitive issues. Brain resources that might otherwise buffer against dementia’s pathologic triggers are consumed earlier due to the demands of managing hearing loss.
The second potential mechanism suggests that hearing loss may have detrimental effects on brain structure and function over time — a theory supported by several recent studies.
These studies show that individuals with more severe hearing loss experience faster rates of brain atrophy. The reduced stimulation from poor auditory signals accelerates brain atrophy, Dr. Lin explained.
The third hypothesis focuses on social isolation. Individuals with hearing loss may engage less in social activities, reducing cognitive stimulation and overall social interaction. It’s well-known that social engagement and cognitive stimulation are crucial for maintaining cognitive health over time, Dr. Lin said.
Overall, Dr. Lin believes that the association between hearing loss and an increased risk for cognitive decline likely involves a combination of all three potential mechanisms. It’s not a matter of one theory being right and the others being wrong, he said.
The Role of Hearing Aids
However, the jury is out on the role of hearing aids in preventing dementia.
A large observational study published in 2023 in Lancet Public Health was hailed by its investigators as providing “the best evidence to date” that hearing aids could mitigate the impact of hearing loss on dementia (Lancet Public Health. 2023 May;8[5]:e329-e338. doi: 10.1016/S2468-2667[23]00048-8). However, the authors voluntarily retracted the paper in December 2023 due to a coding error.
Despite this, a large meta-analysis published in JAMA Neurology suggested that hearing aids might reduce cognitive decline and dementia risk and even enhance short-term cognitive function.
Additionally, the ACHIEVE study, the first randomized trial to investigate these issues, included nearly 1000 older participants from two populations — those from the ARIC study and healthy volunteers. Participants were randomly assigned to receive either a hearing intervention or education on healthy aging.
Although the primary endpoint of change in standardized neurocognitive scores at year 3 showed no significant difference between the hearing intervention and health education groups, the ARIC cohort experienced a notable 48% reduction in cognitive decline with hearing aids compared with education.
Dr. Lin explained that, due to the study’s design, the control group was healthier than the ARIC cohort, which was at higher risk for cognitive decline due to factors such as age and diabetes. This is where they observed a strong effect of hearing intervention in reducing cognitive decline within just 3 years, Dr. Lin said.
Conversely, the hearing aids had minimal impact on the healthy controls, likely because they had not experienced cognitive decline to begin with. Essentially, the benefits of hearing aids were more apparent once cognitive issues were already present.
“It seems sort of obvious. In a group of people who aren’t at risk for cognitive decline, a hearing intervention isn’t going to benefit their cognition” in the short term, Dr. Lin noted. That said, the investigators are continuing to follow the healthy controls to determine whether hearing aids lower dementia risk over the long term.
Which Comes First?
Some experts have questioned the directionality of the link between hearing aids and dementia — do hearing aids reduce dementia risk or are individuals with dementia simply less likely to use them?
Dr. Lin noted that observational studies often have confounders. For instance, people who use hearing aids are often healthier and better educated. This makes it difficult to distinguish the effect of the intervention from the factors that led people to use it, he said.
In contrast, the ACHIEVE trial, a randomized study, was designed to separate these factors from the hearing intervention, Dr. Lin explained.
However, he added that ACHIEVE was not specifically powered to assess dementia development, focusing instead on cognitive decline. The investigators plan long-term follow-up of participants to evaluate the impact on dementia in the future.
So, given the current evidence, what should clinicians tell their patients?
Because all people experience some degree of hearing changes as they age, which can gradually affect communication and social engagement, it’s important for everyone to be aware of their hearing health, Dr. Lin said.
He noted there are apps available that allow individuals to measure their hearing with their phones, including determining their “hearing number.”
With respect to hearing aids, Dr. Lin noted that if individuals have trouble participating in everyday activities, addressing hearing issues and considering a hearing intervention is crucial.
There’s no medical risk associated with hearing aids, he said. Even if they only improve social activities and engagement, that’s a benefit. If they also have potential positive effects on cognitive health, “even better,” he added.
Dr. Lin noted that as of 2022, hearing aids are now available over the counter, a move that has improved accessibility. In addition, new technologies, such as stylish “hearing aid glasses,” are being developed to offer more appealing options and reduce the stigma associated with traditional devices.
People often view hearing loss as a significant life event and are reluctant to admit they need hearing aids. However, focusing on “what’s your hearing?” as a neutral tracking metric could make it easier to adopt new technologies in the future, Lin said.
Alzheimer’s Association Weighs in
Heather Snyder, PhD, vice president, Medical & Scientific Relations at the Alzheimer’s Association, echoed Dr. Lin, noting that there has been substantial research showing a link between hearing loss and cognitive decline.
“This association is something that we have seen repeated and replicated in a number of different studies. What we don’t know is the cause and effect,” Dr. Snyder said.
She noted it is unknown whether there is a causal link between hearing loss and cognitive decline and/or whether cognitive decline may contribute to hearing loss. These are some of the “big questions” that remain, said Dr. Snyder.
Still, she noted that hearing health is an important part of quality of life and overall brain health and “should be part of the conversation” between clinicians and their patients.
Discussing the results of the ACHIEVE study, Dr. Snyder highlighted that while the subgroup at higher risk for cognitive decline did experience significant improvement, the overall population did not show a benefit from the intervention.
The brain “is complex,” and it’s unlikely that a single intervention or target will provide all the benefits, Dr. Snyder said.
She emphasized that addressing hearing loss with hearing aids, combined with managing other modifiable risk factors — such as heart and metabolic health, physical activity, and a balanced diet — appears to offer the greatest potential for synergy and preserving cognition.
Drs. Lin and Snyder reported no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
In addition, some studies suggest that wearing hearing aids may help prevent dementia, though one study was recently voluntarily retracted due to methodological errors.
Given the overall evidence, how robust are these associations? And what guidance should clinicians provide to their patients?
Frank Lin, MD, PhD, a clinician and professor of otolaryngology and epidemiology at Johns Hopkins University School of Medicine, Baltimore, emphasized that the evidence from the past 10-15 years strongly links hearing loss to cognitive decline.
While quantifying the exact increase in risk is challenging, Dr. Lin said, “there’s no doubt about it; it’s not trivial.”
With respect to the potential link between hearing aids and dementia prevention, Dr. Lin is involved in the ongoing ACHIEVE randomized trial. Results presented at the 2023 Alzheimer’s Association International Conference and simultaneously published in The Lancet revealed participants who used hearing aids experienced a significant slowing of cognitive decline compared with those who received health education.
“It’s a no-risk intervention that can benefit social function, and for people at risk for cognitive decline, it can actually benefit cognitive health,” Dr. Lin said.
Potential Mechanisms
Dr. Lin pointed out that the Lancet Commission on Dementia identifies hearing impairment as one of the most significant risk factors for dementia. Overall, the consensus from most studies is that hearing loss definitely increases the risk for cognitive decline and dementia, he said.
Several hypotheses may explain this connection, and Dr. Lin believes that a combination of three key mechanisms is likely to be central to understanding this link.
The first theory focuses on cognitive load. As people experience age-related hearing changes, “the inner ear is no longer sending signals clearly to the brain,” Dr. Lin explained. This forces the brain to work harder, increasing its cognitive load as it reallocates resources to assist with hearing.
Dr. Lin emphasized that this is a hypothesis and does not prove hearing loss directly causes cognitive decline or dementia. Rather, it suggests that hearing loss accelerates the “unmasking” of cognitive issues. Brain resources that might otherwise buffer against dementia’s pathologic triggers are consumed earlier due to the demands of managing hearing loss.
