Conference Coverage

A model that crunches data from routine blood tests can accurately identify cancer patients who will develop acute kidney injury (AKI) up to a month before it happens, according to a cohort study.

The algorithm spotted nearly 74% of the patients who went on to develop AKI within 30 days, providing a window for intervention and possibly prevention, according to investigators.

These results were reported at the AACR Virtual Special Conference: Artificial Intelligence, Diagnosis, and Imaging (abstract PR-11).

“Cancer patients are a high-risk population for AKI due to the nature of their treatment and illness,” said presenter Lauren A. Scanlon, PhD, a data scientist at The Christie NHS Foundation Trust in Huddersfield, England. “AKI causes a huge disruption in treatment and distress for the patient, so it would be amazing if we could, say, predict the AKI before it occurs and prevent it from even happening.”

U.K. health care providers are already using an algorithm to monitor patients’ creatinine levels, comparing new values against historic ones, Dr. Scanlon explained. When that algorithm detects AKI, it issues an alert that triggers implementation of an AKI care bundle, including measures such as fluid monitoring and medication review, within 24 hours.

Taking this concept further, Dr. Scanlon and colleagues developed a random forest model, a type of machine learning algorithm, that incorporates other markers from blood tests routinely obtained for all patients, with the aim of predicting AKI up to 30 days in advance.

“Using routinely collected blood test results will ensure that the model is applicable to all our patients and can be implemented in an automated manner,” Dr. Scanlon noted.

The investigators developed and trained the model using 597,403 blood test results from 48,865 patients undergoing cancer treatment between January 2017 and May 2020.

The model assigns patients to five categories of risk for AKI in the next 30 days: very low, low, medium, high, and very high.

“We wanted the model to output in this way so that it could be used by clinicians alongside their own insight and knowledge on a case-by-case basis,” Dr. Scanlon explained.

The investigators then prospectively validated the model and its risk categories in another 9,913 patients who underwent cancer treatment between June and August 2020.

Using a model threshold of medium risk or higher, the model correctly predicted AKI in 330 (73.8%) of the 447 patients in the validation cohort who ultimately developed AKI.

“This is pretty amazing and shows that this model really is working and can correctly detect these AKIs up to 30 days before they occur, giving a huge window to put in place preventive strategies,” Dr. Scanlon said.

Among the 154 patients in whom the model incorrectly predicted AKI, 9 patients had only a single follow-up blood test and 17 patients did not have any, leaving their actual outcomes unclear.

“Given that AKI detection uses blood tests, an AKI in these patients was never confirmed,” Dr. Scanlon noted. “So this could give a potential benefit of the model that we never intended: It could reduce undiagnosed AKI by flagging those who are at risk.”

“Our next steps are to test the model through a technology clinical trial to see if putting intervention strategies in place does prevent these AKIs from taking place,” Dr. Scanlon concluded. “We are also going to move to ongoing monitoring of the model performance.”

Dr. Scanlon disclosed no conflicts of interest. The study did not receive specific funding.

A model that crunches data from routine blood tests can accurately identify cancer patients who will develop acute kidney injury (AKI) up to a month before it happens, according to a cohort study.

The algorithm spotted nearly 74% of the patients who went on to develop AKI within 30 days, providing a window for intervention and possibly prevention, according to investigators.

These results were reported at the AACR Virtual Special Conference: Artificial Intelligence, Diagnosis, and Imaging (abstract PR-11).

“Cancer patients are a high-risk population for AKI due to the nature of their treatment and illness,” said presenter Lauren A. Scanlon, PhD, a data scientist at The Christie NHS Foundation Trust in Huddersfield, England. “AKI causes a huge disruption in treatment and distress for the patient, so it would be amazing if we could, say, predict the AKI before it occurs and prevent it from even happening.”

U.K. health care providers are already using an algorithm to monitor patients’ creatinine levels, comparing new values against historic ones, Dr. Scanlon explained. When that algorithm detects AKI, it issues an alert that triggers implementation of an AKI care bundle, including measures such as fluid monitoring and medication review, within 24 hours.

Taking this concept further, Dr. Scanlon and colleagues developed a random forest model, a type of machine learning algorithm, that incorporates other markers from blood tests routinely obtained for all patients, with the aim of predicting AKI up to 30 days in advance.

“Using routinely collected blood test results will ensure that the model is applicable to all our patients and can be implemented in an automated manner,” Dr. Scanlon noted.

The investigators developed and trained the model using 597,403 blood test results from 48,865 patients undergoing cancer treatment between January 2017 and May 2020.

The model assigns patients to five categories of risk for AKI in the next 30 days: very low, low, medium, high, and very high.

“We wanted the model to output in this way so that it could be used by clinicians alongside their own insight and knowledge on a case-by-case basis,” Dr. Scanlon explained.

