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The next frontier in cancer detection could be the humble urine test.

Emerging science suggests that the body’s “liquid gold” could be particularly useful for liquid biopsies, offering a convenient, pain-free, and cost-effective way to spot otherwise hard-to-detect cancers.

“The search for cancer biomarkers that can be detected in urine could provide an enormous step forward to decrease cancer patient mortality,” said Kenneth R. Shroyer, MD, PhD, a pathologist at Stony Brook University, Stony Brook, New York, who studies cancer biomarkers.

Physicians have long known that urine can reveal a lot about our health — that’s why urinalysis has been part of medicine for 6000 years. Urine tests can detect diabetes, pregnancy, drug use, and urinary or kidney conditions.

But other conditions leave clues in urine, too, and cancer may be one of the most promising. “Urine testing could detect biomarkers of early-stage cancers, not only from local but also distant sites,” Dr. Shroyer said. It could also help flag recurrence in cancer survivors who have undergone treatment.

Granted, cancer biomarkers in urine are not nearly as widely studied as those in the blood, Dr. Shroyer noted. But a new wave of urine tests suggests research is gaining pace.

“The recent availability of high-throughput screening technologies has enabled researchers to investigate cancer from a top-down, comprehensive approach,” said Pak Kin Wong, PhD, professor of mechanical engineering, biomedical engineering, and surgery at The Pennsylvania State University. “We are starting to understand the rich information that can be obtained from urine.”

Urine is mostly water (about 95%) and urea, a metabolic byproduct that imparts that signature yellow color (about 2%). The other 3% is a mix of waste products, minerals, and other compounds the kidneys removed from the blood. Even in trace amounts, these substances say a lot.

Among them are “exfoliated cancer cells, cell-free DNA, hormones, and the urine microbiota — the collection of microbes in our urinary tract system,” Dr. Wong said.

“It is highly promising to be one of the major biological fluids used for screening, diagnosis, prognosis, and monitoring treatment efficiency in the era of precision medicine,” Dr. Wong said.

How Urine Testing Could Reveal Cancer

Still, as exciting as the prospect is, there’s a lot to consider in the hunt for cancer biomarkers in urine. These biomarkers must be able to pass through the renal nephrons (filtering units), remain stable in urine, and have high-level sensitivity, Dr. Shroyer said. They should also have high specificity for cancer vs benign conditions and be expressed at early stages, before the primary tumor has spread.

“At this stage, few circulating biomarkers have been found that are both sensitive and specific for early-stage disease,” said Dr. Shroyer.

But there are a few promising examples under investigation in humans:

Prostate cancer. Researchers at the University of Michigan have developed a urine test that detects high-grade prostate cancer more accurately than existing tests, including PHI, SelectMDx, 4Kscore, EPI, MPS, and IsoPSA.

The MyProstateScore 2.0 (MPS2) test, which looks for 18 genes associated with high-grade tumors, could reduce unnecessary biopsies in men with elevated prostate-specific antigen levels, according to a paper published in JAMA Oncology.

It makes sense. The prostate gland secretes fluid that becomes part of the semen, traces of which enter urine. After a digital rectal exam, even more prostate fluid enters the urine. If a patient has prostate cancer, genetic material from the cancer cells will infiltrate the urine.

In the MPS2 test, researchers used polymerase chain reaction (PCR) testing in urine. “The technology used for COVID PCR is essentially the same as the PCR used to detect transcripts associated with high-grade prostate cancer in urine,” said study author Arul Chinnaiyan, MD, PhD, director of the Michigan Center for Translational Pathology at the University of Michigan, Ann Arbor. “In the case of the MPS2 test, we are doing PCR on 18 genes simultaneously on urine samples.”

A statistical model uses levels of that genetic material to predict the risk for high-grade disease, helping doctors decide what to do next. At 95% sensitivity, the MPS2 model could eliminate 35%-45% of unnecessary biopsies, compared with 15%-30% for the other tests, and reduce repeat biopsies by 46%-51%, compared with 9%-21% for the other tests.

Head and neck cancer. In a paper published in JCI Insight, researchers described a test that finds ultra-short fragments of DNA in urine to enable early detection of head and neck cancers caused by human papillomavirus.

“Our data show that a relatively small volume of urine (30-60 mL) gives overall detection results comparable to a tube of blood,” said study author Muneesh Tewari, MD, PhD, professor of hematology and oncology at the University of Michigan .

A larger volume of urine could potentially “make cancer detection even more sensitive than blood,” Dr. Tewari said, “allowing cancers to be detected at the earliest stages when they are more curable.”

The team used a technique called droplet digital PCR to detect DNA fragments that are “ultra-short” (less than 50 base pairs long) and usually missed by conventional PCR testing. This transrenal cell-free tumor DNA, which travels from the tumor into the bloodstream, is broken down small enough to pass through the kidneys and into the urine. But the fragments are still long enough to carry information about the tumor’s genetic signature.

This test could spot cancer before a tumor grows big enough — about a centimeter wide and carrying a billion cells — to spot on a CT scan or other imaging test. “When we are instead detecting fragments of DNA released from a tumor,” said Dr. Tewari, “our testing methods are very sensitive and can detect DNA in urine that came from just 5-10 cells in a tumor that died and released their DNA into the blood, which then made its way into the urine.”

Pancreatic cancer. Pancreatic ductal adenocarcinoma is one of the deadliest cancers, largely because it is diagnosed so late. A urine panel now in clinical trials could help doctors diagnose the cancer before it has spread so more people can have the tumor surgically removed, improving prognosis.

Using enzyme-linked immunosorbent assay test, a common lab method that detects antibodies and other proteins, the team measured expression levels for three genes (LYVE1, REG1B, and TFF1) in urine samples collected from people up to 5 years before they were diagnosed with pancreatic cancer. The researchers combined this result with patients’ urinary creatinine levels, a common component of existing urinalysis, and their age to develop a risk score.

This score performed similarly to an existing blood test, CA19-9, in predicting patients’ risk for pancreatic cancer up to 1 year before diagnosis. When combined with CA19-9, the urinary panel helped spot cancer up to 2 years before diagnosis.

According to a paper in the International Journal of Cancer, “the urine panel and affiliated PancRISK are currently being validated in a prospective clinical study (UroPanc).” If all goes well, they could be implemented in clinical practice in a few years as a “noninvasive stratification tool” to identify patients for further testing, speeding up diagnosis, and saving lives.

Limitations and Promises

Each cancer type is different, and more research is needed to map out which substances in urine predict which cancers and to develop tests for mass adoption. “There are medical and technological hurdles to the large-scale implementation of urine analysis for complex diseases such as cancer,” said Dr. Wong.

One possibility: Scientists and clinicians could collaborate and use artificial intelligence techniques to combine urine test results with other data.

“It is likely that future diagnostics may combine urine with other biological samples such as feces and saliva, among others,” said Dr. Wong. “This is especially true when novel data science and machine learning techniques can integrate comprehensive data from patients that span genetic, proteomic, metabolic, microbiomic, and even behavioral data to evaluate a patient’s condition.”

One thing that excites Dr. Tewari about urine-based cancer testing: “We think it could be especially impactful for patients living in rural areas or other areas with less access to healthcare services,” he said.
 

A version of this article appeared on Medscape.com.

The next frontier in cancer detection could be the humble urine test.

Emerging science suggests that the body’s “liquid gold” could be particularly useful for liquid biopsies, offering a convenient, pain-free, and cost-effective way to spot otherwise hard-to-detect cancers.

“The search for cancer biomarkers that can be detected in urine could provide an enormous step forward to decrease cancer patient mortality,” said Kenneth R. Shroyer, MD, PhD, a pathologist at Stony Brook University, Stony Brook, New York, who studies cancer biomarkers.

Physicians have long known that urine can reveal a lot about our health — that’s why urinalysis has been part of medicine for 6000 years. Urine tests can detect diabetes, pregnancy, drug use, and urinary or kidney conditions.

But other conditions leave clues in urine, too, and cancer may be one of the most promising. “Urine testing could detect biomarkers of early-stage cancers, not only from local but also distant sites,” Dr. Shroyer said. It could also help flag recurrence in cancer survivors who have undergone treatment.

Granted, cancer biomarkers in urine are not nearly as widely studied as those in the blood, Dr. Shroyer noted. But a new wave of urine tests suggests research is gaining pace.

“The recent availability of high-throughput screening technologies has enabled researchers to investigate cancer from a top-down, comprehensive approach,” said Pak Kin Wong, PhD, professor of mechanical engineering, biomedical engineering, and surgery at The Pennsylvania State University. “We are starting to understand the rich information that can be obtained from urine.”

Urine is mostly water (about 95%) and urea, a metabolic byproduct that imparts that signature yellow color (about 2%). The other 3% is a mix of waste products, minerals, and other compounds the kidneys removed from the blood. Even in trace amounts, these substances say a lot.

Among them are “exfoliated cancer cells, cell-free DNA, hormones, and the urine microbiota — the collection of microbes in our urinary tract system,” Dr. Wong said.

“It is highly promising to be one of the major biological fluids used for screening, diagnosis, prognosis, and monitoring treatment efficiency in the era of precision medicine,” Dr. Wong said.

How Urine Testing Could Reveal Cancer

Still, as exciting as the prospect is, there’s a lot to consider in the hunt for cancer biomarkers in urine. These biomarkers must be able to pass through the renal nephrons (filtering units), remain stable in urine, and have high-level sensitivity, Dr. Shroyer said. They should also have high specificity for cancer vs benign conditions and be expressed at early stages, before the primary tumor has spread.

“At this stage, few circulating biomarkers have been found that are both sensitive and specific for early-stage disease,” said Dr. Shroyer.

But there are a few promising examples under investigation in humans:

Prostate cancer. Researchers at the University of Michigan have developed a urine test that detects high-grade prostate cancer more accurately than existing tests, including PHI, SelectMDx, 4Kscore, EPI, MPS, and IsoPSA.

The MyProstateScore 2.0 (MPS2) test, which looks for 18 genes associated with high-grade tumors, could reduce unnecessary biopsies in men with elevated prostate-specific antigen levels, according to a paper published in JAMA Oncology.

It makes sense. The prostate gland secretes fluid that becomes part of the semen, traces of which enter urine. After a digital rectal exam, even more prostate fluid enters the urine. If a patient has prostate cancer, genetic material from the cancer cells will infiltrate the urine.

In the MPS2 test, researchers used polymerase chain reaction (PCR) testing in urine. “The technology used for COVID PCR is essentially the same as the PCR used to detect transcripts associated with high-grade prostate cancer in urine,” said study author Arul Chinnaiyan, MD, PhD, director of the Michigan Center for Translational Pathology at the University of Michigan, Ann Arbor. “In the case of the MPS2 test, we are doing PCR on 18 genes simultaneously on urine samples.”

A statistical model uses levels of that genetic material to predict the risk for high-grade disease, helping doctors decide what to do next. At 95% sensitivity, the MPS2 model could eliminate 35%-45% of unnecessary biopsies, compared with 15%-30% for the other tests, and reduce repeat biopsies by 46%-51%, compared with 9%-21% for the other tests.

Head and neck cancer. In a paper published in JCI Insight, researchers described a test that finds ultra-short fragments of DNA in urine to enable early detection of head and neck cancers caused by human papillomavirus.

“Our data show that a relatively small volume of urine (30-60 mL) gives overall detection results comparable to a tube of blood,” said study author Muneesh Tewari, MD, PhD, professor of hematology and oncology at the University of Michigan .

A larger volume of urine could potentially “make cancer detection even more sensitive than blood,” Dr. Tewari said, “allowing cancers to be detected at the earliest stages when they are more curable.”

The team used a technique called droplet digital PCR to detect DNA fragments that are “ultra-short” (less than 50 base pairs long) and usually missed by conventional PCR testing. This transrenal cell-free tumor DNA, which travels from the tumor into the bloodstream, is broken down small enough to pass through the kidneys and into the urine. But the fragments are still long enough to carry information about the tumor’s genetic signature.

This test could spot cancer before a tumor grows big enough — about a centimeter wide and carrying a billion cells — to spot on a CT scan or other imaging test. “When we are instead detecting fragments of DNA released from a tumor,” said Dr. Tewari, “our testing methods are very sensitive and can detect DNA in urine that came from just 5-10 cells in a tumor that died and released their DNA into the blood, which then made its way into the urine.”

Pancreatic cancer. Pancreatic ductal adenocarcinoma is one of the deadliest cancers, largely because it is diagnosed so late. A urine panel now in clinical trials could help doctors diagnose the cancer before it has spread so more people can have the tumor surgically removed, improving prognosis.

Using enzyme-linked immunosorbent assay test, a common lab method that detects antibodies and other proteins, the team measured expression levels for three genes (LYVE1, REG1B, and TFF1) in urine samples collected from people up to 5 years before they were diagnosed with pancreatic cancer. The researchers combined this result with patients’ urinary creatinine levels, a common component of existing urinalysis, and their age to develop a risk score.

This score performed similarly to an existing blood test, CA19-9, in predicting patients’ risk for pancreatic cancer up to 1 year before diagnosis. When combined with CA19-9, the urinary panel helped spot cancer up to 2 years before diagnosis.

According to a paper in the International Journal of Cancer, “the urine panel and affiliated PancRISK are currently being validated in a prospective clinical study (UroPanc).” If all goes well, they could be implemented in clinical practice in a few years as a “noninvasive stratification tool” to identify patients for further testing, speeding up diagnosis, and saving lives.

Limitations and Promises

Each cancer type is different, and more research is needed to map out which substances in urine predict which cancers and to develop tests for mass adoption. “There are medical and technological hurdles to the large-scale implementation of urine analysis for complex diseases such as cancer,” said Dr. Wong.

One possibility: Scientists and clinicians could collaborate and use artificial intelligence techniques to combine urine test results with other data.

“It is likely that future diagnostics may combine urine with other biological samples such as feces and saliva, among others,” said Dr. Wong. “This is especially true when novel data science and machine learning techniques can integrate comprehensive data from patients that span genetic, proteomic, metabolic, microbiomic, and even behavioral data to evaluate a patient’s condition.”

One thing that excites Dr. Tewari about urine-based cancer testing: “We think it could be especially impactful for patients living in rural areas or other areas with less access to healthcare services,” he said.
 

A version of this article appeared on Medscape.com.

The next frontier in cancer detection could be the humble urine test.

Emerging science suggests that the body’s “liquid gold” could be particularly useful for liquid biopsies, offering a convenient, pain-free, and cost-effective way to spot otherwise hard-to-detect cancers.

“The search for cancer biomarkers that can be detected in urine could provide an enormous step forward to decrease cancer patient mortality,” said Kenneth R. Shroyer, MD, PhD, a pathologist at Stony Brook University, Stony Brook, New York, who studies cancer biomarkers.

Physicians have long known that urine can reveal a lot about our health — that’s why urinalysis has been part of medicine for 6000 years. Urine tests can detect diabetes, pregnancy, drug use, and urinary or kidney conditions.

But other conditions leave clues in urine, too, and cancer may be one of the most promising. “Urine testing could detect biomarkers of early-stage cancers, not only from local but also distant sites,” Dr. Shroyer said. It could also help flag recurrence in cancer survivors who have undergone treatment.

Granted, cancer biomarkers in urine are not nearly as widely studied as those in the blood, Dr. Shroyer noted. But a new wave of urine tests suggests research is gaining pace.

“The recent availability of high-throughput screening technologies has enabled researchers to investigate cancer from a top-down, comprehensive approach,” said Pak Kin Wong, PhD, professor of mechanical engineering, biomedical engineering, and surgery at The Pennsylvania State University. “We are starting to understand the rich information that can be obtained from urine.”

Urine is mostly water (about 95%) and urea, a metabolic byproduct that imparts that signature yellow color (about 2%). The other 3% is a mix of waste products, minerals, and other compounds the kidneys removed from the blood. Even in trace amounts, these substances say a lot.

Among them are “exfoliated cancer cells, cell-free DNA, hormones, and the urine microbiota — the collection of microbes in our urinary tract system,” Dr. Wong said.

“It is highly promising to be one of the major biological fluids used for screening, diagnosis, prognosis, and monitoring treatment efficiency in the era of precision medicine,” Dr. Wong said.

How Urine Testing Could Reveal Cancer

Still, as exciting as the prospect is, there’s a lot to consider in the hunt for cancer biomarkers in urine. These biomarkers must be able to pass through the renal nephrons (filtering units), remain stable in urine, and have high-level sensitivity, Dr. Shroyer said. They should also have high specificity for cancer vs benign conditions and be expressed at early stages, before the primary tumor has spread.

“At this stage, few circulating biomarkers have been found that are both sensitive and specific for early-stage disease,” said Dr. Shroyer.

But there are a few promising examples under investigation in humans:

Prostate cancer. Researchers at the University of Michigan have developed a urine test that detects high-grade prostate cancer more accurately than existing tests, including PHI, SelectMDx, 4Kscore, EPI, MPS, and IsoPSA.

The MyProstateScore 2.0 (MPS2) test, which looks for 18 genes associated with high-grade tumors, could reduce unnecessary biopsies in men with elevated prostate-specific antigen levels, according to a paper published in JAMA Oncology.

It makes sense. The prostate gland secretes fluid that becomes part of the semen, traces of which enter urine. After a digital rectal exam, even more prostate fluid enters the urine. If a patient has prostate cancer, genetic material from the cancer cells will infiltrate the urine.

In the MPS2 test, researchers used polymerase chain reaction (PCR) testing in urine. “The technology used for COVID PCR is essentially the same as the PCR used to detect transcripts associated with high-grade prostate cancer in urine,” said study author Arul Chinnaiyan, MD, PhD, director of the Michigan Center for Translational Pathology at the University of Michigan, Ann Arbor. “In the case of the MPS2 test, we are doing PCR on 18 genes simultaneously on urine samples.”

A statistical model uses levels of that genetic material to predict the risk for high-grade disease, helping doctors decide what to do next. At 95% sensitivity, the MPS2 model could eliminate 35%-45% of unnecessary biopsies, compared with 15%-30% for the other tests, and reduce repeat biopsies by 46%-51%, compared with 9%-21% for the other tests.

Head and neck cancer. In a paper published in JCI Insight, researchers described a test that finds ultra-short fragments of DNA in urine to enable early detection of head and neck cancers caused by human papillomavirus.

