Mixed Topics

TOPLINE:

A large international cohort study identified a higher risk for cardiovascular diseases and mortality in patients with prurigo nodularis (PN), particularly among women and White patients.

METHODOLOGY:

• Studies have shown increased risks for cardiovascular diseases in patients with PN, but limited sample sizes have hindered further subgroup analysis. Given PN’s pronounced sex and ethnicity skew, it is important to examine underrepresented groups to accurately assess their cardiovascular risk.
• In this propensity-score matched analysis, researchers identified 64,801 patients (59.44% women) with PN using electronic health reports from the Global Collaborative Network of TriNetX and matched to individuals without PN.
• Researchers calculated risks for 15 cardiovascular endpoints and all-cause mortality within 10 years of diagnosis. Major adverse cardiovascular events (MACE) included acute cerebral and myocardial infarction (MI), heart failure, ventricular arrhythmia, and sudden cardiac death.

TAKEAWAY:

• Patients with PN showed a higher risk for death (hazard ratio [HR], 1.1243) and MACE (HR, 1.117) (P < .0001 for both).
• PN was also associated with a higher risk for heart failure (HR, 1.062), thrombotic venous disease (HR, 1.26), angina pectoris (HR, 1.096), and peripheral arterial diseases (HR, 1.082) (P < .0001 for all) and for acute MI (HR, 1.11; P = .0015) and valve disorders (HR, 1.08; P = .0018).
• White patients with PN had a significantly increased risk for MACE, death, heart failure, cardiac arrest, vascular diseases, and acute MI, but this was not observed in people of color.
• Women exhibited a higher risk for MACE, heart failure, peripheral artery disease, acute MI, conduction disease, and valve disorders, while men did not have an increased risk for major or acute cardiovascular events. Both men and women had a higher risk for death, chronic ischemic heart disease, and venous disease.

IN PRACTICE:

“Although no novel PN-specific treatment rationale can be derived from the presented data, the potential risk of subsequent cardiovascular disease should be considered in the care of patients with PN, which includes screening and optimal management of other additional cardiovascular risk factors,” the authors wrote.

LIMITATIONS:

Retrospective observational design introduced inherent biases. Misdiagnosis or false coding in electronic health records could affect the data accuracy and ethnicity-specific analyses.

SOURCE:

This work, led by Henning Olbrich, from the Department of Dermatology, University of Lübeck, Germany, was published online in eBioMedicine.

DISCLOSURES:

The study was supported by the University of Lübeck, the Deutsche Forschungsgemeinschaft, and the State of Schleswig-Holstein. One author declared financial ties outside this work, and one author is an employee of TriNetX.
 

A version of this article appeared on Medscape.com.

TOPLINE:

A large international cohort study identified a higher risk for cardiovascular diseases and mortality in patients with prurigo nodularis (PN), particularly among women and White patients.

METHODOLOGY:

• Studies have shown increased risks for cardiovascular diseases in patients with PN, but limited sample sizes have hindered further subgroup analysis. Given PN’s pronounced sex and ethnicity skew, it is important to examine underrepresented groups to accurately assess their cardiovascular risk.
• In this propensity-score matched analysis, researchers identified 64,801 patients (59.44% women) with PN using electronic health reports from the Global Collaborative Network of TriNetX and matched to individuals without PN.
• Researchers calculated risks for 15 cardiovascular endpoints and all-cause mortality within 10 years of diagnosis. Major adverse cardiovascular events (MACE) included acute cerebral and myocardial infarction (MI), heart failure, ventricular arrhythmia, and sudden cardiac death.

TAKEAWAY:

• Patients with PN showed a higher risk for death (hazard ratio [HR], 1.1243) and MACE (HR, 1.117) (P < .0001 for both).
• PN was also associated with a higher risk for heart failure (HR, 1.062), thrombotic venous disease (HR, 1.26), angina pectoris (HR, 1.096), and peripheral arterial diseases (HR, 1.082) (P < .0001 for all) and for acute MI (HR, 1.11; P = .0015) and valve disorders (HR, 1.08; P = .0018).
• White patients with PN had a significantly increased risk for MACE, death, heart failure, cardiac arrest, vascular diseases, and acute MI, but this was not observed in people of color.
• Women exhibited a higher risk for MACE, heart failure, peripheral artery disease, acute MI, conduction disease, and valve disorders, while men did not have an increased risk for major or acute cardiovascular events. Both men and women had a higher risk for death, chronic ischemic heart disease, and venous disease.

IN PRACTICE:

“Although no novel PN-specific treatment rationale can be derived from the presented data, the potential risk of subsequent cardiovascular disease should be considered in the care of patients with PN, which includes screening and optimal management of other additional cardiovascular risk factors,” the authors wrote.

LIMITATIONS:

Retrospective observational design introduced inherent biases. Misdiagnosis or false coding in electronic health records could affect the data accuracy and ethnicity-specific analyses.

SOURCE:

This work, led by Henning Olbrich, from the Department of Dermatology, University of Lübeck, Germany, was published online in eBioMedicine.

DISCLOSURES:

The study was supported by the University of Lübeck, the Deutsche Forschungsgemeinschaft, and the State of Schleswig-Holstein. One author declared financial ties outside this work, and one author is an employee of TriNetX.
 

A version of this article appeared on Medscape.com.

TOPLINE:

A large international cohort study identified a higher risk for cardiovascular diseases and mortality in patients with prurigo nodularis (PN), particularly among women and White patients.

METHODOLOGY:

• Studies have shown increased risks for cardiovascular diseases in patients with PN, but limited sample sizes have hindered further subgroup analysis. Given PN’s pronounced sex and ethnicity skew, it is important to examine underrepresented groups to accurately assess their cardiovascular risk.
• In this propensity-score matched analysis, researchers identified 64,801 patients (59.44% women) with PN using electronic health reports from the Global Collaborative Network of TriNetX and matched to individuals without PN.
• Researchers calculated risks for 15 cardiovascular endpoints and all-cause mortality within 10 years of diagnosis. Major adverse cardiovascular events (MACE) included acute cerebral and myocardial infarction (MI), heart failure, ventricular arrhythmia, and sudden cardiac death.

TAKEAWAY:

• Patients with PN showed a higher risk for death (hazard ratio [HR], 1.1243) and MACE (HR, 1.117) (P < .0001 for both).
• PN was also associated with a higher risk for heart failure (HR, 1.062), thrombotic venous disease (HR, 1.26), angina pectoris (HR, 1.096), and peripheral arterial diseases (HR, 1.082) (P < .0001 for all) and for acute MI (HR, 1.11; P = .0015) and valve disorders (HR, 1.08; P = .0018).
• White patients with PN had a significantly increased risk for MACE, death, heart failure, cardiac arrest, vascular diseases, and acute MI, but this was not observed in people of color.
• Women exhibited a higher risk for MACE, heart failure, peripheral artery disease, acute MI, conduction disease, and valve disorders, while men did not have an increased risk for major or acute cardiovascular events. Both men and women had a higher risk for death, chronic ischemic heart disease, and venous disease.

IN PRACTICE:

“Although no novel PN-specific treatment rationale can be derived from the presented data, the potential risk of subsequent cardiovascular disease should be considered in the care of patients with PN, which includes screening and optimal management of other additional cardiovascular risk factors,” the authors wrote.

LIMITATIONS:

Retrospective observational design introduced inherent biases. Misdiagnosis or false coding in electronic health records could affect the data accuracy and ethnicity-specific analyses.

SOURCE:

This work, led by Henning Olbrich, from the Department of Dermatology, University of Lübeck, Germany, was published online in eBioMedicine.

DISCLOSURES:

The study was supported by the University of Lübeck, the Deutsche Forschungsgemeinschaft, and the State of Schleswig-Holstein. One author declared financial ties outside this work, and one author is an employee of TriNetX.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Overall, patients with solid tumors who receive an investigational cancer drug experience small progression-free survival (PFS) and overall survival benefits but much higher toxicity than those who receive a control intervention.

METHODOLOGY:

• The view that patients with cancer benefit from access to investigational drugs in the clinical trial setting is widely held but does necessarily align with trial findings, which often show limited evidence of a clinical benefit. First, most investigational treatments assessed in clinical trials fail to gain regulatory approval, and the minority that are approved tend to offer minimal clinical benefit, experts explained.
• To estimate the survival benefit and toxicities associated with receiving experimental treatments, researchers conducted a meta-analysis of 128 trials comprising 141 comparisons of an investigational drug and a control treatment, which included immunotherapies and targeted therapies.
• The analysis included 42 trials in non–small cell lung cancer (NSCLC), 37 in breast cancer, 15 in hepatobiliary cancer, 13 in pancreatic cancer, 12 in colorectal cancer, and 10 in prostate cancer, involving a total of 47,050 patients.
• The primary outcome was PFS and secondary outcomes were overall survival and grades 3-5 serious adverse events.

TAKEAWAY:

• Overall, the experimental treatment was associated with a 20% improvement in PFS (pooled hazard ratio [HR], 0.80), corresponding to a median 1.25-month PFS advantage. The PFS benefit was seen across all cancer types, except pancreatic cancer.
• Overall survival improved by 8% with experimental agents (HR, 0.92), corresponding to 1.18 additional months. A significant overall survival benefit was seen across NSCLC, breast cancer, and hepatobiliary cancer trials but not pancreatic, prostate, colorectal cancer trials.
• Patients in the experimental intervention group, however, experienced much higher risk for grade 3-5 serious adverse events (risk ratio [RR], 1.27), corresponding to 7.40% increase in absolute risk. The greater risk for serious adverse events was significant for all indications except prostate cancer (RR, 1.13; 95% CI, 0.91-1.40).

IN PRACTICE:

“We believe our findings are best interpreted as suggesting that access to experimental interventions that have not yet received full FDA approval is associated with a marginal but nonzero clinical benefit,” the authors wrote. 

“Although our findings seem to reflect poorly on trials as a vehicle for extending survival for participants, they have reassuring implications for clinical investigators, policymakers, and institutional review boards,” the researchers said, explaining that this “scenario allows clinical trials to continue to pursue promising new treatments — supporting incremental advances that sum to large gains over extended periods of research — without disadvantaging patients in comparator groups.”

SOURCE: 

Renata Iskander, MSc, of McGill University, Montreal, Quebec, Canada, led this work, which was published online on April 29, 2024, in Annals of Internal Medicine.

LIMITATIONS:

There was high heterogeneity across studies due to variations in drugs tested, comparators used, and populations involved. The use of comparators below standard care could have inflated survival benefits. Additionally, data collected from ClinicalTrials.gov might be biased due to some trials not being reported. 

DISCLOSURES:

Canadian Institutes of Health Research supported this work. The authors received grants for this work from McGill University, Rossy Cancer Network, and National Science Foundation. One author received consulting fees outside this work. The other authors declared no competing interests.

A version of this article appeared on Medscape.com.

TOPLINE:

Overall, patients with solid tumors who receive an investigational cancer drug experience small progression-free survival (PFS) and overall survival benefits but much higher toxicity than those who receive a control intervention.

METHODOLOGY:

• The view that patients with cancer benefit from access to investigational drugs in the clinical trial setting is widely held but does necessarily align with trial findings, which often show limited evidence of a clinical benefit. First, most investigational treatments assessed in clinical trials fail to gain regulatory approval, and the minority that are approved tend to offer minimal clinical benefit, experts explained.
• To estimate the survival benefit and toxicities associated with receiving experimental treatments, researchers conducted a meta-analysis of 128 trials comprising 141 comparisons of an investigational drug and a control treatment, which included immunotherapies and targeted therapies.
• The analysis included 42 trials in non–small cell lung cancer (NSCLC), 37 in breast cancer, 15 in hepatobiliary cancer, 13 in pancreatic cancer, 12 in colorectal cancer, and 10 in prostate cancer, involving a total of 47,050 patients.
• The primary outcome was PFS and secondary outcomes were overall survival and grades 3-5 serious adverse events.

TAKEAWAY:

• Overall, the experimental treatment was associated with a 20% improvement in PFS (pooled hazard ratio [HR], 0.80), corresponding to a median 1.25-month PFS advantage. The PFS benefit was seen across all cancer types, except pancreatic cancer.
• Overall survival improved by 8% with experimental agents (HR, 0.92), corresponding to 1.18 additional months. A significant overall survival benefit was seen across NSCLC, breast cancer, and hepatobiliary cancer trials but not pancreatic, prostate, colorectal cancer trials.
• Patients in the experimental intervention group, however, experienced much higher risk for grade 3-5 serious adverse events (risk ratio [RR], 1.27), corresponding to 7.40% increase in absolute risk. The greater risk for serious adverse events was significant for all indications except prostate cancer (RR, 1.13; 95% CI, 0.91-1.40).

IN PRACTICE:

“We believe our findings are best interpreted as suggesting that access to experimental interventions that have not yet received full FDA approval is associated with a marginal but nonzero clinical benefit,” the authors wrote. 

“Although our findings seem to reflect poorly on trials as a vehicle for extending survival for participants, they have reassuring implications for clinical investigators, policymakers, and institutional review boards,” the researchers said, explaining that this “scenario allows clinical trials to continue to pursue promising new treatments — supporting incremental advances that sum to large gains over extended periods of research — without disadvantaging patients in comparator groups.”

SOURCE: 

Renata Iskander, MSc, of McGill University, Montreal, Quebec, Canada, led this work, which was published online on April 29, 2024, in Annals of Internal Medicine.

LIMITATIONS:

There was high heterogeneity across studies due to variations in drugs tested, comparators used, and populations involved. The use of comparators below standard care could have inflated survival benefits. Additionally, data collected from ClinicalTrials.gov might be biased due to some trials not being reported. 

DISCLOSURES:

Canadian Institutes of Health Research supported this work. The authors received grants for this work from McGill University, Rossy Cancer Network, and National Science Foundation. One author received consulting fees outside this work. The other authors declared no competing interests.