The investigators then prospectively validated the model and its risk categories in another 9,913 patients who underwent cancer treatment between June and August 2020.

Using a model threshold of medium risk or higher, the model correctly predicted AKI in 330 (73.8%) of the 447 patients in the validation cohort who ultimately developed AKI.

“This is pretty amazing and shows that this model really is working and can correctly detect these AKIs up to 30 days before they occur, giving a huge window to put in place preventive strategies,” Dr. Scanlon said.

Among the 154 patients in whom the model incorrectly predicted AKI, 9 patients had only a single follow-up blood test and 17 patients did not have any, leaving their actual outcomes unclear.

“Given that AKI detection uses blood tests, an AKI in these patients was never confirmed,” Dr. Scanlon noted. “So this could give a potential benefit of the model that we never intended: It could reduce undiagnosed AKI by flagging those who are at risk.”

“Our next steps are to test the model through a technology clinical trial to see if putting intervention strategies in place does prevent these AKIs from taking place,” Dr. Scanlon concluded. “We are also going to move to ongoing monitoring of the model performance.”

Dr. Scanlon disclosed no conflicts of interest. The study did not receive specific funding.

A model that crunches data from routine blood tests can accurately identify cancer patients who will develop acute kidney injury (AKI) up to a month before it happens, according to a cohort study.

The algorithm spotted nearly 74% of the patients who went on to develop AKI within 30 days, providing a window for intervention and possibly prevention, according to investigators.

These results were reported at the AACR Virtual Special Conference: Artificial Intelligence, Diagnosis, and Imaging (abstract PR-11).

“Cancer patients are a high-risk population for AKI due to the nature of their treatment and illness,” said presenter Lauren A. Scanlon, PhD, a data scientist at The Christie NHS Foundation Trust in Huddersfield, England. “AKI causes a huge disruption in treatment and distress for the patient, so it would be amazing if we could, say, predict the AKI before it occurs and prevent it from even happening.”

U.K. health care providers are already using an algorithm to monitor patients’ creatinine levels, comparing new values against historic ones, Dr. Scanlon explained. When that algorithm detects AKI, it issues an alert that triggers implementation of an AKI care bundle, including measures such as fluid monitoring and medication review, within 24 hours.

Taking this concept further, Dr. Scanlon and colleagues developed a random forest model, a type of machine learning algorithm, that incorporates other markers from blood tests routinely obtained for all patients, with the aim of predicting AKI up to 30 days in advance.

“Using routinely collected blood test results will ensure that the model is applicable to all our patients and can be implemented in an automated manner,” Dr. Scanlon noted.

The investigators developed and trained the model using 597,403 blood test results from 48,865 patients undergoing cancer treatment between January 2017 and May 2020.

The model assigns patients to five categories of risk for AKI in the next 30 days: very low, low, medium, high, and very high.

“We wanted the model to output in this way so that it could be used by clinicians alongside their own insight and knowledge on a case-by-case basis,” Dr. Scanlon explained.

The investigators then prospectively validated the model and its risk categories in another 9,913 patients who underwent cancer treatment between June and August 2020.

Using a model threshold of medium risk or higher, the model correctly predicted AKI in 330 (73.8%) of the 447 patients in the validation cohort who ultimately developed AKI.

“This is pretty amazing and shows that this model really is working and can correctly detect these AKIs up to 30 days before they occur, giving a huge window to put in place preventive strategies,” Dr. Scanlon said.

Among the 154 patients in whom the model incorrectly predicted AKI, 9 patients had only a single follow-up blood test and 17 patients did not have any, leaving their actual outcomes unclear.

“Given that AKI detection uses blood tests, an AKI in these patients was never confirmed,” Dr. Scanlon noted. “So this could give a potential benefit of the model that we never intended: It could reduce undiagnosed AKI by flagging those who are at risk.”

“Our next steps are to test the model through a technology clinical trial to see if putting intervention strategies in place does prevent these AKIs from taking place,” Dr. Scanlon concluded. “We are also going to move to ongoing monitoring of the model performance.”

Dr. Scanlon disclosed no conflicts of interest. The study did not receive specific funding.

Antibodies against SARS-CoV-2 cross the placenta during pregnancy and are detectable in most newborns born to mothers who had COVID-19 during pregnancy, according to findings from a study presented Jan. 28 at the meeting sponsored by the Society for Maternal-Fetal Medicine.

“I think the most striking finding is that we noticed a high degree of neutralizing response to natural infection even among asymptomatic infection, but of course a higher degree was seen in those with symptomatic infection,” Naima Joseph, MD, MPH, of Emory University, Atlanta, said in an interview.