The second potential mechanism suggests that hearing loss may have detrimental effects on brain structure and function over time — a theory supported by several recent studies.
These studies show that individuals with more severe hearing loss experience faster rates of brain atrophy. The reduced stimulation from poor auditory signals accelerates brain atrophy, Dr. Lin explained.
The third hypothesis focuses on social isolation. Individuals with hearing loss may engage less in social activities, reducing cognitive stimulation and overall social interaction. It’s well-known that social engagement and cognitive stimulation are crucial for maintaining cognitive health over time, Dr. Lin said.
Overall, Dr. Lin believes that the association between hearing loss and an increased risk for cognitive decline likely involves a combination of all three potential mechanisms. It’s not a matter of one theory being right and the others being wrong, he said.
The Role of Hearing Aids
However, the jury is out on the role of hearing aids in preventing dementia.
A large observational study published in 2023 in Lancet Public Health was hailed by its investigators as providing “the best evidence to date” that hearing aids could mitigate the impact of hearing loss on dementia (Lancet Public Health. 2023 May;8[5]:e329-e338. doi: 10.1016/S2468-2667[23]00048-8). However, the authors voluntarily retracted the paper in December 2023 due to a coding error.
Despite this, a large meta-analysis published in JAMA Neurology suggested that hearing aids might reduce cognitive decline and dementia risk and even enhance short-term cognitive function.
Additionally, the ACHIEVE study, the first randomized trial to investigate these issues, included nearly 1000 older participants from two populations — those from the ARIC study and healthy volunteers. Participants were randomly assigned to receive either a hearing intervention or education on healthy aging.
Although the primary endpoint of change in standardized neurocognitive scores at year 3 showed no significant difference between the hearing intervention and health education groups, the ARIC cohort experienced a notable 48% reduction in cognitive decline with hearing aids compared with education.
Dr. Lin explained that, due to the study’s design, the control group was healthier than the ARIC cohort, which was at higher risk for cognitive decline due to factors such as age and diabetes. This is where they observed a strong effect of hearing intervention in reducing cognitive decline within just 3 years, Dr. Lin said.
Conversely, the hearing aids had minimal impact on the healthy controls, likely because they had not experienced cognitive decline to begin with. Essentially, the benefits of hearing aids were more apparent once cognitive issues were already present.
“It seems sort of obvious. In a group of people who aren’t at risk for cognitive decline, a hearing intervention isn’t going to benefit their cognition” in the short term, Dr. Lin noted. That said, the investigators are continuing to follow the healthy controls to determine whether hearing aids lower dementia risk over the long term.
Which Comes First?
Some experts have questioned the directionality of the link between hearing aids and dementia — do hearing aids reduce dementia risk or are individuals with dementia simply less likely to use them?
Dr. Lin noted that observational studies often have confounders. For instance, people who use hearing aids are often healthier and better educated. This makes it difficult to distinguish the effect of the intervention from the factors that led people to use it, he said.
In contrast, the ACHIEVE trial, a randomized study, was designed to separate these factors from the hearing intervention, Dr. Lin explained.
However, he added that ACHIEVE was not specifically powered to assess dementia development, focusing instead on cognitive decline. The investigators plan long-term follow-up of participants to evaluate the impact on dementia in the future.
So, given the current evidence, what should clinicians tell their patients?
Because all people experience some degree of hearing changes as they age, which can gradually affect communication and social engagement, it’s important for everyone to be aware of their hearing health, Dr. Lin said.
He noted there are apps available that allow individuals to measure their hearing with their phones, including determining their “hearing number.”
With respect to hearing aids, Dr. Lin noted that if individuals have trouble participating in everyday activities, addressing hearing issues and considering a hearing intervention is crucial.
There’s no medical risk associated with hearing aids, he said. Even if they only improve social activities and engagement, that’s a benefit. If they also have potential positive effects on cognitive health, “even better,” he added.
Dr. Lin noted that as of 2022, hearing aids are now available over the counter, a move that has improved accessibility. In addition, new technologies, such as stylish “hearing aid glasses,” are being developed to offer more appealing options and reduce the stigma associated with traditional devices.
People often view hearing loss as a significant life event and are reluctant to admit they need hearing aids. However, focusing on “what’s your hearing?” as a neutral tracking metric could make it easier to adopt new technologies in the future, Lin said.
Alzheimer’s Association Weighs in
Heather Snyder, PhD, vice president, Medical & Scientific Relations at the Alzheimer’s Association, echoed Dr. Lin, noting that there has been substantial research showing a link between hearing loss and cognitive decline.
“This association is something that we have seen repeated and replicated in a number of different studies. What we don’t know is the cause and effect,” Dr. Snyder said.
She noted it is unknown whether there is a causal link between hearing loss and cognitive decline and/or whether cognitive decline may contribute to hearing loss. These are some of the “big questions” that remain, said Dr. Snyder.
Still, she noted that hearing health is an important part of quality of life and overall brain health and “should be part of the conversation” between clinicians and their patients.
Discussing the results of the ACHIEVE study, Dr. Snyder highlighted that while the subgroup at higher risk for cognitive decline did experience significant improvement, the overall population did not show a benefit from the intervention.
The brain “is complex,” and it’s unlikely that a single intervention or target will provide all the benefits, Dr. Snyder said.
She emphasized that addressing hearing loss with hearing aids, combined with managing other modifiable risk factors — such as heart and metabolic health, physical activity, and a balanced diet — appears to offer the greatest potential for synergy and preserving cognition.
Drs. Lin and Snyder reported no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
FDA OKs First-Line Lazertinib With Amivantamab for NSCLC
This marks the first approval for lazertinib. Amivantamab was initially approved by the FDA in 2021 and carries a few indications for locally advanced or metastatic NSCLC. Both drugs are manufactured by Janssen Biotech Inc.
“Patients will now have the option of a potential new first-line standard of care with significant clinical benefits over osimertinib,” study investigator Alexander Spira, MD, PhD, director, Virginia Cancer Specialists Research Institute, said in a news release from Johnson & Johnson .
Lazertinib is an oral, highly selective, third-generation EGFR tyrosine kinase inhibitor that can penetrate the brain and amivantamab is a bispecific antibody targeting EGFR and MET.
The approval was based on results from the phase 3 MARIPOSA trial, which showed that the combination reduced the risk of disease progression or death by 30% compared with osimertinib.
The MARIPOSA trial randomly allocated 1074 patients with exon 19 deletion or exon 21 L858R substitution mutation-positive locally advanced or metastatic NSCLC and no prior systemic therapy for advanced disease to amivantamab plus lazertinib, osimertinib alone, or lazertinib alone.
Lazertinib plus amivantamab demonstrated a statistically significant improvement in progression-free survival compared with osimertinib (hazard ratio, 0.70; P < .001). Median progression-free survival was 23.7 months with the combination vs 16.6 months osimertinib alone and 18.5 months with lazertinib alone.
The median duration of response was 9 months longer with the combination compared with osimertinib (25.8 months vs 16.7 months).
The most common adverse reactions (≥ 20%) were rash, nail toxicity, infusion-related reactions (amivantamab), musculoskeletal pain, edema, stomatitis, venous thromboembolism, paresthesia, fatigue, diarrhea, constipation, COVID-19, hemorrhage, dry skin, decreased appetite, pruritus, nausea, and ocular toxicity.