A version of this article appeared on Medscape.com.

TOPLINE:

Overall, patients with solid tumors who receive an investigational cancer drug experience small progression-free survival (PFS) and overall survival benefits but much higher toxicity than those who receive a control intervention.

METHODOLOGY:

• The view that patients with cancer benefit from access to investigational drugs in the clinical trial setting is widely held but does necessarily align with trial findings, which often show limited evidence of a clinical benefit. First, most investigational treatments assessed in clinical trials fail to gain regulatory approval, and the minority that are approved tend to offer minimal clinical benefit, experts explained.
• To estimate the survival benefit and toxicities associated with receiving experimental treatments, researchers conducted a meta-analysis of 128 trials comprising 141 comparisons of an investigational drug and a control treatment, which included immunotherapies and targeted therapies.
• The analysis included 42 trials in non–small cell lung cancer (NSCLC), 37 in breast cancer, 15 in hepatobiliary cancer, 13 in pancreatic cancer, 12 in colorectal cancer, and 10 in prostate cancer, involving a total of 47,050 patients.
• The primary outcome was PFS and secondary outcomes were overall survival and grades 3-5 serious adverse events.

TAKEAWAY:

• Overall, the experimental treatment was associated with a 20% improvement in PFS (pooled hazard ratio [HR], 0.80), corresponding to a median 1.25-month PFS advantage. The PFS benefit was seen across all cancer types, except pancreatic cancer.
• Overall survival improved by 8% with experimental agents (HR, 0.92), corresponding to 1.18 additional months. A significant overall survival benefit was seen across NSCLC, breast cancer, and hepatobiliary cancer trials but not pancreatic, prostate, colorectal cancer trials.
• Patients in the experimental intervention group, however, experienced much higher risk for grade 3-5 serious adverse events (risk ratio [RR], 1.27), corresponding to 7.40% increase in absolute risk. The greater risk for serious adverse events was significant for all indications except prostate cancer (RR, 1.13; 95% CI, 0.91-1.40).

IN PRACTICE:

“We believe our findings are best interpreted as suggesting that access to experimental interventions that have not yet received full FDA approval is associated with a marginal but nonzero clinical benefit,” the authors wrote. 

“Although our findings seem to reflect poorly on trials as a vehicle for extending survival for participants, they have reassuring implications for clinical investigators, policymakers, and institutional review boards,” the researchers said, explaining that this “scenario allows clinical trials to continue to pursue promising new treatments — supporting incremental advances that sum to large gains over extended periods of research — without disadvantaging patients in comparator groups.”

SOURCE: 

Renata Iskander, MSc, of McGill University, Montreal, Quebec, Canada, led this work, which was published online on April 29, 2024, in Annals of Internal Medicine.

LIMITATIONS:

There was high heterogeneity across studies due to variations in drugs tested, comparators used, and populations involved. The use of comparators below standard care could have inflated survival benefits. Additionally, data collected from ClinicalTrials.gov might be biased due to some trials not being reported. 

DISCLOSURES:

Canadian Institutes of Health Research supported this work. The authors received grants for this work from McGill University, Rossy Cancer Network, and National Science Foundation. One author received consulting fees outside this work. The other authors declared no competing interests.

A version of this article appeared on Medscape.com.

Health-related social needs and medical financial hardship are associated with increased risk of mortality in adult cancer survivors, based on data from more than 10,000 individuals.

Little is known about the specific association between health-related social needs (HRSNs) and mortality risk even though HRSNs, defined as challenges in affording food, housing, and other necessities of daily living, are potential challenges for cancer survivors, wrote Zhiyuan Zheng, PhD, of the American Cancer Society, Atlanta, and colleagues.

A 2020 study by Dr. Zheng and colleagues published in the Journal of the National Comprehensive Cancer Network (NCCN) showed that food insecurity and financial worries had a negative impact on cancer survivorship. In the new study, published in Cancer, the researchers identified cancer survivors using the 2013-2018 National Health Interview Survey (NHIS) and the NHIS Mortality File through December 31, 2019. The researchers examined mortality using the data from the Centers for Disease Control and Prevention’s National Death Index (NDI) through December 31, 2019, which links to the National Health Interview Survey Data used in the study.

Individuals’ HRSNs were categorized into three groups: severe, moderate, and minor/none. HRSNs included food insecurity and nonmedical financial concerns, such as housing costs (rent, mortgage). Medical financial hardship included material, psychological, and behavioral domains and was divided into three groups: 2-3 domains, 1 domain, or 0 domains.
 

What Are the Potential Financial Implications of this Research?

The high costs of cancer care often cause medical financial hardships for cancer survivors, and expenses also may cause psychological distress and nonmedical financial hardship as survivors try to make ends meet while facing medical bills, wrote Dr. Zheng and colleagues.

Policy makers are increasingly interested in adding HRSNs to insurance coverage; recent guidance from the Centers for Medicare & Medicaid Services (CMS) allows individual states to apply to provide nutrition and housing supports through state Medicaid programs, according to authors of a 2023 article published in JAMA Health Forum.

The new study adds to the understanding of how HRSNs impact people with cancer by examining the association with mortality risk, Yelak Biru, MSc, president and chief executive officer of the International Myeloma Foundation, said in an interview.

“This is a key area of study for addressing the disparities in treatments and outcomes that result in inequities,” said Mr. Biru, a patient advocate and multiple myeloma survivor who was not involved in the study.
 

What Does the New Study Show?

The new study characterized HRSNs in 5,855 adult cancer survivors aged 18-64 years and 5,918 aged 65-79 years. In the 18- to 64-year-old group, 25.5% reported moderate levels of HRSNs, and 18.3% reported severe HRSNs. In patients aged 65-79 years, 15.6% and 6.6% reported moderate HRSNs and severe HRSNs, respectively.

Severe HRSN was significantly associated with higher mortality risk in an adjusted analysis in patients aged 18-64 years (hazard ratio 2.00, P < .001).

Among adults aged 65-79 years, severe HRSN was not associated with higher mortality risk; however, in this older age group, those with 2-3 domains of medical financial hardship had significantly increased mortality risk compared with adults aged 65-79 years with zero domains of medical financial hardship (HR 1.58, P = .007).

Although the findings that HRSNs were associated with increased mortality risk, especially in the younger group, were not surprising, they serve as a call to action to address how HRSNs are contributing to cancer mortality, Mr. Biru said in an interview. “HRSNs, like food or housing insecurity, can lead to patients being unable to undergo the best treatment approach for their cancer,” he said.
 

What Are the Limitations and Research Gaps?

The study findings were limited by several factors including the use of self-reports to measure medical financial hardship, food insecurity, and nonmedical financial concerns in the NHIS, the researchers wrote in their discussion. More research with longer follow-up time beyond 1-5 years is needed, wrote Dr. Zheng and colleagues.

Studies also are needed to illustrate how patient navigation can help prevent patients from falling through the cracks with regard to social needs and financial hardships, Mr. Biru told this news organization.

Other areas for research include how addressing social needs affects health outcomes and whether programs designed to address social needs are effective, he said.

“Finally, qualitative research is needed to capture the lived experiences of cancer survivors facing these challenges. This knowledge can inform the development of more patient-centered interventions and policies that effectively address the social determinants of health and improve overall outcomes for all cancer survivors,” Mr. Biru said.
 

What Is the Takeaway Message for Clinicians?

HRSNs and financial hardship are significantly associated with increased risk of mortality in adult cancer survivors, Dr. Zheng and colleagues concluded. Looking ahead, comprehensive assessment of HRSNs and financial hardship may help clinicians connect patients with relevant services to mitigate the social and financial impacts of cancer, they wrote.

“The takeaway message for oncologists in practice is that addressing [HRSNs] and financial hardship is crucial for providing comprehensive and equitable cancer care,” Mr. Biru said during his interview.

“The impact of social determinants of health on cancer outcomes cannot be ignored, and oncologists play a vital role in identifying and addressing these needs,” he said. Sensitive, discussion-based screenings are needed to identify core needs such as food and transportation, but clinicians also can consider broader social factors and work with a team to connect patients to appropriate resources, he added.

“By recognizing the importance of HRSN screening and taking proactive steps to address these needs, oncologists can contribute to improving health outcomes, reducing healthcare disparities, and providing more equitable cancer care for their patients,” he said.
 

What Other Guidance Is Available?

“High-quality cancer care requires treating the whole person; measuring and addressing anything in their life that could result in poorer health outcomes is a key component of comprehensive care,” Mr. Biru emphasized.

In September 2023, the National Comprehensive Cancer Network (NCCN) convened a working group cochaired by Mr. Biru that developed recommendations for how oncology practices should routinely measure HRSNs (NCCN.org/social-needs).

“The working group proposed that every cancer patient be assessed for food, transportation access, and financial and housing security at least once a year, and be reassessed at every care transition point as well,” Mr. Biru said. Such screenings should include follow-up to connect patients with services to address any HRSNs they are experiencing, he added.

Lead author Dr. Zheng is employed by the American Cancer Society, which as a nonprofit receives funds from the public through fundraising and contributions, as well as some support from corporations and industry to support its mission programs and services. Mr. Biru had no financial conflicts to disclose.

Health-related social needs and medical financial hardship are associated with increased risk of mortality in adult cancer survivors, based on data from more than 10,000 individuals.

Little is known about the specific association between health-related social needs (HRSNs) and mortality risk even though HRSNs, defined as challenges in affording food, housing, and other necessities of daily living, are potential challenges for cancer survivors, wrote Zhiyuan Zheng, PhD, of the American Cancer Society, Atlanta, and colleagues.

A 2020 study by Dr. Zheng and colleagues published in the Journal of the National Comprehensive Cancer Network (NCCN) showed that food insecurity and financial worries had a negative impact on cancer survivorship. In the new study, published in Cancer, the researchers identified cancer survivors using the 2013-2018 National Health Interview Survey (NHIS) and the NHIS Mortality File through December 31, 2019. The researchers examined mortality using the data from the Centers for Disease Control and Prevention’s National Death Index (NDI) through December 31, 2019, which links to the National Health Interview Survey Data used in the study.

Individuals’ HRSNs were categorized into three groups: severe, moderate, and minor/none. HRSNs included food insecurity and nonmedical financial concerns, such as housing costs (rent, mortgage). Medical financial hardship included material, psychological, and behavioral domains and was divided into three groups: 2-3 domains, 1 domain, or 0 domains.
 

What Are the Potential Financial Implications of this Research?

The high costs of cancer care often cause medical financial hardships for cancer survivors, and expenses also may cause psychological distress and nonmedical financial hardship as survivors try to make ends meet while facing medical bills, wrote Dr. Zheng and colleagues.

Policy makers are increasingly interested in adding HRSNs to insurance coverage; recent guidance from the Centers for Medicare & Medicaid Services (CMS) allows individual states to apply to provide nutrition and housing supports through state Medicaid programs, according to authors of a 2023 article published in JAMA Health Forum.

The new study adds to the understanding of how HRSNs impact people with cancer by examining the association with mortality risk, Yelak Biru, MSc, president and chief executive officer of the International Myeloma Foundation, said in an interview.

“This is a key area of study for addressing the disparities in treatments and outcomes that result in inequities,” said Mr. Biru, a patient advocate and multiple myeloma survivor who was not involved in the study.
 

What Does the New Study Show?

The new study characterized HRSNs in 5,855 adult cancer survivors aged 18-64 years and 5,918 aged 65-79 years. In the 18- to 64-year-old group, 25.5% reported moderate levels of HRSNs, and 18.3% reported severe HRSNs. In patients aged 65-79 years, 15.6% and 6.6% reported moderate HRSNs and severe HRSNs, respectively.

Severe HRSN was significantly associated with higher mortality risk in an adjusted analysis in patients aged 18-64 years (hazard ratio 2.00, P < .001).

Among adults aged 65-79 years, severe HRSN was not associated with higher mortality risk; however, in this older age group, those with 2-3 domains of medical financial hardship had significantly increased mortality risk compared with adults aged 65-79 years with zero domains of medical financial hardship (HR 1.58, P = .007).

Although the findings that HRSNs were associated with increased mortality risk, especially in the younger group, were not surprising, they serve as a call to action to address how HRSNs are contributing to cancer mortality, Mr. Biru said in an interview. “HRSNs, like food or housing insecurity, can lead to patients being unable to undergo the best treatment approach for their cancer,” he said.
 

What Are the Limitations and Research Gaps?

The study findings were limited by several factors including the use of self-reports to measure medical financial hardship, food insecurity, and nonmedical financial concerns in the NHIS, the researchers wrote in their discussion. More research with longer follow-up time beyond 1-5 years is needed, wrote Dr. Zheng and colleagues.

Studies also are needed to illustrate how patient navigation can help prevent patients from falling through the cracks with regard to social needs and financial hardships, Mr. Biru told this news organization.

Other areas for research include how addressing social needs affects health outcomes and whether programs designed to address social needs are effective, he said.

“Finally, qualitative research is needed to capture the lived experiences of cancer survivors facing these challenges. This knowledge can inform the development of more patient-centered interventions and policies that effectively address the social determinants of health and improve overall outcomes for all cancer survivors,” Mr. Biru said.
 

What Is the Takeaway Message for Clinicians?

HRSNs and financial hardship are significantly associated with increased risk of mortality in adult cancer survivors, Dr. Zheng and colleagues concluded. Looking ahead, comprehensive assessment of HRSNs and financial hardship may help clinicians connect patients with relevant services to mitigate the social and financial impacts of cancer, they wrote.

“The takeaway message for oncologists in practice is that addressing [HRSNs] and financial hardship is crucial for providing comprehensive and equitable cancer care,” Mr. Biru said during his interview.

“The impact of social determinants of health on cancer outcomes cannot be ignored, and oncologists play a vital role in identifying and addressing these needs,” he said. Sensitive, discussion-based screenings are needed to identify core needs such as food and transportation, but clinicians also can consider broader social factors and work with a team to connect patients to appropriate resources, he added.