“Our data demonstrate maternal capacity to mount an appropriate and robust immune response,” and maternal protective immunity lasted at least 28 days after infection, Dr. Joseph said. “Also, we noted higher neonatal cord blood titers in moms with higher titers, which suggests a relationship, but we need to better understand how transplacental transfer occurs as well as establish neonatal correlates of protection in order to see if and how maternal immunity may also benefit neonates.”

The researchers analyzed the amount of IgG and IgM antibodies in maternal and cord blood samples prospectively collected at delivery from women who tested positive for COVID-19 at any time while pregnant. They used enzyme-linked immunosorbent assay to assess for antibodies for the receptor binding domain of the SARS-CoV-2 spike protein.

The 32 pairs of mothers and infants in the study were predominantly non-Hispanic Black (72%) and Hispanic (25%), and 84% used Medicaid as their payer. Most of the mothers (72%) had at least one comorbidity, most commonly obesity, hypertension, and asthma or pulmonary disease. Just over half the women (53%) were symptomatic while they were infected, and 88% were ill with COVID-19 during the third trimester. The average time from infection to delivery was 28 days.

All the mothers had IgG antibodies, 94% had IgM antibodies, and 94% had neutralizing antibodies against SARS-CoV-2. Among the cord blood samples, 91% had IgG antibodies, 9% had IgM antibodies, and 25% had neutralizing antibodies.

“It’s reassuring that, so far, the physiological response is exactly what we expected it to be,” Judette Louis, MD, MPH, an associate professor of ob.gyn. and the ob.gyn. department chair at the University of South Florida, Tampa, said in an interview. “It’s what we would expect, but it’s always helpful to have more data to support that. Otherwise, you’re extrapolating from what you know from other conditions,” said Dr. Louis, who moderated the oral abstracts session.

Symptomatic infection was associated with significantly higher IgG titers than asymptomatic infection (P = .03), but no correlation was seen for IgM or neutralizing antibodies. In addition, although mothers who delivered more than 28 days after their infection had higher IgG titers (P = .05), no differences existed in IgM or neutralizing response.

Infants’ cord blood titers were significantly lower than their corresponding maternal samples, independently of symptoms or latency from infection to delivery (P < .001), Dr. Joseph reported.

“Transplacental efficiency in other pathogens has been shown to be correlated with neonatal immunity when the ratio of cord to maternal blood is greater than 1,” Dr. Joseph said in her presentation. Their data showed “suboptimal efficiency” at a ratio of 0.81.

The study’s small sample size and lack of a control group were weaknesses, but a major strength was having a population at disproportionately higher risk for infection and severe morbidity than the general population.
 

Implications for maternal COVID-19 vaccination

Although the data are not yet available, Dr. Joseph said they have expanded their protocol to include vaccinated pregnant women.

“The key to developing an effective vaccine [for pregnant people] is in really characterizing adaptive immunity in pregnancy,” Dr. Joseph told SMFM attendees. “I think that these findings inform further vaccine development in demonstrating that maternal immunity is robust.”

The World Health Organization recently recommended withholding COVID-19 vaccines from pregnant people, but the SMFM and American College of Obstetricians and Gynecologists subsequently issued a joint statement reaffirming that the COVID-19 vaccines authorized by the FDA “should not be withheld from pregnant individuals who choose to receive the vaccine.”

“One of the questions people ask is whether in pregnancy you’re going to mount a good response to the vaccine the way you would outside of pregnancy,” Dr. Louis said. “If we can demonstrate that you do, that may provide the information that some mothers need to make their decisions.” Data such as those from Dr. Joseph’s study can also inform recommendations on timing of maternal vaccination.

“For instance, Dr. Joseph demonstrated that, 28 days out from the infection, you had more antibodies, so there may be a scenario where we say this vaccine may be more beneficial in the middle of the pregnancy for the purpose of forming those antibodies,” Dr. Louis said.
 

Consensus emerging from maternal antibodies data

The findings from Dr. Joseph’s study mirror those reported in a study published online Jan. 29 in JAMA Pediatrics. That study, led by Dustin D. Flannery, DO, MSCE, of Children’s Hospital of Philadelphia, also examined maternal and neonatal levels of IgG and IgM antibodies against the receptor binding domain of the SARS-CoV-2 spike protein. They also found a positive correlation between cord blood and maternal IgG concentrations (P < .001), but notably, the ratio of cord to maternal blood titers was greater than 1, unlike in Dr. Joseph’s study.

For their study, Dr. Flannery and colleagues obtained maternal and cord blood sera at the time of delivery from 1471 pairs of mothers and infants, independently of COVID status during pregnancy. The average maternal age was 32 years, and just over a quarter of the population (26%) were Black, non-Hispanic women. About half (51%) were White, 12% were Hispanic, and 7% were Asian.