“A serious safety signal of venous thromboembolic events was observed with lazertinib in combination with amivantamab and prophylactic anticoagulation should be administered for the first four months of therapy,” the FDA noted in a statement announcing the approval.
Results from MARIPOSA were first presented at the European Society for Medical Oncology 2023 Congress and published in The New England Journal of Medicine in June. Longer-term follow-up data from MARIPOSA will be presented at the International Association for the Study of Lung Cancer 2024 World Congress on Lung Cancer in September.
A version of this article appeared on Medscape.com.
This marks the first approval for lazertinib. Amivantamab was initially approved by the FDA in 2021 and carries a few indications for locally advanced or metastatic NSCLC. Both drugs are manufactured by Janssen Biotech Inc.
“Patients will now have the option of a potential new first-line standard of care with significant clinical benefits over osimertinib,” study investigator Alexander Spira, MD, PhD, director, Virginia Cancer Specialists Research Institute, said in a news release from Johnson & Johnson .
Lazertinib is an oral, highly selective, third-generation EGFR tyrosine kinase inhibitor that can penetrate the brain and amivantamab is a bispecific antibody targeting EGFR and MET.
The approval was based on results from the phase 3 MARIPOSA trial, which showed that the combination reduced the risk of disease progression or death by 30% compared with osimertinib.
The MARIPOSA trial randomly allocated 1074 patients with exon 19 deletion or exon 21 L858R substitution mutation-positive locally advanced or metastatic NSCLC and no prior systemic therapy for advanced disease to amivantamab plus lazertinib, osimertinib alone, or lazertinib alone.
Lazertinib plus amivantamab demonstrated a statistically significant improvement in progression-free survival compared with osimertinib (hazard ratio, 0.70; P < .001). Median progression-free survival was 23.7 months with the combination vs 16.6 months osimertinib alone and 18.5 months with lazertinib alone.
The median duration of response was 9 months longer with the combination compared with osimertinib (25.8 months vs 16.7 months).
The most common adverse reactions (≥ 20%) were rash, nail toxicity, infusion-related reactions (amivantamab), musculoskeletal pain, edema, stomatitis, venous thromboembolism, paresthesia, fatigue, diarrhea, constipation, COVID-19, hemorrhage, dry skin, decreased appetite, pruritus, nausea, and ocular toxicity.
“A serious safety signal of venous thromboembolic events was observed with lazertinib in combination with amivantamab and prophylactic anticoagulation should be administered for the first four months of therapy,” the FDA noted in a statement announcing the approval.
Results from MARIPOSA were first presented at the European Society for Medical Oncology 2023 Congress and published in The New England Journal of Medicine in June. Longer-term follow-up data from MARIPOSA will be presented at the International Association for the Study of Lung Cancer 2024 World Congress on Lung Cancer in September.
A version of this article appeared on Medscape.com.
This marks the first approval for lazertinib. Amivantamab was initially approved by the FDA in 2021 and carries a few indications for locally advanced or metastatic NSCLC. Both drugs are manufactured by Janssen Biotech Inc.
“Patients will now have the option of a potential new first-line standard of care with significant clinical benefits over osimertinib,” study investigator Alexander Spira, MD, PhD, director, Virginia Cancer Specialists Research Institute, said in a news release from Johnson & Johnson .
Lazertinib is an oral, highly selective, third-generation EGFR tyrosine kinase inhibitor that can penetrate the brain and amivantamab is a bispecific antibody targeting EGFR and MET.
The approval was based on results from the phase 3 MARIPOSA trial, which showed that the combination reduced the risk of disease progression or death by 30% compared with osimertinib.
The MARIPOSA trial randomly allocated 1074 patients with exon 19 deletion or exon 21 L858R substitution mutation-positive locally advanced or metastatic NSCLC and no prior systemic therapy for advanced disease to amivantamab plus lazertinib, osimertinib alone, or lazertinib alone.
Lazertinib plus amivantamab demonstrated a statistically significant improvement in progression-free survival compared with osimertinib (hazard ratio, 0.70; P < .001). Median progression-free survival was 23.7 months with the combination vs 16.6 months osimertinib alone and 18.5 months with lazertinib alone.
The median duration of response was 9 months longer with the combination compared with osimertinib (25.8 months vs 16.7 months).
The most common adverse reactions (≥ 20%) were rash, nail toxicity, infusion-related reactions (amivantamab), musculoskeletal pain, edema, stomatitis, venous thromboembolism, paresthesia, fatigue, diarrhea, constipation, COVID-19, hemorrhage, dry skin, decreased appetite, pruritus, nausea, and ocular toxicity.
“A serious safety signal of venous thromboembolic events was observed with lazertinib in combination with amivantamab and prophylactic anticoagulation should be administered for the first four months of therapy,” the FDA noted in a statement announcing the approval.
Results from MARIPOSA were first presented at the European Society for Medical Oncology 2023 Congress and published in The New England Journal of Medicine in June. Longer-term follow-up data from MARIPOSA will be presented at the International Association for the Study of Lung Cancer 2024 World Congress on Lung Cancer in September.
A version of this article appeared on Medscape.com.
When Childhood Cancer Survivors Face Sexual Challenges
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.
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.
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.
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.
Will Compounding ‘Best Practices’ Guide Reassure Clinicians?
A new “best practices” guide released by the Alliance for Pharmacy Compounding (APC) aims to educate compounding pharmacists and reassure prescribers about the ethical, legal, and practical considerations that must be addressed to ensure quality standards and protect patients’ health.
Endocrinologists have expressed skepticism about the quality of compounded drugs, particularly the popular glucagon-like peptide 1 (GLP-1) semaglutide. The Food and Drug Administration (FDA) recently issued an alert linking hospitalizations to overdoses of compounded semaglutide.
“This document goes beyond today’s media-grabbing shortages,” APC Board Chair-Elect Gina Besteman, RPh, of Belmar Pharma Solutions told this news organization. “We developed these best practices to apply to all shortage drug compounding, and especially in this moment when so many are compounding GLP-1s. These serve as a reminder about what compliance and care look like.”
Prescribers determine whether a patient needs a compounded medication, not pharmacists, Ms. Besteman noted. “A patient-specific prescription order must be authorized for a compounded medication to be dispensed. Prescribers should ensure pharmacies they work with regularly check the FDA Drug Shortage List, as compounding of ‘essential copies’ of FDA-approved drugs is only allowed when a drug is listed as ‘currently in shortage.’ ”
Framework for Compounding
“With fake and illegal online stores popping up, it’s critical for legitimate, state-licensed compounding pharmacies to maintain the profession’s high standards,” the APC said in a media communication.
Highlights of its best practices, which are directed toward 503A state-licensed compounding pharmacies, include the following, among others:
- Pharmacies should check the FDA drug shortage list prior to preparing a copy of an FDA-approved drug and maintain documentation to demonstrate to regulators that the drug was in shortage at the time it was compounded.
- Pharmacies may only source active pharmaceutical ingredients (APIs) from state-licensed wholesalers who purchase from FDA-registered manufacturers or order directly from FDA-registered manufacturers.
- Verify from the wholesaler that the manufacturer is registered with the FDA and the API meets all the requirements of section 503A, and that both hold the appropriate permits or licenses in their home state and the shipped to state.
- Adhere to USP Chapter <797> testing requirements for sterility, endotoxin, stability, particulate, antimicrobial effectiveness, and container closure integrity studies.
- Counseling must be offered to the patient or the patient’s agent/caregiver. Providing written information that assists in the understanding of how to properly use the compounded medication is advised.