“By recognizing the importance of HRSN screening and taking proactive steps to address these needs, oncologists can contribute to improving health outcomes, reducing healthcare disparities, and providing more equitable cancer care for their patients,” he said.
 

What Other Guidance Is Available?

“High-quality cancer care requires treating the whole person; measuring and addressing anything in their life that could result in poorer health outcomes is a key component of comprehensive care,” Mr. Biru emphasized.

In September 2023, the National Comprehensive Cancer Network (NCCN) convened a working group cochaired by Mr. Biru that developed recommendations for how oncology practices should routinely measure HRSNs (NCCN.org/social-needs).

“The working group proposed that every cancer patient be assessed for food, transportation access, and financial and housing security at least once a year, and be reassessed at every care transition point as well,” Mr. Biru said. Such screenings should include follow-up to connect patients with services to address any HRSNs they are experiencing, he added.

Lead author Dr. Zheng is employed by the American Cancer Society, which as a nonprofit receives funds from the public through fundraising and contributions, as well as some support from corporations and industry to support its mission programs and services. Mr. Biru had no financial conflicts to disclose.

Health-related social needs and medical financial hardship are associated with increased risk of mortality in adult cancer survivors, based on data from more than 10,000 individuals.

Little is known about the specific association between health-related social needs (HRSNs) and mortality risk even though HRSNs, defined as challenges in affording food, housing, and other necessities of daily living, are potential challenges for cancer survivors, wrote Zhiyuan Zheng, PhD, of the American Cancer Society, Atlanta, and colleagues.

A 2020 study by Dr. Zheng and colleagues published in the Journal of the National Comprehensive Cancer Network (NCCN) showed that food insecurity and financial worries had a negative impact on cancer survivorship. In the new study, published in Cancer, the researchers identified cancer survivors using the 2013-2018 National Health Interview Survey (NHIS) and the NHIS Mortality File through December 31, 2019. The researchers examined mortality using the data from the Centers for Disease Control and Prevention’s National Death Index (NDI) through December 31, 2019, which links to the National Health Interview Survey Data used in the study.

Individuals’ HRSNs were categorized into three groups: severe, moderate, and minor/none. HRSNs included food insecurity and nonmedical financial concerns, such as housing costs (rent, mortgage). Medical financial hardship included material, psychological, and behavioral domains and was divided into three groups: 2-3 domains, 1 domain, or 0 domains.
 

What Are the Potential Financial Implications of this Research?

The high costs of cancer care often cause medical financial hardships for cancer survivors, and expenses also may cause psychological distress and nonmedical financial hardship as survivors try to make ends meet while facing medical bills, wrote Dr. Zheng and colleagues.

Policy makers are increasingly interested in adding HRSNs to insurance coverage; recent guidance from the Centers for Medicare & Medicaid Services (CMS) allows individual states to apply to provide nutrition and housing supports through state Medicaid programs, according to authors of a 2023 article published in JAMA Health Forum.

The new study adds to the understanding of how HRSNs impact people with cancer by examining the association with mortality risk, Yelak Biru, MSc, president and chief executive officer of the International Myeloma Foundation, said in an interview.

“This is a key area of study for addressing the disparities in treatments and outcomes that result in inequities,” said Mr. Biru, a patient advocate and multiple myeloma survivor who was not involved in the study.
 

What Does the New Study Show?

The new study characterized HRSNs in 5,855 adult cancer survivors aged 18-64 years and 5,918 aged 65-79 years. In the 18- to 64-year-old group, 25.5% reported moderate levels of HRSNs, and 18.3% reported severe HRSNs. In patients aged 65-79 years, 15.6% and 6.6% reported moderate HRSNs and severe HRSNs, respectively.

Severe HRSN was significantly associated with higher mortality risk in an adjusted analysis in patients aged 18-64 years (hazard ratio 2.00, P < .001).

Among adults aged 65-79 years, severe HRSN was not associated with higher mortality risk; however, in this older age group, those with 2-3 domains of medical financial hardship had significantly increased mortality risk compared with adults aged 65-79 years with zero domains of medical financial hardship (HR 1.58, P = .007).

Although the findings that HRSNs were associated with increased mortality risk, especially in the younger group, were not surprising, they serve as a call to action to address how HRSNs are contributing to cancer mortality, Mr. Biru said in an interview. “HRSNs, like food or housing insecurity, can lead to patients being unable to undergo the best treatment approach for their cancer,” he said.
 

What Are the Limitations and Research Gaps?

The study findings were limited by several factors including the use of self-reports to measure medical financial hardship, food insecurity, and nonmedical financial concerns in the NHIS, the researchers wrote in their discussion. More research with longer follow-up time beyond 1-5 years is needed, wrote Dr. Zheng and colleagues.

Studies also are needed to illustrate how patient navigation can help prevent patients from falling through the cracks with regard to social needs and financial hardships, Mr. Biru told this news organization.

Other areas for research include how addressing social needs affects health outcomes and whether programs designed to address social needs are effective, he said.

“Finally, qualitative research is needed to capture the lived experiences of cancer survivors facing these challenges. This knowledge can inform the development of more patient-centered interventions and policies that effectively address the social determinants of health and improve overall outcomes for all cancer survivors,” Mr. Biru said.
 

What Is the Takeaway Message for Clinicians?

HRSNs and financial hardship are significantly associated with increased risk of mortality in adult cancer survivors, Dr. Zheng and colleagues concluded. Looking ahead, comprehensive assessment of HRSNs and financial hardship may help clinicians connect patients with relevant services to mitigate the social and financial impacts of cancer, they wrote.

“The takeaway message for oncologists in practice is that addressing [HRSNs] and financial hardship is crucial for providing comprehensive and equitable cancer care,” Mr. Biru said during his interview.

“The impact of social determinants of health on cancer outcomes cannot be ignored, and oncologists play a vital role in identifying and addressing these needs,” he said. Sensitive, discussion-based screenings are needed to identify core needs such as food and transportation, but clinicians also can consider broader social factors and work with a team to connect patients to appropriate resources, he added.

“By recognizing the importance of HRSN screening and taking proactive steps to address these needs, oncologists can contribute to improving health outcomes, reducing healthcare disparities, and providing more equitable cancer care for their patients,” he said.
 

What Other Guidance Is Available?

“High-quality cancer care requires treating the whole person; measuring and addressing anything in their life that could result in poorer health outcomes is a key component of comprehensive care,” Mr. Biru emphasized.

In September 2023, the National Comprehensive Cancer Network (NCCN) convened a working group cochaired by Mr. Biru that developed recommendations for how oncology practices should routinely measure HRSNs (NCCN.org/social-needs).

“The working group proposed that every cancer patient be assessed for food, transportation access, and financial and housing security at least once a year, and be reassessed at every care transition point as well,” Mr. Biru said. Such screenings should include follow-up to connect patients with services to address any HRSNs they are experiencing, he added.

Lead author Dr. Zheng is employed by the American Cancer Society, which as a nonprofit receives funds from the public through fundraising and contributions, as well as some support from corporations and industry to support its mission programs and services. Mr. Biru had no financial conflicts to disclose.

What’s most important to patients with terminal cancer and their caregivers?

New research found that patients and caregivers both tend to prioritize symptom control over life extension but often preferring a balance. Patients and caregivers, however, are less aligned on decisions about cost containment, with patients more likely to prioritize cost containment.

“Our research has revealed that patients and caregivers generally share similar end-of-life goals,” with a “notable exception” when it comes to costs, first author Semra Ozdemir, PhD, with the Lien Centre for Palliative Care, Duke-NUS Medical School, Singapore, told this news organization.

However, when patients and caregivers have a better understanding of the patient’s prognosis, both may be more inclined to avoid costly life-extending treatments and prioritize symptom management.

In other words, the survey suggests that “knowing the prognosis helps patients and their families set realistic expectations for care and adequately prepare for end-of-life decisions,” said Dr. Ozdemir.

This study was published online in JAMA Network Open.

Patients with advanced cancer often face difficult decisions: Do they opt for treatments that may — or may not — extend life or do they focus more on symptom control?

Family caregivers, who also play an important role in this decision-making process, may have different care goals. Some research suggests that caregivers tend to prioritize treatments that could extend life, whereas patients prioritize symptom management, but it’s less clear how these priorities may change over time and how patients and caregivers may influence each other.

In the current study, the researchers examined goals of care among patients with stage IV solid tumors and caregivers during the last 2 years of life, focusing on life extension vs symptom management and cost containment, as well as how these goals changed over time.

The survey included 210 patient-caregiver pairs, recruited from outpatient clinics at two major cancer centers in Singapore. Patients had a mean age of 63 years, and about half were men. The caregivers had a mean age of 49 years, and almost two third (63%) were women.

Overall, 34% patients and 29% caregivers prioritized symptom management over life extension, whereas 24% patients and 19% caregivers prioritized life extension. Most patients and caregivers preferred balancing the two, with 34%-47% patients and 37%-69% caregivers supporting this approach.

When balancing cost and treatment decisions, however, patients were more likely to prioritize containing costs — 28% vs 17% for caregivers — over extending life — 26% of patients vs 35% of caregivers.

Cost containment tended to be more of a priority for older patients, those with a higher symptom burden, and those with less family caregiver support. For caregivers, cost containment was more of a priority for those who reported that caregiving had a big impact on their finances, those with worse self-esteem related to their caregiving abilities, as well as those caring for older patients.

To better align cost containment priorities between patients and caregivers, it’s essential for families to engage in open and thorough discussions about the allocation of resources, Dr. Ozdemir said.

Although “patients, families, and physicians often avoid discussions about prognosis,” such conversations are essential for setting realistic expectations for care and adequately preparing for end-of-life decisions, Dr. Ozdemir told this news organization.

“These conversations should aim to balance competing interests and create care plans that are mutually acceptable to both patients and caregivers,” she said, adding that “this approach will help in minimizing any potential conflicts and ensure that both parties feel respected and understood in their decision-making process.”

Managing Unrealistic Expectations

As patients approached the end of life, neither patients nor caregivers shifted their priorities from life extension to symptom management.

This finding raises concerns because it suggests that many patients hold unrealistic expectations regarding their care and “underscores the need for continuous dialogue and reassessment of care goals throughout the progression of illness,” Dr. Ozdemir said.

“This stability in preferences over time suggests that initial care decisions are deeply ingrained or that there may be a lack of ongoing communication about evolving care needs and possibilities as conditions change,” Ozdemir said.

Yet, it can be hard to define what unrealistic expectations mean, said Olivia Seecof, MD, who wasn’t involved in the study.

“I think people are hopeful that a devastating diagnosis won’t lead to the end of their life and that there will be a treatment or something that will change [their prognosis], and they’ll get better,” said Dr. Seecof, palliative care expert with the Supportive Oncology Program at NYU Langone Health’s Perlmutter Cancer Center in New York City.

Giving patients and caregivers a realistic understanding of the prognosis is important, but “there’s more to it than just telling the patient their diagnosis,” she said.

“We have to plan for end of life, what it can look like,” said Dr. Seecof, adding that “often we don’t do a very good job of talking about that early on in an illness course.”

Overall, though, Dr. Seecof stressed that no two patients or situations are the same, and it’s important to understand what’s important in each scenario. End-of-life care requires “an individual approach because every patient is different, even if they have the same diagnosis as someone else,” she said.

This work was supported by funding from the Singapore Millennium Foundation and the Lien Centre for Palliative Care. Dr. Ozdemir and Dr. Seecof had no relevant disclosures.

A version of this article appeared on Medscape.com.

What’s most important to patients with terminal cancer and their caregivers?

New research found that patients and caregivers both tend to prioritize symptom control over life extension but often preferring a balance. Patients and caregivers, however, are less aligned on decisions about cost containment, with patients more likely to prioritize cost containment.

“Our research has revealed that patients and caregivers generally share similar end-of-life goals,” with a “notable exception” when it comes to costs, first author Semra Ozdemir, PhD, with the Lien Centre for Palliative Care, Duke-NUS Medical School, Singapore, told this news organization.

However, when patients and caregivers have a better understanding of the patient’s prognosis, both may be more inclined to avoid costly life-extending treatments and prioritize symptom management.

In other words, the survey suggests that “knowing the prognosis helps patients and their families set realistic expectations for care and adequately prepare for end-of-life decisions,” said Dr. Ozdemir.

This study was published online in JAMA Network Open.

Patients with advanced cancer often face difficult decisions: Do they opt for treatments that may — or may not — extend life or do they focus more on symptom control?

Family caregivers, who also play an important role in this decision-making process, may have different care goals. Some research suggests that caregivers tend to prioritize treatments that could extend life, whereas patients prioritize symptom management, but it’s less clear how these priorities may change over time and how patients and caregivers may influence each other.

In the current study, the researchers examined goals of care among patients with stage IV solid tumors and caregivers during the last 2 years of life, focusing on life extension vs symptom management and cost containment, as well as how these goals changed over time.

The survey included 210 patient-caregiver pairs, recruited from outpatient clinics at two major cancer centers in Singapore. Patients had a mean age of 63 years, and about half were men. The caregivers had a mean age of 49 years, and almost two third (63%) were women.

Overall, 34% patients and 29% caregivers prioritized symptom management over life extension, whereas 24% patients and 19% caregivers prioritized life extension. Most patients and caregivers preferred balancing the two, with 34%-47% patients and 37%-69% caregivers supporting this approach.

When balancing cost and treatment decisions, however, patients were more likely to prioritize containing costs — 28% vs 17% for caregivers — over extending life — 26% of patients vs 35% of caregivers.

Cost containment tended to be more of a priority for older patients, those with a higher symptom burden, and those with less family caregiver support. For caregivers, cost containment was more of a priority for those who reported that caregiving had a big impact on their finances, those with worse self-esteem related to their caregiving abilities, as well as those caring for older patients.