About 6% of the women had either IgG or IgM antibodies at delivery, and 87% of infants born to those mothers had measurable IgG in their cord blood. No infants had IgM antibodies. As with the study presented at SMFM, the mothers’ infections included asymptomatic, mild, moderate, and severe cases, and the degree of severity of cases had no apparent effect on infant antibody concentrations. Most of the women who tested positive for COVID-19 (60%) were asymptomatic.

Among the 11 mothers who had antibodies but whose infants’ cord blood did not, 5 had only IgM antibodies, and 6 had significantly lower IgG concentrations than those seen in the other mothers.

In a commentary about the JAMA Pediatrics study, Flor Munoz, MD, of the Baylor College of Medicine, Houston, suggested that the findings are grounds for optimism about a maternal vaccination strategy to protect infants from COVID-19.

“However, the timing of maternal vaccination to protect the infant, as opposed to the mother alone, would necessitate an adequate interval from vaccination to delivery (of at least 4 weeks), while vaccination early in gestation and even late in the third trimester could still be protective for the mother,” Dr. Munoz wrote.

Given the interval between two-dose vaccination regimens and the fact that transplacental transfer begins at about the 17th week of gestation, “maternal vaccination starting in the early second trimester of gestation might be optimal to achieve the highest levels of antibodies in the newborn,” Dr. Munoz wrote. But questions remain, such as how effective the neonatal antibodies would be in protecting against COVID-19 and how long they last after birth.

No external funding was used in Dr. Joseph’s study. Dr. Joseph and Dr. Louis have disclosed no relevant financial relationships. The JAMA Pediatrics study was funded by the Children’s Hospital of Philadelphia. One coauthor received consultancy fees from Sanofi Pasteur, Lumen, Novavax, and Merck unrelated to the study. Dr. Munoz served on the data and safety monitoring boards of Moderna, Pfizer, Virometix, and Meissa Vaccines and has received grants from Novavax Research and Gilead Research.

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

Antibodies against SARS-CoV-2 cross the placenta during pregnancy and are detectable in most newborns born to mothers who had COVID-19 during pregnancy, according to findings from a study presented Jan. 28 at the meeting sponsored by the Society for Maternal-Fetal Medicine.

“I think the most striking finding is that we noticed a high degree of neutralizing response to natural infection even among asymptomatic infection, but of course a higher degree was seen in those with symptomatic infection,” Naima Joseph, MD, MPH, of Emory University, Atlanta, said in an interview.

“Our data demonstrate maternal capacity to mount an appropriate and robust immune response,” and maternal protective immunity lasted at least 28 days after infection, Dr. Joseph said. “Also, we noted higher neonatal cord blood titers in moms with higher titers, which suggests a relationship, but we need to better understand how transplacental transfer occurs as well as establish neonatal correlates of protection in order to see if and how maternal immunity may also benefit neonates.”

The researchers analyzed the amount of IgG and IgM antibodies in maternal and cord blood samples prospectively collected at delivery from women who tested positive for COVID-19 at any time while pregnant. They used enzyme-linked immunosorbent assay to assess for antibodies for the receptor binding domain of the SARS-CoV-2 spike protein.

The 32 pairs of mothers and infants in the study were predominantly non-Hispanic Black (72%) and Hispanic (25%), and 84% used Medicaid as their payer. Most of the mothers (72%) had at least one comorbidity, most commonly obesity, hypertension, and asthma or pulmonary disease. Just over half the women (53%) were symptomatic while they were infected, and 88% were ill with COVID-19 during the third trimester. The average time from infection to delivery was 28 days.

All the mothers had IgG antibodies, 94% had IgM antibodies, and 94% had neutralizing antibodies against SARS-CoV-2. Among the cord blood samples, 91% had IgG antibodies, 9% had IgM antibodies, and 25% had neutralizing antibodies.

“It’s reassuring that, so far, the physiological response is exactly what we expected it to be,” Judette Louis, MD, MPH, an associate professor of ob.gyn. and the ob.gyn. department chair at the University of South Florida, Tampa, said in an interview. “It’s what we would expect, but it’s always helpful to have more data to support that. Otherwise, you’re extrapolating from what you know from other conditions,” said Dr. Louis, who moderated the oral abstracts session.

Symptomatic infection was associated with significantly higher IgG titers than asymptomatic infection (P = .03), but no correlation was seen for IgM or neutralizing antibodies. In addition, although mothers who delivered more than 28 days after their infection had higher IgG titers (P = .05), no differences existed in IgM or neutralizing response.

Infants’ cord blood titers were significantly lower than their corresponding maternal samples, independently of symptoms or latency from infection to delivery (P < .001), Dr. Joseph reported.

“Transplacental efficiency in other pathogens has been shown to be correlated with neonatal immunity when the ratio of cord to maternal blood is greater than 1,” Dr. Joseph said in her presentation. Their data showed “suboptimal efficiency” at a ratio of 0.81.