- Instructions should be written in a way that a layperson can understand (especially directions including dosage titrations and conversions between milligrams and milliliters or units).
- Like all medications, compounded drugs can only be prescribed in the presence of a valid patient-practitioner relationship and can only be dispensed by a pharmacy after receipt of a valid patient-specific prescription order.
- When marketing, never make claims of safety or efficacy of the compounded product.
- Advertising that patients will/may save money using compounded medications, compared with manufactured products is not allowed.
“Compounding FDA-approved drugs during shortages is nothing new — pharmacies have been doing it well before GLP-1s came on the scene, and they’ll continue long after this current shortage ends,” Ms. Besteman said. “Prescribers should be aware of APC’s guidelines because they provide a framework for ethically and legally compounding medications during drug shortages.
“To paraphrase The Police,” she concluded, “every move you make, every step you take, they’ll be watching you. Make sure they see those best practices in action.”
‘Reduces the Risks’
Commenting on the best practices guidance, Ivania Rizo, MD, director of Obesity Medicine and Diabetes and clinical colead at Boston Medical Center’s Health Equity Accelerator in Massachusetts, said: “These best practices will hopefully make a difference in the quality of compounded drugs.”
“The emphasis on rigorous testing of APIs and adherence to USP standards is particularly important for maintaining drug quality,” she noted. “This structured approach reduces the risk of variability and ensures that compounded drugs meet high-quality standards, thus enhancing their reliability.”
“Knowing that compounding pharmacies are adhering to rigorous standards for sourcing, testing, and compounding can at least reassure clinicians that specific steps are being taken for the safety and efficacy of these medications,” she said. “The transparency in documenting compliance with FDA guidelines and maintaining high-quality control measures can enhance trust among healthcare providers.”
Although clinicians are likely to have more confidence in compounded drugs when these best practices are followed, she said, “overall, we all hope that the shortages of medications such as tirzepatide are resolved promptly, allowing patients to access FDA-approved drugs without the need for compounding.”
“While the implementation of best practices for compounding during shortages is a positive and necessary step, our ultimate goal remains to address and resolve these shortages in the near future,” she concluded.
Dr. Rizo declared no competing interests.
A version of this article first appeared on Medscape.com.
A new “best practices” guide released by the Alliance for Pharmacy Compounding (APC) aims to educate compounding pharmacists and reassure prescribers about the ethical, legal, and practical considerations that must be addressed to ensure quality standards and protect patients’ health.
Endocrinologists have expressed skepticism about the quality of compounded drugs, particularly the popular glucagon-like peptide 1 (GLP-1) semaglutide. The Food and Drug Administration (FDA) recently issued an alert linking hospitalizations to overdoses of compounded semaglutide.
“This document goes beyond today’s media-grabbing shortages,” APC Board Chair-Elect Gina Besteman, RPh, of Belmar Pharma Solutions told this news organization. “We developed these best practices to apply to all shortage drug compounding, and especially in this moment when so many are compounding GLP-1s. These serve as a reminder about what compliance and care look like.”
Prescribers determine whether a patient needs a compounded medication, not pharmacists, Ms. Besteman noted. “A patient-specific prescription order must be authorized for a compounded medication to be dispensed. Prescribers should ensure pharmacies they work with regularly check the FDA Drug Shortage List, as compounding of ‘essential copies’ of FDA-approved drugs is only allowed when a drug is listed as ‘currently in shortage.’ ”
Framework for Compounding
“With fake and illegal online stores popping up, it’s critical for legitimate, state-licensed compounding pharmacies to maintain the profession’s high standards,” the APC said in a media communication.
Highlights of its best practices, which are directed toward 503A state-licensed compounding pharmacies, include the following, among others:
- Pharmacies should check the FDA drug shortage list prior to preparing a copy of an FDA-approved drug and maintain documentation to demonstrate to regulators that the drug was in shortage at the time it was compounded.
- Pharmacies may only source active pharmaceutical ingredients (APIs) from state-licensed wholesalers who purchase from FDA-registered manufacturers or order directly from FDA-registered manufacturers.
- Verify from the wholesaler that the manufacturer is registered with the FDA and the API meets all the requirements of section 503A, and that both hold the appropriate permits or licenses in their home state and the shipped to state.
- Adhere to USP Chapter <797> testing requirements for sterility, endotoxin, stability, particulate, antimicrobial effectiveness, and container closure integrity studies.
- Counseling must be offered to the patient or the patient’s agent/caregiver. Providing written information that assists in the understanding of how to properly use the compounded medication is advised.
- Instructions should be written in a way that a layperson can understand (especially directions including dosage titrations and conversions between milligrams and milliliters or units).
- Like all medications, compounded drugs can only be prescribed in the presence of a valid patient-practitioner relationship and can only be dispensed by a pharmacy after receipt of a valid patient-specific prescription order.
- When marketing, never make claims of safety or efficacy of the compounded product.
- Advertising that patients will/may save money using compounded medications, compared with manufactured products is not allowed.
“Compounding FDA-approved drugs during shortages is nothing new — pharmacies have been doing it well before GLP-1s came on the scene, and they’ll continue long after this current shortage ends,” Ms. Besteman said. “Prescribers should be aware of APC’s guidelines because they provide a framework for ethically and legally compounding medications during drug shortages.
“To paraphrase The Police,” she concluded, “every move you make, every step you take, they’ll be watching you. Make sure they see those best practices in action.”
‘Reduces the Risks’
Commenting on the best practices guidance, Ivania Rizo, MD, director of Obesity Medicine and Diabetes and clinical colead at Boston Medical Center’s Health Equity Accelerator in Massachusetts, said: “These best practices will hopefully make a difference in the quality of compounded drugs.”
“The emphasis on rigorous testing of APIs and adherence to USP standards is particularly important for maintaining drug quality,” she noted. “This structured approach reduces the risk of variability and ensures that compounded drugs meet high-quality standards, thus enhancing their reliability.”
“Knowing that compounding pharmacies are adhering to rigorous standards for sourcing, testing, and compounding can at least reassure clinicians that specific steps are being taken for the safety and efficacy of these medications,” she said. “The transparency in documenting compliance with FDA guidelines and maintaining high-quality control measures can enhance trust among healthcare providers.”
Although clinicians are likely to have more confidence in compounded drugs when these best practices are followed, she said, “overall, we all hope that the shortages of medications such as tirzepatide are resolved promptly, allowing patients to access FDA-approved drugs without the need for compounding.”
“While the implementation of best practices for compounding during shortages is a positive and necessary step, our ultimate goal remains to address and resolve these shortages in the near future,” she concluded.
Dr. Rizo declared no competing interests.
A version of this article first appeared on Medscape.com.
A new “best practices” guide released by the Alliance for Pharmacy Compounding (APC) aims to educate compounding pharmacists and reassure prescribers about the ethical, legal, and practical considerations that must be addressed to ensure quality standards and protect patients’ health.
Endocrinologists have expressed skepticism about the quality of compounded drugs, particularly the popular glucagon-like peptide 1 (GLP-1) semaglutide. The Food and Drug Administration (FDA) recently issued an alert linking hospitalizations to overdoses of compounded semaglutide.
“This document goes beyond today’s media-grabbing shortages,” APC Board Chair-Elect Gina Besteman, RPh, of Belmar Pharma Solutions told this news organization. “We developed these best practices to apply to all shortage drug compounding, and especially in this moment when so many are compounding GLP-1s. These serve as a reminder about what compliance and care look like.”