“Our data show that a relatively small volume of urine (30-60 mL) gives overall detection results comparable to a tube of blood,” said study author Muneesh Tewari, MD, PhD, professor of hematology and oncology at the University of Michigan .

A larger volume of urine could potentially “make cancer detection even more sensitive than blood,” Dr. Tewari said, “allowing cancers to be detected at the earliest stages when they are more curable.”

The team used a technique called droplet digital PCR to detect DNA fragments that are “ultra-short” (less than 50 base pairs long) and usually missed by conventional PCR testing. This transrenal cell-free tumor DNA, which travels from the tumor into the bloodstream, is broken down small enough to pass through the kidneys and into the urine. But the fragments are still long enough to carry information about the tumor’s genetic signature.

This test could spot cancer before a tumor grows big enough — about a centimeter wide and carrying a billion cells — to spot on a CT scan or other imaging test. “When we are instead detecting fragments of DNA released from a tumor,” said Dr. Tewari, “our testing methods are very sensitive and can detect DNA in urine that came from just 5-10 cells in a tumor that died and released their DNA into the blood, which then made its way into the urine.”

Pancreatic cancer. Pancreatic ductal adenocarcinoma is one of the deadliest cancers, largely because it is diagnosed so late. A urine panel now in clinical trials could help doctors diagnose the cancer before it has spread so more people can have the tumor surgically removed, improving prognosis.

Using enzyme-linked immunosorbent assay test, a common lab method that detects antibodies and other proteins, the team measured expression levels for three genes (LYVE1, REG1B, and TFF1) in urine samples collected from people up to 5 years before they were diagnosed with pancreatic cancer. The researchers combined this result with patients’ urinary creatinine levels, a common component of existing urinalysis, and their age to develop a risk score.

This score performed similarly to an existing blood test, CA19-9, in predicting patients’ risk for pancreatic cancer up to 1 year before diagnosis. When combined with CA19-9, the urinary panel helped spot cancer up to 2 years before diagnosis.

According to a paper in the International Journal of Cancer, “the urine panel and affiliated PancRISK are currently being validated in a prospective clinical study (UroPanc).” If all goes well, they could be implemented in clinical practice in a few years as a “noninvasive stratification tool” to identify patients for further testing, speeding up diagnosis, and saving lives.

Limitations and Promises

Each cancer type is different, and more research is needed to map out which substances in urine predict which cancers and to develop tests for mass adoption. “There are medical and technological hurdles to the large-scale implementation of urine analysis for complex diseases such as cancer,” said Dr. Wong.

One possibility: Scientists and clinicians could collaborate and use artificial intelligence techniques to combine urine test results with other data.

“It is likely that future diagnostics may combine urine with other biological samples such as feces and saliva, among others,” said Dr. Wong. “This is especially true when novel data science and machine learning techniques can integrate comprehensive data from patients that span genetic, proteomic, metabolic, microbiomic, and even behavioral data to evaluate a patient’s condition.”

One thing that excites Dr. Tewari about urine-based cancer testing: “We think it could be especially impactful for patients living in rural areas or other areas with less access to healthcare services,” he said.
 

A version of this article appeared on Medscape.com.

Breast cancer mortality was significantly lower among patients who used statins than in those who did not use these cholesterol-lowering drugs, a new study finds.

Previous research examining the association between cholesterol and breast cancer metabolism suggests that cholesterol-lowering medications such as statins may improve outcomes in breast cancer patients, Sixten Harborg, a medical student and PhD student at Aarhus University, Denmark, said in a presentation at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

In addition, cardiovascular-related death is the second most common cause of death for breast cancer survivors, and given the survival rates in early breast cancer, there is a demand for cardioprotective initiatives and maintenance of cardioprotective drugs after diagnosis, he said in an interview.
 

What Is Known About Statins and Breast Cancer?

Statins are the most common drugs used to lower cholesterol and may deprive tumor cells of the cholesterol needed for cell membrane synthesis, Mr. Harborg said in his presentation.

Data from a randomized trial published in the Journal of Clinical Oncology in 2017 showed significantly improved disease-free survival, breast cancer–free interval, and distant recurrence–free interval in early stage breast cancer patients randomized to cholesterol-lowering medication vs. those who did not receive cholesterol-lowering medication.

The 2017 study prompted the creation of the MASTER study, a randomized, multicenter, double-blind, placebo-controlled trial comparing standard adjuvant therapy plus placebo to standard adjuvant therapy plus atorvastatin in patients with early breast cancer (NCT04601116), Mr. Harborg said. The MASTER trial is currently recruiting patients in Denmark.
 

How Was the Current Study Designed?

To provide preliminary analysis, Mr. Harborg and colleagues used an emulation trial design based on electronic health care data from 110,160 females with a diagnosis of stage I, II, or III breast cancer who were part of the Danish Breast Cancer Group, a national clinical registry in Denmark, between 2000 and 2020.

As defined in the European Journal of Epidemiology in 2017, target trial emulation involves application of randomized trial designs to observational data with the goal of improving the quality of observational epidemiology when a comparator trial is not yet available.

The researchers created a cohort of patients based on electronic health care data to simulate a target trial of the use of atorvastatin after breast cancer diagnosis. Patients were randomized to one of two treatment strategies: starting to use statins within 36 months of diagnosis, or not using statins. The primary outcome was death from breast cancer. The follow-up for the MASTER study starts with inclusion and ends with death, emigration from Denmark, end of clinical follow-up, or 10 years of follow-up (whichever comes first); the follow-up was the same in the current study.

The researchers calculated hazard ratios (HR) of breast cancer mortality in statin users vs. non–statin users and used a technique known as inverse-probability of censoring-weighting (IPCW) to estimate the effects of statin use based on prognostic factors.
 

What Did the Results Show?

The results favored statin use for improved survival in early breast cancer patients, Mr. Harborg said. Overall, the hazard ratio for breast cancer mortality was 0.96 in statin users compared with non–statin users, and was similar in both a Cox regression analysis (HR 0.81), and in a 10-year landmark analysis (HR 0.86).

The difference in mortality between statin and non–statin users was even stronger in patients who were receiving adjuvant chemotherapy (HR 0.94, 0.64, and 0.76 on the IPCW, Cox, and landmark analyses, respectively).

The results were in line with previous reports of statins’ effect on breast cancer survival, Mr. Harborg said in an interview.

“We believe the results encourage the continuous effort of the currently enrolling MASTER trial,” he said.

The results also suggest that deprescribing statins at the time of breast cancer diagnosis is not recommended, and that statin treatment can safely be prescribed to breast cancer patients with increased cardiovascular disease risk and/or dyslipidemia, Mr. Harborg said in the interview.
 

What Is the Takeaway Message for Clinical Practice?

“The clinical takeaway from our study is that statin use is associated with reduced risk of dying from breast cancer, but that it is not possible to determine the true effect of statins on breast cancer survival without a randomized, placebo-controlled trial,” Mr. Harborg told this publication. “Statins are inexpensive and well-tolerated drugs and may have a beneficial effect in terms of survival for breast cancer patients. However, with the current level of evidence [because the MASTER study is ongoing], we still cannot recommend that oncologists prescribe statins to prevent mortality from breast cancer,” he said.

What Are the Next Steps for Research?

The findings were limited by the study design, and real-world data are needed, Dr. Harborg said. Other limitations include the presence of residual bias, and the use of data based on prescription codes, but these were not considered to have an effect on the main conclusion of the study, Mr. Harborg said in the interview.

However, the results suggest that the addition of statins may improve outcomes for early breast cancer patients, especially when used with chemotherapy, and support the value of the ongoing MASTER study, he concluded.

Ultimately, the MASTER study will provide a more definitive answer to the question of whether statins should be added to the adjuvant treatment regimen of breast cancer to improve breast cancer outcomes, he said.
 

What Do Clinicians Think of the Study?

The current study is timely and highlights the need for phase 3 trials to examine the potential of statin use for breast cancer outcomes, Malinda T. West, MD, a medical oncologist and breast oncologist at the University of Wisconsin Carbone Cancer Center, Madison, said in an interview.

Questions for future research include whether statins can be used in combination with adjuvant abemaciclib if indicated, or how to best sequence these agents, said Dr. West, who was not involved in the study. Other questions raised by the current study include whether other cholesterol-lowering agents have a potential adjuvant benefit in reducing breast cancer recurrent and/or mortality, and whether the addition of statins would benefit subgroups such as HER2+ and triple negative breast cancer, she said.

“I was not surprised to see another study reporting benefit with statins and reduced risk of breast cancer recurrence and/or mortality, but I think the larger question is defining the subgroups who benefit the most, and identifying predictors for benefit or resistance,” Dr. West said in an interview.

Previous studies have shown that cholesterol elevation, specifically LDL levels, can be linked to increased tumor growth in breast cancer, so the lower mortality risk associated with lipid-lowering therapies in the current study was consistent, Peyton L. Reves, MD, a hematology/oncology fellow, also at the University of Wisconsin, said in an interview. In practice, data from the current study and previous research could be especially useful for patients with elevated LDL levels, said Dr. Reves, who was not involved in the study.

“These results could impact clinical practice in many ways, including leading to routine cholesterol monitoring in breast cancer patients on adjuvant therapy as well as the addition of lipid-lowering therapy with statins in these patients,” Dr. Reves said.

The findings showing particular benefit for patients on adjuvant chemotherapy highlight the need for more research on this specific population and the effect of statins on overall breast cancer mortality, to explore the extent to which the results of the current study were driven by the benefit seen in patients receiving adjuvant chemotherapy, Dr. Reves said.

The study was supported by Director Michael Hermann Nielsen’s Memorial Grant, Manufacturer Einar Willumsen’s Memorial Grant, Astrid Thaysen’s Grant for Medical Basic Research, Eva and Henry Fraenkel’s Memorial Fund, and the Novo Nordisk Foundation.

The researchers had no financial conflicts to disclose. Dr. West and Dr. Reves had no financial conflicts to disclose.

Breast cancer mortality was significantly lower among patients who used statins than in those who did not use these cholesterol-lowering drugs, a new study finds.

Previous research examining the association between cholesterol and breast cancer metabolism suggests that cholesterol-lowering medications such as statins may improve outcomes in breast cancer patients, Sixten Harborg, a medical student and PhD student at Aarhus University, Denmark, said in a presentation at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

In addition, cardiovascular-related death is the second most common cause of death for breast cancer survivors, and given the survival rates in early breast cancer, there is a demand for cardioprotective initiatives and maintenance of cardioprotective drugs after diagnosis, he said in an interview.
 

What Is Known About Statins and Breast Cancer?

Statins are the most common drugs used to lower cholesterol and may deprive tumor cells of the cholesterol needed for cell membrane synthesis, Mr. Harborg said in his presentation.

Data from a randomized trial published in the Journal of Clinical Oncology in 2017 showed significantly improved disease-free survival, breast cancer–free interval, and distant recurrence–free interval in early stage breast cancer patients randomized to cholesterol-lowering medication vs. those who did not receive cholesterol-lowering medication.

The 2017 study prompted the creation of the MASTER study, a randomized, multicenter, double-blind, placebo-controlled trial comparing standard adjuvant therapy plus placebo to standard adjuvant therapy plus atorvastatin in patients with early breast cancer (NCT04601116), Mr. Harborg said. The MASTER trial is currently recruiting patients in Denmark.
 

How Was the Current Study Designed?

To provide preliminary analysis, Mr. Harborg and colleagues used an emulation trial design based on electronic health care data from 110,160 females with a diagnosis of stage I, II, or III breast cancer who were part of the Danish Breast Cancer Group, a national clinical registry in Denmark, between 2000 and 2020.

As defined in the European Journal of Epidemiology in 2017, target trial emulation involves application of randomized trial designs to observational data with the goal of improving the quality of observational epidemiology when a comparator trial is not yet available.

The researchers created a cohort of patients based on electronic health care data to simulate a target trial of the use of atorvastatin after breast cancer diagnosis. Patients were randomized to one of two treatment strategies: starting to use statins within 36 months of diagnosis, or not using statins. The primary outcome was death from breast cancer. The follow-up for the MASTER study starts with inclusion and ends with death, emigration from Denmark, end of clinical follow-up, or 10 years of follow-up (whichever comes first); the follow-up was the same in the current study.

The researchers calculated hazard ratios (HR) of breast cancer mortality in statin users vs. non–statin users and used a technique known as inverse-probability of censoring-weighting (IPCW) to estimate the effects of statin use based on prognostic factors.
 

What Did the Results Show?

The results favored statin use for improved survival in early breast cancer patients, Mr. Harborg said. Overall, the hazard ratio for breast cancer mortality was 0.96 in statin users compared with non–statin users, and was similar in both a Cox regression analysis (HR 0.81), and in a 10-year landmark analysis (HR 0.86).

The difference in mortality between statin and non–statin users was even stronger in patients who were receiving adjuvant chemotherapy (HR 0.94, 0.64, and 0.76 on the IPCW, Cox, and landmark analyses, respectively).

The results were in line with previous reports of statins’ effect on breast cancer survival, Mr. Harborg said in an interview.

“We believe the results encourage the continuous effort of the currently enrolling MASTER trial,” he said.

The results also suggest that deprescribing statins at the time of breast cancer diagnosis is not recommended, and that statin treatment can safely be prescribed to breast cancer patients with increased cardiovascular disease risk and/or dyslipidemia, Mr. Harborg said in the interview.
 

What Is the Takeaway Message for Clinical Practice?

“The clinical takeaway from our study is that statin use is associated with reduced risk of dying from breast cancer, but that it is not possible to determine the true effect of statins on breast cancer survival without a randomized, placebo-controlled trial,” Mr. Harborg told this publication. “Statins are inexpensive and well-tolerated drugs and may have a beneficial effect in terms of survival for breast cancer patients. However, with the current level of evidence [because the MASTER study is ongoing], we still cannot recommend that oncologists prescribe statins to prevent mortality from breast cancer,” he said.

What Are the Next Steps for Research?

The findings were limited by the study design, and real-world data are needed, Dr. Harborg said. Other limitations include the presence of residual bias, and the use of data based on prescription codes, but these were not considered to have an effect on the main conclusion of the study, Mr. Harborg said in the interview.

However, the results suggest that the addition of statins may improve outcomes for early breast cancer patients, especially when used with chemotherapy, and support the value of the ongoing MASTER study, he concluded.

Ultimately, the MASTER study will provide a more definitive answer to the question of whether statins should be added to the adjuvant treatment regimen of breast cancer to improve breast cancer outcomes, he said.
 

What Do Clinicians Think of the Study?

The current study is timely and highlights the need for phase 3 trials to examine the potential of statin use for breast cancer outcomes, Malinda T. West, MD, a medical oncologist and breast oncologist at the University of Wisconsin Carbone Cancer Center, Madison, said in an interview.

Questions for future research include whether statins can be used in combination with adjuvant abemaciclib if indicated, or how to best sequence these agents, said Dr. West, who was not involved in the study. Other questions raised by the current study include whether other cholesterol-lowering agents have a potential adjuvant benefit in reducing breast cancer recurrent and/or mortality, and whether the addition of statins would benefit subgroups such as HER2+ and triple negative breast cancer, she said.

“I was not surprised to see another study reporting benefit with statins and reduced risk of breast cancer recurrence and/or mortality, but I think the larger question is defining the subgroups who benefit the most, and identifying predictors for benefit or resistance,” Dr. West said in an interview.

Previous studies have shown that cholesterol elevation, specifically LDL levels, can be linked to increased tumor growth in breast cancer, so the lower mortality risk associated with lipid-lowering therapies in the current study was consistent, Peyton L. Reves, MD, a hematology/oncology fellow, also at the University of Wisconsin, said in an interview. In practice, data from the current study and previous research could be especially useful for patients with elevated LDL levels, said Dr. Reves, who was not involved in the study.

“These results could impact clinical practice in many ways, including leading to routine cholesterol monitoring in breast cancer patients on adjuvant therapy as well as the addition of lipid-lowering therapy with statins in these patients,” Dr. Reves said.

The findings showing particular benefit for patients on adjuvant chemotherapy highlight the need for more research on this specific population and the effect of statins on overall breast cancer mortality, to explore the extent to which the results of the current study were driven by the benefit seen in patients receiving adjuvant chemotherapy, Dr. Reves said.

The study was supported by Director Michael Hermann Nielsen’s Memorial Grant, Manufacturer Einar Willumsen’s Memorial Grant, Astrid Thaysen’s Grant for Medical Basic Research, Eva and Henry Fraenkel’s Memorial Fund, and the Novo Nordisk Foundation.

The researchers had no financial conflicts to disclose. Dr. West and Dr. Reves had no financial conflicts to disclose.

Breast cancer mortality was significantly lower among patients who used statins than in those who did not use these cholesterol-lowering drugs, a new study finds.

Previous research examining the association between cholesterol and breast cancer metabolism suggests that cholesterol-lowering medications such as statins may improve outcomes in breast cancer patients, Sixten Harborg, a medical student and PhD student at Aarhus University, Denmark, said in a presentation at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

In addition, cardiovascular-related death is the second most common cause of death for breast cancer survivors, and given the survival rates in early breast cancer, there is a demand for cardioprotective initiatives and maintenance of cardioprotective drugs after diagnosis, he said in an interview.
 

What Is Known About Statins and Breast Cancer?

Statins are the most common drugs used to lower cholesterol and may deprive tumor cells of the cholesterol needed for cell membrane synthesis, Mr. Harborg said in his presentation.

Data from a randomized trial published in the Journal of Clinical Oncology in 2017 showed significantly improved disease-free survival, breast cancer–free interval, and distant recurrence–free interval in early stage breast cancer patients randomized to cholesterol-lowering medication vs. those who did not receive cholesterol-lowering medication.

The 2017 study prompted the creation of the MASTER study, a randomized, multicenter, double-blind, placebo-controlled trial comparing standard adjuvant therapy plus placebo to standard adjuvant therapy plus atorvastatin in patients with early breast cancer (NCT04601116), Mr. Harborg said. The MASTER trial is currently recruiting patients in Denmark.
 

How Was the Current Study Designed?

To provide preliminary analysis, Mr. Harborg and colleagues used an emulation trial design based on electronic health care data from 110,160 females with a diagnosis of stage I, II, or III breast cancer who were part of the Danish Breast Cancer Group, a national clinical registry in Denmark, between 2000 and 2020.