The study’s small sample size and lack of a control group were weaknesses, but a major strength was having a population at disproportionately higher risk for infection and severe morbidity than the general population.
 

Implications for maternal COVID-19 vaccination

Although the data are not yet available, Dr. Joseph said they have expanded their protocol to include vaccinated pregnant women.

“The key to developing an effective vaccine [for pregnant people] is in really characterizing adaptive immunity in pregnancy,” Dr. Joseph told SMFM attendees. “I think that these findings inform further vaccine development in demonstrating that maternal immunity is robust.”

The World Health Organization recently recommended withholding COVID-19 vaccines from pregnant people, but the SMFM and American College of Obstetricians and Gynecologists subsequently issued a joint statement reaffirming that the COVID-19 vaccines authorized by the FDA “should not be withheld from pregnant individuals who choose to receive the vaccine.”

“One of the questions people ask is whether in pregnancy you’re going to mount a good response to the vaccine the way you would outside of pregnancy,” Dr. Louis said. “If we can demonstrate that you do, that may provide the information that some mothers need to make their decisions.” Data such as those from Dr. Joseph’s study can also inform recommendations on timing of maternal vaccination.

“For instance, Dr. Joseph demonstrated that, 28 days out from the infection, you had more antibodies, so there may be a scenario where we say this vaccine may be more beneficial in the middle of the pregnancy for the purpose of forming those antibodies,” Dr. Louis said.
 

Consensus emerging from maternal antibodies data

The findings from Dr. Joseph’s study mirror those reported in a study published online Jan. 29 in JAMA Pediatrics. That study, led by Dustin D. Flannery, DO, MSCE, of Children’s Hospital of Philadelphia, also examined maternal and neonatal levels of IgG and IgM antibodies against the receptor binding domain of the SARS-CoV-2 spike protein. They also found a positive correlation between cord blood and maternal IgG concentrations (P < .001), but notably, the ratio of cord to maternal blood titers was greater than 1, unlike in Dr. Joseph’s study.

For their study, Dr. Flannery and colleagues obtained maternal and cord blood sera at the time of delivery from 1471 pairs of mothers and infants, independently of COVID status during pregnancy. The average maternal age was 32 years, and just over a quarter of the population (26%) were Black, non-Hispanic women. About half (51%) were White, 12% were Hispanic, and 7% were Asian.

About 6% of the women had either IgG or IgM antibodies at delivery, and 87% of infants born to those mothers had measurable IgG in their cord blood. No infants had IgM antibodies. As with the study presented at SMFM, the mothers’ infections included asymptomatic, mild, moderate, and severe cases, and the degree of severity of cases had no apparent effect on infant antibody concentrations. Most of the women who tested positive for COVID-19 (60%) were asymptomatic.

Among the 11 mothers who had antibodies but whose infants’ cord blood did not, 5 had only IgM antibodies, and 6 had significantly lower IgG concentrations than those seen in the other mothers.

In a commentary about the JAMA Pediatrics study, Flor Munoz, MD, of the Baylor College of Medicine, Houston, suggested that the findings are grounds for optimism about a maternal vaccination strategy to protect infants from COVID-19.

“However, the timing of maternal vaccination to protect the infant, as opposed to the mother alone, would necessitate an adequate interval from vaccination to delivery (of at least 4 weeks), while vaccination early in gestation and even late in the third trimester could still be protective for the mother,” Dr. Munoz wrote.

Given the interval between two-dose vaccination regimens and the fact that transplacental transfer begins at about the 17th week of gestation, “maternal vaccination starting in the early second trimester of gestation might be optimal to achieve the highest levels of antibodies in the newborn,” Dr. Munoz wrote. But questions remain, such as how effective the neonatal antibodies would be in protecting against COVID-19 and how long they last after birth.

No external funding was used in Dr. Joseph’s study. Dr. Joseph and Dr. Louis have disclosed no relevant financial relationships. The JAMA Pediatrics study was funded by the Children’s Hospital of Philadelphia. One coauthor received consultancy fees from Sanofi Pasteur, Lumen, Novavax, and Merck unrelated to the study. Dr. Munoz served on the data and safety monitoring boards of Moderna, Pfizer, Virometix, and Meissa Vaccines and has received grants from Novavax Research and Gilead Research.

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

Antibodies against SARS-CoV-2 cross the placenta during pregnancy and are detectable in most newborns born to mothers who had COVID-19 during pregnancy, according to findings from a study presented Jan. 28 at the meeting sponsored by the Society for Maternal-Fetal Medicine.

“I think the most striking finding is that we noticed a high degree of neutralizing response to natural infection even among asymptomatic infection, but of course a higher degree was seen in those with symptomatic infection,” Naima Joseph, MD, MPH, of Emory University, Atlanta, said in an interview.