Prescribers determine whether a patient needs a compounded medication, not pharmacists, Ms. Besteman noted. “A patient-specific prescription order must be authorized for a compounded medication to be dispensed. Prescribers should ensure pharmacies they work with regularly check the FDA Drug Shortage List, as compounding of ‘essential copies’ of FDA-approved drugs is only allowed when a drug is listed as ‘currently in shortage.’ ”
Framework for Compounding
“With fake and illegal online stores popping up, it’s critical for legitimate, state-licensed compounding pharmacies to maintain the profession’s high standards,” the APC said in a media communication.
Highlights of its best practices, which are directed toward 503A state-licensed compounding pharmacies, include the following, among others:
- Pharmacies should check the FDA drug shortage list prior to preparing a copy of an FDA-approved drug and maintain documentation to demonstrate to regulators that the drug was in shortage at the time it was compounded.
- Pharmacies may only source active pharmaceutical ingredients (APIs) from state-licensed wholesalers who purchase from FDA-registered manufacturers or order directly from FDA-registered manufacturers.
- Verify from the wholesaler that the manufacturer is registered with the FDA and the API meets all the requirements of section 503A, and that both hold the appropriate permits or licenses in their home state and the shipped to state.
- Adhere to USP Chapter <797> testing requirements for sterility, endotoxin, stability, particulate, antimicrobial effectiveness, and container closure integrity studies.
- Counseling must be offered to the patient or the patient’s agent/caregiver. Providing written information that assists in the understanding of how to properly use the compounded medication is advised.
- Instructions should be written in a way that a layperson can understand (especially directions including dosage titrations and conversions between milligrams and milliliters or units).
- Like all medications, compounded drugs can only be prescribed in the presence of a valid patient-practitioner relationship and can only be dispensed by a pharmacy after receipt of a valid patient-specific prescription order.
- When marketing, never make claims of safety or efficacy of the compounded product.
- Advertising that patients will/may save money using compounded medications, compared with manufactured products is not allowed.
“Compounding FDA-approved drugs during shortages is nothing new — pharmacies have been doing it well before GLP-1s came on the scene, and they’ll continue long after this current shortage ends,” Ms. Besteman said. “Prescribers should be aware of APC’s guidelines because they provide a framework for ethically and legally compounding medications during drug shortages.
“To paraphrase The Police,” she concluded, “every move you make, every step you take, they’ll be watching you. Make sure they see those best practices in action.”
‘Reduces the Risks’
Commenting on the best practices guidance, Ivania Rizo, MD, director of Obesity Medicine and Diabetes and clinical colead at Boston Medical Center’s Health Equity Accelerator in Massachusetts, said: “These best practices will hopefully make a difference in the quality of compounded drugs.”
“The emphasis on rigorous testing of APIs and adherence to USP standards is particularly important for maintaining drug quality,” she noted. “This structured approach reduces the risk of variability and ensures that compounded drugs meet high-quality standards, thus enhancing their reliability.”
“Knowing that compounding pharmacies are adhering to rigorous standards for sourcing, testing, and compounding can at least reassure clinicians that specific steps are being taken for the safety and efficacy of these medications,” she said. “The transparency in documenting compliance with FDA guidelines and maintaining high-quality control measures can enhance trust among healthcare providers.”
Although clinicians are likely to have more confidence in compounded drugs when these best practices are followed, she said, “overall, we all hope that the shortages of medications such as tirzepatide are resolved promptly, allowing patients to access FDA-approved drugs without the need for compounding.”
“While the implementation of best practices for compounding during shortages is a positive and necessary step, our ultimate goal remains to address and resolve these shortages in the near future,” she concluded.
Dr. Rizo declared no competing interests.
A version of this article first appeared on Medscape.com.
Do You Have Patients With JAKne — JAK Inhibitor–Associated Acne? Here’s What to Know
Since the first Food and Drug Administration approval of a Janus kinase (JAK) inhibitor in 2011, the number of these medications available — and their treatment indications — have continued to grow. Prescribing physicians are familiar with the benefits and risks for these drugs, including higher risk for cardiac events and malignancy; however, one adverse effect may be overlooked, especially by specialties outside of dermatology: acne. Though less serious than some other side effects, JAK inhibitor–associated acne — JAKne, for short — can be a concern for patients.
“Your physical appearance and how you present yourself to the world is an important part of your self-confidence and living life on your own terms,” said Arash Mostaghimi, MD, the director of inpatient dermatology at Brigham and Women’s Hospital in Boston, Massachusetts. “I think letting people know about [JAKne] and then addressing it when it occurs should be a normal part of managing these medications.”
What Is JAKne?
JAKne generally looks like other kinds of acne, explained Janelle Nassim, MD, director of laser and cosmetic dermatology at the Indiana University School of Medicine, Indianapolis. “It can affect the same areas that typical acne affects, including the face, chest, back, neck, and upper shoulders.”
Though it appears like typical forms of acne, it is not clear what drives these skin eruptions in patients taking JAK inhibitors.
“We don’t understand the underlying pathophysiology,” Dr. Mostaghimi said. “It looks like acne, but we don’t know if the exact underlying inflammatory process is the same or if it’s different.”
In a 2023 systematic review of clinical studies, Dr. Mostaghimi and colleagues found that patients on any JAK inhibitor were nearly four times more likely to experience acne than patients who received placebo, but risk varied between medications. Patients taking JAK inhibitors for skin conditions had higher risk for acne than those given the medications for other indications. However, Dr. Mostaghimi thinks this finding is the result of selection bias.
Participants may not mention side effects like acne in trials for rheumatologic or gastrointestinal conditions, he said, unlike in trials for skin conditions. “Clinically, I’ve seen it in patients across every indication.”
Patients with a history of acne seem to be more likely to develop this side effect, though formal studies looking into risk factors are lacking. In Dr. Mostaghimi’s own clinical experience, JAKne is also more common in younger patients, but it can happen to anyone. “I’ve seen 70-year-olds develop acne — patients who’ve never had an issue their whole life — when they’re taking a JAK inhibitor.”
This issue also appears to be more common earlier in treatment, he added, and may improve over time as a patient continues with the medication.
How Do You Treat It?
“I think in other specialties, you will often feel awkward addressing skin conditions or pointing out acne,” Dr. Mostaghimi said. The most important steps are being aware of this potential side effect, and if you see it practice, to bring it up.
“Say: I’m noticing there’s some changes in your skin. Some patients on JAK inhibitors develop more acne. Have you noticed this? And if so, is this bothering you?”
Generally, JAKne is mild to moderate, explained Dr. Nassim, and if non-dermatologists are comfortable, they can prescribe a first-line topical regimen for patients. Dr. Mostaghimi recommends prescribing a clindamycin 1% lotion or gel. In addition, patients can use a benzoyl peroxide wash (4% or 10%) combined with a gentle retinoid, such as adapalene. (Both of these treatments are now available over the counter.)
In patients with scalp or hairline involvement, he often prescribes a ketoconazole 2% shampoo, which patients can use to wash their scalp, face, chest, and back in the shower.
If they aren’t responding to these initial treatments, then refer to a dermatologist for further assessment.
“Ultimately, referring to a dermatologist is the best course of action,” Dr. Nassim said. “I have had patients on JAK inhibitors who improved with topical acne treatments, and some that required more aggressive treatment with oral medications.”