To better align cost containment priorities between patients and caregivers, it’s essential for families to engage in open and thorough discussions about the allocation of resources, Dr. Ozdemir said.

Although “patients, families, and physicians often avoid discussions about prognosis,” such conversations are essential for setting realistic expectations for care and adequately preparing for end-of-life decisions, Dr. Ozdemir told this news organization.

“These conversations should aim to balance competing interests and create care plans that are mutually acceptable to both patients and caregivers,” she said, adding that “this approach will help in minimizing any potential conflicts and ensure that both parties feel respected and understood in their decision-making process.”

Managing Unrealistic Expectations

As patients approached the end of life, neither patients nor caregivers shifted their priorities from life extension to symptom management.

This finding raises concerns because it suggests that many patients hold unrealistic expectations regarding their care and “underscores the need for continuous dialogue and reassessment of care goals throughout the progression of illness,” Dr. Ozdemir said.

“This stability in preferences over time suggests that initial care decisions are deeply ingrained or that there may be a lack of ongoing communication about evolving care needs and possibilities as conditions change,” Ozdemir said.

Yet, it can be hard to define what unrealistic expectations mean, said Olivia Seecof, MD, who wasn’t involved in the study.

“I think people are hopeful that a devastating diagnosis won’t lead to the end of their life and that there will be a treatment or something that will change [their prognosis], and they’ll get better,” said Dr. Seecof, palliative care expert with the Supportive Oncology Program at NYU Langone Health’s Perlmutter Cancer Center in New York City.

Giving patients and caregivers a realistic understanding of the prognosis is important, but “there’s more to it than just telling the patient their diagnosis,” she said.

“We have to plan for end of life, what it can look like,” said Dr. Seecof, adding that “often we don’t do a very good job of talking about that early on in an illness course.”

Overall, though, Dr. Seecof stressed that no two patients or situations are the same, and it’s important to understand what’s important in each scenario. End-of-life care requires “an individual approach because every patient is different, even if they have the same diagnosis as someone else,” she said.

This work was supported by funding from the Singapore Millennium Foundation and the Lien Centre for Palliative Care. Dr. Ozdemir and Dr. Seecof had no relevant disclosures.

A version of this article appeared on Medscape.com.

What’s most important to patients with terminal cancer and their caregivers?

New research found that patients and caregivers both tend to prioritize symptom control over life extension but often preferring a balance. Patients and caregivers, however, are less aligned on decisions about cost containment, with patients more likely to prioritize cost containment.

“Our research has revealed that patients and caregivers generally share similar end-of-life goals,” with a “notable exception” when it comes to costs, first author Semra Ozdemir, PhD, with the Lien Centre for Palliative Care, Duke-NUS Medical School, Singapore, told this news organization.

However, when patients and caregivers have a better understanding of the patient’s prognosis, both may be more inclined to avoid costly life-extending treatments and prioritize symptom management.

In other words, the survey suggests that “knowing the prognosis helps patients and their families set realistic expectations for care and adequately prepare for end-of-life decisions,” said Dr. Ozdemir.

This study was published online in JAMA Network Open.

Patients with advanced cancer often face difficult decisions: Do they opt for treatments that may — or may not — extend life or do they focus more on symptom control?

Family caregivers, who also play an important role in this decision-making process, may have different care goals. Some research suggests that caregivers tend to prioritize treatments that could extend life, whereas patients prioritize symptom management, but it’s less clear how these priorities may change over time and how patients and caregivers may influence each other.

In the current study, the researchers examined goals of care among patients with stage IV solid tumors and caregivers during the last 2 years of life, focusing on life extension vs symptom management and cost containment, as well as how these goals changed over time.

The survey included 210 patient-caregiver pairs, recruited from outpatient clinics at two major cancer centers in Singapore. Patients had a mean age of 63 years, and about half were men. The caregivers had a mean age of 49 years, and almost two third (63%) were women.

Overall, 34% patients and 29% caregivers prioritized symptom management over life extension, whereas 24% patients and 19% caregivers prioritized life extension. Most patients and caregivers preferred balancing the two, with 34%-47% patients and 37%-69% caregivers supporting this approach.

When balancing cost and treatment decisions, however, patients were more likely to prioritize containing costs — 28% vs 17% for caregivers — over extending life — 26% of patients vs 35% of caregivers.

Cost containment tended to be more of a priority for older patients, those with a higher symptom burden, and those with less family caregiver support. For caregivers, cost containment was more of a priority for those who reported that caregiving had a big impact on their finances, those with worse self-esteem related to their caregiving abilities, as well as those caring for older patients.

To better align cost containment priorities between patients and caregivers, it’s essential for families to engage in open and thorough discussions about the allocation of resources, Dr. Ozdemir said.

Although “patients, families, and physicians often avoid discussions about prognosis,” such conversations are essential for setting realistic expectations for care and adequately preparing for end-of-life decisions, Dr. Ozdemir told this news organization.

“These conversations should aim to balance competing interests and create care plans that are mutually acceptable to both patients and caregivers,” she said, adding that “this approach will help in minimizing any potential conflicts and ensure that both parties feel respected and understood in their decision-making process.”

Managing Unrealistic Expectations

As patients approached the end of life, neither patients nor caregivers shifted their priorities from life extension to symptom management.

This finding raises concerns because it suggests that many patients hold unrealistic expectations regarding their care and “underscores the need for continuous dialogue and reassessment of care goals throughout the progression of illness,” Dr. Ozdemir said.

“This stability in preferences over time suggests that initial care decisions are deeply ingrained or that there may be a lack of ongoing communication about evolving care needs and possibilities as conditions change,” Ozdemir said.

Yet, it can be hard to define what unrealistic expectations mean, said Olivia Seecof, MD, who wasn’t involved in the study.

“I think people are hopeful that a devastating diagnosis won’t lead to the end of their life and that there will be a treatment or something that will change [their prognosis], and they’ll get better,” said Dr. Seecof, palliative care expert with the Supportive Oncology Program at NYU Langone Health’s Perlmutter Cancer Center in New York City.

Giving patients and caregivers a realistic understanding of the prognosis is important, but “there’s more to it than just telling the patient their diagnosis,” she said.

“We have to plan for end of life, what it can look like,” said Dr. Seecof, adding that “often we don’t do a very good job of talking about that early on in an illness course.”

Overall, though, Dr. Seecof stressed that no two patients or situations are the same, and it’s important to understand what’s important in each scenario. End-of-life care requires “an individual approach because every patient is different, even if they have the same diagnosis as someone else,” she said.

This work was supported by funding from the Singapore Millennium Foundation and the Lien Centre for Palliative Care. Dr. Ozdemir and Dr. Seecof had no relevant disclosures.

A version of this article appeared on Medscape.com.

Practice Gap

Orodynia (OD)—together with glossodynia colloquially termed “burning mouth syndrome”—is a chronic disorder characterized by a burning sensation within the oral cavity without objective clinical signs. It is most common in perimenopausal and postmenopausal women.^1,2

Orodynia is a diagnosis of exclusion and is considered after 4 to 6 months of normal imaging and laboratory test results.^1,2 Its pathophysiology is poorly understood, as it can be intermittent or continuous, manifest with a variety of symptoms, and affect various entities of the oral cavity.^3,4 The most common structure affected is the tongue, and symptoms may include xerostomia, dysgeusia, and discomfort.^1,2 Orodynia is a frustrating condition, as many patients do not respond to treatment and experience symptoms for years.^1-4

The current approach to management of OD typically involves a combination of psychosocial strategies and pharmacologic agents. The psychosocial component consists of coping mechanisms (eg, stress management techniques and behavioral therapies) aimed at alleviating the psychological impact of the condition. Pharmacologic agents such as antidepressants, anticonvulsants, and topical medications often are prescribed to address neuropathic pain and dry mouth symptoms.^1,2 Additionally, oral rinses, saliva substitutes, and dietary supplements may be recommended to counteract the discomfort associated with xerostomia.^1,2 However, there is no stepwise protocol, leaving these treatments to be trialed in a disorganized manner.²

The Tools

In our unique approach to managing OD, physicians may employ a variety of tools, including autoantibody profiles, noninvasive salivary gland analysis, saliva analysis, patch testing for allergens, and—if deemed necessary—a minor salivary gland biopsy. The use of specific prescription medications is included in the later stages of our approach.

The Technique

First, exclude inflammatory conditions such as geographic tongue, oral lichen planus, autoimmune bullous disorders, and other treatable conditions such as dyspepsia and Sjögren syndrome using the tools described above. Noninvasive modalities should be exhausted first, and dermatologists/clinicians should exercise clinical judgement to determine whether all options should be trialed, including more invasive/costly ones.

If symptoms persist, clinicians may want to obtain a culture for oral candida. If results are positive, candida may be treated quickly with oral fluconazole. If that treatment fails and fissuring is present, advise the patient on treating the tongue; we recommend lightly brushing the tongue once daily with a hydrogen peroxide 3% solution, followed by rinsing. Next, the patient can allow an active probiotic yogurt to sit on the tongue for at least 1 minute to repopulate it with healthy oral bacteria.

If symptoms persist, prescribe gabapentin 100 to 300 mg to be taken at bedtime. Cevimeline 30 mg 3 times daily can be added to treat symptoms of xerostomia. As a last resort, a low daily dose of trifluoperazine 1 to 2 mg may alleviate the dysesthesia of OD. Because this medication is an antipsychotic, there is an increased risk for adverse effects such as tardive dyskinesia; however, given that we recommend using at most one-twentieth of the dose recommended for psychiatric illnesses such as schizophrenia, the risk appears to be minimal.⁵

We have found this protocol to be more structured, and in our practice, it has led to better outcomes than previously described therapeutic interventions.

Practice Implications

As a chronic condition, OD can be frustrating for patients, as many of them have attempted multiple treatments without success. It also may be challenging for dermatologists who are unfamiliar with its management. This approach to OD provides simple step-by-step diagnostic and therapeutic plans for a condition with an often-uncertain etiology and stubborn response to initial treatments. By following this protocol, dermatologists can be confident in their ability to help patients find relief from OD.

Practice Gap

Orodynia (OD)—together with glossodynia colloquially termed “burning mouth syndrome”—is a chronic disorder characterized by a burning sensation within the oral cavity without objective clinical signs. It is most common in perimenopausal and postmenopausal women.^1,2

Orodynia is a diagnosis of exclusion and is considered after 4 to 6 months of normal imaging and laboratory test results.^1,2 Its pathophysiology is poorly understood, as it can be intermittent or continuous, manifest with a variety of symptoms, and affect various entities of the oral cavity.^3,4 The most common structure affected is the tongue, and symptoms may include xerostomia, dysgeusia, and discomfort.^1,2 Orodynia is a frustrating condition, as many patients do not respond to treatment and experience symptoms for years.^1-4

The current approach to management of OD typically involves a combination of psychosocial strategies and pharmacologic agents. The psychosocial component consists of coping mechanisms (eg, stress management techniques and behavioral therapies) aimed at alleviating the psychological impact of the condition. Pharmacologic agents such as antidepressants, anticonvulsants, and topical medications often are prescribed to address neuropathic pain and dry mouth symptoms.^1,2 Additionally, oral rinses, saliva substitutes, and dietary supplements may be recommended to counteract the discomfort associated with xerostomia.^1,2 However, there is no stepwise protocol, leaving these treatments to be trialed in a disorganized manner.²

The Tools

In our unique approach to managing OD, physicians may employ a variety of tools, including autoantibody profiles, noninvasive salivary gland analysis, saliva analysis, patch testing for allergens, and—if deemed necessary—a minor salivary gland biopsy. The use of specific prescription medications is included in the later stages of our approach.

The Technique

First, exclude inflammatory conditions such as geographic tongue, oral lichen planus, autoimmune bullous disorders, and other treatable conditions such as dyspepsia and Sjögren syndrome using the tools described above. Noninvasive modalities should be exhausted first, and dermatologists/clinicians should exercise clinical judgement to determine whether all options should be trialed, including more invasive/costly ones.

If symptoms persist, clinicians may want to obtain a culture for oral candida. If results are positive, candida may be treated quickly with oral fluconazole. If that treatment fails and fissuring is present, advise the patient on treating the tongue; we recommend lightly brushing the tongue once daily with a hydrogen peroxide 3% solution, followed by rinsing. Next, the patient can allow an active probiotic yogurt to sit on the tongue for at least 1 minute to repopulate it with healthy oral bacteria.

If symptoms persist, prescribe gabapentin 100 to 300 mg to be taken at bedtime. Cevimeline 30 mg 3 times daily can be added to treat symptoms of xerostomia. As a last resort, a low daily dose of trifluoperazine 1 to 2 mg may alleviate the dysesthesia of OD. Because this medication is an antipsychotic, there is an increased risk for adverse effects such as tardive dyskinesia; however, given that we recommend using at most one-twentieth of the dose recommended for psychiatric illnesses such as schizophrenia, the risk appears to be minimal.⁵

We have found this protocol to be more structured, and in our practice, it has led to better outcomes than previously described therapeutic interventions.

Practice Implications

As a chronic condition, OD can be frustrating for patients, as many of them have attempted multiple treatments without success. It also may be challenging for dermatologists who are unfamiliar with its management. This approach to OD provides simple step-by-step diagnostic and therapeutic plans for a condition with an often-uncertain etiology and stubborn response to initial treatments. By following this protocol, dermatologists can be confident in their ability to help patients find relief from OD.