“Our data demonstrate maternal capacity to mount an appropriate and robust immune response,” and maternal protective immunity lasted at least 28 days after infection, Dr. Joseph said. “Also, we noted higher neonatal cord blood titers in moms with higher titers, which suggests a relationship, but we need to better understand how transplacental transfer occurs as well as establish neonatal correlates of protection in order to see if and how maternal immunity may also benefit neonates.”

The researchers analyzed the amount of IgG and IgM antibodies in maternal and cord blood samples prospectively collected at delivery from women who tested positive for COVID-19 at any time while pregnant. They used enzyme-linked immunosorbent assay to assess for antibodies for the receptor binding domain of the SARS-CoV-2 spike protein.

The 32 pairs of mothers and infants in the study were predominantly non-Hispanic Black (72%) and Hispanic (25%), and 84% used Medicaid as their payer. Most of the mothers (72%) had at least one comorbidity, most commonly obesity, hypertension, and asthma or pulmonary disease. Just over half the women (53%) were symptomatic while they were infected, and 88% were ill with COVID-19 during the third trimester. The average time from infection to delivery was 28 days.

All the mothers had IgG antibodies, 94% had IgM antibodies, and 94% had neutralizing antibodies against SARS-CoV-2. Among the cord blood samples, 91% had IgG antibodies, 9% had IgM antibodies, and 25% had neutralizing antibodies.

“It’s reassuring that, so far, the physiological response is exactly what we expected it to be,” Judette Louis, MD, MPH, an associate professor of ob.gyn. and the ob.gyn. department chair at the University of South Florida, Tampa, said in an interview. “It’s what we would expect, but it’s always helpful to have more data to support that. Otherwise, you’re extrapolating from what you know from other conditions,” said Dr. Louis, who moderated the oral abstracts session.

Symptomatic infection was associated with significantly higher IgG titers than asymptomatic infection (P = .03), but no correlation was seen for IgM or neutralizing antibodies. In addition, although mothers who delivered more than 28 days after their infection had higher IgG titers (P = .05), no differences existed in IgM or neutralizing response.

Infants’ cord blood titers were significantly lower than their corresponding maternal samples, independently of symptoms or latency from infection to delivery (P < .001), Dr. Joseph reported.

“Transplacental efficiency in other pathogens has been shown to be correlated with neonatal immunity when the ratio of cord to maternal blood is greater than 1,” Dr. Joseph said in her presentation. Their data showed “suboptimal efficiency” at a ratio of 0.81.

The study’s small sample size and lack of a control group were weaknesses, but a major strength was having a population at disproportionately higher risk for infection and severe morbidity than the general population.
 

Implications for maternal COVID-19 vaccination

Although the data are not yet available, Dr. Joseph said they have expanded their protocol to include vaccinated pregnant women.

“The key to developing an effective vaccine [for pregnant people] is in really characterizing adaptive immunity in pregnancy,” Dr. Joseph told SMFM attendees. “I think that these findings inform further vaccine development in demonstrating that maternal immunity is robust.”

The World Health Organization recently recommended withholding COVID-19 vaccines from pregnant people, but the SMFM and American College of Obstetricians and Gynecologists subsequently issued a joint statement reaffirming that the COVID-19 vaccines authorized by the FDA “should not be withheld from pregnant individuals who choose to receive the vaccine.”

“One of the questions people ask is whether in pregnancy you’re going to mount a good response to the vaccine the way you would outside of pregnancy,” Dr. Louis said. “If we can demonstrate that you do, that may provide the information that some mothers need to make their decisions.” Data such as those from Dr. Joseph’s study can also inform recommendations on timing of maternal vaccination.

“For instance, Dr. Joseph demonstrated that, 28 days out from the infection, you had more antibodies, so there may be a scenario where we say this vaccine may be more beneficial in the middle of the pregnancy for the purpose of forming those antibodies,” Dr. Louis said.
 

Consensus emerging from maternal antibodies data

The findings from Dr. Joseph’s study mirror those reported in a study published online Jan. 29 in JAMA Pediatrics. That study, led by Dustin D. Flannery, DO, MSCE, of Children’s Hospital of Philadelphia, also examined maternal and neonatal levels of IgG and IgM antibodies against the receptor binding domain of the SARS-CoV-2 spike protein. They also found a positive correlation between cord blood and maternal IgG concentrations (P < .001), but notably, the ratio of cord to maternal blood titers was greater than 1, unlike in Dr. Joseph’s study.

For their study, Dr. Flannery and colleagues obtained maternal and cord blood sera at the time of delivery from 1471 pairs of mothers and infants, independently of COVID status during pregnancy. The average maternal age was 32 years, and just over a quarter of the population (26%) were Black, non-Hispanic women. About half (51%) were White, 12% were Hispanic, and 7% were Asian.