Dr. Mostaghimi reported consulting fees from AbbVie, Concert Pharmaceuticals, Pfizer, and 3Derm Systems; research funding from Incyte, Aclaris Therapeutics, Eli Lilly, and Concert Pharmaceuticals; personal fees from Equillium, ASLAN Pharmaceuticals, ACOM, and Boehringer Ingelheim; and advisory board fees from Fig.1 Beauty, Eli Lilly, Pfizer, and Hims & Hers Health. Dr. Nassim had no relevant disclosures.
A version of this article first appeared on Medscape.com.
Since the first Food and Drug Administration approval of a Janus kinase (JAK) inhibitor in 2011, the number of these medications available — and their treatment indications — have continued to grow. Prescribing physicians are familiar with the benefits and risks for these drugs, including higher risk for cardiac events and malignancy; however, one adverse effect may be overlooked, especially by specialties outside of dermatology: acne. Though less serious than some other side effects, JAK inhibitor–associated acne — JAKne, for short — can be a concern for patients.
“Your physical appearance and how you present yourself to the world is an important part of your self-confidence and living life on your own terms,” said Arash Mostaghimi, MD, the director of inpatient dermatology at Brigham and Women’s Hospital in Boston, Massachusetts. “I think letting people know about [JAKne] and then addressing it when it occurs should be a normal part of managing these medications.”
What Is JAKne?
JAKne generally looks like other kinds of acne, explained Janelle Nassim, MD, director of laser and cosmetic dermatology at the Indiana University School of Medicine, Indianapolis. “It can affect the same areas that typical acne affects, including the face, chest, back, neck, and upper shoulders.”
Though it appears like typical forms of acne, it is not clear what drives these skin eruptions in patients taking JAK inhibitors.
“We don’t understand the underlying pathophysiology,” Dr. Mostaghimi said. “It looks like acne, but we don’t know if the exact underlying inflammatory process is the same or if it’s different.”
In a 2023 systematic review of clinical studies, Dr. Mostaghimi and colleagues found that patients on any JAK inhibitor were nearly four times more likely to experience acne than patients who received placebo, but risk varied between medications. Patients taking JAK inhibitors for skin conditions had higher risk for acne than those given the medications for other indications. However, Dr. Mostaghimi thinks this finding is the result of selection bias.
Participants may not mention side effects like acne in trials for rheumatologic or gastrointestinal conditions, he said, unlike in trials for skin conditions. “Clinically, I’ve seen it in patients across every indication.”
Patients with a history of acne seem to be more likely to develop this side effect, though formal studies looking into risk factors are lacking. In Dr. Mostaghimi’s own clinical experience, JAKne is also more common in younger patients, but it can happen to anyone. “I’ve seen 70-year-olds develop acne — patients who’ve never had an issue their whole life — when they’re taking a JAK inhibitor.”
This issue also appears to be more common earlier in treatment, he added, and may improve over time as a patient continues with the medication.
How Do You Treat It?
“I think in other specialties, you will often feel awkward addressing skin conditions or pointing out acne,” Dr. Mostaghimi said. The most important steps are being aware of this potential side effect, and if you see it practice, to bring it up.
“Say: I’m noticing there’s some changes in your skin. Some patients on JAK inhibitors develop more acne. Have you noticed this? And if so, is this bothering you?”
Generally, JAKne is mild to moderate, explained Dr. Nassim, and if non-dermatologists are comfortable, they can prescribe a first-line topical regimen for patients. Dr. Mostaghimi recommends prescribing a clindamycin 1% lotion or gel. In addition, patients can use a benzoyl peroxide wash (4% or 10%) combined with a gentle retinoid, such as adapalene. (Both of these treatments are now available over the counter.)
In patients with scalp or hairline involvement, he often prescribes a ketoconazole 2% shampoo, which patients can use to wash their scalp, face, chest, and back in the shower.
If they aren’t responding to these initial treatments, then refer to a dermatologist for further assessment.
“Ultimately, referring to a dermatologist is the best course of action,” Dr. Nassim said. “I have had patients on JAK inhibitors who improved with topical acne treatments, and some that required more aggressive treatment with oral medications.”
Dr. Mostaghimi reported consulting fees from AbbVie, Concert Pharmaceuticals, Pfizer, and 3Derm Systems; research funding from Incyte, Aclaris Therapeutics, Eli Lilly, and Concert Pharmaceuticals; personal fees from Equillium, ASLAN Pharmaceuticals, ACOM, and Boehringer Ingelheim; and advisory board fees from Fig.1 Beauty, Eli Lilly, Pfizer, and Hims & Hers Health. Dr. Nassim had no relevant disclosures.
A version of this article first appeared on Medscape.com.
Since the first Food and Drug Administration approval of a Janus kinase (JAK) inhibitor in 2011, the number of these medications available — and their treatment indications — have continued to grow. Prescribing physicians are familiar with the benefits and risks for these drugs, including higher risk for cardiac events and malignancy; however, one adverse effect may be overlooked, especially by specialties outside of dermatology: acne. Though less serious than some other side effects, JAK inhibitor–associated acne — JAKne, for short — can be a concern for patients.
“Your physical appearance and how you present yourself to the world is an important part of your self-confidence and living life on your own terms,” said Arash Mostaghimi, MD, the director of inpatient dermatology at Brigham and Women’s Hospital in Boston, Massachusetts. “I think letting people know about [JAKne] and then addressing it when it occurs should be a normal part of managing these medications.”
What Is JAKne?
JAKne generally looks like other kinds of acne, explained Janelle Nassim, MD, director of laser and cosmetic dermatology at the Indiana University School of Medicine, Indianapolis. “It can affect the same areas that typical acne affects, including the face, chest, back, neck, and upper shoulders.”
Though it appears like typical forms of acne, it is not clear what drives these skin eruptions in patients taking JAK inhibitors.
“We don’t understand the underlying pathophysiology,” Dr. Mostaghimi said. “It looks like acne, but we don’t know if the exact underlying inflammatory process is the same or if it’s different.”
In a 2023 systematic review of clinical studies, Dr. Mostaghimi and colleagues found that patients on any JAK inhibitor were nearly four times more likely to experience acne than patients who received placebo, but risk varied between medications. Patients taking JAK inhibitors for skin conditions had higher risk for acne than those given the medications for other indications. However, Dr. Mostaghimi thinks this finding is the result of selection bias.
Participants may not mention side effects like acne in trials for rheumatologic or gastrointestinal conditions, he said, unlike in trials for skin conditions. “Clinically, I’ve seen it in patients across every indication.”
Patients with a history of acne seem to be more likely to develop this side effect, though formal studies looking into risk factors are lacking. In Dr. Mostaghimi’s own clinical experience, JAKne is also more common in younger patients, but it can happen to anyone. “I’ve seen 70-year-olds develop acne — patients who’ve never had an issue their whole life — when they’re taking a JAK inhibitor.”
This issue also appears to be more common earlier in treatment, he added, and may improve over time as a patient continues with the medication.
How Do You Treat It?
“I think in other specialties, you will often feel awkward addressing skin conditions or pointing out acne,” Dr. Mostaghimi said. The most important steps are being aware of this potential side effect, and if you see it practice, to bring it up.
“Say: I’m noticing there’s some changes in your skin. Some patients on JAK inhibitors develop more acne. Have you noticed this? And if so, is this bothering you?”
Generally, JAKne is mild to moderate, explained Dr. Nassim, and if non-dermatologists are comfortable, they can prescribe a first-line topical regimen for patients. Dr. Mostaghimi recommends prescribing a clindamycin 1% lotion or gel. In addition, patients can use a benzoyl peroxide wash (4% or 10%) combined with a gentle retinoid, such as adapalene. (Both of these treatments are now available over the counter.)