As defined in the European Journal of Epidemiology in 2017, target trial emulation involves application of randomized trial designs to observational data with the goal of improving the quality of observational epidemiology when a comparator trial is not yet available.

The researchers created a cohort of patients based on electronic health care data to simulate a target trial of the use of atorvastatin after breast cancer diagnosis. Patients were randomized to one of two treatment strategies: starting to use statins within 36 months of diagnosis, or not using statins. The primary outcome was death from breast cancer. The follow-up for the MASTER study starts with inclusion and ends with death, emigration from Denmark, end of clinical follow-up, or 10 years of follow-up (whichever comes first); the follow-up was the same in the current study.

The researchers calculated hazard ratios (HR) of breast cancer mortality in statin users vs. non–statin users and used a technique known as inverse-probability of censoring-weighting (IPCW) to estimate the effects of statin use based on prognostic factors.
 

What Did the Results Show?

The results favored statin use for improved survival in early breast cancer patients, Mr. Harborg said. Overall, the hazard ratio for breast cancer mortality was 0.96 in statin users compared with non–statin users, and was similar in both a Cox regression analysis (HR 0.81), and in a 10-year landmark analysis (HR 0.86).

The difference in mortality between statin and non–statin users was even stronger in patients who were receiving adjuvant chemotherapy (HR 0.94, 0.64, and 0.76 on the IPCW, Cox, and landmark analyses, respectively).

The results were in line with previous reports of statins’ effect on breast cancer survival, Mr. Harborg said in an interview.

“We believe the results encourage the continuous effort of the currently enrolling MASTER trial,” he said.

The results also suggest that deprescribing statins at the time of breast cancer diagnosis is not recommended, and that statin treatment can safely be prescribed to breast cancer patients with increased cardiovascular disease risk and/or dyslipidemia, Mr. Harborg said in the interview.
 

What Is the Takeaway Message for Clinical Practice?

“The clinical takeaway from our study is that statin use is associated with reduced risk of dying from breast cancer, but that it is not possible to determine the true effect of statins on breast cancer survival without a randomized, placebo-controlled trial,” Mr. Harborg told this publication. “Statins are inexpensive and well-tolerated drugs and may have a beneficial effect in terms of survival for breast cancer patients. However, with the current level of evidence [because the MASTER study is ongoing], we still cannot recommend that oncologists prescribe statins to prevent mortality from breast cancer,” he said.

What Are the Next Steps for Research?

The findings were limited by the study design, and real-world data are needed, Dr. Harborg said. Other limitations include the presence of residual bias, and the use of data based on prescription codes, but these were not considered to have an effect on the main conclusion of the study, Mr. Harborg said in the interview.

However, the results suggest that the addition of statins may improve outcomes for early breast cancer patients, especially when used with chemotherapy, and support the value of the ongoing MASTER study, he concluded.

Ultimately, the MASTER study will provide a more definitive answer to the question of whether statins should be added to the adjuvant treatment regimen of breast cancer to improve breast cancer outcomes, he said.
 

What Do Clinicians Think of the Study?

The current study is timely and highlights the need for phase 3 trials to examine the potential of statin use for breast cancer outcomes, Malinda T. West, MD, a medical oncologist and breast oncologist at the University of Wisconsin Carbone Cancer Center, Madison, said in an interview.

Questions for future research include whether statins can be used in combination with adjuvant abemaciclib if indicated, or how to best sequence these agents, said Dr. West, who was not involved in the study. Other questions raised by the current study include whether other cholesterol-lowering agents have a potential adjuvant benefit in reducing breast cancer recurrent and/or mortality, and whether the addition of statins would benefit subgroups such as HER2+ and triple negative breast cancer, she said.

“I was not surprised to see another study reporting benefit with statins and reduced risk of breast cancer recurrence and/or mortality, but I think the larger question is defining the subgroups who benefit the most, and identifying predictors for benefit or resistance,” Dr. West said in an interview.

Previous studies have shown that cholesterol elevation, specifically LDL levels, can be linked to increased tumor growth in breast cancer, so the lower mortality risk associated with lipid-lowering therapies in the current study was consistent, Peyton L. Reves, MD, a hematology/oncology fellow, also at the University of Wisconsin, said in an interview. In practice, data from the current study and previous research could be especially useful for patients with elevated LDL levels, said Dr. Reves, who was not involved in the study.

“These results could impact clinical practice in many ways, including leading to routine cholesterol monitoring in breast cancer patients on adjuvant therapy as well as the addition of lipid-lowering therapy with statins in these patients,” Dr. Reves said.

The findings showing particular benefit for patients on adjuvant chemotherapy highlight the need for more research on this specific population and the effect of statins on overall breast cancer mortality, to explore the extent to which the results of the current study were driven by the benefit seen in patients receiving adjuvant chemotherapy, Dr. Reves said.

The study was supported by Director Michael Hermann Nielsen’s Memorial Grant, Manufacturer Einar Willumsen’s Memorial Grant, Astrid Thaysen’s Grant for Medical Basic Research, Eva and Henry Fraenkel’s Memorial Fund, and the Novo Nordisk Foundation.

The researchers had no financial conflicts to disclose. Dr. West and Dr. Reves had no financial conflicts to disclose.

A California jury has awarded $14 million to a former University of California, Los Angeles (UCLA) oncologist who claimed she was paid thousands less than her male colleagues and wrongfully terminated after her complaints of gender-based harassment and intimidation were ignored by program leadership.

The decision comes after a lengthy 8-year legal battle in which an appellate judge reversed a previous jury decision in her favor.

Lauren Pinter-Brown, MD, a hematologic oncologist, was hired in 2005 by the University of California, Los Angeles School of Medicine — now called UCLA’s David Geffen School of Medicine. As the school’s lymphoma program director, she conducted clinical research alongside other oncology doctors, including Sven de Vos, MD.

She claimed that her professional relationship with Dr. de Vos became contentious after he demonstrated “oppositional” and “disrespectful” behavior at team meetings, such as talking over her and turning his chair so Dr. Pinter-Brown faced his back. Court documents indicated that Dr. de Vos refused to use Dr. Pinter-Brown’s title in front of colleagues despite doing so for male counterparts.

Dr. Pinter-Brown argued that she was treated as the “butt of a joke” by Dr. de Vos and other male colleagues. In 2016, she sued Dr. de Vos, the university, and its governing body, the Board of Regents, for wrongful termination.

She was awarded a $13 million verdict in 2018. However, the California Court of Appeals overturned it in 2020 after concluding that several mistakes during the court proceedings impeded the school’s right to a fair and impartial trial. The case was retried, culminating in the even higher award of $14 million issued on May 9.

“Two juries have come to virtually identical findings showing multiple problems at UCLA involving gender discrimination,” Dr. Pinter-Brown’s attorney, Carney R. Shegerian, JD, told this news organization.

A spokesperson from UCLA’s David Geffen School of Medicine said administrators are carefully reviewing the new decision.

The spokesperson told this news organization that the medical school and its health system remain “deeply committed to maintaining a workplace free from discrimination, intimidation, retaliation, or harassment of any kind” and fostering a “respectful and inclusive environment ... in research, medical education, and patient care.”
 

Gender Pay Disparities Persist in Medicine

The gender pay gap in medicine is well documented. The 2024 Medscape Physician Compensation Report found that male doctors earn about 29% more than their female counterparts, with the disparity growing larger among specialists. In addition, a recent JAMA Health Forum study found that male physicians earned 21%-24% more per hour than female physicians.

Dr. Pinter-Brown, who now works at the University of California, Irvine, alleged that she was paid $200,000 less annually, on average, than her male colleagues.

That’s not surprising, says Martha Gulati, MD, professor and director of preventive cardiology at Cedars-Sinai Smidt Heart Institute, Los Angeles. She coauthored a commentary about gender disparities in JAMA Network Open. Dr. Gulati told this news organization that even a “small” pay disparity of $100,000 annually adds up.

“Let’s say the [male physician] invests it at 3% and adds to it yearly. Even without a raise, in 20 years, that is approximately $3 million,” Dr. Gulati explained. “Once you find out you are paid less than your male colleagues, you are upset. Your sense of value and self-worth disappears.”

Eileen Barrett, MD, MPH, president-elect of the American Medical Women’s Association, said that gender discrimination is likely more prevalent than research indicates. She told this news organization that self-doubt and fear of retaliation keep many from exposing the mistreatment.

Although more women are entering medicine, too few rise to the highest positions, Dr. Barrett said.

“Unfortunately, many are pulled and pushed into specialties and subspecialties that have lower compensation and are not promoted to leadership, so just having numbers isn’t enough to achieve equity,” Dr. Barrett said.

Dr. Pinter-Brown claimed she was repeatedly harassed and intimidated by Dr. de Vos from 2008 to 2015. Despite voicing concerns multiple times about the discriminatory behavior, the only resolutions offered by the male-dominated program leadership were for her to separate from the group and conduct lymphoma research independently or to avoid interacting with Dr. de Vos, court records said.

Even the school’s male Title IX officer, Jan Tillisch, MD, who handled gender-based discrimination complaints, reportedly made sexist comments. When Dr. Pinter-Brown sought his help, he allegedly told her that she had a reputation as an “angry woman” and “diva,” court records showed.

According to court documents, Dr. Pinter-Brown endured nitpicking and research audits as retaliation for speaking out, temporarily suspending her research privileges. She said she was subsequently removed from the director position and replaced by Dr. de Vos.

Female physicians who report discriminatory behavior often have unfavorable outcomes and risk future career prospects, Dr. Gulati said.

To shift this dynamic, she said institutions must increase transparency and practices that support female doctors receiving “equal pay for equal work.”
 

A version of this article appeared on Medscape.com.

A California jury has awarded $14 million to a former University of California, Los Angeles (UCLA) oncologist who claimed she was paid thousands less than her male colleagues and wrongfully terminated after her complaints of gender-based harassment and intimidation were ignored by program leadership.

The decision comes after a lengthy 8-year legal battle in which an appellate judge reversed a previous jury decision in her favor.

Lauren Pinter-Brown, MD, a hematologic oncologist, was hired in 2005 by the University of California, Los Angeles School of Medicine — now called UCLA’s David Geffen School of Medicine. As the school’s lymphoma program director, she conducted clinical research alongside other oncology doctors, including Sven de Vos, MD.

She claimed that her professional relationship with Dr. de Vos became contentious after he demonstrated “oppositional” and “disrespectful” behavior at team meetings, such as talking over her and turning his chair so Dr. Pinter-Brown faced his back. Court documents indicated that Dr. de Vos refused to use Dr. Pinter-Brown’s title in front of colleagues despite doing so for male counterparts.

Dr. Pinter-Brown argued that she was treated as the “butt of a joke” by Dr. de Vos and other male colleagues. In 2016, she sued Dr. de Vos, the university, and its governing body, the Board of Regents, for wrongful termination.

She was awarded a $13 million verdict in 2018. However, the California Court of Appeals overturned it in 2020 after concluding that several mistakes during the court proceedings impeded the school’s right to a fair and impartial trial. The case was retried, culminating in the even higher award of $14 million issued on May 9.

“Two juries have come to virtually identical findings showing multiple problems at UCLA involving gender discrimination,” Dr. Pinter-Brown’s attorney, Carney R. Shegerian, JD, told this news organization.

A spokesperson from UCLA’s David Geffen School of Medicine said administrators are carefully reviewing the new decision.

The spokesperson told this news organization that the medical school and its health system remain “deeply committed to maintaining a workplace free from discrimination, intimidation, retaliation, or harassment of any kind” and fostering a “respectful and inclusive environment ... in research, medical education, and patient care.”
 

Gender Pay Disparities Persist in Medicine

The gender pay gap in medicine is well documented. The 2024 Medscape Physician Compensation Report found that male doctors earn about 29% more than their female counterparts, with the disparity growing larger among specialists. In addition, a recent JAMA Health Forum study found that male physicians earned 21%-24% more per hour than female physicians.

Dr. Pinter-Brown, who now works at the University of California, Irvine, alleged that she was paid $200,000 less annually, on average, than her male colleagues.

That’s not surprising, says Martha Gulati, MD, professor and director of preventive cardiology at Cedars-Sinai Smidt Heart Institute, Los Angeles. She coauthored a commentary about gender disparities in JAMA Network Open. Dr. Gulati told this news organization that even a “small” pay disparity of $100,000 annually adds up.

“Let’s say the [male physician] invests it at 3% and adds to it yearly. Even without a raise, in 20 years, that is approximately $3 million,” Dr. Gulati explained. “Once you find out you are paid less than your male colleagues, you are upset. Your sense of value and self-worth disappears.”

Eileen Barrett, MD, MPH, president-elect of the American Medical Women’s Association, said that gender discrimination is likely more prevalent than research indicates. She told this news organization that self-doubt and fear of retaliation keep many from exposing the mistreatment.

Although more women are entering medicine, too few rise to the highest positions, Dr. Barrett said.

“Unfortunately, many are pulled and pushed into specialties and subspecialties that have lower compensation and are not promoted to leadership, so just having numbers isn’t enough to achieve equity,” Dr. Barrett said.

Dr. Pinter-Brown claimed she was repeatedly harassed and intimidated by Dr. de Vos from 2008 to 2015. Despite voicing concerns multiple times about the discriminatory behavior, the only resolutions offered by the male-dominated program leadership were for her to separate from the group and conduct lymphoma research independently or to avoid interacting with Dr. de Vos, court records said.

Even the school’s male Title IX officer, Jan Tillisch, MD, who handled gender-based discrimination complaints, reportedly made sexist comments. When Dr. Pinter-Brown sought his help, he allegedly told her that she had a reputation as an “angry woman” and “diva,” court records showed.

According to court documents, Dr. Pinter-Brown endured nitpicking and research audits as retaliation for speaking out, temporarily suspending her research privileges. She said she was subsequently removed from the director position and replaced by Dr. de Vos.

Female physicians who report discriminatory behavior often have unfavorable outcomes and risk future career prospects, Dr. Gulati said.

To shift this dynamic, she said institutions must increase transparency and practices that support female doctors receiving “equal pay for equal work.”
 

A version of this article appeared on Medscape.com.

A California jury has awarded $14 million to a former University of California, Los Angeles (UCLA) oncologist who claimed she was paid thousands less than her male colleagues and wrongfully terminated after her complaints of gender-based harassment and intimidation were ignored by program leadership.

The decision comes after a lengthy 8-year legal battle in which an appellate judge reversed a previous jury decision in her favor.

Lauren Pinter-Brown, MD, a hematologic oncologist, was hired in 2005 by the University of California, Los Angeles School of Medicine — now called UCLA’s David Geffen School of Medicine. As the school’s lymphoma program director, she conducted clinical research alongside other oncology doctors, including Sven de Vos, MD.

She claimed that her professional relationship with Dr. de Vos became contentious after he demonstrated “oppositional” and “disrespectful” behavior at team meetings, such as talking over her and turning his chair so Dr. Pinter-Brown faced his back. Court documents indicated that Dr. de Vos refused to use Dr. Pinter-Brown’s title in front of colleagues despite doing so for male counterparts.

Dr. Pinter-Brown argued that she was treated as the “butt of a joke” by Dr. de Vos and other male colleagues. In 2016, she sued Dr. de Vos, the university, and its governing body, the Board of Regents, for wrongful termination.

She was awarded a $13 million verdict in 2018. However, the California Court of Appeals overturned it in 2020 after concluding that several mistakes during the court proceedings impeded the school’s right to a fair and impartial trial. The case was retried, culminating in the even higher award of $14 million issued on May 9.

“Two juries have come to virtually identical findings showing multiple problems at UCLA involving gender discrimination,” Dr. Pinter-Brown’s attorney, Carney R. Shegerian, JD, told this news organization.

A spokesperson from UCLA’s David Geffen School of Medicine said administrators are carefully reviewing the new decision.

The spokesperson told this news organization that the medical school and its health system remain “deeply committed to maintaining a workplace free from discrimination, intimidation, retaliation, or harassment of any kind” and fostering a “respectful and inclusive environment ... in research, medical education, and patient care.”
 

Gender Pay Disparities Persist in Medicine

The gender pay gap in medicine is well documented. The 2024 Medscape Physician Compensation Report found that male doctors earn about 29% more than their female counterparts, with the disparity growing larger among specialists. In addition, a recent JAMA Health Forum study found that male physicians earned 21%-24% more per hour than female physicians.

Dr. Pinter-Brown, who now works at the University of California, Irvine, alleged that she was paid $200,000 less annually, on average, than her male colleagues.

That’s not surprising, says Martha Gulati, MD, professor and director of preventive cardiology at Cedars-Sinai Smidt Heart Institute, Los Angeles. She coauthored a commentary about gender disparities in JAMA Network Open. Dr. Gulati told this news organization that even a “small” pay disparity of $100,000 annually adds up.

“Let’s say the [male physician] invests it at 3% and adds to it yearly. Even without a raise, in 20 years, that is approximately $3 million,” Dr. Gulati explained. “Once you find out you are paid less than your male colleagues, you are upset. Your sense of value and self-worth disappears.”

Eileen Barrett, MD, MPH, president-elect of the American Medical Women’s Association, said that gender discrimination is likely more prevalent than research indicates. She told this news organization that self-doubt and fear of retaliation keep many from exposing the mistreatment.

Although more women are entering medicine, too few rise to the highest positions, Dr. Barrett said.

“Unfortunately, many are pulled and pushed into specialties and subspecialties that have lower compensation and are not promoted to leadership, so just having numbers isn’t enough to achieve equity,” Dr. Barrett said.

Dr. Pinter-Brown claimed she was repeatedly harassed and intimidated by Dr. de Vos from 2008 to 2015. Despite voicing concerns multiple times about the discriminatory behavior, the only resolutions offered by the male-dominated program leadership were for her to separate from the group and conduct lymphoma research independently or to avoid interacting with Dr. de Vos, court records said.

Even the school’s male Title IX officer, Jan Tillisch, MD, who handled gender-based discrimination complaints, reportedly made sexist comments. When Dr. Pinter-Brown sought his help, he allegedly told her that she had a reputation as an “angry woman” and “diva,” court records showed.