About 6% of the women had either IgG or IgM antibodies at delivery, and 87% of infants born to those mothers had measurable IgG in their cord blood. No infants had IgM antibodies. As with the study presented at SMFM, the mothers’ infections included asymptomatic, mild, moderate, and severe cases, and the degree of severity of cases had no apparent effect on infant antibody concentrations. Most of the women who tested positive for COVID-19 (60%) were asymptomatic.

Among the 11 mothers who had antibodies but whose infants’ cord blood did not, 5 had only IgM antibodies, and 6 had significantly lower IgG concentrations than those seen in the other mothers.

In a commentary about the JAMA Pediatrics study, Flor Munoz, MD, of the Baylor College of Medicine, Houston, suggested that the findings are grounds for optimism about a maternal vaccination strategy to protect infants from COVID-19.

“However, the timing of maternal vaccination to protect the infant, as opposed to the mother alone, would necessitate an adequate interval from vaccination to delivery (of at least 4 weeks), while vaccination early in gestation and even late in the third trimester could still be protective for the mother,” Dr. Munoz wrote.

Given the interval between two-dose vaccination regimens and the fact that transplacental transfer begins at about the 17th week of gestation, “maternal vaccination starting in the early second trimester of gestation might be optimal to achieve the highest levels of antibodies in the newborn,” Dr. Munoz wrote. But questions remain, such as how effective the neonatal antibodies would be in protecting against COVID-19 and how long they last after birth.

No external funding was used in Dr. Joseph’s study. Dr. Joseph and Dr. Louis have disclosed no relevant financial relationships. The JAMA Pediatrics study was funded by the Children’s Hospital of Philadelphia. One coauthor received consultancy fees from Sanofi Pasteur, Lumen, Novavax, and Merck unrelated to the study. Dr. Munoz served on the data and safety monitoring boards of Moderna, Pfizer, Virometix, and Meissa Vaccines and has received grants from Novavax Research and Gilead Research.

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

Emerging data support the clinical validity and use of DecisionDx-SCC as a prognostic 40-gene expression profile test for patients with high-risk squamous cell carcinoma (SCC), according to Anna A. Bar, MD.

“The incidence of SCC has been growing rapidly, and the disease-related mortality is actually more than that of melanoma,” Dr. Bar, associate professor of dermatology at Oregon Health & Science University, Portland, said during a virtual forum on cutaneous malignancies jointly presented by Postgraduate Institute for Medicine and Global Academy for Medical Education.

“Like many cancers, SCC management plans are guided by the risk of metastasis. The current staging systems, like NCCN, AJCC, or Brigham and Women’s systems, struggle to provide accurate data of the metastatic potential of an individual’s SCC,” she said. “Furthermore, the predictive accuracy of these systems in SCC is variable, and many patients who have high risk factors do not experience poor outcomes, while others initially classified as having less concerning tumors will go on to have metastatic disease. That is where new gene expression tests come into play.”

Developed by and commercially available from Castle Biosciences, DecisionDx-SCC classifies an individual SCC patient’s tumor into one of the categories: low (class 1), moderate (class 2A), or high (class 2B) biologic risk of metastasis. “We’re hoping that DecisionDx results can help make management decisions within established guidelines,” Dr. Bar said. The test is indicated for patients with high-risk features including tumor size greater than 2 cm; tumor location on the head, neck, hands, genitals, feet, or pretibial surface; immunosuppression; a rapidly growing tumor; a tumor with poorly defined borders; a tumor at the site of prior radiation or chronic inflammation; perineural invasion; poorly defined tumor grade, and a deep tumor beyond the subcutaneous fat.

One validity study and three clinical utility studies of DecisionDx-SCC have been published that include data from more than 1,100 patients (see Curr Med Res Opin. 2020 Aug;36[8]:1301-7; Curr Med Res Opin. 2020 Aug;36[8]:1295-1300, and J Drugs Dermatol. 2019 Oct 1;18[10]:980-4). “This is a work in progress,” said Dr. Bar, director of the university’s Mohs micrographic surgery and cutaneous oncology fellowship.

The test was validated in an another study, which was prospectively designed and used archival tissue from 33 independent academic and community centers, including Oregon Health & Science University. All 420 patients in the clinical validation study had one or more high-risk factors, meeting the definition of high risk by NCCN or Mohs Appropriate Use Criteria (AUC). Their mean age was 71 years, 73% were male, 99% were White, and 25% were immune deficient.