Practice Gap

Orodynia (OD)—together with glossodynia colloquially termed “burning mouth syndrome”—is a chronic disorder characterized by a burning sensation within the oral cavity without objective clinical signs. It is most common in perimenopausal and postmenopausal women.^1,2

Orodynia is a diagnosis of exclusion and is considered after 4 to 6 months of normal imaging and laboratory test results.^1,2 Its pathophysiology is poorly understood, as it can be intermittent or continuous, manifest with a variety of symptoms, and affect various entities of the oral cavity.^3,4 The most common structure affected is the tongue, and symptoms may include xerostomia, dysgeusia, and discomfort.^1,2 Orodynia is a frustrating condition, as many patients do not respond to treatment and experience symptoms for years.^1-4

The current approach to management of OD typically involves a combination of psychosocial strategies and pharmacologic agents. The psychosocial component consists of coping mechanisms (eg, stress management techniques and behavioral therapies) aimed at alleviating the psychological impact of the condition. Pharmacologic agents such as antidepressants, anticonvulsants, and topical medications often are prescribed to address neuropathic pain and dry mouth symptoms.^1,2 Additionally, oral rinses, saliva substitutes, and dietary supplements may be recommended to counteract the discomfort associated with xerostomia.^1,2 However, there is no stepwise protocol, leaving these treatments to be trialed in a disorganized manner.²

The Tools

In our unique approach to managing OD, physicians may employ a variety of tools, including autoantibody profiles, noninvasive salivary gland analysis, saliva analysis, patch testing for allergens, and—if deemed necessary—a minor salivary gland biopsy. The use of specific prescription medications is included in the later stages of our approach.

The Technique

First, exclude inflammatory conditions such as geographic tongue, oral lichen planus, autoimmune bullous disorders, and other treatable conditions such as dyspepsia and Sjögren syndrome using the tools described above. Noninvasive modalities should be exhausted first, and dermatologists/clinicians should exercise clinical judgement to determine whether all options should be trialed, including more invasive/costly ones.

If symptoms persist, clinicians may want to obtain a culture for oral candida. If results are positive, candida may be treated quickly with oral fluconazole. If that treatment fails and fissuring is present, advise the patient on treating the tongue; we recommend lightly brushing the tongue once daily with a hydrogen peroxide 3% solution, followed by rinsing. Next, the patient can allow an active probiotic yogurt to sit on the tongue for at least 1 minute to repopulate it with healthy oral bacteria.

If symptoms persist, prescribe gabapentin 100 to 300 mg to be taken at bedtime. Cevimeline 30 mg 3 times daily can be added to treat symptoms of xerostomia. As a last resort, a low daily dose of trifluoperazine 1 to 2 mg may alleviate the dysesthesia of OD. Because this medication is an antipsychotic, there is an increased risk for adverse effects such as tardive dyskinesia; however, given that we recommend using at most one-twentieth of the dose recommended for psychiatric illnesses such as schizophrenia, the risk appears to be minimal.⁵

We have found this protocol to be more structured, and in our practice, it has led to better outcomes than previously described therapeutic interventions.

Practice Implications

As a chronic condition, OD can be frustrating for patients, as many of them have attempted multiple treatments without success. It also may be challenging for dermatologists who are unfamiliar with its management. This approach to OD provides simple step-by-step diagnostic and therapeutic plans for a condition with an often-uncertain etiology and stubborn response to initial treatments. By following this protocol, dermatologists can be confident in their ability to help patients find relief from OD.

Sunscreen is a cornerstone of skin cancer prevention. The first commercial sunscreen was developed nearly 100 years ago,¹ yet questions and concerns about the safety of these essential topical photoprotective agents continue to occupy our minds. This article serves as an update on some of the big sunscreen questions, as informed by the available evidence.

Are sunscreens safe?

The story of sunscreen regulation in the United States is long and dry. The major pain point is that sunscreens are regulated by the US Food and Drug Administration (FDA) as over-the-counter drugs rather than cosmetics (as in Europe).² Regulatory hurdles created a situation wherein no new active sunscreen ingredient has been approved by the FDA since 1999, except ecamsule for use in one product line. There is hope that changes enacted under the CARES Act will streamline and expedite the sunscreen approval process in the future.³

Amid the ongoing regulatory slog, the FDA became interested in learning more about sunscreen safety. Specifically, they sought to determine the GRASE (generally regarded as safe and effective) status of the active ingredients in sunscreens. In 2019, only the inorganic (physical/mineral) UV filters zinc oxide and titanium dioxide were considered GRASE.⁴ Trolamine salicylate and para-aminobenzoic acid were not GRASE, but they currently are not used in sunscreens in the United States. For all the remaining organic (chemical) filters, additional safety data were required to establish GRASE status.⁴ In 2024, the situation remains largely unchanged. Industry is working with the FDA on testing requirements.⁵

Why the focus on safety? After all, sunscreens have been used widely for decades without any major safety signals; their only well-established adverse effects are contact dermatitis and staining of clothing.⁶ Although preclinical studies raised concerns that chemical sunscreens could be associated with endocrine, reproductive, and neurologic toxicities, to date there are no high-quality human studies demonstrating negative effects.^7,8

However, exposure patterns have evolved. Sunscreen is recommended to be applied (and reapplied) daily. Also, chemical UV filters are used in many nonsunscreen products such as cosmetics, shampoos, fragrances, and plastics. In the United States, exposure to chemical sunscreens is ubiquitous; according to data from the National Health and Nutrition Examination Survey 2003-2004, oxybenzone was detected in 97% of more than 2500 urine samples, implying systemic absorption but not harm.⁹

The FDA confirmed the implication of systemic absorption via 2 maximal usage trials published in 2019 and 2020.^10,11 In both studies, several chemical sunscreens were applied at the recommended density of 2 mg/cm² to 75% of the body surface area multiple times over 4 days. For all tested organic UV filters, blood levels exceeded the predetermined FDA cutoff (0.5 ng/mL), even after one application.^10,11 What’s the takeaway? Simply that the FDA now requires additional safety data for chemical sunscreen filters⁵; the findings in no way imply any associated harm. Two potential mitigating factors are that no one applies sunscreen at 2 mg/cm², and the FDA’s blood level cutoff was a general estimate not specific to sunscreens.^4,12

Nevertheless, a good long-term safety record for sunscreens does not negate the need for enhanced safety data when there is clear evidence of systemic absorption. In the meantime, concerned patients should be counseled that the physical/mineral sunscreens containing zinc oxide and titanium dioxide are considered GRASE by the FDA; even in nanoparticle form, they generally have not been found to penetrate beneath the stratum corneum.^7,13

Dermatologists are confronting the conundrum of rising cases of frontal fibrosing alopecia (FFA). Several theories on the pathogenesis of this idiopathic scarring alopecia have been raised, one of which involves increased use of sunscreen. Proposed explanations for sunscreen’s role in FFA include a lichenoid reaction inducing hair follicle autoimmunity through an unclear mechanism; a T cell–mediated allergic reaction, which is unlikely according to contact dermatitis experts¹⁴; reactive oxygen species production by titanium nanoparticles, yet titanium has been detected in hair follicles of both patients with FFA and controls¹⁵; and endocrine disruption following systemic absorption, which has not been supported by any high-quality human studies.⁷

An association between facial sunscreen use and FFA has been reported in case-control studies¹⁶; however, they have been criticized due to methodologic issues and biases, and they provide no evidence of causality.^17,18 The jury remains out on the controversial association between sunscreen and FFA, with a need for more convincing data.

Does sunscreen impact coral reef health?

Coral reefs—crucial sources of aquatic biodiversity—are under attack from several different directions including climate change and pollution. As much as 14,000 tons of sunscreen enter coral reefs each year, and chemical sunscreen filters are detectable in waterways throughout the world—even in the Arctic.^19,20 Thus, sunscreen has come under scrutiny as a potential environmental threat, particularly with coral bleaching.

Bleaching is a process in which corals exposed to an environmental stressor expel their symbiotic photosynthetic algae and turn white; if conditions fail to improve, the corals are vulnerable to death. In a highly cited 2016 study, coral larvae exposed to oxybenzone in artificial laboratory conditions displayed concentration-dependent mortality and decreased chlorophyll fluorescence, which suggested bleaching.¹⁹ These findings influenced legislation in Hawaii and other localities banning sunscreens containing oxybenzone. Problematically, the study has been criticized for acutely exposing the most susceptible coral life-forms to unrealistic oxybenzone concentrations; more broadly, there is no standardized approach to coral toxicity testing.²¹

The bigger picture (and elephant in the room) is that the primary cause of coral bleaching is undoubtedly climate change/ocean warming.⁷ More recent studies suggest that oxybenzone probably adds insult to injury for corals already debilitated by ocean warming.^22,23

It has been posited that a narrow focus on sunscreens detracts attention from the climate issue.²⁴ Individuals can take a number of actions to reduce their carbon footprint in an effort to preserve our environment, specifically coral reefs.²⁵ Concerned patients should be counseled to use sunscreens containing the physical/mineral UV filters zinc oxide and titanium dioxide, which are unlikely to contribute to coral bleaching as commercially formulated.⁷

Ongoing Questions

A lot of unknowns about sunscreen safety remain, and much hubbub has been made over studies that often are preliminary at best. At the time of this writing, absent a crystal ball, this author continues to wear chemical sunscreens; spends a lot more time worrying about their carbon footprint than what type of sunscreen to use at the beach; and believes the association of FFA with sunscreen is unlikely to be causal. Hopefully much-needed rigorous evidence will guide our future approach to sunscreen formulation and use.

Sunscreen is a cornerstone of skin cancer prevention. The first commercial sunscreen was developed nearly 100 years ago,¹ yet questions and concerns about the safety of these essential topical photoprotective agents continue to occupy our minds. This article serves as an update on some of the big sunscreen questions, as informed by the available evidence.

Are sunscreens safe?

The story of sunscreen regulation in the United States is long and dry. The major pain point is that sunscreens are regulated by the US Food and Drug Administration (FDA) as over-the-counter drugs rather than cosmetics (as in Europe).² Regulatory hurdles created a situation wherein no new active sunscreen ingredient has been approved by the FDA since 1999, except ecamsule for use in one product line. There is hope that changes enacted under the CARES Act will streamline and expedite the sunscreen approval process in the future.³

Amid the ongoing regulatory slog, the FDA became interested in learning more about sunscreen safety. Specifically, they sought to determine the GRASE (generally regarded as safe and effective) status of the active ingredients in sunscreens. In 2019, only the inorganic (physical/mineral) UV filters zinc oxide and titanium dioxide were considered GRASE.⁴ Trolamine salicylate and para-aminobenzoic acid were not GRASE, but they currently are not used in sunscreens in the United States. For all the remaining organic (chemical) filters, additional safety data were required to establish GRASE status.⁴ In 2024, the situation remains largely unchanged. Industry is working with the FDA on testing requirements.⁵

Why the focus on safety? After all, sunscreens have been used widely for decades without any major safety signals; their only well-established adverse effects are contact dermatitis and staining of clothing.⁶ Although preclinical studies raised concerns that chemical sunscreens could be associated with endocrine, reproductive, and neurologic toxicities, to date there are no high-quality human studies demonstrating negative effects.^7,8

However, exposure patterns have evolved. Sunscreen is recommended to be applied (and reapplied) daily. Also, chemical UV filters are used in many nonsunscreen products such as cosmetics, shampoos, fragrances, and plastics. In the United States, exposure to chemical sunscreens is ubiquitous; according to data from the National Health and Nutrition Examination Survey 2003-2004, oxybenzone was detected in 97% of more than 2500 urine samples, implying systemic absorption but not harm.⁹

The FDA confirmed the implication of systemic absorption via 2 maximal usage trials published in 2019 and 2020.^10,11 In both studies, several chemical sunscreens were applied at the recommended density of 2 mg/cm² to 75% of the body surface area multiple times over 4 days. For all tested organic UV filters, blood levels exceeded the predetermined FDA cutoff (0.5 ng/mL), even after one application.^10,11 What’s the takeaway? Simply that the FDA now requires additional safety data for chemical sunscreen filters⁵; the findings in no way imply any associated harm. Two potential mitigating factors are that no one applies sunscreen at 2 mg/cm², and the FDA’s blood level cutoff was a general estimate not specific to sunscreens.^4,12

Nevertheless, a good long-term safety record for sunscreens does not negate the need for enhanced safety data when there is clear evidence of systemic absorption. In the meantime, concerned patients should be counseled that the physical/mineral sunscreens containing zinc oxide and titanium dioxide are considered GRASE by the FDA; even in nanoparticle form, they generally have not been found to penetrate beneath the stratum corneum.^7,13

Dermatologists are confronting the conundrum of rising cases of frontal fibrosing alopecia (FFA). Several theories on the pathogenesis of this idiopathic scarring alopecia have been raised, one of which involves increased use of sunscreen. Proposed explanations for sunscreen’s role in FFA include a lichenoid reaction inducing hair follicle autoimmunity through an unclear mechanism; a T cell–mediated allergic reaction, which is unlikely according to contact dermatitis experts¹⁴; reactive oxygen species production by titanium nanoparticles, yet titanium has been detected in hair follicles of both patients with FFA and controls¹⁵; and endocrine disruption following systemic absorption, which has not been supported by any high-quality human studies.⁷

An association between facial sunscreen use and FFA has been reported in case-control studies¹⁶; however, they have been criticized due to methodologic issues and biases, and they provide no evidence of causality.^17,18 The jury remains out on the controversial association between sunscreen and FFA, with a need for more convincing data.

Does sunscreen impact coral reef health?

Coral reefs—crucial sources of aquatic biodiversity—are under attack from several different directions including climate change and pollution. As much as 14,000 tons of sunscreen enter coral reefs each year, and chemical sunscreen filters are detectable in waterways throughout the world—even in the Arctic.^19,20 Thus, sunscreen has come under scrutiny as a potential environmental threat, particularly with coral bleaching.