According to court documents, Dr. Pinter-Brown endured nitpicking and research audits as retaliation for speaking out, temporarily suspending her research privileges. She said she was subsequently removed from the director position and replaced by Dr. de Vos.

Female physicians who report discriminatory behavior often have unfavorable outcomes and risk future career prospects, Dr. Gulati said.

To shift this dynamic, she said institutions must increase transparency and practices that support female doctors receiving “equal pay for equal work.”
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved ColoSense (Geneoscopy, Inc), a multitarget stool RNA (mt-sRNA) test for colorectal cancer (CRC) screening in adults aged 45 years or older who are at average risk for CRC.

ColoSense, which had breakthrough device designation by the FDA, detects colorectal neoplasia–associated RNA markers and the presence of occult hemoglobin in human stool. 

A positive ColoSense test result may indicate the presence of CRC, advanced adenomas, or serrated precancerous lesions and should be followed by a colonoscopy, the company said in a news release. 

The FDA approval was based on results of the CRC-PREVENT trial, which evaluated the ColoSense mt-sRNA test in a diverse group of adults undergoing colonoscopy. 

Olivier Le Moal/Getty Images

The mt-sRNA test results were compared with the colonoscopy results.

Among all average-risk individuals, the sensitivity of the mt-sRNA test was 93% for CRC, 100% for early (stage I) CRC, and 45% for advanced adenomas. In a subgroup of those aged 45-49 years, the sensitivity was 100% for CRC and 44% for advanced adenomas.

The trial results were presented last year at the American College of Gastroenterology annual meeting and simultaneously published in JAMA .

CRC is the second deadliest cancer in the United States, and adherence rates to recommended colonoscopies as a screening modality have remained consistently low at roughly 60%. 

Cases of CRC are also rising among people younger than age 50 years, leading the United States Preventive Services Task Force to recommend initiation of CRC screening at age 45 years.

“The growing number of adults diagnosed with colorectal cancer underscores the urgent need for innovative approaches in screening. It’s essential to eliminate obstacles and broaden the availability of screening methods for healthcare providers and patients,” Anjee Davis, president of Fight CRC, said in the news release. 

“We hope that introducing new FDA-approved diagnostic tools, including stool-based tests like ColoSense, will help to advance access and increase screening rates, ultimately reducing the impact of late-stage colorectal cancer diagnoses,” Ms. Davis said. 

The company plans to make ColoSense available in the United States later this year or early in 2025.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved ColoSense (Geneoscopy, Inc), a multitarget stool RNA (mt-sRNA) test for colorectal cancer (CRC) screening in adults aged 45 years or older who are at average risk for CRC.

ColoSense, which had breakthrough device designation by the FDA, detects colorectal neoplasia–associated RNA markers and the presence of occult hemoglobin in human stool. 

A positive ColoSense test result may indicate the presence of CRC, advanced adenomas, or serrated precancerous lesions and should be followed by a colonoscopy, the company said in a news release. 

The FDA approval was based on results of the CRC-PREVENT trial, which evaluated the ColoSense mt-sRNA test in a diverse group of adults undergoing colonoscopy. 

Olivier Le Moal/Getty Images

The mt-sRNA test results were compared with the colonoscopy results.

Among all average-risk individuals, the sensitivity of the mt-sRNA test was 93% for CRC, 100% for early (stage I) CRC, and 45% for advanced adenomas. In a subgroup of those aged 45-49 years, the sensitivity was 100% for CRC and 44% for advanced adenomas.

The trial results were presented last year at the American College of Gastroenterology annual meeting and simultaneously published in JAMA .

CRC is the second deadliest cancer in the United States, and adherence rates to recommended colonoscopies as a screening modality have remained consistently low at roughly 60%. 

Cases of CRC are also rising among people younger than age 50 years, leading the United States Preventive Services Task Force to recommend initiation of CRC screening at age 45 years.

“The growing number of adults diagnosed with colorectal cancer underscores the urgent need for innovative approaches in screening. It’s essential to eliminate obstacles and broaden the availability of screening methods for healthcare providers and patients,” Anjee Davis, president of Fight CRC, said in the news release. 

“We hope that introducing new FDA-approved diagnostic tools, including stool-based tests like ColoSense, will help to advance access and increase screening rates, ultimately reducing the impact of late-stage colorectal cancer diagnoses,” Ms. Davis said. 

The company plans to make ColoSense available in the United States later this year or early in 2025.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved ColoSense (Geneoscopy, Inc), a multitarget stool RNA (mt-sRNA) test for colorectal cancer (CRC) screening in adults aged 45 years or older who are at average risk for CRC.

ColoSense, which had breakthrough device designation by the FDA, detects colorectal neoplasia–associated RNA markers and the presence of occult hemoglobin in human stool. 

A positive ColoSense test result may indicate the presence of CRC, advanced adenomas, or serrated precancerous lesions and should be followed by a colonoscopy, the company said in a news release. 

The FDA approval was based on results of the CRC-PREVENT trial, which evaluated the ColoSense mt-sRNA test in a diverse group of adults undergoing colonoscopy. 

Olivier Le Moal/Getty Images

The mt-sRNA test results were compared with the colonoscopy results.

Among all average-risk individuals, the sensitivity of the mt-sRNA test was 93% for CRC, 100% for early (stage I) CRC, and 45% for advanced adenomas. In a subgroup of those aged 45-49 years, the sensitivity was 100% for CRC and 44% for advanced adenomas.

The trial results were presented last year at the American College of Gastroenterology annual meeting and simultaneously published in JAMA .

CRC is the second deadliest cancer in the United States, and adherence rates to recommended colonoscopies as a screening modality have remained consistently low at roughly 60%. 

Cases of CRC are also rising among people younger than age 50 years, leading the United States Preventive Services Task Force to recommend initiation of CRC screening at age 45 years.

“The growing number of adults diagnosed with colorectal cancer underscores the urgent need for innovative approaches in screening. It’s essential to eliminate obstacles and broaden the availability of screening methods for healthcare providers and patients,” Anjee Davis, president of Fight CRC, said in the news release. 

“We hope that introducing new FDA-approved diagnostic tools, including stool-based tests like ColoSense, will help to advance access and increase screening rates, ultimately reducing the impact of late-stage colorectal cancer diagnoses,” Ms. Davis said. 

The company plans to make ColoSense available in the United States later this year or early in 2025.

A version of this article appeared on Medscape.com.

The topic of head and neck cancer is especially timely since the disease is evolving. A hematologist/oncologist with the Association of VA Hematology/Oncology (AVAHO) told colleagues that specialists are grappling with how to de-escalate treatment.

Molly Tokaz, MD, of Veterans Affairs Puget Sound Health Care and the University of Washington said tobacco is fading as a cause as fewer people smoke, and that human papillomavirus (HPV) is triggering more cases. HPV-positive patients have better prognoses, raising the prospect that their treatment could be adjusted.

“Instead of increasing the amount of therapy we're giving, we’re trying to peel it back,” she said. “If they’re going to respond no matter what we do, why are we going in with these huge weapons of mass destruction if we can get the same results with something more like a light infantry?”

Tokaz spoke about deescalating therapy at a May 2024 regional AVAHO meeting in Seattle that was focused on head and neck cancer. She elaborated on her presentation in an interview with Federal Practitioner. according to Tokaz, 90% of head and neck cancers are mucosal squamous cell carcinomas (SCC). HPV is associated specifically with nasopharyngeal cancer, which is distinct from SCC, and oropharyngeal cancer, which has been linked to better prognoses.

HPV-positive head and neck cancer is a unique entity with its own epidemiology, clinical prognosis, and treatment. “Patients tend to be younger without the same number of comorbid conditions,” Tokaz said. “Some of them are never smokers or light smokers. So, it's a different demographic than we’ve seen traditionally.”

The bad news is that HPV-associated head and neck cancer numbers are on the rise. Fortunately, outcomes tend to be better for the HPV-positive forms.

As for therapy for head and neck cancer, immunotherapy and targeted therapy play smaller roles than in some other cancers because the form tends to be diagnosed in early stages before metastases appear. Surgery, chemotherapy, and radiation remain the major treatments. According to Tokaz’s presentation, surgery, or radiation—often with minimal adjuvant chemotherapy—can be appropriate for the earliest stage I and II cases of head and neck SCC. (She noted that HPV-positive oropharyngeal squamous cell carcinoma has its own staging system.)

Stage I and II cases make up 15% of new diagnoses and have a 5-year survival rate of > 70%. “In the earliest days, our main role was to make radiation work better and reduce it while adding a minimum amount of toxicity mutations,” she said. “Chemotherapy can help, but it’s only demonstrated improvement in overall survival in patients with positive surgical margins and extracapsular extension.”

In Stage III, IVA, and IVB cases, which make up 70% of new diagnoses, chemotherapy plus radiation is recommended. Five-year survival drops to 30% to 50%. Finally, 10% of new diagnoses are Stage IVC, which is incurable and median survival is < 1 year.

Since HPV-positive patients generally have better prognoses, oncologists are considering how to adjust their treatment. However, Tokaz notes that clinical trials have not shown a benefit from less intensive treatment in these patients. “At this point, we still treat them the same way as HPV-negative patients. But it's an ongoing area of research.”

Researchers are also exploring how to optimize regimens in patients ineligible for treatment with the chemotherapy agent cisplatin. “These folks have been traditionally excluded from clinical trials because they’re sicker,” Tokaz explained. “Researchers normally want the fittest and the best patients [in trials]. If you give a drug to someone with a lot of other comorbid conditions, they might not do as well with it, and it makes your drug look bad.”

Figuring out how to treat these patients is an especially urgent task in head and neck cancer because so many patients are frail and have comorbidities. More globally, Tokaz said the rise of HPV-related head and neck cancer highlights the importance of HPV vaccination, which is crucial for preventing cervical and anal cancer in addition to head and neck cancer. “HPV vaccination for children and young adults is crucial.”

Molly Tokaz, MD, reported no relevant financial relationships.

The topic of head and neck cancer is especially timely since the disease is evolving. A hematologist/oncologist with the Association of VA Hematology/Oncology (AVAHO) told colleagues that specialists are grappling with how to de-escalate treatment.

Molly Tokaz, MD, of Veterans Affairs Puget Sound Health Care and the University of Washington said tobacco is fading as a cause as fewer people smoke, and that human papillomavirus (HPV) is triggering more cases. HPV-positive patients have better prognoses, raising the prospect that their treatment could be adjusted.

“Instead of increasing the amount of therapy we're giving, we’re trying to peel it back,” she said. “If they’re going to respond no matter what we do, why are we going in with these huge weapons of mass destruction if we can get the same results with something more like a light infantry?”

Tokaz spoke about deescalating therapy at a May 2024 regional AVAHO meeting in Seattle that was focused on head and neck cancer. She elaborated on her presentation in an interview with Federal Practitioner. according to Tokaz, 90% of head and neck cancers are mucosal squamous cell carcinomas (SCC). HPV is associated specifically with nasopharyngeal cancer, which is distinct from SCC, and oropharyngeal cancer, which has been linked to better prognoses.

HPV-positive head and neck cancer is a unique entity with its own epidemiology, clinical prognosis, and treatment. “Patients tend to be younger without the same number of comorbid conditions,” Tokaz said. “Some of them are never smokers or light smokers. So, it's a different demographic than we’ve seen traditionally.”

The bad news is that HPV-associated head and neck cancer numbers are on the rise. Fortunately, outcomes tend to be better for the HPV-positive forms.

As for therapy for head and neck cancer, immunotherapy and targeted therapy play smaller roles than in some other cancers because the form tends to be diagnosed in early stages before metastases appear. Surgery, chemotherapy, and radiation remain the major treatments. According to Tokaz’s presentation, surgery, or radiation—often with minimal adjuvant chemotherapy—can be appropriate for the earliest stage I and II cases of head and neck SCC. (She noted that HPV-positive oropharyngeal squamous cell carcinoma has its own staging system.)

Stage I and II cases make up 15% of new diagnoses and have a 5-year survival rate of > 70%. “In the earliest days, our main role was to make radiation work better and reduce it while adding a minimum amount of toxicity mutations,” she said. “Chemotherapy can help, but it’s only demonstrated improvement in overall survival in patients with positive surgical margins and extracapsular extension.”

In Stage III, IVA, and IVB cases, which make up 70% of new diagnoses, chemotherapy plus radiation is recommended. Five-year survival drops to 30% to 50%. Finally, 10% of new diagnoses are Stage IVC, which is incurable and median survival is < 1 year.

Since HPV-positive patients generally have better prognoses, oncologists are considering how to adjust their treatment. However, Tokaz notes that clinical trials have not shown a benefit from less intensive treatment in these patients. “At this point, we still treat them the same way as HPV-negative patients. But it's an ongoing area of research.”

Researchers are also exploring how to optimize regimens in patients ineligible for treatment with the chemotherapy agent cisplatin. “These folks have been traditionally excluded from clinical trials because they’re sicker,” Tokaz explained. “Researchers normally want the fittest and the best patients [in trials]. If you give a drug to someone with a lot of other comorbid conditions, they might not do as well with it, and it makes your drug look bad.”

Figuring out how to treat these patients is an especially urgent task in head and neck cancer because so many patients are frail and have comorbidities. More globally, Tokaz said the rise of HPV-related head and neck cancer highlights the importance of HPV vaccination, which is crucial for preventing cervical and anal cancer in addition to head and neck cancer. “HPV vaccination for children and young adults is crucial.”

Molly Tokaz, MD, reported no relevant financial relationships.

The topic of head and neck cancer is especially timely since the disease is evolving. A hematologist/oncologist with the Association of VA Hematology/Oncology (AVAHO) told colleagues that specialists are grappling with how to de-escalate treatment.

Molly Tokaz, MD, of Veterans Affairs Puget Sound Health Care and the University of Washington said tobacco is fading as a cause as fewer people smoke, and that human papillomavirus (HPV) is triggering more cases. HPV-positive patients have better prognoses, raising the prospect that their treatment could be adjusted.

“Instead of increasing the amount of therapy we're giving, we’re trying to peel it back,” she said. “If they’re going to respond no matter what we do, why are we going in with these huge weapons of mass destruction if we can get the same results with something more like a light infantry?”

Tokaz spoke about deescalating therapy at a May 2024 regional AVAHO meeting in Seattle that was focused on head and neck cancer. She elaborated on her presentation in an interview with Federal Practitioner. according to Tokaz, 90% of head and neck cancers are mucosal squamous cell carcinomas (SCC). HPV is associated specifically with nasopharyngeal cancer, which is distinct from SCC, and oropharyngeal cancer, which has been linked to better prognoses.

HPV-positive head and neck cancer is a unique entity with its own epidemiology, clinical prognosis, and treatment. “Patients tend to be younger without the same number of comorbid conditions,” Tokaz said. “Some of them are never smokers or light smokers. So, it's a different demographic than we’ve seen traditionally.”

The bad news is that HPV-associated head and neck cancer numbers are on the rise. Fortunately, outcomes tend to be better for the HPV-positive forms.

As for therapy for head and neck cancer, immunotherapy and targeted therapy play smaller roles than in some other cancers because the form tends to be diagnosed in early stages before metastases appear. Surgery, chemotherapy, and radiation remain the major treatments. According to Tokaz’s presentation, surgery, or radiation—often with minimal adjuvant chemotherapy—can be appropriate for the earliest stage I and II cases of head and neck SCC. (She noted that HPV-positive oropharyngeal squamous cell carcinoma has its own staging system.)

Stage I and II cases make up 15% of new diagnoses and have a 5-year survival rate of > 70%. “In the earliest days, our main role was to make radiation work better and reduce it while adding a minimum amount of toxicity mutations,” she said. “Chemotherapy can help, but it’s only demonstrated improvement in overall survival in patients with positive surgical margins and extracapsular extension.”

In Stage III, IVA, and IVB cases, which make up 70% of new diagnoses, chemotherapy plus radiation is recommended. Five-year survival drops to 30% to 50%. Finally, 10% of new diagnoses are Stage IVC, which is incurable and median survival is < 1 year.

Since HPV-positive patients generally have better prognoses, oncologists are considering how to adjust their treatment. However, Tokaz notes that clinical trials have not shown a benefit from less intensive treatment in these patients. “At this point, we still treat them the same way as HPV-negative patients. But it's an ongoing area of research.”

Researchers are also exploring how to optimize regimens in patients ineligible for treatment with the chemotherapy agent cisplatin. “These folks have been traditionally excluded from clinical trials because they’re sicker,” Tokaz explained. “Researchers normally want the fittest and the best patients [in trials]. If you give a drug to someone with a lot of other comorbid conditions, they might not do as well with it, and it makes your drug look bad.”

Figuring out how to treat these patients is an especially urgent task in head and neck cancer because so many patients are frail and have comorbidities. More globally, Tokaz said the rise of HPV-related head and neck cancer highlights the importance of HPV vaccination, which is crucial for preventing cervical and anal cancer in addition to head and neck cancer. “HPV vaccination for children and young adults is crucial.”

Molly Tokaz, MD, reported no relevant financial relationships.

WASHINGTON, DC – A mouth rinse used to identify oral microbiome composition could serve as an early-detection tool for gastric cancer, new evidence suggests.

Researchers found distinct bacterial composition differences in patient samples that point to the potential for oral microbial signatures to be used as biomarkers for assessing gastric cancer risk. 

“Too many patients are being diagnosed too late. There are no formal screening guidelines for gastric cancer, and more than half of patients with gastric cancer do not receive a diagnosis until their cancer is already at an advanced stage,” said Shruthi Reddy Perati, MD, a general surgery resident at Rutgers University Robert Wood Johnson School of Medicine in New Brunswick, New Jersey.

Detecting gastric cancer now generally requires an invasive procedure, such as endoscopy. Therefore, a noninvasive “swish and spit” test could be more accessible and allow for more widespread screening, Dr. Perati said at a May 8 press briefing during which her research (Abstract 949) was previewed for Digestive Disease Week^® (DDW).

Gastric cancer, also known as stomach cancer, is the fourth most common cause of cancer-related death in the world. The United States can expect 26,890 new cases and 10,880 deaths from this type of cancer in 2024, the American Cancer Society estimates.
 

Microbial Signatures Found

Dr. Perati and colleagues collected oral rinse samples from 98 patients: 30 known to have gastric cancer , 30 with precancerous gastric conditions (pre–gastric cancer), and 38 control participants without pre-gastric or gastric cancer. Sixty-two percent were women, 32% were Hispanic, 31% had diabetes, and 18% were smokers.