In patients with scalp or hairline involvement, he often prescribes a ketoconazole 2% shampoo, which patients can use to wash their scalp, face, chest, and back in the shower.
If they aren’t responding to these initial treatments, then refer to a dermatologist for further assessment.
“Ultimately, referring to a dermatologist is the best course of action,” Dr. Nassim said. “I have had patients on JAK inhibitors who improved with topical acne treatments, and some that required more aggressive treatment with oral medications.”
Dr. Mostaghimi reported consulting fees from AbbVie, Concert Pharmaceuticals, Pfizer, and 3Derm Systems; research funding from Incyte, Aclaris Therapeutics, Eli Lilly, and Concert Pharmaceuticals; personal fees from Equillium, ASLAN Pharmaceuticals, ACOM, and Boehringer Ingelheim; and advisory board fees from Fig.1 Beauty, Eli Lilly, Pfizer, and Hims & Hers Health. Dr. Nassim had no relevant disclosures.
A version of this article first appeared on Medscape.com.
Do New Blood Tests for Cancer Meet the Right Standards?
Biotech startups worldwide are rushing to market screening tests that they claim can detect various cancers in early stages with just a few drops of blood. The tests allegedly will simplify cancer care by eliminating tedious scans, scopes, and swabs at the doctor’s office.
The promise of these early detection tests is truly “enticing,” Hilary A. Robbins, PhD, from the International Agency for Research on Cancer of the World Health Organization in Lyon, France, said in an interview.
In an opinion article in The New England Journal of Medicine, she emphasized that the new cancer tests are much less cumbersome than traditional screening strategies for individual cancers. Moreover, they could enable the early detection of dozens of cancer types for which no screening has been available so far.
Meeting the Criteria
The problem is that these tests have not met the strict criteria typically required for traditional cancer screening tests. To be considered for introduction as a screening procedure, a test usually needs to meet the following four minimum requirements:
- The disease that the test screens for must have a presymptomatic form.
- The screening test must be able to identify this presymptomatic disease.
- Treating the disease in the presymptomatic phase improves prognosis (specifically, it affects cancer-specific mortality in a randomized controlled trial).
- The screening test is feasible, and the benefits outweigh potential risks.
“The new blood tests for multiple cancers have so far only met the second criteria, showing they can detect presymptomatic cancer,” Dr. Robbins wrote.
The next step would be to demonstrate that they affect cancer-specific mortality. “But currently, commercial interests seem to be influencing the evidence standards for these cancer tests,” said Dr. Robbins.
Inappropriate Endpoints?
Some proponents of such tests argue that, unlike for previous cancer screening procedures, initial approval should not depend on the endpoint of cancer-specific mortality. It would take too long to gather sufficient outcome data, and in the meantime, people would die, they argue.
Eric A. Klein, MD, from the Glickman Urological and Kidney Institute in Cleveland, Ohio, and colleagues advocate for alternative endpoints such as the incidence of late-stage cancer in an article published in Cancer Epidemiology, Biomarkers & Prevention.
“The concept would be,” they wrote, “that a negative signal would not indicate a mortality benefit, leading to the study being stopped. A positive signal, on the other hand, could result in provisional approval until mortality data and real-world evidence of effectiveness are available. This would resemble the accelerated approval of new cancer drugs, which often is based on progression-free survival until there postmarketing data on overall survival emerge.”
Dr. Klein is also employed at the US biotech start-up Grail, which developed the Galleri test, which is one of the best-known and most advanced cancer screening tests. The Galleri test uses cell-free DNA and machine learning to detect a common cancer signal in more than 50 cancer types and predict the origin of the cancer signal. Consumers in the United States can already order and perform the test.
An NHS Study
Arguments for different endpoints apparently resonated with the United Kingdom’s National Health Service (NHS). Three years ago, they initiated the Galleri study, a large randomized controlled trial to assess the effectiveness of Grail’s cancer test. The primary endpoint was not cancer-specific mortality, but the incidence of stage III or IV cancer.
The results are expected in 2026. But recruitment was stopped after 140,000 participants were enrolled. The NHS reported that the initial results were not convincing enough to continue the trial. Exact numbers were not disclosed.
The Galleri study deviates from the standard randomized controlled trial design for cancer screening procedures not only in terms of the primary endpoint, but also in blinding. The only participants who were unblinded and informed of their test results are those in the intervention group with a positive cancer test.
False Security
This trial design encourages participants to undergo blood tests once per year. But according to Dr. Robbins, it prevents the exploration of the phenomenon of “false security,” which is a potential drawback of the new cancer tests.
“Women with a negative mammogram can reasonably assume that they probably do not have breast cancer. But individuals with a negative cancer blood test could mistakenly believe they cannot have any cancer at all. As a result, they may not undergo standard early detection screenings or seek medical help early enough for potential cancer symptoms,” said Dr. Robbins.
To assess the actual risk-benefit ratio of the Galleri test, participants must receive their test results, she said. “Under real-world conditions, benefits and risks can come from positive and negative results.”
Upcoming Trial
More illuminating results may come from a large trial planned by the National Cancer Institute in the United States. Several new cancer tests will be evaluated for their ability to reduce cancer-specific mortality. A pilot phase will start later in 2024. “This study may be the only one with sufficient statistical power to determine whether an approach based on these cancer tests can reduce cancer-specific mortality,” said Dr. Robbins.
For the new blood tests for multiple cancers, it is crucial that health authorities “set a high bar for a benefit,” she said. This, according to her, also means that they must show an effect on cancer-specific mortality before being introduced. “This evidence must come from studies in which commercial interests do not influence the design, execution, data management, or data analysis.”
This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version appeared on Medscape.com.
Biotech startups worldwide are rushing to market screening tests that they claim can detect various cancers in early stages with just a few drops of blood. The tests allegedly will simplify cancer care by eliminating tedious scans, scopes, and swabs at the doctor’s office.
The promise of these early detection tests is truly “enticing,” Hilary A. Robbins, PhD, from the International Agency for Research on Cancer of the World Health Organization in Lyon, France, said in an interview.
In an opinion article in The New England Journal of Medicine, she emphasized that the new cancer tests are much less cumbersome than traditional screening strategies for individual cancers. Moreover, they could enable the early detection of dozens of cancer types for which no screening has been available so far.
Meeting the Criteria
The problem is that these tests have not met the strict criteria typically required for traditional cancer screening tests. To be considered for introduction as a screening procedure, a test usually needs to meet the following four minimum requirements:
- The disease that the test screens for must have a presymptomatic form.
- The screening test must be able to identify this presymptomatic disease.
- Treating the disease in the presymptomatic phase improves prognosis (specifically, it affects cancer-specific mortality in a randomized controlled trial).
- The screening test is feasible, and the benefits outweigh potential risks.
“The new blood tests for multiple cancers have so far only met the second criteria, showing they can detect presymptomatic cancer,” Dr. Robbins wrote.
The next step would be to demonstrate that they affect cancer-specific mortality. “But currently, commercial interests seem to be influencing the evidence standards for these cancer tests,” said Dr. Robbins.
Inappropriate Endpoints?
Some proponents of such tests argue that, unlike for previous cancer screening procedures, initial approval should not depend on the endpoint of cancer-specific mortality. It would take too long to gather sufficient outcome data, and in the meantime, people would die, they argue.