Bleaching is a process in which corals exposed to an environmental stressor expel their symbiotic photosynthetic algae and turn white; if conditions fail to improve, the corals are vulnerable to death. In a highly cited 2016 study, coral larvae exposed to oxybenzone in artificial laboratory conditions displayed concentration-dependent mortality and decreased chlorophyll fluorescence, which suggested bleaching.¹⁹ These findings influenced legislation in Hawaii and other localities banning sunscreens containing oxybenzone. Problematically, the study has been criticized for acutely exposing the most susceptible coral life-forms to unrealistic oxybenzone concentrations; more broadly, there is no standardized approach to coral toxicity testing.²¹

The bigger picture (and elephant in the room) is that the primary cause of coral bleaching is undoubtedly climate change/ocean warming.⁷ More recent studies suggest that oxybenzone probably adds insult to injury for corals already debilitated by ocean warming.^22,23

It has been posited that a narrow focus on sunscreens detracts attention from the climate issue.²⁴ Individuals can take a number of actions to reduce their carbon footprint in an effort to preserve our environment, specifically coral reefs.²⁵ Concerned patients should be counseled to use sunscreens containing the physical/mineral UV filters zinc oxide and titanium dioxide, which are unlikely to contribute to coral bleaching as commercially formulated.⁷

Ongoing Questions

A lot of unknowns about sunscreen safety remain, and much hubbub has been made over studies that often are preliminary at best. At the time of this writing, absent a crystal ball, this author continues to wear chemical sunscreens; spends a lot more time worrying about their carbon footprint than what type of sunscreen to use at the beach; and believes the association of FFA with sunscreen is unlikely to be causal. Hopefully much-needed rigorous evidence will guide our future approach to sunscreen formulation and use.

Sunscreen is a cornerstone of skin cancer prevention. The first commercial sunscreen was developed nearly 100 years ago,¹ yet questions and concerns about the safety of these essential topical photoprotective agents continue to occupy our minds. This article serves as an update on some of the big sunscreen questions, as informed by the available evidence.

Are sunscreens safe?

The story of sunscreen regulation in the United States is long and dry. The major pain point is that sunscreens are regulated by the US Food and Drug Administration (FDA) as over-the-counter drugs rather than cosmetics (as in Europe).² Regulatory hurdles created a situation wherein no new active sunscreen ingredient has been approved by the FDA since 1999, except ecamsule for use in one product line. There is hope that changes enacted under the CARES Act will streamline and expedite the sunscreen approval process in the future.³

Amid the ongoing regulatory slog, the FDA became interested in learning more about sunscreen safety. Specifically, they sought to determine the GRASE (generally regarded as safe and effective) status of the active ingredients in sunscreens. In 2019, only the inorganic (physical/mineral) UV filters zinc oxide and titanium dioxide were considered GRASE.⁴ Trolamine salicylate and para-aminobenzoic acid were not GRASE, but they currently are not used in sunscreens in the United States. For all the remaining organic (chemical) filters, additional safety data were required to establish GRASE status.⁴ In 2024, the situation remains largely unchanged. Industry is working with the FDA on testing requirements.⁵

Why the focus on safety? After all, sunscreens have been used widely for decades without any major safety signals; their only well-established adverse effects are contact dermatitis and staining of clothing.⁶ Although preclinical studies raised concerns that chemical sunscreens could be associated with endocrine, reproductive, and neurologic toxicities, to date there are no high-quality human studies demonstrating negative effects.^7,8

However, exposure patterns have evolved. Sunscreen is recommended to be applied (and reapplied) daily. Also, chemical UV filters are used in many nonsunscreen products such as cosmetics, shampoos, fragrances, and plastics. In the United States, exposure to chemical sunscreens is ubiquitous; according to data from the National Health and Nutrition Examination Survey 2003-2004, oxybenzone was detected in 97% of more than 2500 urine samples, implying systemic absorption but not harm.⁹

The FDA confirmed the implication of systemic absorption via 2 maximal usage trials published in 2019 and 2020.^10,11 In both studies, several chemical sunscreens were applied at the recommended density of 2 mg/cm² to 75% of the body surface area multiple times over 4 days. For all tested organic UV filters, blood levels exceeded the predetermined FDA cutoff (0.5 ng/mL), even after one application.^10,11 What’s the takeaway? Simply that the FDA now requires additional safety data for chemical sunscreen filters⁵; the findings in no way imply any associated harm. Two potential mitigating factors are that no one applies sunscreen at 2 mg/cm², and the FDA’s blood level cutoff was a general estimate not specific to sunscreens.^4,12

Nevertheless, a good long-term safety record for sunscreens does not negate the need for enhanced safety data when there is clear evidence of systemic absorption. In the meantime, concerned patients should be counseled that the physical/mineral sunscreens containing zinc oxide and titanium dioxide are considered GRASE by the FDA; even in nanoparticle form, they generally have not been found to penetrate beneath the stratum corneum.^7,13

Dermatologists are confronting the conundrum of rising cases of frontal fibrosing alopecia (FFA). Several theories on the pathogenesis of this idiopathic scarring alopecia have been raised, one of which involves increased use of sunscreen. Proposed explanations for sunscreen’s role in FFA include a lichenoid reaction inducing hair follicle autoimmunity through an unclear mechanism; a T cell–mediated allergic reaction, which is unlikely according to contact dermatitis experts¹⁴; reactive oxygen species production by titanium nanoparticles, yet titanium has been detected in hair follicles of both patients with FFA and controls¹⁵; and endocrine disruption following systemic absorption, which has not been supported by any high-quality human studies.⁷

An association between facial sunscreen use and FFA has been reported in case-control studies¹⁶; however, they have been criticized due to methodologic issues and biases, and they provide no evidence of causality.^17,18 The jury remains out on the controversial association between sunscreen and FFA, with a need for more convincing data.

Does sunscreen impact coral reef health?

Coral reefs—crucial sources of aquatic biodiversity—are under attack from several different directions including climate change and pollution. As much as 14,000 tons of sunscreen enter coral reefs each year, and chemical sunscreen filters are detectable in waterways throughout the world—even in the Arctic.^19,20 Thus, sunscreen has come under scrutiny as a potential environmental threat, particularly with coral bleaching.

Bleaching is a process in which corals exposed to an environmental stressor expel their symbiotic photosynthetic algae and turn white; if conditions fail to improve, the corals are vulnerable to death. In a highly cited 2016 study, coral larvae exposed to oxybenzone in artificial laboratory conditions displayed concentration-dependent mortality and decreased chlorophyll fluorescence, which suggested bleaching.¹⁹ These findings influenced legislation in Hawaii and other localities banning sunscreens containing oxybenzone. Problematically, the study has been criticized for acutely exposing the most susceptible coral life-forms to unrealistic oxybenzone concentrations; more broadly, there is no standardized approach to coral toxicity testing.²¹

The bigger picture (and elephant in the room) is that the primary cause of coral bleaching is undoubtedly climate change/ocean warming.⁷ More recent studies suggest that oxybenzone probably adds insult to injury for corals already debilitated by ocean warming.^22,23

It has been posited that a narrow focus on sunscreens detracts attention from the climate issue.²⁴ Individuals can take a number of actions to reduce their carbon footprint in an effort to preserve our environment, specifically coral reefs.²⁵ Concerned patients should be counseled to use sunscreens containing the physical/mineral UV filters zinc oxide and titanium dioxide, which are unlikely to contribute to coral bleaching as commercially formulated.⁷

Ongoing Questions

A lot of unknowns about sunscreen safety remain, and much hubbub has been made over studies that often are preliminary at best. At the time of this writing, absent a crystal ball, this author continues to wear chemical sunscreens; spends a lot more time worrying about their carbon footprint than what type of sunscreen to use at the beach; and believes the association of FFA with sunscreen is unlikely to be causal. Hopefully much-needed rigorous evidence will guide our future approach to sunscreen formulation and use.

A contentious scientific debate is clouding prospects for a deeper understanding of the microbiome’s role in cancer, a relatively young field of research that some believe could lead to breakthroughs in the diagnosis and treatment of the second-leading cause of death in the United States. 

Last year, the controversy heightened when experts questioned a high-profile study — a 2020 analysis claiming that the tumors of 33 different cancers had their own unique microbiomes — on whether the “signature” of these bacterial compositions could help diagnose cancer.

The incident renewed the spotlight on “tumor microbiomes” because of the bold claims of the original paper and the strongly worded refutations of those claims. The broader field has focused primarily on ways the body’s microbiome interacts with cancers and cancer treatment.

This controversy has highlighted the challenges of making headway in a field where researchers may not even have the tools yet to puzzle-out the wide-ranging implications the microbiome holds for cancer diagnosis and treatment.

But it is also part of a provocative question within that larger field: whether tumors in the body, far from the natural microbiome in the gut, have their own thriving communities of bacteria, viruses, and fungi. And, if they do, how do those tumor microbiomes affect the development and progression of the cancer and the effectiveness of cancer therapies? 
 

Cancer Controversy

The evidence is undeniable that some microbes can directly cause certain cancers and that the human gut microbiome can influence the effectiveness of certain therapies. Beyond that established science, however, the research has raised as many questions as answers about what we do and don’t know about microbiota and cancer.

The only confirmed microbiomes are on the skin and in the gut, mouth, and vagina, which are all areas with an easy direct route for bacteria to enter and grow in or on the body. A series of papers in recent years have suggested that other internal organs, and tumors within them, may have their own microbiomes. 

“Whether microbes exist in tumors of internal organs beyond body surfaces exposed to the environment is a different matter,” said Ivan Vujkovic-Cvijin, PhD, an assistant professor of biomedical sciences and gastroenterology at Cedars-Sinai Medical Center in Los Angeles, whose lab studies how human gut microbes affect inflammatory diseases. “We’ve only recently had the tools to study that question on a molecular level, and the reported results have been conflicting.” 

For example, research allegedly identified microbiota in the human placenta nearly one decade ago. But subsequent research contradicted those claims and showed that the source of the “placental microbiome” was actually contamination. Subsequent similar studies for other parts of the body faced the same scrutiny and, often, eventual debunking.

“Most likely, our immune system has undergone selective pressure to eliminate everything that crosses the gut barrier because there’s not much benefit to the body to have bacteria run amok in our internal organs,” Dr. Vujkovic-Cvijin said. “That can only disrupt the functioning of our tissues, to have an external organism living inside them.” 

The controversy that erupted last summer, surrounding research from the lab of Rob Knight, PhD, at the University of California, San Diego, centered on a slightly different but related question: Could tumors harbor their own microbiomes?

This news organization spoke with two of the authors who published a paper contesting Dr. Knight’s findings: Steven Salzberg, PhD, a professor of biomedical engineering at John Hopkins Medicine, Baltimore, Maryland, and Abraham Gihawi, PhD, a research fellow at Norwich Medical School at the University of East Anglia in the United Kingdom. 

Dr. Salzberg described two major problems with Dr. Knight’s study. 

“What they found were false positives because of contamination in the database and flaws in their methods,” Dr. Salzberg said. “I can’t prove there’s no cancer microbiome, but I can say the cancer microbiomes that they reported don’t exist because the species they were finding aren’t there.”

Dr. Knight disagrees with Dr. Salzberg’s findings, noting that Dr. Salzberg and his co-authors did not examine the publicly available databases used in his study. In a written response, he said that his team’s examination of the database revealed that less than 1% of the microbial genomes overlapped with human ones and that removing them did not change their findings.

Dr. Knight also noted that his team could still “distinguish cancer types by their microbiome” even after running their analysis without the technique that Dr. Salzberg found fault with.

Dr. Salzberg said that the database linked above is not the one Dr. Knight’s study used, however. “The primary database in their study was never made public (it’s too large, they said), and it has/had about 69,000 genomes,” Dr. Salzberg said by email. “But even if we did, this is irrelevant. He’s trying to distract from the primary errors in their study,” which Dr. Salzberg said Dr. Knight’s team has not addressed. 

The critiques Dr. Salzberg raised have been leveled at other studies investigating microbiomes specifically within tumors and independent of the body’s microbiome.

For example, a 2019 study in Nature described a fungal microbiome in pancreatic cancer that a Nature paper 4 years later directly contradicted, citing flaws that invalidated the original findings. A different 2019 study in Cell examined pancreatic tumor microbiota and patient outcomes, but it’s unclear whether the microorganisms moved from the gut to the pancreas or “constitute a durably colonized community that lives inside the tumor,” which remains a matter of debate, Dr. Vujkovic-Cvijin said.

A 2020 study in Science suggested diverse microbial communities in seven tumor types, but those findings were similarly called into question. That study stated that “bacteria were first detected in human tumors more than 100 years ago” and that “bacteria are well-known residents in human tumors,” but Dr. Salzberg considers those statements misleading. 

It’s true that bacteria and viruses have been detected in tumors because “there’s very good evidence that an acute infection caused by a very small number of viruses and bacteria can cause a tumor,” Dr. Salzberg said. Human papillomavirus, for example, can cause six different types of cancer. Inflammation and ulcers caused by Helicobacter pylori may progress to stomach cancer, and Fusobacterium nucleatum and Enterococcus faecalis have been shown to contribute to colorectal cancer. Those examples differ from a microbiome; this “a community of bacteria and possibly other microscopic bugs, like fungi, that are happily living in the tumor” the same way microbes reside in our guts, he said.

Dr. Knight said that many bacteria his team identified “have been confirmed independently in subsequent work.” He acknowledged, however, that more research is needed. 

Several of the contested studies above were among a lengthy list that Dr. Knight provided, noting that most of the disagreements “have two sides to them, and critiques from one particular group does not immediately invalidate a reported finding.” 

Yet, many of the papers Dr. Knight listed are precisely the types that skeptics like Dr. Salzberg believe are too flawed to draw reliable conclusions. 

“I think many agree that microbes may exist within tumors that are exposed to the environment, like tumors of the skin, gut, and mouth,” Dr. Vujkovic-Cvijin said. It’s less clear, however, whether tumors further from the body’s microbiome harbor any microbes or where they came from if they do. Microbial signals in organs elsewhere in the body become faint quickly, he said.
 

Underdeveloped Technology 

Though Dr. Salzberg said that the concept of a tumor microbiome is “implausible” because there’s no easy route for bacteria to reach internal organs, it’s unclear whether scientists have the technology yet to adequately answer this question. 