The researchers analyzed the samples for alpha and beta diversity and conducted differential analysis using the framework called analysis of compositions of microbiomes.

They found distinct differences between the oral microbiomes of the healthy group and those of the groups with gastric cancer and pre–gastric cancer. In addition, the microbiomes of participants with cancer and of those with precancerous conditions were similar.

The results suggest that the microbiome changes may occur as soon as the stomach environment starts to undergo changes that can eventually turn into cancer.

“The oral microbiome may serve as a window into the composition of the stomach environment,” Dr. Perati said.

The investigators created a screening model to detect the most relevant 13 bacterial genera that differed between the control group and the gastric cancer and pre–gastric cancer groups. The tenfold cross-validation model demonstrated good ability to discriminate using bacteria alone (area under the curve [AUC], 0.74) and was further improved with the addition of clinical variables, including demographics and comorbidities (AUC, 0.91), the researchers noted.

As the investigators noted, the model’s performance improved with the addition of clinical variables, said Loren Laine, MD, professor of medicine (digestive diseases) at Yale School of Medicine and chair of DDW 2024.

An AUC of 0.74 using bacteria alone, which increased to 0.91 by adding demographics and comorbidities, “[is] starting to be really meaningful,” Dr. Laine said.

Further studies should evaluate the test’s sensitivity and specificity, Dr. Laine added.
 

Additional Considerations

The microbiome can vary between people and within the same individual over time. Probiotics, antibiotics, and diet can lead to changes in the microbiome, Dr. Perati said.

When asked how these changes could affect the accuracy of an oral rinse test, Dr. Perati said “it’s known that, in general, dietary modifications can have an impact on the diversity and the prevalence of certain bacteria throughout the GI tract.”

Though variance is expected, we’re hoping to see that the differences in the microbiome composition between the malignant groups and the control groups are more significant than those lower-level background changes due to dietary modifications, for example, she added.

The research is in its early days, and the results need to be validated in a larger study, Dr. Perati said.

Ninety-eight patients is “still a very small number,” said Dr. Laine, who co-moderated the press briefing. “More research is needed.”

Still, the study “has huge implications that could eventually lead to the development of noninvasive and accessible early screening for gastric cancer,” she said.

Dr. Perati and Dr. Laine reported no relevant financial relationships. The study was independently supported.

A version of this article appeared on Medscape.com.

WASHINGTON, DC – A mouth rinse used to identify oral microbiome composition could serve as an early-detection tool for gastric cancer, new evidence suggests.

Researchers found distinct bacterial composition differences in patient samples that point to the potential for oral microbial signatures to be used as biomarkers for assessing gastric cancer risk. 

“Too many patients are being diagnosed too late. There are no formal screening guidelines for gastric cancer, and more than half of patients with gastric cancer do not receive a diagnosis until their cancer is already at an advanced stage,” said Shruthi Reddy Perati, MD, a general surgery resident at Rutgers University Robert Wood Johnson School of Medicine in New Brunswick, New Jersey.

Detecting gastric cancer now generally requires an invasive procedure, such as endoscopy. Therefore, a noninvasive “swish and spit” test could be more accessible and allow for more widespread screening, Dr. Perati said at a May 8 press briefing during which her research (Abstract 949) was previewed for Digestive Disease Week^® (DDW).

Gastric cancer, also known as stomach cancer, is the fourth most common cause of cancer-related death in the world. The United States can expect 26,890 new cases and 10,880 deaths from this type of cancer in 2024, the American Cancer Society estimates.
 

Microbial Signatures Found

Dr. Perati and colleagues collected oral rinse samples from 98 patients: 30 known to have gastric cancer , 30 with precancerous gastric conditions (pre–gastric cancer), and 38 control participants without pre-gastric or gastric cancer. Sixty-two percent were women, 32% were Hispanic, 31% had diabetes, and 18% were smokers.

The researchers analyzed the samples for alpha and beta diversity and conducted differential analysis using the framework called analysis of compositions of microbiomes.

They found distinct differences between the oral microbiomes of the healthy group and those of the groups with gastric cancer and pre–gastric cancer. In addition, the microbiomes of participants with cancer and of those with precancerous conditions were similar.

The results suggest that the microbiome changes may occur as soon as the stomach environment starts to undergo changes that can eventually turn into cancer.

“The oral microbiome may serve as a window into the composition of the stomach environment,” Dr. Perati said.

The investigators created a screening model to detect the most relevant 13 bacterial genera that differed between the control group and the gastric cancer and pre–gastric cancer groups. The tenfold cross-validation model demonstrated good ability to discriminate using bacteria alone (area under the curve [AUC], 0.74) and was further improved with the addition of clinical variables, including demographics and comorbidities (AUC, 0.91), the researchers noted.

As the investigators noted, the model’s performance improved with the addition of clinical variables, said Loren Laine, MD, professor of medicine (digestive diseases) at Yale School of Medicine and chair of DDW 2024.

An AUC of 0.74 using bacteria alone, which increased to 0.91 by adding demographics and comorbidities, “[is] starting to be really meaningful,” Dr. Laine said.

Further studies should evaluate the test’s sensitivity and specificity, Dr. Laine added.
 

Additional Considerations

The microbiome can vary between people and within the same individual over time. Probiotics, antibiotics, and diet can lead to changes in the microbiome, Dr. Perati said.

When asked how these changes could affect the accuracy of an oral rinse test, Dr. Perati said “it’s known that, in general, dietary modifications can have an impact on the diversity and the prevalence of certain bacteria throughout the GI tract.”

Though variance is expected, we’re hoping to see that the differences in the microbiome composition between the malignant groups and the control groups are more significant than those lower-level background changes due to dietary modifications, for example, she added.

The research is in its early days, and the results need to be validated in a larger study, Dr. Perati said.

Ninety-eight patients is “still a very small number,” said Dr. Laine, who co-moderated the press briefing. “More research is needed.”

Still, the study “has huge implications that could eventually lead to the development of noninvasive and accessible early screening for gastric cancer,” she said.

Dr. Perati and Dr. Laine reported no relevant financial relationships. The study was independently supported.

A version of this article appeared on Medscape.com.

WASHINGTON, DC – A mouth rinse used to identify oral microbiome composition could serve as an early-detection tool for gastric cancer, new evidence suggests.

Researchers found distinct bacterial composition differences in patient samples that point to the potential for oral microbial signatures to be used as biomarkers for assessing gastric cancer risk. 

“Too many patients are being diagnosed too late. There are no formal screening guidelines for gastric cancer, and more than half of patients with gastric cancer do not receive a diagnosis until their cancer is already at an advanced stage,” said Shruthi Reddy Perati, MD, a general surgery resident at Rutgers University Robert Wood Johnson School of Medicine in New Brunswick, New Jersey.

Detecting gastric cancer now generally requires an invasive procedure, such as endoscopy. Therefore, a noninvasive “swish and spit” test could be more accessible and allow for more widespread screening, Dr. Perati said at a May 8 press briefing during which her research (Abstract 949) was previewed for Digestive Disease Week^® (DDW).

Gastric cancer, also known as stomach cancer, is the fourth most common cause of cancer-related death in the world. The United States can expect 26,890 new cases and 10,880 deaths from this type of cancer in 2024, the American Cancer Society estimates.
 

Microbial Signatures Found

Dr. Perati and colleagues collected oral rinse samples from 98 patients: 30 known to have gastric cancer , 30 with precancerous gastric conditions (pre–gastric cancer), and 38 control participants without pre-gastric or gastric cancer. Sixty-two percent were women, 32% were Hispanic, 31% had diabetes, and 18% were smokers.

The researchers analyzed the samples for alpha and beta diversity and conducted differential analysis using the framework called analysis of compositions of microbiomes.

They found distinct differences between the oral microbiomes of the healthy group and those of the groups with gastric cancer and pre–gastric cancer. In addition, the microbiomes of participants with cancer and of those with precancerous conditions were similar.

The results suggest that the microbiome changes may occur as soon as the stomach environment starts to undergo changes that can eventually turn into cancer.

“The oral microbiome may serve as a window into the composition of the stomach environment,” Dr. Perati said.

The investigators created a screening model to detect the most relevant 13 bacterial genera that differed between the control group and the gastric cancer and pre–gastric cancer groups. The tenfold cross-validation model demonstrated good ability to discriminate using bacteria alone (area under the curve [AUC], 0.74) and was further improved with the addition of clinical variables, including demographics and comorbidities (AUC, 0.91), the researchers noted.

As the investigators noted, the model’s performance improved with the addition of clinical variables, said Loren Laine, MD, professor of medicine (digestive diseases) at Yale School of Medicine and chair of DDW 2024.

An AUC of 0.74 using bacteria alone, which increased to 0.91 by adding demographics and comorbidities, “[is] starting to be really meaningful,” Dr. Laine said.

Further studies should evaluate the test’s sensitivity and specificity, Dr. Laine added.
 

Additional Considerations

The microbiome can vary between people and within the same individual over time. Probiotics, antibiotics, and diet can lead to changes in the microbiome, Dr. Perati said.

When asked how these changes could affect the accuracy of an oral rinse test, Dr. Perati said “it’s known that, in general, dietary modifications can have an impact on the diversity and the prevalence of certain bacteria throughout the GI tract.”

Though variance is expected, we’re hoping to see that the differences in the microbiome composition between the malignant groups and the control groups are more significant than those lower-level background changes due to dietary modifications, for example, she added.

The research is in its early days, and the results need to be validated in a larger study, Dr. Perati said.

Ninety-eight patients is “still a very small number,” said Dr. Laine, who co-moderated the press briefing. “More research is needed.”

Still, the study “has huge implications that could eventually lead to the development of noninvasive and accessible early screening for gastric cancer,” she said.

Dr. Perati and Dr. Laine reported no relevant financial relationships. The study was independently supported.

A version of this article appeared on Medscape.com.

TOPLINE:

A hypofractionated intensity-modulated radiotherapy (IMRT) may be safe and well-tolerated in women with cervical cancer undergoing pelvic irradiation with concurrent chemotherapy following surgical resection, results from the phase 2 POHIM-CCRT trial suggested.

METHODOLOGY:

• To date, no studies have assessed the treatment outcomes and toxic effects of hypofractionated IMRT following radical hysterectomy in patients with cervical cancer undergoing curative radiotherapy.
• The team analyzed outcomes from 79 patients undergoing hypofractionated IMRT for cervical cancer after radical hysterectomy and pelvic lymph node dissection.
• Patients were a median age of 48; 29.5% had stage IB to IIA disease, another 29.5% had stage IIB disease, and 41% had stage III disease. Patients also had at least one of the following criteria following radical hysterectomy and pelvic lymph node dissection: lymph node metastasis (39.7%), parametrial invasion (54.4%), and positive resection margin (5.1%).
• The prescribed dose to the planning target volume was 40 Gy, delivered in 16 fractions to the whole pelvis, with any type of IMRT permitted. Overall, 71 patients also underwent concurrent weekly cisplatin (40 mg/m² of body surface area for three cycles), and eight received fluorouracil (1000 mg/m² on days 1-5) with cisplatin (60 mg/m² for two cycles).
• The primary endpoint was the incidence of acute grade 3 or higher gastrointestinal tract, genitourinary, and hematologic toxic effects during radiotherapy or within 3 months of completing radiotherapy.

TAKEAWAY:

• After radiotherapy, only two patients (2.5%) experienced acute grade 3 or higher toxic effects. One was hospitalized for enterocolitis on the last day of radiotherapy and developed grade 3 anemia 3 months after completing radiotherapy; the other experienced hematologic toxic effects and also developed grade 3 anemia 3 months after completing radiotherapy.
• No patients experienced late grade 3 or higher toxic effects.
• When assessing toxic effects of any grade, acute and late gastrointestinal tract toxicities occurred in 76% and 31.6% of patients, respectively; acute and late genitourinary toxicities, all grade 1, occurred in 19% and 24.1% of patients, respectively; and hematologic toxicities occurred in 29.1% and 6.3% of patients, respectively.
• Overall, at 3 years, 79.3% of patients were disease-free and 98% were alive. After a median follow-up of 43 months, 16 patients (20.3%) experienced disease recurrence, four of whom were salvaged and three of whom died.

IN PRACTICE:

“This nonrandomized controlled trial is the first prospective trial, to our knowledge, to show acceptable acute toxic effects of hypofractionated IMRT for cervical cancer in a postoperative concurrent chemoradiotherapy setting,” the authors said, adding that the rate of grade 3 or higher acute toxic effects of 2.5% reported in this study was “substantially lower than our initial hypothesis of less than 15%.”

However , in an accompanying editorial, Mark E. Bernard, MD, of the University of Kentucky College of Medicine, Lexington, highlighted caveats to the study design and raised two core questions: “Should acute toxic effects be the primary endpoint of a single-group, phase 2 study using hypofractionation with fewer cycles of concurrent chemotherapy? Should the primary endpoint rather have been a cancer control endpoint, such as disease-free survival, overall survival, or local control?”

Still, Dr. Bernard wrote, “This trial does help lay the foundation for future pelvic hypofractionated trials with concurrent chemotherapy, especially for gynecological malignant tumors.”

SOURCE:

The research, led by Won Park, MD, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea, was published in JAMA Oncology.

LIMITATIONS:

The trial is a single-arm study, with a short follow-up time. In the editorial, Bernard listed several limitations, including the fact that patients received fewer cycles of concurrent chemotherapy than what’s typically given in this population.

DISCLOSURES:

No funding or relevant financial relationships were declared.

A version of this article appeared on Medscape.com.

TOPLINE:

A hypofractionated intensity-modulated radiotherapy (IMRT) may be safe and well-tolerated in women with cervical cancer undergoing pelvic irradiation with concurrent chemotherapy following surgical resection, results from the phase 2 POHIM-CCRT trial suggested.

METHODOLOGY:

• To date, no studies have assessed the treatment outcomes and toxic effects of hypofractionated IMRT following radical hysterectomy in patients with cervical cancer undergoing curative radiotherapy.
• The team analyzed outcomes from 79 patients undergoing hypofractionated IMRT for cervical cancer after radical hysterectomy and pelvic lymph node dissection.
• Patients were a median age of 48; 29.5% had stage IB to IIA disease, another 29.5% had stage IIB disease, and 41% had stage III disease. Patients also had at least one of the following criteria following radical hysterectomy and pelvic lymph node dissection: lymph node metastasis (39.7%), parametrial invasion (54.4%), and positive resection margin (5.1%).
• The prescribed dose to the planning target volume was 40 Gy, delivered in 16 fractions to the whole pelvis, with any type of IMRT permitted. Overall, 71 patients also underwent concurrent weekly cisplatin (40 mg/m² of body surface area for three cycles), and eight received fluorouracil (1000 mg/m² on days 1-5) with cisplatin (60 mg/m² for two cycles).
• The primary endpoint was the incidence of acute grade 3 or higher gastrointestinal tract, genitourinary, and hematologic toxic effects during radiotherapy or within 3 months of completing radiotherapy.

TAKEAWAY:

• After radiotherapy, only two patients (2.5%) experienced acute grade 3 or higher toxic effects. One was hospitalized for enterocolitis on the last day of radiotherapy and developed grade 3 anemia 3 months after completing radiotherapy; the other experienced hematologic toxic effects and also developed grade 3 anemia 3 months after completing radiotherapy.
• No patients experienced late grade 3 or higher toxic effects.
• When assessing toxic effects of any grade, acute and late gastrointestinal tract toxicities occurred in 76% and 31.6% of patients, respectively; acute and late genitourinary toxicities, all grade 1, occurred in 19% and 24.1% of patients, respectively; and hematologic toxicities occurred in 29.1% and 6.3% of patients, respectively.
• Overall, at 3 years, 79.3% of patients were disease-free and 98% were alive. After a median follow-up of 43 months, 16 patients (20.3%) experienced disease recurrence, four of whom were salvaged and three of whom died.

IN PRACTICE:

“This nonrandomized controlled trial is the first prospective trial, to our knowledge, to show acceptable acute toxic effects of hypofractionated IMRT for cervical cancer in a postoperative concurrent chemoradiotherapy setting,” the authors said, adding that the rate of grade 3 or higher acute toxic effects of 2.5% reported in this study was “substantially lower than our initial hypothesis of less than 15%.”

However , in an accompanying editorial, Mark E. Bernard, MD, of the University of Kentucky College of Medicine, Lexington, highlighted caveats to the study design and raised two core questions: “Should acute toxic effects be the primary endpoint of a single-group, phase 2 study using hypofractionation with fewer cycles of concurrent chemotherapy? Should the primary endpoint rather have been a cancer control endpoint, such as disease-free survival, overall survival, or local control?”

Still, Dr. Bernard wrote, “This trial does help lay the foundation for future pelvic hypofractionated trials with concurrent chemotherapy, especially for gynecological malignant tumors.”

SOURCE:

The research, led by Won Park, MD, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea, was published in JAMA Oncology.

LIMITATIONS:

The trial is a single-arm study, with a short follow-up time. In the editorial, Bernard listed several limitations, including the fact that patients received fewer cycles of concurrent chemotherapy than what’s typically given in this population.

DISCLOSURES:

No funding or relevant financial relationships were declared.

A version of this article appeared on Medscape.com.

TOPLINE:

A hypofractionated intensity-modulated radiotherapy (IMRT) may be safe and well-tolerated in women with cervical cancer undergoing pelvic irradiation with concurrent chemotherapy following surgical resection, results from the phase 2 POHIM-CCRT trial suggested.

METHODOLOGY:

• To date, no studies have assessed the treatment outcomes and toxic effects of hypofractionated IMRT following radical hysterectomy in patients with cervical cancer undergoing curative radiotherapy.
• The team analyzed outcomes from 79 patients undergoing hypofractionated IMRT for cervical cancer after radical hysterectomy and pelvic lymph node dissection.
• Patients were a median age of 48; 29.5% had stage IB to IIA disease, another 29.5% had stage IIB disease, and 41% had stage III disease. Patients also had at least one of the following criteria following radical hysterectomy and pelvic lymph node dissection: lymph node metastasis (39.7%), parametrial invasion (54.4%), and positive resection margin (5.1%).
• The prescribed dose to the planning target volume was 40 Gy, delivered in 16 fractions to the whole pelvis, with any type of IMRT permitted. Overall, 71 patients also underwent concurrent weekly cisplatin (40 mg/m² of body surface area for three cycles), and eight received fluorouracil (1000 mg/m² on days 1-5) with cisplatin (60 mg/m² for two cycles).
• The primary endpoint was the incidence of acute grade 3 or higher gastrointestinal tract, genitourinary, and hematologic toxic effects during radiotherapy or within 3 months of completing radiotherapy.