Eric A. Klein, MD, from the Glickman Urological and Kidney Institute in Cleveland, Ohio, and colleagues advocate for alternative endpoints such as the incidence of late-stage cancer in an article published in Cancer Epidemiology, Biomarkers & Prevention.
“The concept would be,” they wrote, “that a negative signal would not indicate a mortality benefit, leading to the study being stopped. A positive signal, on the other hand, could result in provisional approval until mortality data and real-world evidence of effectiveness are available. This would resemble the accelerated approval of new cancer drugs, which often is based on progression-free survival until there postmarketing data on overall survival emerge.”
Dr. Klein is also employed at the US biotech start-up Grail, which developed the Galleri test, which is one of the best-known and most advanced cancer screening tests. The Galleri test uses cell-free DNA and machine learning to detect a common cancer signal in more than 50 cancer types and predict the origin of the cancer signal. Consumers in the United States can already order and perform the test.
An NHS Study
Arguments for different endpoints apparently resonated with the United Kingdom’s National Health Service (NHS). Three years ago, they initiated the Galleri study, a large randomized controlled trial to assess the effectiveness of Grail’s cancer test. The primary endpoint was not cancer-specific mortality, but the incidence of stage III or IV cancer.
The results are expected in 2026. But recruitment was stopped after 140,000 participants were enrolled. The NHS reported that the initial results were not convincing enough to continue the trial. Exact numbers were not disclosed.
The Galleri study deviates from the standard randomized controlled trial design for cancer screening procedures not only in terms of the primary endpoint, but also in blinding. The only participants who were unblinded and informed of their test results are those in the intervention group with a positive cancer test.
False Security
This trial design encourages participants to undergo blood tests once per year. But according to Dr. Robbins, it prevents the exploration of the phenomenon of “false security,” which is a potential drawback of the new cancer tests.
“Women with a negative mammogram can reasonably assume that they probably do not have breast cancer. But individuals with a negative cancer blood test could mistakenly believe they cannot have any cancer at all. As a result, they may not undergo standard early detection screenings or seek medical help early enough for potential cancer symptoms,” said Dr. Robbins.
To assess the actual risk-benefit ratio of the Galleri test, participants must receive their test results, she said. “Under real-world conditions, benefits and risks can come from positive and negative results.”
Upcoming Trial
More illuminating results may come from a large trial planned by the National Cancer Institute in the United States. Several new cancer tests will be evaluated for their ability to reduce cancer-specific mortality. A pilot phase will start later in 2024. “This study may be the only one with sufficient statistical power to determine whether an approach based on these cancer tests can reduce cancer-specific mortality,” said Dr. Robbins.
For the new blood tests for multiple cancers, it is crucial that health authorities “set a high bar for a benefit,” she said. This, according to her, also means that they must show an effect on cancer-specific mortality before being introduced. “This evidence must come from studies in which commercial interests do not influence the design, execution, data management, or data analysis.”
This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version appeared on Medscape.com.
Biotech startups worldwide are rushing to market screening tests that they claim can detect various cancers in early stages with just a few drops of blood. The tests allegedly will simplify cancer care by eliminating tedious scans, scopes, and swabs at the doctor’s office.
The promise of these early detection tests is truly “enticing,” Hilary A. Robbins, PhD, from the International Agency for Research on Cancer of the World Health Organization in Lyon, France, said in an interview.
In an opinion article in The New England Journal of Medicine, she emphasized that the new cancer tests are much less cumbersome than traditional screening strategies for individual cancers. Moreover, they could enable the early detection of dozens of cancer types for which no screening has been available so far.
Meeting the Criteria
The problem is that these tests have not met the strict criteria typically required for traditional cancer screening tests. To be considered for introduction as a screening procedure, a test usually needs to meet the following four minimum requirements:
- The disease that the test screens for must have a presymptomatic form.
- The screening test must be able to identify this presymptomatic disease.
- Treating the disease in the presymptomatic phase improves prognosis (specifically, it affects cancer-specific mortality in a randomized controlled trial).
- The screening test is feasible, and the benefits outweigh potential risks.
“The new blood tests for multiple cancers have so far only met the second criteria, showing they can detect presymptomatic cancer,” Dr. Robbins wrote.
The next step would be to demonstrate that they affect cancer-specific mortality. “But currently, commercial interests seem to be influencing the evidence standards for these cancer tests,” said Dr. Robbins.
Inappropriate Endpoints?
Some proponents of such tests argue that, unlike for previous cancer screening procedures, initial approval should not depend on the endpoint of cancer-specific mortality. It would take too long to gather sufficient outcome data, and in the meantime, people would die, they argue.
Eric A. Klein, MD, from the Glickman Urological and Kidney Institute in Cleveland, Ohio, and colleagues advocate for alternative endpoints such as the incidence of late-stage cancer in an article published in Cancer Epidemiology, Biomarkers & Prevention.
“The concept would be,” they wrote, “that a negative signal would not indicate a mortality benefit, leading to the study being stopped. A positive signal, on the other hand, could result in provisional approval until mortality data and real-world evidence of effectiveness are available. This would resemble the accelerated approval of new cancer drugs, which often is based on progression-free survival until there postmarketing data on overall survival emerge.”
Dr. Klein is also employed at the US biotech start-up Grail, which developed the Galleri test, which is one of the best-known and most advanced cancer screening tests. The Galleri test uses cell-free DNA and machine learning to detect a common cancer signal in more than 50 cancer types and predict the origin of the cancer signal. Consumers in the United States can already order and perform the test.
An NHS Study
Arguments for different endpoints apparently resonated with the United Kingdom’s National Health Service (NHS). Three years ago, they initiated the Galleri study, a large randomized controlled trial to assess the effectiveness of Grail’s cancer test. The primary endpoint was not cancer-specific mortality, but the incidence of stage III or IV cancer.
The results are expected in 2026. But recruitment was stopped after 140,000 participants were enrolled. The NHS reported that the initial results were not convincing enough to continue the trial. Exact numbers were not disclosed.
The Galleri study deviates from the standard randomized controlled trial design for cancer screening procedures not only in terms of the primary endpoint, but also in blinding. The only participants who were unblinded and informed of their test results are those in the intervention group with a positive cancer test.
False Security
This trial design encourages participants to undergo blood tests once per year. But according to Dr. Robbins, it prevents the exploration of the phenomenon of “false security,” which is a potential drawback of the new cancer tests.
“Women with a negative mammogram can reasonably assume that they probably do not have breast cancer. But individuals with a negative cancer blood test could mistakenly believe they cannot have any cancer at all. As a result, they may not undergo standard early detection screenings or seek medical help early enough for potential cancer symptoms,” said Dr. Robbins.
To assess the actual risk-benefit ratio of the Galleri test, participants must receive their test results, she said. “Under real-world conditions, benefits and risks can come from positive and negative results.”
Upcoming Trial
More illuminating results may come from a large trial planned by the National Cancer Institute in the United States. Several new cancer tests will be evaluated for their ability to reduce cancer-specific mortality. A pilot phase will start later in 2024. “This study may be the only one with sufficient statistical power to determine whether an approach based on these cancer tests can reduce cancer-specific mortality,” said Dr. Robbins.
For the new blood tests for multiple cancers, it is crucial that health authorities “set a high bar for a benefit,” she said. This, according to her, also means that they must show an effect on cancer-specific mortality before being introduced. “This evidence must come from studies in which commercial interests do not influence the design, execution, data management, or data analysis.”
This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version appeared on Medscape.com.