For one thing, samples in these types of studies are typically “ultra-low biomass samples, where the signal — the amount of microbes in the sample — is so low that it’s comparable to how much would be expected to be found in reagents and environmental contamination through processing,” Dr. Vujkovic-Cvijin explained. Many polymerases used to amplify a DNA signal, for example, are made in bacteria and may retain trace amounts identified in these studies. 

Dr. Knight agreed that low biomass is a challenge in this field but is not an unsurmountable one. 

Another challenge is that study samples, as with Dr. Knight’s work, were collected during routine surgeries without the intent to find a microbial signal. Simply using a scalpel to cut through the skin means cutting through a layer of bacteria, and surgery rooms are not designed to eliminate all bacteria. Some work has even shown there is a “hospital microbiome,” so “you can easily have that creep into your signal and mistake it for tumor-resident bacteria,” Dr. Vujkovic-Cvijin said. 

Dr. Knight asserted that the samples are taken under sterile conditions, but other researchers do not think the level of sterility necessary for completely clean samples is possible. 

“Just because it’s in your sample doesn’t mean it was in your tumor,” Dr. Gihawi said.

Even if scientists can retrieve a reliable sample without contamination, analyzing it requires comparing the genetic material to existing databases of microbial genomes. Yet, contamination and misclassification of genetic sequences can be problems in those reference genomes too, Dr. Gihawi explained.

Machine learning algorithms have a role in interpreting data, but “we need to be careful of what we use them for,” he added.

“These techniques are in their infancy, and we’re starting to chase them down, which is why we need to move microbiome research in a way that can be used clinically,” Dr. Gihawi said. 
 

Influence on Cancer Treatment Outcomes

Again, however, the question of whether microbiomes exist within tumors is only one slice of the much larger field looking at microbiomes and cancer, including its influence on cancer treatment outcomes. Although much remains to be learned, less controversy exists over the thousands of studies in the past two decades that have gradually revealed how the body’s microbiome can affect both the course of a cancer and the effectiveness of different treatments.

The growing research showing the importance of the gut microbiome in cancer treatments is not surprising given its role in immunity more broadly. Because the human immune system must recognize and defend against microbes, the microbiome helps train it, Dr. Vujkovic-Cvijin said. 

Some bacteria can escape the gut — a phenomenon called bacterial translocation — and may aid in fighting tumors. To grow large enough to be seen on imaging, tumors need to evolve several abilities, such as growing enough vascularization to receive blood flow and shutting down local immune responses.

“Any added boost, like immunotherapy, has a chance of breaking through that immune forcefield and killing the tumor cells,” Dr. Vujkovic-Cvijin said. Escaped gut bacteria may provide that boost. 

“There’s a lot of evidence that depletion of the gut microbiome impairs immunotherapy and chemotherapy. The thinking behind some of those studies is that gut microbes can cross the gut barrier and when they do, they activate the immune system,” he said. 

In mice engineered to have sterile guts, for example, the lack of bacteria results in less effective immune systems, Dr. Vujkovic-Cvijin pointed out. A host of research has shown that antibiotic exposure during and even 6 months before immunotherapy dramatically reduces survival rates. “That’s pretty convincing to me that gut microbes are important,” he said. 

Dr. Vujkovic-Cvijin cautioned that there continues to be controversy on understanding which bacteria are important for response to immunotherapy. “The field is still in its infancy in terms of understanding which bacteria are most important for these effects,” he said.

Dr. Knight suggested that escaped bacteria may be the genesis of the ones that he and other researchers believe exist in tumors. “Because tumor microbes must come from somewhere, it is to be expected that some of those microbes will be co-opted from body-site specific commensals.”

It’s also possible that metabolites released from gut bacteria escape the gut and could theoretically affect distant tumor growth, Dr. Gihawi said. The most promising avenue of research in this area is metabolites being used as biomarkers, added Dr. Gihawi, whose lab published research on a link between bacteria detected in men’s urine and a more aggressive subset of prostate cancers. But that research is not far enough along to develop lab tests for clinical use, he noted. 
 

No Consensus Yet

Even before the controversy erupted around Dr. Knight’s research, he co-founded the company Micronoma to develop cancer tests based on his microbe findings. The company has raised $17.5 million from private investors as of August 2023 and received the US Food and Drug Administration’s Breakthrough Device designation, allowing the firm to fast-track clinical trials testing the technology. The recent critiques have not changed the company’s plans. 

It’s safe to say that scientists will continue to research and debate the possibility of tumor microbiomes until a consensus emerges. 

“The field is evolving and studies testing the reproducibility of tumor-resident microbial signals are essential for developing our understanding in this area,” Dr. Vujkovic-Cvijin said.

Even if that path ultimately leads nowhere, as Dr. Salzberg expects, research into microbiomes and cancer has plenty of other directions to go.

“I’m actually quite an optimist,” Dr. Gihawi said. “I think there’s a lot of scope for some really good research here, especially in the sites where we know there is a strong microbiome, such as the gastrointestinal tract.”

A version of this article appeared on Medscape.com.

A contentious scientific debate is clouding prospects for a deeper understanding of the microbiome’s role in cancer, a relatively young field of research that some believe could lead to breakthroughs in the diagnosis and treatment of the second-leading cause of death in the United States. 

Last year, the controversy heightened when experts questioned a high-profile study — a 2020 analysis claiming that the tumors of 33 different cancers had their own unique microbiomes — on whether the “signature” of these bacterial compositions could help diagnose cancer.

The incident renewed the spotlight on “tumor microbiomes” because of the bold claims of the original paper and the strongly worded refutations of those claims. The broader field has focused primarily on ways the body’s microbiome interacts with cancers and cancer treatment.

This controversy has highlighted the challenges of making headway in a field where researchers may not even have the tools yet to puzzle-out the wide-ranging implications the microbiome holds for cancer diagnosis and treatment.

But it is also part of a provocative question within that larger field: whether tumors in the body, far from the natural microbiome in the gut, have their own thriving communities of bacteria, viruses, and fungi. And, if they do, how do those tumor microbiomes affect the development and progression of the cancer and the effectiveness of cancer therapies? 
 

Cancer Controversy

The evidence is undeniable that some microbes can directly cause certain cancers and that the human gut microbiome can influence the effectiveness of certain therapies. Beyond that established science, however, the research has raised as many questions as answers about what we do and don’t know about microbiota and cancer.

The only confirmed microbiomes are on the skin and in the gut, mouth, and vagina, which are all areas with an easy direct route for bacteria to enter and grow in or on the body. A series of papers in recent years have suggested that other internal organs, and tumors within them, may have their own microbiomes. 

“Whether microbes exist in tumors of internal organs beyond body surfaces exposed to the environment is a different matter,” said Ivan Vujkovic-Cvijin, PhD, an assistant professor of biomedical sciences and gastroenterology at Cedars-Sinai Medical Center in Los Angeles, whose lab studies how human gut microbes affect inflammatory diseases. “We’ve only recently had the tools to study that question on a molecular level, and the reported results have been conflicting.” 

For example, research allegedly identified microbiota in the human placenta nearly one decade ago. But subsequent research contradicted those claims and showed that the source of the “placental microbiome” was actually contamination. Subsequent similar studies for other parts of the body faced the same scrutiny and, often, eventual debunking.

“Most likely, our immune system has undergone selective pressure to eliminate everything that crosses the gut barrier because there’s not much benefit to the body to have bacteria run amok in our internal organs,” Dr. Vujkovic-Cvijin said. “That can only disrupt the functioning of our tissues, to have an external organism living inside them.” 

The controversy that erupted last summer, surrounding research from the lab of Rob Knight, PhD, at the University of California, San Diego, centered on a slightly different but related question: Could tumors harbor their own microbiomes?

This news organization spoke with two of the authors who published a paper contesting Dr. Knight’s findings: Steven Salzberg, PhD, a professor of biomedical engineering at John Hopkins Medicine, Baltimore, Maryland, and Abraham Gihawi, PhD, a research fellow at Norwich Medical School at the University of East Anglia in the United Kingdom. 

Dr. Salzberg described two major problems with Dr. Knight’s study. 

“What they found were false positives because of contamination in the database and flaws in their methods,” Dr. Salzberg said. “I can’t prove there’s no cancer microbiome, but I can say the cancer microbiomes that they reported don’t exist because the species they were finding aren’t there.”

Dr. Knight disagrees with Dr. Salzberg’s findings, noting that Dr. Salzberg and his co-authors did not examine the publicly available databases used in his study. In a written response, he said that his team’s examination of the database revealed that less than 1% of the microbial genomes overlapped with human ones and that removing them did not change their findings.

Dr. Knight also noted that his team could still “distinguish cancer types by their microbiome” even after running their analysis without the technique that Dr. Salzberg found fault with.

Dr. Salzberg said that the database linked above is not the one Dr. Knight’s study used, however. “The primary database in their study was never made public (it’s too large, they said), and it has/had about 69,000 genomes,” Dr. Salzberg said by email. “But even if we did, this is irrelevant. He’s trying to distract from the primary errors in their study,” which Dr. Salzberg said Dr. Knight’s team has not addressed. 

The critiques Dr. Salzberg raised have been leveled at other studies investigating microbiomes specifically within tumors and independent of the body’s microbiome.

For example, a 2019 study in Nature described a fungal microbiome in pancreatic cancer that a Nature paper 4 years later directly contradicted, citing flaws that invalidated the original findings. A different 2019 study in Cell examined pancreatic tumor microbiota and patient outcomes, but it’s unclear whether the microorganisms moved from the gut to the pancreas or “constitute a durably colonized community that lives inside the tumor,” which remains a matter of debate, Dr. Vujkovic-Cvijin said.

A 2020 study in Science suggested diverse microbial communities in seven tumor types, but those findings were similarly called into question. That study stated that “bacteria were first detected in human tumors more than 100 years ago” and that “bacteria are well-known residents in human tumors,” but Dr. Salzberg considers those statements misleading. 

It’s true that bacteria and viruses have been detected in tumors because “there’s very good evidence that an acute infection caused by a very small number of viruses and bacteria can cause a tumor,” Dr. Salzberg said. Human papillomavirus, for example, can cause six different types of cancer. Inflammation and ulcers caused by Helicobacter pylori may progress to stomach cancer, and Fusobacterium nucleatum and Enterococcus faecalis have been shown to contribute to colorectal cancer. Those examples differ from a microbiome; this “a community of bacteria and possibly other microscopic bugs, like fungi, that are happily living in the tumor” the same way microbes reside in our guts, he said.

Dr. Knight said that many bacteria his team identified “have been confirmed independently in subsequent work.” He acknowledged, however, that more research is needed. 

Several of the contested studies above were among a lengthy list that Dr. Knight provided, noting that most of the disagreements “have two sides to them, and critiques from one particular group does not immediately invalidate a reported finding.” 

Yet, many of the papers Dr. Knight listed are precisely the types that skeptics like Dr. Salzberg believe are too flawed to draw reliable conclusions. 

“I think many agree that microbes may exist within tumors that are exposed to the environment, like tumors of the skin, gut, and mouth,” Dr. Vujkovic-Cvijin said. It’s less clear, however, whether tumors further from the body’s microbiome harbor any microbes or where they came from if they do. Microbial signals in organs elsewhere in the body become faint quickly, he said.
 

Underdeveloped Technology 

Though Dr. Salzberg said that the concept of a tumor microbiome is “implausible” because there’s no easy route for bacteria to reach internal organs, it’s unclear whether scientists have the technology yet to adequately answer this question. 

For one thing, samples in these types of studies are typically “ultra-low biomass samples, where the signal — the amount of microbes in the sample — is so low that it’s comparable to how much would be expected to be found in reagents and environmental contamination through processing,” Dr. Vujkovic-Cvijin explained. Many polymerases used to amplify a DNA signal, for example, are made in bacteria and may retain trace amounts identified in these studies. 

Dr. Knight agreed that low biomass is a challenge in this field but is not an unsurmountable one. 

Another challenge is that study samples, as with Dr. Knight’s work, were collected during routine surgeries without the intent to find a microbial signal. Simply using a scalpel to cut through the skin means cutting through a layer of bacteria, and surgery rooms are not designed to eliminate all bacteria. Some work has even shown there is a “hospital microbiome,” so “you can easily have that creep into your signal and mistake it for tumor-resident bacteria,” Dr. Vujkovic-Cvijin said. 

Dr. Knight asserted that the samples are taken under sterile conditions, but other researchers do not think the level of sterility necessary for completely clean samples is possible. 

“Just because it’s in your sample doesn’t mean it was in your tumor,” Dr. Gihawi said.

Even if scientists can retrieve a reliable sample without contamination, analyzing it requires comparing the genetic material to existing databases of microbial genomes. Yet, contamination and misclassification of genetic sequences can be problems in those reference genomes too, Dr. Gihawi explained.

Machine learning algorithms have a role in interpreting data, but “we need to be careful of what we use them for,” he added.

“These techniques are in their infancy, and we’re starting to chase them down, which is why we need to move microbiome research in a way that can be used clinically,” Dr. Gihawi said. 
 

Influence on Cancer Treatment Outcomes

Again, however, the question of whether microbiomes exist within tumors is only one slice of the much larger field looking at microbiomes and cancer, including its influence on cancer treatment outcomes. Although much remains to be learned, less controversy exists over the thousands of studies in the past two decades that have gradually revealed how the body’s microbiome can affect both the course of a cancer and the effectiveness of different treatments.

The growing research showing the importance of the gut microbiome in cancer treatments is not surprising given its role in immunity more broadly. Because the human immune system must recognize and defend against microbes, the microbiome helps train it, Dr. Vujkovic-Cvijin said. 

Some bacteria can escape the gut — a phenomenon called bacterial translocation — and may aid in fighting tumors. To grow large enough to be seen on imaging, tumors need to evolve several abilities, such as growing enough vascularization to receive blood flow and shutting down local immune responses.