TAKEAWAY:

• After radiotherapy, only two patients (2.5%) experienced acute grade 3 or higher toxic effects. One was hospitalized for enterocolitis on the last day of radiotherapy and developed grade 3 anemia 3 months after completing radiotherapy; the other experienced hematologic toxic effects and also developed grade 3 anemia 3 months after completing radiotherapy.
• No patients experienced late grade 3 or higher toxic effects.
• When assessing toxic effects of any grade, acute and late gastrointestinal tract toxicities occurred in 76% and 31.6% of patients, respectively; acute and late genitourinary toxicities, all grade 1, occurred in 19% and 24.1% of patients, respectively; and hematologic toxicities occurred in 29.1% and 6.3% of patients, respectively.
• Overall, at 3 years, 79.3% of patients were disease-free and 98% were alive. After a median follow-up of 43 months, 16 patients (20.3%) experienced disease recurrence, four of whom were salvaged and three of whom died.

IN PRACTICE:

“This nonrandomized controlled trial is the first prospective trial, to our knowledge, to show acceptable acute toxic effects of hypofractionated IMRT for cervical cancer in a postoperative concurrent chemoradiotherapy setting,” the authors said, adding that the rate of grade 3 or higher acute toxic effects of 2.5% reported in this study was “substantially lower than our initial hypothesis of less than 15%.”

However , in an accompanying editorial, Mark E. Bernard, MD, of the University of Kentucky College of Medicine, Lexington, highlighted caveats to the study design and raised two core questions: “Should acute toxic effects be the primary endpoint of a single-group, phase 2 study using hypofractionation with fewer cycles of concurrent chemotherapy? Should the primary endpoint rather have been a cancer control endpoint, such as disease-free survival, overall survival, or local control?”

Still, Dr. Bernard wrote, “This trial does help lay the foundation for future pelvic hypofractionated trials with concurrent chemotherapy, especially for gynecological malignant tumors.”

SOURCE:

The research, led by Won Park, MD, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea, was published in JAMA Oncology.

LIMITATIONS:

The trial is a single-arm study, with a short follow-up time. In the editorial, Bernard listed several limitations, including the fact that patients received fewer cycles of concurrent chemotherapy than what’s typically given in this population.

DISCLOSURES:

No funding or relevant financial relationships were declared.

A version of this article appeared on Medscape.com.

BERLIN — To date, mRNA vaccines have had their largest global presence in combating the COVID-19 pandemic. Intensive research is underway on many other potential applications for this vaccine technology, which suggests a promising future. Martina Prelog, MD, a pediatric and adolescent medicine specialist at the University Hospital of Würzburg in Germany, reported on the principles, research status, and perspectives for these vaccines at the 25th Travel and Health Forum of the Center for Travel Medicine in Berlin.

To understand the future, the immunologist first examined the past. “The induction of cellular and humoral immune responses by externally injected mRNA was discovered in the 1990s,” she said.
 

Instability Challenge

Significant hurdles in mRNA vaccinations included the instability of mRNA and the immune system’s ability to identify foreign mRNA as a threat and destroy mRNA fragments. “The breakthrough toward vaccination came through Dr. Katalin Karikó, who, along with Dr. Drew Weissman, both of the University of Pennsylvania School of Medicine, discovered in 2005 that modifications of mRNA (replacing the nucleoside uridine with pseudouridine) enable better stability of mRNA, reduced immunogenicity, and higher translational capacity at the ribosomes,” said Dr. Prelog.

With this discovery, the two researchers paved the way for the development of mRNA vaccines against COVID-19 and other diseases. They were awarded the Nobel Prize in medicine for their discovery last year.
 

Improved Scalability

“Since 2009, mRNA vaccines have been studied as a treatment option for cancer,” said Dr. Prelog. “Since 2012, they have been studied for the influenza virus and respiratory syncytial virus [RSV].” Consequently, several mRNA vaccines are currently in development or in approval studies. “The mRNA technology offers the advantage of quickly and flexibly responding to new variants of pathogens and the ability to scale up production when there is high demand for a particular vaccine.”

Different forms and designations of mRNA vaccines are used, depending on the application and desired effect, said Dr. Prelog.

In nucleoside-modified mRNA vaccines, modifications in the mRNA sequence enable the mRNA to remain in the body longer and to induce protein synthesis more effectively.

Lipid nanoparticle (LNP)–encapsulated mRNA vaccines protect the coding mRNA sequences against degradation by the body’s enzymes and facilitate the uptake of mRNA into cells, where it then triggers the production of the desired protein. In addition, LNPs are involved in cell stimulation and support the self-adjuvant effect of mRNA vaccines, thus eliminating the need for adjuvants.

Self-amplifying mRNA vaccines include a special mRNA that replicates itself in the cell and contains a sequence for RNA replicase, in addition to the coding sequence for the protein. This composition enables increased production of the target protein without the need for a high amount of external mRNA administration. Such vaccines could trigger a longer and stronger immune response because the immune system has more time to interact with the protein.
 

Cancer Immunotherapy

Dr. Prelog also discussed personalized vaccines for cancer immunotherapy. Personalized mRNA vaccines are tailored to the patient’s genetic characteristics and antigens. They could be used in cancer immunotherapy to activate the immune system selectively against tumor cells.

Multivalent mRNA vaccines contain mRNA that codes for multiple antigens rather than just one protein to generate an immune response. These vaccines could be particularly useful in fighting pathogens with variable or changing surface structures or in eliciting protection against multiple pathogens simultaneously.

The technology of mRNA-encoded antibodies involves introducing mRNA into the cell, which creates light and heavy chains of antibodies. This step leads to the formation of antibodies targeted against toxins (eg, diphtheria and tetanus), animal venoms, infectious agents, or tumor cells.
 

Genetic Engineering

Dr. Prelog also reviewed genetic engineering techniques. In regenerative therapy or protein replacement therapy, skin fibroblasts or other cells are transfected with mRNA to enable conversion into induced pluripotent stem cells. This approach avoids the risk for DNA integration into the genome and associated mutation risks.

Another approach is making post-transcriptional modifications through RNA interference. For example, RNA structures can be used to inhibit the translation of disease-causing proteins. This technique is currently being tested against HIV and tumors such as melanoma.

In addition, mRNA technologies can be combined with CRISPR/Cas9 technology (“gene scissors”) to influence the creation of gene products even more precisely. The advantage of this technique is that mRNA is only transiently expressed, thus preventing unwanted side effects. Furthermore, mRNA is translated directly in the cytoplasm, leading to a faster initiation of gene editing.

Of the numerous ongoing clinical mRNA vaccine studies, around 70% focus on infections, about 12% on cancer, and the rest on autoimmune diseases and neurodegenerative disorders, said Dr. Prelog.
 

Research in Infections

Research in the fields of infectious diseases and oncology is the most advanced: mRNA vaccines against influenza and RSV are already in advanced clinical trials, Dr. Prelog told this news organization.

“Conventional influenza vaccines contain immunogenic surface molecules against hemagglutinin and neuraminidase in various combinations of influenza strains A and B and are produced in egg or cell cultures,” she said. “This is a time-consuming manufacturing process that takes months and, particularly with the egg-based process, bears the risk of changing the vaccine strain.”

“Additionally, influenza viruses undergo antigenic shift and drift through recombination, thus requiring annual adjustments to the vaccines. Thus, these influenza vaccines often lose accuracy in targeting circulating seasonal influenza strains.”

Several mRNA vaccines being tested contain not only coding sequences against hemagglutinin and neuraminidase but also for structural proteins of influenza viruses. “These are more conserved and mutate less easily, meaning they could serve as the basis for universal pandemic influenza vaccines,” said Dr. Prelog.

An advantage of mRNA vaccines, she added, is the strong cellular immune response that they elicit. This response is intended to provide additional protection alongside specific antibodies. An mRNA vaccine with coding sequences for the pre-fusion protein of RSV is in phase 3 trials for approval for vaccination in patients aged 60 years and older. It shows high effectiveness even in older patients and those with comorbidities.
 

Elaborate Purification Process

Bacterial origin plasmid DNA is used to produce mRNA vaccines. The mRNA vaccines for COVID-19 raised concerns that production-related DNA residues could pose a safety risk and cause autoimmune diseases.

These vaccines “typically undergo a very elaborate purification process,” said Dr. Prelog. “This involves enzymatic digestion with DNase to fragment and deplete plasmid DNA, followed by purification using chromatography columns, so that no safety-relevant DNA fragments should remain afterward.”

Thus, the Paul-Ehrlich-Institut also pointed out the very small, fragmented plasmid DNA residues of bacterial origin in mRNA COVID-19 vaccines pose no risk, unlike residual DNA from animal cell culture might pose in other vaccines.
 

Prevention and Therapy

In addition to the numerous advantages of mRNA vaccines (such as rapid adaptability to new or mutated pathogens, scalability, rapid production capability, self-adjuvant effect, strong induction of cellular immune responses, and safety), there are also challenges in RNA technology as a preventive and therapeutic measure, according to Dr. Prelog.

“Stability and storability, as well as the costs of new vaccine developments, play a role, as do the long-term effects regarding the persistence of antibody and cellular responses,” she said. The COVID-19 mRNA vaccines, for example, showed a well-maintained cellular immune response despite a tendency toward a rapid decline in humoral immune response.

“The experience with COVID-19 mRNA vaccines and the new vaccine developments based on mRNA technology give hope for an efficient and safe preventive and therapeutic use, particularly in the fields of infectious diseases and oncology,” Dr. Prelog concluded.

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

BERLIN — To date, mRNA vaccines have had their largest global presence in combating the COVID-19 pandemic. Intensive research is underway on many other potential applications for this vaccine technology, which suggests a promising future. Martina Prelog, MD, a pediatric and adolescent medicine specialist at the University Hospital of Würzburg in Germany, reported on the principles, research status, and perspectives for these vaccines at the 25th Travel and Health Forum of the Center for Travel Medicine in Berlin.

To understand the future, the immunologist first examined the past. “The induction of cellular and humoral immune responses by externally injected mRNA was discovered in the 1990s,” she said.
 

Instability Challenge

Significant hurdles in mRNA vaccinations included the instability of mRNA and the immune system’s ability to identify foreign mRNA as a threat and destroy mRNA fragments. “The breakthrough toward vaccination came through Dr. Katalin Karikó, who, along with Dr. Drew Weissman, both of the University of Pennsylvania School of Medicine, discovered in 2005 that modifications of mRNA (replacing the nucleoside uridine with pseudouridine) enable better stability of mRNA, reduced immunogenicity, and higher translational capacity at the ribosomes,” said Dr. Prelog.

With this discovery, the two researchers paved the way for the development of mRNA vaccines against COVID-19 and other diseases. They were awarded the Nobel Prize in medicine for their discovery last year.
 

Improved Scalability

“Since 2009, mRNA vaccines have been studied as a treatment option for cancer,” said Dr. Prelog. “Since 2012, they have been studied for the influenza virus and respiratory syncytial virus [RSV].” Consequently, several mRNA vaccines are currently in development or in approval studies. “The mRNA technology offers the advantage of quickly and flexibly responding to new variants of pathogens and the ability to scale up production when there is high demand for a particular vaccine.”

Different forms and designations of mRNA vaccines are used, depending on the application and desired effect, said Dr. Prelog.

In nucleoside-modified mRNA vaccines, modifications in the mRNA sequence enable the mRNA to remain in the body longer and to induce protein synthesis more effectively.

Lipid nanoparticle (LNP)–encapsulated mRNA vaccines protect the coding mRNA sequences against degradation by the body’s enzymes and facilitate the uptake of mRNA into cells, where it then triggers the production of the desired protein. In addition, LNPs are involved in cell stimulation and support the self-adjuvant effect of mRNA vaccines, thus eliminating the need for adjuvants.

Self-amplifying mRNA vaccines include a special mRNA that replicates itself in the cell and contains a sequence for RNA replicase, in addition to the coding sequence for the protein. This composition enables increased production of the target protein without the need for a high amount of external mRNA administration. Such vaccines could trigger a longer and stronger immune response because the immune system has more time to interact with the protein.
 

Cancer Immunotherapy

Dr. Prelog also discussed personalized vaccines for cancer immunotherapy. Personalized mRNA vaccines are tailored to the patient’s genetic characteristics and antigens. They could be used in cancer immunotherapy to activate the immune system selectively against tumor cells.

Multivalent mRNA vaccines contain mRNA that codes for multiple antigens rather than just one protein to generate an immune response. These vaccines could be particularly useful in fighting pathogens with variable or changing surface structures or in eliciting protection against multiple pathogens simultaneously.

The technology of mRNA-encoded antibodies involves introducing mRNA into the cell, which creates light and heavy chains of antibodies. This step leads to the formation of antibodies targeted against toxins (eg, diphtheria and tetanus), animal venoms, infectious agents, or tumor cells.
 

Genetic Engineering

Dr. Prelog also reviewed genetic engineering techniques. In regenerative therapy or protein replacement therapy, skin fibroblasts or other cells are transfected with mRNA to enable conversion into induced pluripotent stem cells. This approach avoids the risk for DNA integration into the genome and associated mutation risks.

Another approach is making post-transcriptional modifications through RNA interference. For example, RNA structures can be used to inhibit the translation of disease-causing proteins. This technique is currently being tested against HIV and tumors such as melanoma.

In addition, mRNA technologies can be combined with CRISPR/Cas9 technology (“gene scissors”) to influence the creation of gene products even more precisely. The advantage of this technique is that mRNA is only transiently expressed, thus preventing unwanted side effects. Furthermore, mRNA is translated directly in the cytoplasm, leading to a faster initiation of gene editing.

Of the numerous ongoing clinical mRNA vaccine studies, around 70% focus on infections, about 12% on cancer, and the rest on autoimmune diseases and neurodegenerative disorders, said Dr. Prelog.
 

Research in Infections

Research in the fields of infectious diseases and oncology is the most advanced: mRNA vaccines against influenza and RSV are already in advanced clinical trials, Dr. Prelog told this news organization.

“Conventional influenza vaccines contain immunogenic surface molecules against hemagglutinin and neuraminidase in various combinations of influenza strains A and B and are produced in egg or cell cultures,” she said. “This is a time-consuming manufacturing process that takes months and, particularly with the egg-based process, bears the risk of changing the vaccine strain.”

“Additionally, influenza viruses undergo antigenic shift and drift through recombination, thus requiring annual adjustments to the vaccines. Thus, these influenza vaccines often lose accuracy in targeting circulating seasonal influenza strains.”

Several mRNA vaccines being tested contain not only coding sequences against hemagglutinin and neuraminidase but also for structural proteins of influenza viruses. “These are more conserved and mutate less easily, meaning they could serve as the basis for universal pandemic influenza vaccines,” said Dr. Prelog.

An advantage of mRNA vaccines, she added, is the strong cellular immune response that they elicit. This response is intended to provide additional protection alongside specific antibodies. An mRNA vaccine with coding sequences for the pre-fusion protein of RSV is in phase 3 trials for approval for vaccination in patients aged 60 years and older. It shows high effectiveness even in older patients and those with comorbidities.
 

Elaborate Purification Process

Bacterial origin plasmid DNA is used to produce mRNA vaccines. The mRNA vaccines for COVID-19 raised concerns that production-related DNA residues could pose a safety risk and cause autoimmune diseases.

These vaccines “typically undergo a very elaborate purification process,” said Dr. Prelog. “This involves enzymatic digestion with DNase to fragment and deplete plasmid DNA, followed by purification using chromatography columns, so that no safety-relevant DNA fragments should remain afterward.”

Thus, the Paul-Ehrlich-Institut also pointed out the very small, fragmented plasmid DNA residues of bacterial origin in mRNA COVID-19 vaccines pose no risk, unlike residual DNA from animal cell culture might pose in other vaccines.
 

Prevention and Therapy

In addition to the numerous advantages of mRNA vaccines (such as rapid adaptability to new or mutated pathogens, scalability, rapid production capability, self-adjuvant effect, strong induction of cellular immune responses, and safety), there are also challenges in RNA technology as a preventive and therapeutic measure, according to Dr. Prelog.

“Stability and storability, as well as the costs of new vaccine developments, play a role, as do the long-term effects regarding the persistence of antibody and cellular responses,” she said. The COVID-19 mRNA vaccines, for example, showed a well-maintained cellular immune response despite a tendency toward a rapid decline in humoral immune response.

“The experience with COVID-19 mRNA vaccines and the new vaccine developments based on mRNA technology give hope for an efficient and safe preventive and therapeutic use, particularly in the fields of infectious diseases and oncology,” Dr. Prelog concluded.

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

BERLIN — To date, mRNA vaccines have had their largest global presence in combating the COVID-19 pandemic. Intensive research is underway on many other potential applications for this vaccine technology, which suggests a promising future. Martina Prelog, MD, a pediatric and adolescent medicine specialist at the University Hospital of Würzburg in Germany, reported on the principles, research status, and perspectives for these vaccines at the 25th Travel and Health Forum of the Center for Travel Medicine in Berlin.

To understand the future, the immunologist first examined the past. “The induction of cellular and humoral immune responses by externally injected mRNA was discovered in the 1990s,” she said.
 

Instability Challenge

Significant hurdles in mRNA vaccinations included the instability of mRNA and the immune system’s ability to identify foreign mRNA as a threat and destroy mRNA fragments. “The breakthrough toward vaccination came through Dr. Katalin Karikó, who, along with Dr. Drew Weissman, both of the University of Pennsylvania School of Medicine, discovered in 2005 that modifications of mRNA (replacing the nucleoside uridine with pseudouridine) enable better stability of mRNA, reduced immunogenicity, and higher translational capacity at the ribosomes,” said Dr. Prelog.

With this discovery, the two researchers paved the way for the development of mRNA vaccines against COVID-19 and other diseases. They were awarded the Nobel Prize in medicine for their discovery last year.
 

Improved Scalability

“Since 2009, mRNA vaccines have been studied as a treatment option for cancer,” said Dr. Prelog. “Since 2012, they have been studied for the influenza virus and respiratory syncytial virus [RSV].” Consequently, several mRNA vaccines are currently in development or in approval studies. “The mRNA technology offers the advantage of quickly and flexibly responding to new variants of pathogens and the ability to scale up production when there is high demand for a particular vaccine.”

Different forms and designations of mRNA vaccines are used, depending on the application and desired effect, said Dr. Prelog.

In nucleoside-modified mRNA vaccines, modifications in the mRNA sequence enable the mRNA to remain in the body longer and to induce protein synthesis more effectively.

Lipid nanoparticle (LNP)–encapsulated mRNA vaccines protect the coding mRNA sequences against degradation by the body’s enzymes and facilitate the uptake of mRNA into cells, where it then triggers the production of the desired protein. In addition, LNPs are involved in cell stimulation and support the self-adjuvant effect of mRNA vaccines, thus eliminating the need for adjuvants.

Self-amplifying mRNA vaccines include a special mRNA that replicates itself in the cell and contains a sequence for RNA replicase, in addition to the coding sequence for the protein. This composition enables increased production of the target protein without the need for a high amount of external mRNA administration. Such vaccines could trigger a longer and stronger immune response because the immune system has more time to interact with the protein.
 

Cancer Immunotherapy

Dr. Prelog also discussed personalized vaccines for cancer immunotherapy. Personalized mRNA vaccines are tailored to the patient’s genetic characteristics and antigens. They could be used in cancer immunotherapy to activate the immune system selectively against tumor cells.

Multivalent mRNA vaccines contain mRNA that codes for multiple antigens rather than just one protein to generate an immune response. These vaccines could be particularly useful in fighting pathogens with variable or changing surface structures or in eliciting protection against multiple pathogens simultaneously.

The technology of mRNA-encoded antibodies involves introducing mRNA into the cell, which creates light and heavy chains of antibodies. This step leads to the formation of antibodies targeted against toxins (eg, diphtheria and tetanus), animal venoms, infectious agents, or tumor cells.
 

Genetic Engineering

Dr. Prelog also reviewed genetic engineering techniques. In regenerative therapy or protein replacement therapy, skin fibroblasts or other cells are transfected with mRNA to enable conversion into induced pluripotent stem cells. This approach avoids the risk for DNA integration into the genome and associated mutation risks.

Another approach is making post-transcriptional modifications through RNA interference. For example, RNA structures can be used to inhibit the translation of disease-causing proteins. This technique is currently being tested against HIV and tumors such as melanoma.

In addition, mRNA technologies can be combined with CRISPR/Cas9 technology (“gene scissors”) to influence the creation of gene products even more precisely. The advantage of this technique is that mRNA is only transiently expressed, thus preventing unwanted side effects. Furthermore, mRNA is translated directly in the cytoplasm, leading to a faster initiation of gene editing.

Of the numerous ongoing clinical mRNA vaccine studies, around 70% focus on infections, about 12% on cancer, and the rest on autoimmune diseases and neurodegenerative disorders, said Dr. Prelog.
 

Research in Infections

Research in the fields of infectious diseases and oncology is the most advanced: mRNA vaccines against influenza and RSV are already in advanced clinical trials, Dr. Prelog told this news organization.

“Conventional influenza vaccines contain immunogenic surface molecules against hemagglutinin and neuraminidase in various combinations of influenza strains A and B and are produced in egg or cell cultures,” she said. “This is a time-consuming manufacturing process that takes months and, particularly with the egg-based process, bears the risk of changing the vaccine strain.”

“Additionally, influenza viruses undergo antigenic shift and drift through recombination, thus requiring annual adjustments to the vaccines. Thus, these influenza vaccines often lose accuracy in targeting circulating seasonal influenza strains.”

Several mRNA vaccines being tested contain not only coding sequences against hemagglutinin and neuraminidase but also for structural proteins of influenza viruses. “These are more conserved and mutate less easily, meaning they could serve as the basis for universal pandemic influenza vaccines,” said Dr. Prelog.

An advantage of mRNA vaccines, she added, is the strong cellular immune response that they elicit. This response is intended to provide additional protection alongside specific antibodies. An mRNA vaccine with coding sequences for the pre-fusion protein of RSV is in phase 3 trials for approval for vaccination in patients aged 60 years and older. It shows high effectiveness even in older patients and those with comorbidities.
 

Elaborate Purification Process

Bacterial origin plasmid DNA is used to produce mRNA vaccines. The mRNA vaccines for COVID-19 raised concerns that production-related DNA residues could pose a safety risk and cause autoimmune diseases.

These vaccines “typically undergo a very elaborate purification process,” said Dr. Prelog. “This involves enzymatic digestion with DNase to fragment and deplete plasmid DNA, followed by purification using chromatography columns, so that no safety-relevant DNA fragments should remain afterward.”

Thus, the Paul-Ehrlich-Institut also pointed out the very small, fragmented plasmid DNA residues of bacterial origin in mRNA COVID-19 vaccines pose no risk, unlike residual DNA from animal cell culture might pose in other vaccines.
 

Prevention and Therapy

In addition to the numerous advantages of mRNA vaccines (such as rapid adaptability to new or mutated pathogens, scalability, rapid production capability, self-adjuvant effect, strong induction of cellular immune responses, and safety), there are also challenges in RNA technology as a preventive and therapeutic measure, according to Dr. Prelog.

“Stability and storability, as well as the costs of new vaccine developments, play a role, as do the long-term effects regarding the persistence of antibody and cellular responses,” she said. The COVID-19 mRNA vaccines, for example, showed a well-maintained cellular immune response despite a tendency toward a rapid decline in humoral immune response.

“The experience with COVID-19 mRNA vaccines and the new vaccine developments based on mRNA technology give hope for an efficient and safe preventive and therapeutic use, particularly in the fields of infectious diseases and oncology,” Dr. Prelog concluded.

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

Cisplatin is a preferred treatment for a wide range of cancers, including breast, head and neck, lung, ovary, and more. However, its side effects — particularly nephrotoxicity — can be severe. Kidney injury on cisplatin is associated with higher mortality and can jeopardize a patient’s eligibility for other therapies.

Now, in a large study using data from six US cancer centers, researchers have developed a risk algorithm to predict acute kidney injury (AKI) after cisplatin administration.

A risk prediction calculator based on the algorithm is available online for patients and providers to determine an individual patient›s risk for kidney injury from cisplatin using readily available clinical data.

Other risk scores and risk prediction models have been developed to help clinicians assess in advance whether a patient might develop AKI after receiving cisplatin, so that more careful monitoring, dose adjustments, or an alternative treatment, if available, might be considered.

However, previous models were limited by factors such as small sample sizes, lack of external validation, older data, and liberal definitions of AKI, said Shruti Gupta, MD, MPH, director of onco-nephrology at Brigham and Women’s Hospital (BWH) and Dana-Farber Cancer Institute, and David E. Leaf, MD, MMSc, director of clinical and translational research in AKI, Division of Renal Medicine, BWH, Boston.

Dr. Gupta and Dr. Leaf believe their risk score for predicting severe AKI after intravenous (IV) cisplatin, published online in The BMJ, is “more accurate and generalizable than prior models for several reasons,” they told this news organization in a joint email.

“First, we externally validated our findings across cancer centers other than the one where it was developed,” they said. “Second, we focused on moderate to severe kidney injury, the most clinically relevant form of kidney damage, whereas prior models examined more mild forms of kidney injury. Third, we collected data on nearly 25,000 patients receiving their first dose of IV cisplatin, which is larger than all previous studies combined.”
 

‘Herculean Effort’

“We conceived of this study back in 2018, contacted collaborators at each participating cancer center, and had numerous meetings to try to gather granular data on patients treated with their first dose of intravenous (IV) cisplatin,” Dr. Gupta and Dr. Leaf explained. They also incorporated patient feedback from focus groups and surveys.

“This was truly a Herculean effort that involved physicians, programmers, research coordinators, and patients,” they said.

The multicenter study included 24,717 patients — 11,766 in the derivation cohort and 12,951 in the validation cohort. Overall, the median age was about 60 years, about 58% were men, and about 78% were White.

The primary outcome was cisplatin-induced AKI (CP-AKI), defined as a twofold or greater increase in serum creatinine or kidney replacement therapy within 14 days of a first dose of IV cisplatin.

The researchers found that the incidence of CP-AKI was 5.2% in the derivation cohort and 3.3% in the validation cohort. Their simple risk score consisting of nine covariates — age, hypertension, type 2 diabetes, hemoglobin level, white blood cell count, platelet count, serum albumin level, serum magnesium level, and cisplatin dose — predicted a higher risk for CP-AKI in both cohorts.

Notably, adding serum creatinine to the model did not change the area under the curve, and therefore, serum creatinine, though also an independent risk factor for CP-AKI, was not included in the score.

Patients in the highest risk category had 24-fold higher odds of CP-AKI in the derivation cohort and close to 18-fold higher odds in the validation cohort than those in the lowest risk category.

The primary model had a C statistic of 0.75 (95% CI, 0.73-0.76) and showed better discrimination for CP-AKI than previously published models, for which the C statistics ranged from 0.60 to 0.68. The first author of a paper on an earlier model, Shveta Motwani, MD, MMSc, of BWH and Dana-Farber Cancer Institute in Boston, is also a coauthor of the new study.

Greater severity of CP-AKI was associated with shorter 90-day survival (adjusted hazard ratio, 4.63; 95% CI, 3.56-6.02) for stage III CP-AKI vs no CP-AKI.
 

‘Definitive Work’

Joel M. Topf, MD, a nephrologist with expertise in chronic kidney disease in Detroit, who wasn’t involved in the development of the risk score, called the study “a definitive work on an important concept in oncology and nephrology.”

“While this is not the first attempt to devise a risk score, it is by far the biggest,” he told this news organization. Furthermore, the authors “used a diverse population, recruiting patients with a variety of cancers (previous attempts had often used a homogenous diagnosis, putting into question how generalizable the results were) from six different cancer centers.”

In addition, he said, “The authors did not restrict patients with chronic kidney disease or other significant comorbidities and used the geographic diversity to produce a cohort that has an age, gender, racial, and ethnic distribution, which is more representative of the US than previous, single-center attempts to risk score patients.”

An earlier model used the Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI of an increase in serum creatinine of 0.3 mg/dL, he noted. “While a sensitive definition of AKI, it captures mild, hemodynamic increases in creatinine of questionable significance,” he said.

By contrast, the new score uses KDIGO stage II and above to define AKI. “This is a better choice, as we do not want to dissuade patients and doctors from choosing chemotherapy due to a fear of insignificant kidney damage,” he said.

All that said, Dr. Topf noted that neither the current score nor the earlier model included serum creatinine. “This is curious to me and may represent the small number of patients with representative elevated creatinine in the derivation cohort (only 1.3% with an estimated glomerular filtration rate [eGFR] < 45).”

“Since the cohort is made up of people who received cis-platinum, the low prevalence of eGFRs < 45 may be due to physicians steering away from cis-platinum in this group,” he suggested. “It would be unfortunate if this risk score gave an unintentional ‘green light’ to these patients, exposing them to predictable harm.”
 

‘Certainly Useful’

Anushree Shirali, MD, an associate professor in the Section of Nephrology and consulting physician, Yale Onco-Nephrology, Yale School of Medicine, in New Haven, Connecticut, said that having a prediction score for which patients are more likely to develop AKI after a single dose of cisplatin would be helpful for oncologists, as well as nephrologists.

As a nephrologist, Dr. Shirali mostly sees patients who already have AKI, she told this news organization. But there are circumstances in which the tool could still be helpful.

“Let’s say someone has abnormal kidney function at baseline — ie, creatinine is higher than the normal range — and they were on dialysis 5 years ago for something else, and now, they have cancer and may be given cisplatin. They worry about their chances of getting AKI and needing dialysis again,” she said. “That’s just one scenario in which I might be asked to answer that question and the tool would certainly be useful.”

Other scenarios could include someone who has just one kidney because they donated a kidney for transplant years ago, and now, they have a malignancy and wonder what their actual risk is of getting kidney issues on cisplatin.

Oncologists could use the tool to determine whether a patient should be treated with cisplatin, or if they’re at high risk, whether an alternative that’s not nephrotoxic might be used. By contrast, “if somebody’s low risk and an oncologist thinks cisplatin is the best agent they have, then they might want to go ahead and use it,” Dr. Shirali said.

Future research could take into consideration that CP-AKI is dose dependent, she suggested, because a prediction score that included the number of cisplatin doses could be even more helpful to determine risk. And, even though the derivation and validation cohorts for the new tool are representative of the US population, additional research should also include more racial/ethnic diversity, she said.

Dr. Gupta and Dr. Leaf hope their tool “will be utilized immediately by patients and providers to help predict an individual’s risk of cisplatin-associated kidney damage. It is easy to use, available for free online, and incorporates readily available clinical variables.”

If a patient is at high risk, the clinical team can consider preventive measures such as administering more IV fluids before receiving cisplatin or monitoring kidney function more closely afterward, they suggested.

Dr. Gupta reported research support from the National Institutes of Health (NIH) and the National Institute of Diabetes and Digestive and Kidney Diseases. She also reported research funding from BTG International, GE HealthCare, and AstraZeneca outside the submitted work. She is a member of GlaxoSmithKline’s Global Anemia Council, a consultant for Secretome and Proletariat Therapeutics, and founder and president emeritus of the American Society of Onconephrology (unpaid). Dr. Leaf is supported by NIH grants, reported research support from BioPorto, BTG International, and Metro International Biotech, and has served as a consultant. Dr. Topf reported an ownership stake in a few DaVita-run dialysis clinics. He also runs a vascular access center and has participated in advisory boards with Cara Therapeutics, Vifor, Astra Zeneca, Bayer, Renibus Therapeutics, Travere Therapeutics, and GlaxoSmithKline. He is president of NephJC, a nonprofit educational organization with no industry support. Dr. Shirali declared no competing interests.

A version of this article appeared on Medscape.com.

Cisplatin is a preferred treatment for a wide range of cancers, including breast, head and neck, lung, ovary, and more. However, its side effects — particularly nephrotoxicity — can be severe. Kidney injury on cisplatin is associated with higher mortality and can jeopardize a patient’s eligibility for other therapies.

Now, in a large study using data from six US cancer centers, researchers have developed a risk algorithm to predict acute kidney injury (AKI) after cisplatin administration.

A risk prediction calculator based on the algorithm is available online for patients and providers to determine an individual patient›s risk for kidney injury from cisplatin using readily available clinical data.

Other risk scores and risk prediction models have been developed to help clinicians assess in advance whether a patient might develop AKI after receiving cisplatin, so that more careful monitoring, dose adjustments, or an alternative treatment, if available, might be considered.

However, previous models were limited by factors such as small sample sizes, lack of external validation, older data, and liberal definitions of AKI, said Shruti Gupta, MD, MPH, director of onco-nephrology at Brigham and Women’s Hospital (BWH) and Dana-Farber Cancer Institute, and David E. Leaf, MD, MMSc, director of clinical and translational research in AKI, Division of Renal Medicine, BWH, Boston.

Dr. Gupta and Dr. Leaf believe their risk score for predicting severe AKI after intravenous (IV) cisplatin, published online in The BMJ, is “more accurate and generalizable than prior models for several reasons,” they told this news organization in a joint email.

“First, we externally validated our findings across cancer centers other than the one where it was developed,” they said. “Second, we focused on moderate to severe kidney injury, the most clinically relevant form of kidney damage, whereas prior models examined more mild forms of kidney injury. Third, we collected data on nearly 25,000 patients receiving their first dose of IV cisplatin, which is larger than all previous studies combined.”
 

‘Herculean Effort’

“We conceived of this study back in 2018, contacted collaborators at each participating cancer center, and had numerous meetings to try to gather granular data on patients treated with their first dose of intravenous (IV) cisplatin,” Dr. Gupta and Dr. Leaf explained. They also incorporated patient feedback from focus groups and surveys.

“This was truly a Herculean effort that involved physicians, programmers, research coordinators, and patients,” they said.

The multicenter study included 24,717 patients — 11,766 in the derivation cohort and 12,951 in the validation cohort. Overall, the median age was about 60 years, about 58% were men, and about 78% were White.

The primary outcome was cisplatin-induced AKI (CP-AKI), defined as a twofold or greater increase in serum creatinine or kidney replacement therapy within 14 days of a first dose of IV cisplatin.

The researchers found that the incidence of CP-AKI was 5.2% in the derivation cohort and 3.3% in the validation cohort. Their simple risk score consisting of nine covariates — age, hypertension, type 2 diabetes, hemoglobin level, white blood cell count, platelet count, serum albumin level, serum magnesium level, and cisplatin dose — predicted a higher risk for CP-AKI in both cohorts.

Notably, adding serum creatinine to the model did not change the area under the curve, and therefore, serum creatinine, though also an independent risk factor for CP-AKI, was not included in the score.

Patients in the highest risk category had 24-fold higher odds of CP-AKI in the derivation cohort and close to 18-fold higher odds in the validation cohort than those in the lowest risk category.

The primary model had a C statistic of 0.75 (95% CI, 0.73-0.76) and showed better discrimination for CP-AKI than previously published models, for which the C statistics ranged from 0.60 to 0.68. The first author of a paper on an earlier model, Shveta Motwani, MD, MMSc, of BWH and Dana-Farber Cancer Institute in Boston, is also a coauthor of the new study.

Greater severity of CP-AKI was associated with shorter 90-day survival (adjusted hazard ratio, 4.63; 95% CI, 3.56-6.02) for stage III CP-AKI vs no CP-AKI.
 

‘Definitive Work’

Joel M. Topf, MD, a nephrologist with expertise in chronic kidney disease in Detroit, who wasn’t involved in the development of the risk score, called the study “a definitive work on an important concept in oncology and nephrology.”

“While this is not the first attempt to devise a risk score, it is by far the biggest,” he told this news organization. Furthermore, the authors “used a diverse population, recruiting patients with a variety of cancers (previous attempts had often used a homogenous diagnosis, putting into question how generalizable the results were) from six different cancer centers.”