“Any added boost, like immunotherapy, has a chance of breaking through that immune forcefield and killing the tumor cells,” Dr. Vujkovic-Cvijin said. Escaped gut bacteria may provide that boost. 

“There’s a lot of evidence that depletion of the gut microbiome impairs immunotherapy and chemotherapy. The thinking behind some of those studies is that gut microbes can cross the gut barrier and when they do, they activate the immune system,” he said. 

In mice engineered to have sterile guts, for example, the lack of bacteria results in less effective immune systems, Dr. Vujkovic-Cvijin pointed out. A host of research has shown that antibiotic exposure during and even 6 months before immunotherapy dramatically reduces survival rates. “That’s pretty convincing to me that gut microbes are important,” he said. 

Dr. Vujkovic-Cvijin cautioned that there continues to be controversy on understanding which bacteria are important for response to immunotherapy. “The field is still in its infancy in terms of understanding which bacteria are most important for these effects,” he said.

Dr. Knight suggested that escaped bacteria may be the genesis of the ones that he and other researchers believe exist in tumors. “Because tumor microbes must come from somewhere, it is to be expected that some of those microbes will be co-opted from body-site specific commensals.”

It’s also possible that metabolites released from gut bacteria escape the gut and could theoretically affect distant tumor growth, Dr. Gihawi said. The most promising avenue of research in this area is metabolites being used as biomarkers, added Dr. Gihawi, whose lab published research on a link between bacteria detected in men’s urine and a more aggressive subset of prostate cancers. But that research is not far enough along to develop lab tests for clinical use, he noted. 
 

No Consensus Yet

Even before the controversy erupted around Dr. Knight’s research, he co-founded the company Micronoma to develop cancer tests based on his microbe findings. The company has raised $17.5 million from private investors as of August 2023 and received the US Food and Drug Administration’s Breakthrough Device designation, allowing the firm to fast-track clinical trials testing the technology. The recent critiques have not changed the company’s plans. 

It’s safe to say that scientists will continue to research and debate the possibility of tumor microbiomes until a consensus emerges. 

“The field is evolving and studies testing the reproducibility of tumor-resident microbial signals are essential for developing our understanding in this area,” Dr. Vujkovic-Cvijin said.

Even if that path ultimately leads nowhere, as Dr. Salzberg expects, research into microbiomes and cancer has plenty of other directions to go.

“I’m actually quite an optimist,” Dr. Gihawi said. “I think there’s a lot of scope for some really good research here, especially in the sites where we know there is a strong microbiome, such as the gastrointestinal tract.”

A version of this article appeared on Medscape.com.

A contentious scientific debate is clouding prospects for a deeper understanding of the microbiome’s role in cancer, a relatively young field of research that some believe could lead to breakthroughs in the diagnosis and treatment of the second-leading cause of death in the United States. 

Last year, the controversy heightened when experts questioned a high-profile study — a 2020 analysis claiming that the tumors of 33 different cancers had their own unique microbiomes — on whether the “signature” of these bacterial compositions could help diagnose cancer.

The incident renewed the spotlight on “tumor microbiomes” because of the bold claims of the original paper and the strongly worded refutations of those claims. The broader field has focused primarily on ways the body’s microbiome interacts with cancers and cancer treatment.

This controversy has highlighted the challenges of making headway in a field where researchers may not even have the tools yet to puzzle-out the wide-ranging implications the microbiome holds for cancer diagnosis and treatment.

But it is also part of a provocative question within that larger field: whether tumors in the body, far from the natural microbiome in the gut, have their own thriving communities of bacteria, viruses, and fungi. And, if they do, how do those tumor microbiomes affect the development and progression of the cancer and the effectiveness of cancer therapies? 
 

Cancer Controversy

The evidence is undeniable that some microbes can directly cause certain cancers and that the human gut microbiome can influence the effectiveness of certain therapies. Beyond that established science, however, the research has raised as many questions as answers about what we do and don’t know about microbiota and cancer.

The only confirmed microbiomes are on the skin and in the gut, mouth, and vagina, which are all areas with an easy direct route for bacteria to enter and grow in or on the body. A series of papers in recent years have suggested that other internal organs, and tumors within them, may have their own microbiomes. 

“Whether microbes exist in tumors of internal organs beyond body surfaces exposed to the environment is a different matter,” said Ivan Vujkovic-Cvijin, PhD, an assistant professor of biomedical sciences and gastroenterology at Cedars-Sinai Medical Center in Los Angeles, whose lab studies how human gut microbes affect inflammatory diseases. “We’ve only recently had the tools to study that question on a molecular level, and the reported results have been conflicting.” 

For example, research allegedly identified microbiota in the human placenta nearly one decade ago. But subsequent research contradicted those claims and showed that the source of the “placental microbiome” was actually contamination. Subsequent similar studies for other parts of the body faced the same scrutiny and, often, eventual debunking.

“Most likely, our immune system has undergone selective pressure to eliminate everything that crosses the gut barrier because there’s not much benefit to the body to have bacteria run amok in our internal organs,” Dr. Vujkovic-Cvijin said. “That can only disrupt the functioning of our tissues, to have an external organism living inside them.” 

The controversy that erupted last summer, surrounding research from the lab of Rob Knight, PhD, at the University of California, San Diego, centered on a slightly different but related question: Could tumors harbor their own microbiomes?

This news organization spoke with two of the authors who published a paper contesting Dr. Knight’s findings: Steven Salzberg, PhD, a professor of biomedical engineering at John Hopkins Medicine, Baltimore, Maryland, and Abraham Gihawi, PhD, a research fellow at Norwich Medical School at the University of East Anglia in the United Kingdom. 

Dr. Salzberg described two major problems with Dr. Knight’s study. 

“What they found were false positives because of contamination in the database and flaws in their methods,” Dr. Salzberg said. “I can’t prove there’s no cancer microbiome, but I can say the cancer microbiomes that they reported don’t exist because the species they were finding aren’t there.”

Dr. Knight disagrees with Dr. Salzberg’s findings, noting that Dr. Salzberg and his co-authors did not examine the publicly available databases used in his study. In a written response, he said that his team’s examination of the database revealed that less than 1% of the microbial genomes overlapped with human ones and that removing them did not change their findings.

Dr. Knight also noted that his team could still “distinguish cancer types by their microbiome” even after running their analysis without the technique that Dr. Salzberg found fault with.

Dr. Salzberg said that the database linked above is not the one Dr. Knight’s study used, however. “The primary database in their study was never made public (it’s too large, they said), and it has/had about 69,000 genomes,” Dr. Salzberg said by email. “But even if we did, this is irrelevant. He’s trying to distract from the primary errors in their study,” which Dr. Salzberg said Dr. Knight’s team has not addressed. 

The critiques Dr. Salzberg raised have been leveled at other studies investigating microbiomes specifically within tumors and independent of the body’s microbiome.

For example, a 2019 study in Nature described a fungal microbiome in pancreatic cancer that a Nature paper 4 years later directly contradicted, citing flaws that invalidated the original findings. A different 2019 study in Cell examined pancreatic tumor microbiota and patient outcomes, but it’s unclear whether the microorganisms moved from the gut to the pancreas or “constitute a durably colonized community that lives inside the tumor,” which remains a matter of debate, Dr. Vujkovic-Cvijin said.

A 2020 study in Science suggested diverse microbial communities in seven tumor types, but those findings were similarly called into question. That study stated that “bacteria were first detected in human tumors more than 100 years ago” and that “bacteria are well-known residents in human tumors,” but Dr. Salzberg considers those statements misleading. 

It’s true that bacteria and viruses have been detected in tumors because “there’s very good evidence that an acute infection caused by a very small number of viruses and bacteria can cause a tumor,” Dr. Salzberg said. Human papillomavirus, for example, can cause six different types of cancer. Inflammation and ulcers caused by Helicobacter pylori may progress to stomach cancer, and Fusobacterium nucleatum and Enterococcus faecalis have been shown to contribute to colorectal cancer. Those examples differ from a microbiome; this “a community of bacteria and possibly other microscopic bugs, like fungi, that are happily living in the tumor” the same way microbes reside in our guts, he said.

Dr. Knight said that many bacteria his team identified “have been confirmed independently in subsequent work.” He acknowledged, however, that more research is needed. 

Several of the contested studies above were among a lengthy list that Dr. Knight provided, noting that most of the disagreements “have two sides to them, and critiques from one particular group does not immediately invalidate a reported finding.” 

Yet, many of the papers Dr. Knight listed are precisely the types that skeptics like Dr. Salzberg believe are too flawed to draw reliable conclusions. 

“I think many agree that microbes may exist within tumors that are exposed to the environment, like tumors of the skin, gut, and mouth,” Dr. Vujkovic-Cvijin said. It’s less clear, however, whether tumors further from the body’s microbiome harbor any microbes or where they came from if they do. Microbial signals in organs elsewhere in the body become faint quickly, he said.
 

Underdeveloped Technology 

Though Dr. Salzberg said that the concept of a tumor microbiome is “implausible” because there’s no easy route for bacteria to reach internal organs, it’s unclear whether scientists have the technology yet to adequately answer this question. 

For one thing, samples in these types of studies are typically “ultra-low biomass samples, where the signal — the amount of microbes in the sample — is so low that it’s comparable to how much would be expected to be found in reagents and environmental contamination through processing,” Dr. Vujkovic-Cvijin explained. Many polymerases used to amplify a DNA signal, for example, are made in bacteria and may retain trace amounts identified in these studies. 

Dr. Knight agreed that low biomass is a challenge in this field but is not an unsurmountable one. 

Another challenge is that study samples, as with Dr. Knight’s work, were collected during routine surgeries without the intent to find a microbial signal. Simply using a scalpel to cut through the skin means cutting through a layer of bacteria, and surgery rooms are not designed to eliminate all bacteria. Some work has even shown there is a “hospital microbiome,” so “you can easily have that creep into your signal and mistake it for tumor-resident bacteria,” Dr. Vujkovic-Cvijin said. 

Dr. Knight asserted that the samples are taken under sterile conditions, but other researchers do not think the level of sterility necessary for completely clean samples is possible. 

“Just because it’s in your sample doesn’t mean it was in your tumor,” Dr. Gihawi said.

Even if scientists can retrieve a reliable sample without contamination, analyzing it requires comparing the genetic material to existing databases of microbial genomes. Yet, contamination and misclassification of genetic sequences can be problems in those reference genomes too, Dr. Gihawi explained.

Machine learning algorithms have a role in interpreting data, but “we need to be careful of what we use them for,” he added.

“These techniques are in their infancy, and we’re starting to chase them down, which is why we need to move microbiome research in a way that can be used clinically,” Dr. Gihawi said. 
 

Influence on Cancer Treatment Outcomes

Again, however, the question of whether microbiomes exist within tumors is only one slice of the much larger field looking at microbiomes and cancer, including its influence on cancer treatment outcomes. Although much remains to be learned, less controversy exists over the thousands of studies in the past two decades that have gradually revealed how the body’s microbiome can affect both the course of a cancer and the effectiveness of different treatments.

The growing research showing the importance of the gut microbiome in cancer treatments is not surprising given its role in immunity more broadly. Because the human immune system must recognize and defend against microbes, the microbiome helps train it, Dr. Vujkovic-Cvijin said. 

Some bacteria can escape the gut — a phenomenon called bacterial translocation — and may aid in fighting tumors. To grow large enough to be seen on imaging, tumors need to evolve several abilities, such as growing enough vascularization to receive blood flow and shutting down local immune responses.

“Any added boost, like immunotherapy, has a chance of breaking through that immune forcefield and killing the tumor cells,” Dr. Vujkovic-Cvijin said. Escaped gut bacteria may provide that boost. 

“There’s a lot of evidence that depletion of the gut microbiome impairs immunotherapy and chemotherapy. The thinking behind some of those studies is that gut microbes can cross the gut barrier and when they do, they activate the immune system,” he said. 

In mice engineered to have sterile guts, for example, the lack of bacteria results in less effective immune systems, Dr. Vujkovic-Cvijin pointed out. A host of research has shown that antibiotic exposure during and even 6 months before immunotherapy dramatically reduces survival rates. “That’s pretty convincing to me that gut microbes are important,” he said. 

Dr. Vujkovic-Cvijin cautioned that there continues to be controversy on understanding which bacteria are important for response to immunotherapy. “The field is still in its infancy in terms of understanding which bacteria are most important for these effects,” he said.

Dr. Knight suggested that escaped bacteria may be the genesis of the ones that he and other researchers believe exist in tumors. “Because tumor microbes must come from somewhere, it is to be expected that some of those microbes will be co-opted from body-site specific commensals.”

It’s also possible that metabolites released from gut bacteria escape the gut and could theoretically affect distant tumor growth, Dr. Gihawi said. The most promising avenue of research in this area is metabolites being used as biomarkers, added Dr. Gihawi, whose lab published research on a link between bacteria detected in men’s urine and a more aggressive subset of prostate cancers. But that research is not far enough along to develop lab tests for clinical use, he noted. 
 

No Consensus Yet

Even before the controversy erupted around Dr. Knight’s research, he co-founded the company Micronoma to develop cancer tests based on his microbe findings. The company has raised $17.5 million from private investors as of August 2023 and received the US Food and Drug Administration’s Breakthrough Device designation, allowing the firm to fast-track clinical trials testing the technology. The recent critiques have not changed the company’s plans. 

It’s safe to say that scientists will continue to research and debate the possibility of tumor microbiomes until a consensus emerges. 

“The field is evolving and studies testing the reproducibility of tumor-resident microbial signals are essential for developing our understanding in this area,” Dr. Vujkovic-Cvijin said.

Even if that path ultimately leads nowhere, as Dr. Salzberg expects, research into microbiomes and cancer has plenty of other directions to go.

“I’m actually quite an optimist,” Dr. Gihawi said. “I think there’s a lot of scope for some really good research here, especially in the sites where we know there is a strong microbiome, such as the gastrointestinal tract.”

A version of this article appeared on Medscape.com.