In addition, he said, “The authors did not restrict patients with chronic kidney disease or other significant comorbidities and used the geographic diversity to produce a cohort that has an age, gender, racial, and ethnic distribution, which is more representative of the US than previous, single-center attempts to risk score patients.”

An earlier model used the Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI of an increase in serum creatinine of 0.3 mg/dL, he noted. “While a sensitive definition of AKI, it captures mild, hemodynamic increases in creatinine of questionable significance,” he said.

By contrast, the new score uses KDIGO stage II and above to define AKI. “This is a better choice, as we do not want to dissuade patients and doctors from choosing chemotherapy due to a fear of insignificant kidney damage,” he said.

All that said, Dr. Topf noted that neither the current score nor the earlier model included serum creatinine. “This is curious to me and may represent the small number of patients with representative elevated creatinine in the derivation cohort (only 1.3% with an estimated glomerular filtration rate [eGFR] < 45).”

“Since the cohort is made up of people who received cis-platinum, the low prevalence of eGFRs < 45 may be due to physicians steering away from cis-platinum in this group,” he suggested. “It would be unfortunate if this risk score gave an unintentional ‘green light’ to these patients, exposing them to predictable harm.”
 

‘Certainly Useful’

Anushree Shirali, MD, an associate professor in the Section of Nephrology and consulting physician, Yale Onco-Nephrology, Yale School of Medicine, in New Haven, Connecticut, said that having a prediction score for which patients are more likely to develop AKI after a single dose of cisplatin would be helpful for oncologists, as well as nephrologists.

As a nephrologist, Dr. Shirali mostly sees patients who already have AKI, she told this news organization. But there are circumstances in which the tool could still be helpful.

“Let’s say someone has abnormal kidney function at baseline — ie, creatinine is higher than the normal range — and they were on dialysis 5 years ago for something else, and now, they have cancer and may be given cisplatin. They worry about their chances of getting AKI and needing dialysis again,” she said. “That’s just one scenario in which I might be asked to answer that question and the tool would certainly be useful.”

Other scenarios could include someone who has just one kidney because they donated a kidney for transplant years ago, and now, they have a malignancy and wonder what their actual risk is of getting kidney issues on cisplatin.

Oncologists could use the tool to determine whether a patient should be treated with cisplatin, or if they’re at high risk, whether an alternative that’s not nephrotoxic might be used. By contrast, “if somebody’s low risk and an oncologist thinks cisplatin is the best agent they have, then they might want to go ahead and use it,” Dr. Shirali said.

Future research could take into consideration that CP-AKI is dose dependent, she suggested, because a prediction score that included the number of cisplatin doses could be even more helpful to determine risk. And, even though the derivation and validation cohorts for the new tool are representative of the US population, additional research should also include more racial/ethnic diversity, she said.

Dr. Gupta and Dr. Leaf hope their tool “will be utilized immediately by patients and providers to help predict an individual’s risk of cisplatin-associated kidney damage. It is easy to use, available for free online, and incorporates readily available clinical variables.”

If a patient is at high risk, the clinical team can consider preventive measures such as administering more IV fluids before receiving cisplatin or monitoring kidney function more closely afterward, they suggested.

Dr. Gupta reported research support from the National Institutes of Health (NIH) and the National Institute of Diabetes and Digestive and Kidney Diseases. She also reported research funding from BTG International, GE HealthCare, and AstraZeneca outside the submitted work. She is a member of GlaxoSmithKline’s Global Anemia Council, a consultant for Secretome and Proletariat Therapeutics, and founder and president emeritus of the American Society of Onconephrology (unpaid). Dr. Leaf is supported by NIH grants, reported research support from BioPorto, BTG International, and Metro International Biotech, and has served as a consultant. Dr. Topf reported an ownership stake in a few DaVita-run dialysis clinics. He also runs a vascular access center and has participated in advisory boards with Cara Therapeutics, Vifor, Astra Zeneca, Bayer, Renibus Therapeutics, Travere Therapeutics, and GlaxoSmithKline. He is president of NephJC, a nonprofit educational organization with no industry support. Dr. Shirali declared no competing interests.

A version of this article appeared on Medscape.com.

Cisplatin is a preferred treatment for a wide range of cancers, including breast, head and neck, lung, ovary, and more. However, its side effects — particularly nephrotoxicity — can be severe. Kidney injury on cisplatin is associated with higher mortality and can jeopardize a patient’s eligibility for other therapies.

Now, in a large study using data from six US cancer centers, researchers have developed a risk algorithm to predict acute kidney injury (AKI) after cisplatin administration.

A risk prediction calculator based on the algorithm is available online for patients and providers to determine an individual patient›s risk for kidney injury from cisplatin using readily available clinical data.

Other risk scores and risk prediction models have been developed to help clinicians assess in advance whether a patient might develop AKI after receiving cisplatin, so that more careful monitoring, dose adjustments, or an alternative treatment, if available, might be considered.

However, previous models were limited by factors such as small sample sizes, lack of external validation, older data, and liberal definitions of AKI, said Shruti Gupta, MD, MPH, director of onco-nephrology at Brigham and Women’s Hospital (BWH) and Dana-Farber Cancer Institute, and David E. Leaf, MD, MMSc, director of clinical and translational research in AKI, Division of Renal Medicine, BWH, Boston.

Dr. Gupta and Dr. Leaf believe their risk score for predicting severe AKI after intravenous (IV) cisplatin, published online in The BMJ, is “more accurate and generalizable than prior models for several reasons,” they told this news organization in a joint email.

“First, we externally validated our findings across cancer centers other than the one where it was developed,” they said. “Second, we focused on moderate to severe kidney injury, the most clinically relevant form of kidney damage, whereas prior models examined more mild forms of kidney injury. Third, we collected data on nearly 25,000 patients receiving their first dose of IV cisplatin, which is larger than all previous studies combined.”
 

‘Herculean Effort’

“We conceived of this study back in 2018, contacted collaborators at each participating cancer center, and had numerous meetings to try to gather granular data on patients treated with their first dose of intravenous (IV) cisplatin,” Dr. Gupta and Dr. Leaf explained. They also incorporated patient feedback from focus groups and surveys.

“This was truly a Herculean effort that involved physicians, programmers, research coordinators, and patients,” they said.

The multicenter study included 24,717 patients — 11,766 in the derivation cohort and 12,951 in the validation cohort. Overall, the median age was about 60 years, about 58% were men, and about 78% were White.

The primary outcome was cisplatin-induced AKI (CP-AKI), defined as a twofold or greater increase in serum creatinine or kidney replacement therapy within 14 days of a first dose of IV cisplatin.

The researchers found that the incidence of CP-AKI was 5.2% in the derivation cohort and 3.3% in the validation cohort. Their simple risk score consisting of nine covariates — age, hypertension, type 2 diabetes, hemoglobin level, white blood cell count, platelet count, serum albumin level, serum magnesium level, and cisplatin dose — predicted a higher risk for CP-AKI in both cohorts.

Notably, adding serum creatinine to the model did not change the area under the curve, and therefore, serum creatinine, though also an independent risk factor for CP-AKI, was not included in the score.

Patients in the highest risk category had 24-fold higher odds of CP-AKI in the derivation cohort and close to 18-fold higher odds in the validation cohort than those in the lowest risk category.

The primary model had a C statistic of 0.75 (95% CI, 0.73-0.76) and showed better discrimination for CP-AKI than previously published models, for which the C statistics ranged from 0.60 to 0.68. The first author of a paper on an earlier model, Shveta Motwani, MD, MMSc, of BWH and Dana-Farber Cancer Institute in Boston, is also a coauthor of the new study.

Greater severity of CP-AKI was associated with shorter 90-day survival (adjusted hazard ratio, 4.63; 95% CI, 3.56-6.02) for stage III CP-AKI vs no CP-AKI.
 

‘Definitive Work’

Joel M. Topf, MD, a nephrologist with expertise in chronic kidney disease in Detroit, who wasn’t involved in the development of the risk score, called the study “a definitive work on an important concept in oncology and nephrology.”

“While this is not the first attempt to devise a risk score, it is by far the biggest,” he told this news organization. Furthermore, the authors “used a diverse population, recruiting patients with a variety of cancers (previous attempts had often used a homogenous diagnosis, putting into question how generalizable the results were) from six different cancer centers.”

In addition, he said, “The authors did not restrict patients with chronic kidney disease or other significant comorbidities and used the geographic diversity to produce a cohort that has an age, gender, racial, and ethnic distribution, which is more representative of the US than previous, single-center attempts to risk score patients.”

An earlier model used the Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI of an increase in serum creatinine of 0.3 mg/dL, he noted. “While a sensitive definition of AKI, it captures mild, hemodynamic increases in creatinine of questionable significance,” he said.

By contrast, the new score uses KDIGO stage II and above to define AKI. “This is a better choice, as we do not want to dissuade patients and doctors from choosing chemotherapy due to a fear of insignificant kidney damage,” he said.

All that said, Dr. Topf noted that neither the current score nor the earlier model included serum creatinine. “This is curious to me and may represent the small number of patients with representative elevated creatinine in the derivation cohort (only 1.3% with an estimated glomerular filtration rate [eGFR] < 45).”

“Since the cohort is made up of people who received cis-platinum, the low prevalence of eGFRs < 45 may be due to physicians steering away from cis-platinum in this group,” he suggested. “It would be unfortunate if this risk score gave an unintentional ‘green light’ to these patients, exposing them to predictable harm.”
 

‘Certainly Useful’

Anushree Shirali, MD, an associate professor in the Section of Nephrology and consulting physician, Yale Onco-Nephrology, Yale School of Medicine, in New Haven, Connecticut, said that having a prediction score for which patients are more likely to develop AKI after a single dose of cisplatin would be helpful for oncologists, as well as nephrologists.

As a nephrologist, Dr. Shirali mostly sees patients who already have AKI, she told this news organization. But there are circumstances in which the tool could still be helpful.

“Let’s say someone has abnormal kidney function at baseline — ie, creatinine is higher than the normal range — and they were on dialysis 5 years ago for something else, and now, they have cancer and may be given cisplatin. They worry about their chances of getting AKI and needing dialysis again,” she said. “That’s just one scenario in which I might be asked to answer that question and the tool would certainly be useful.”

Other scenarios could include someone who has just one kidney because they donated a kidney for transplant years ago, and now, they have a malignancy and wonder what their actual risk is of getting kidney issues on cisplatin.

Oncologists could use the tool to determine whether a patient should be treated with cisplatin, or if they’re at high risk, whether an alternative that’s not nephrotoxic might be used. By contrast, “if somebody’s low risk and an oncologist thinks cisplatin is the best agent they have, then they might want to go ahead and use it,” Dr. Shirali said.

Future research could take into consideration that CP-AKI is dose dependent, she suggested, because a prediction score that included the number of cisplatin doses could be even more helpful to determine risk. And, even though the derivation and validation cohorts for the new tool are representative of the US population, additional research should also include more racial/ethnic diversity, she said.

Dr. Gupta and Dr. Leaf hope their tool “will be utilized immediately by patients and providers to help predict an individual’s risk of cisplatin-associated kidney damage. It is easy to use, available for free online, and incorporates readily available clinical variables.”

If a patient is at high risk, the clinical team can consider preventive measures such as administering more IV fluids before receiving cisplatin or monitoring kidney function more closely afterward, they suggested.

Dr. Gupta reported research support from the National Institutes of Health (NIH) and the National Institute of Diabetes and Digestive and Kidney Diseases. She also reported research funding from BTG International, GE HealthCare, and AstraZeneca outside the submitted work. She is a member of GlaxoSmithKline’s Global Anemia Council, a consultant for Secretome and Proletariat Therapeutics, and founder and president emeritus of the American Society of Onconephrology (unpaid). Dr. Leaf is supported by NIH grants, reported research support from BioPorto, BTG International, and Metro International Biotech, and has served as a consultant. Dr. Topf reported an ownership stake in a few DaVita-run dialysis clinics. He also runs a vascular access center and has participated in advisory boards with Cara Therapeutics, Vifor, Astra Zeneca, Bayer, Renibus Therapeutics, Travere Therapeutics, and GlaxoSmithKline. He is president of NephJC, a nonprofit educational organization with no industry support. Dr. Shirali declared no competing interests.

A version of this article appeared on Medscape.com.

TOPLINE:

The recommended 10-year interval between screening colonoscopies may be safely extended to 15 years in adults with no family history of colorectal cancer (CRC) whose first colonoscopy is negative for CRC, a population-based study suggests.

METHODOLOGY:

• Using Swedish nationwide registry data, researchers compared 110,074 individuals who had a first colonoscopy with negative findings for CRC at age 45-69 years (exposed group) with more than 1.9 million matched controls who either did not have a colonoscopy during the study period or underwent colonoscopy that led to a CRC diagnosis.
• They calculated 10-year standardized incidence ratio (SIR) and standardized mortality ratio (SMR) to compare risks for CRC and CRC-specific death in the exposed and control groups based on different follow-up screening intervals.

TAKEAWAY:

• During up to 29 years of follow-up, 484 incident CRCs and 112 CRC deaths occurred in the group with a negative initial colonoscopy.
• Up to 15 years after negative colonoscopy, the 10-year cumulative risk for CRC and CRC mortality was lower than in the control group, with an SIR of 0.72 and SMR of 0.55, respectively.
• Extending the screening interval from 10 to 15 years would miss early detection of only two CRC cases and prevention of only one CRC death per 1000 individuals, while potentially avoiding 1000 colonoscopies.

IN PRACTICE:

“This study provides evidence for recommending a longer colonoscopy screening interval than what is currently recommended in most guidelines for populations with no familial risk of CRC,” the authors wrote. “A longer interval between colonoscopy screenings could be beneficial in avoiding unnecessary invasive examinations.”

SOURCE:

The study, with first author Qunfeng Liang, MSc, with the German Cancer Research Center, Heidelberg, Germany, was published online on May 2 in JAMA Oncology.

LIMITATIONS:

The study population primarily included White individuals, particularly ethnic Swedish individuals, so external validation would be necessary to generalize the recommendation to other populations. The researchers lacked data on non-endoscopic tests, such as fecal occult blood tests, which could have been performed as a substitution for colonoscopy during the interval between colonoscopy screenings.

DISCLOSURES:

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

A version of this article appeared on Medscape.com.

TOPLINE:

The recommended 10-year interval between screening colonoscopies may be safely extended to 15 years in adults with no family history of colorectal cancer (CRC) whose first colonoscopy is negative for CRC, a population-based study suggests.

METHODOLOGY:

• Using Swedish nationwide registry data, researchers compared 110,074 individuals who had a first colonoscopy with negative findings for CRC at age 45-69 years (exposed group) with more than 1.9 million matched controls who either did not have a colonoscopy during the study period or underwent colonoscopy that led to a CRC diagnosis.
• They calculated 10-year standardized incidence ratio (SIR) and standardized mortality ratio (SMR) to compare risks for CRC and CRC-specific death in the exposed and control groups based on different follow-up screening intervals.

TAKEAWAY:

• During up to 29 years of follow-up, 484 incident CRCs and 112 CRC deaths occurred in the group with a negative initial colonoscopy.
• Up to 15 years after negative colonoscopy, the 10-year cumulative risk for CRC and CRC mortality was lower than in the control group, with an SIR of 0.72 and SMR of 0.55, respectively.
• Extending the screening interval from 10 to 15 years would miss early detection of only two CRC cases and prevention of only one CRC death per 1000 individuals, while potentially avoiding 1000 colonoscopies.

IN PRACTICE:

“This study provides evidence for recommending a longer colonoscopy screening interval than what is currently recommended in most guidelines for populations with no familial risk of CRC,” the authors wrote. “A longer interval between colonoscopy screenings could be beneficial in avoiding unnecessary invasive examinations.”

SOURCE:

The study, with first author Qunfeng Liang, MSc, with the German Cancer Research Center, Heidelberg, Germany, was published online on May 2 in JAMA Oncology.

LIMITATIONS:

The study population primarily included White individuals, particularly ethnic Swedish individuals, so external validation would be necessary to generalize the recommendation to other populations. The researchers lacked data on non-endoscopic tests, such as fecal occult blood tests, which could have been performed as a substitution for colonoscopy during the interval between colonoscopy screenings.

DISCLOSURES:

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

A version of this article appeared on Medscape.com.

TOPLINE:

The recommended 10-year interval between screening colonoscopies may be safely extended to 15 years in adults with no family history of colorectal cancer (CRC) whose first colonoscopy is negative for CRC, a population-based study suggests.

METHODOLOGY:

• Using Swedish nationwide registry data, researchers compared 110,074 individuals who had a first colonoscopy with negative findings for CRC at age 45-69 years (exposed group) with more than 1.9 million matched controls who either did not have a colonoscopy during the study period or underwent colonoscopy that led to a CRC diagnosis.
• They calculated 10-year standardized incidence ratio (SIR) and standardized mortality ratio (SMR) to compare risks for CRC and CRC-specific death in the exposed and control groups based on different follow-up screening intervals.

TAKEAWAY:

• During up to 29 years of follow-up, 484 incident CRCs and 112 CRC deaths occurred in the group with a negative initial colonoscopy.
• Up to 15 years after negative colonoscopy, the 10-year cumulative risk for CRC and CRC mortality was lower than in the control group, with an SIR of 0.72 and SMR of 0.55, respectively.
• Extending the screening interval from 10 to 15 years would miss early detection of only two CRC cases and prevention of only one CRC death per 1000 individuals, while potentially avoiding 1000 colonoscopies.

IN PRACTICE:

“This study provides evidence for recommending a longer colonoscopy screening interval than what is currently recommended in most guidelines for populations with no familial risk of CRC,” the authors wrote. “A longer interval between colonoscopy screenings could be beneficial in avoiding unnecessary invasive examinations.”

SOURCE:

The study, with first author Qunfeng Liang, MSc, with the German Cancer Research Center, Heidelberg, Germany, was published online on May 2 in JAMA Oncology.

LIMITATIONS:

The study population primarily included White individuals, particularly ethnic Swedish individuals, so external validation would be necessary to generalize the recommendation to other populations. The researchers lacked data on non-endoscopic tests, such as fecal occult blood tests, which could have been performed as a substitution for colonoscopy during the interval between colonoscopy screenings.

DISCLOSURES:

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

A version of this article appeared on Medscape.com.