Of the 420 patients, 63 had metastasis, and 86% of metastases were located on the head and neck. About 30% of metastasized lesions had perineural involvement, 27% had invasion beyond subcutaneous fat, and metastasized lesions were about 1 cm wider compared with lesions that were not. The overall metastasis rate at 3 years was 15%, “which is similar to that seen in the medical literature for high-risk populations,” Dr. Bar said.

The median time to metastasis was 0.9 years and the 95th percentile was 2.7 years. “This means that the 3-year horizon for identifying events in this study enabled identification of most patients who eventually experienced metastatic events,” she said. In this cohort, approximately half of the metastatic events occurred around 11 months post diagnosis, which “may provide guidance about the timeline and duration of high-intensity follow-up with frequency of clinical visits and imaging for patients at highest risk within the first year.”

The positive predictive value of the DecisionDx-SCC is 52%, meaning that half of class 2B lesions will metastasize. “This compares favorably when you look at the lower positive predictive value of the other staging systems,” Dr. Bar said. “The negative predictive value is 93%, meaning there are not a lot of false negatives. This also compares favorably to the other staging systems.”

Kaplan-Meier analysis of metastasis-free survival showed strong separation between patients with class 1, class 2A, and class 2B results, Dr. Bar said. While the overall risk of metastasis in this patient cohort was 15%, the risk among those with a class 1 result was less than half of that. “Patients with a class 2A result behave similarly to those with traditional risk factors such as deep invasion and poor differentiation, having about a 20% risk of metastasis,” she said. “The class 2B result identifies the most worrisome SCCs, with a greater than 50% risk of metastasis. While the results distribution from routine clinical testing is not yet known, this large validation study of high-risk SCC revealed that approximately half of the patients were class 1, less than half were class 2A, and about 1 in 18 had a class 2B result.”

On univariate analyses with traditional risk factors and use of the Brigham and Women’s staging system, the hazard ratio (HR) for class 2A lesions was 3.2, “which is similar to deep invasion, poor differentiation, or perineural involvement,” Dr. Bar said. At the same time, the HR for class 2B lesions was 11.6, “so class 2B is the strongest predictor of metastasis. The class 2B HR remained statistically significant in the multivariate analysis and is three times higher than that of the next highest HR in this cohort. For example, a high-risk SCC with deep invasion is already two times more likely to metastasize. Adding a class 2B score would be over 14 times more likely to metastasize than a tumor with a class 1 result.”

DecisionDx-SCC test results can inform management decisions within established guidelines. For example, for a high-risk SCC patient who has a class 1 result, or low risk of metastasis, “you may proceed with surgery and clinical nodal exam, and then follow up a couple of times a year,” Dr. Bar said. “For a high-risk patient with a 2A or moderate risk result, you might proceed with surgical treatment plus consider imaging studies such as ultrasound, CT, PET CT, and consider referral to other specialties.”

For a high-risk patient with a 2B or high risk result, she continued, “you may want to proceed with imaging studies right away in addition to surgery and consider consultation with radiation oncology or medical oncology, as well as more frequent follow-up with nodal exams, because the class 2B patients have been shown to have a greater than 50% risk of metastasis.”

Global Academy for Medical Education and this news organization are owned by the same parent company.

Dr. Bar disclosed that Oregon Health & Science University has received research funding from Castle Biosciences.

dbrunk@mdedge.com

Emerging data support the clinical validity and use of DecisionDx-SCC as a prognostic 40-gene expression profile test for patients with high-risk squamous cell carcinoma (SCC), according to Anna A. Bar, MD.

“The incidence of SCC has been growing rapidly, and the disease-related mortality is actually more than that of melanoma,” Dr. Bar, associate professor of dermatology at Oregon Health & Science University, Portland, said during a virtual forum on cutaneous malignancies jointly presented by Postgraduate Institute for Medicine and Global Academy for Medical Education.

“Like many cancers, SCC management plans are guided by the risk of metastasis. The current staging systems, like NCCN, AJCC, or Brigham and Women’s systems, struggle to provide accurate data of the metastatic potential of an individual’s SCC,” she said. “Furthermore, the predictive accuracy of these systems in SCC is variable, and many patients who have high risk factors do not experience poor outcomes, while others initially classified as having less concerning tumors will go on to have metastatic disease. That is where new gene expression tests come into play.”

Developed by and commercially available from Castle Biosciences, DecisionDx-SCC classifies an individual SCC patient’s tumor into one of the categories: low (class 1), moderate (class 2A), or high (class 2B) biologic risk of metastasis. “We’re hoping that DecisionDx results can help make management decisions within established guidelines,” Dr. Bar said. The test is indicated for patients with high-risk features including tumor size greater than 2 cm; tumor location on the head, neck, hands, genitals, feet, or pretibial surface; immunosuppression; a rapidly growing tumor; a tumor with poorly defined borders; a tumor at the site of prior radiation or chronic inflammation; perineural invasion; poorly defined tumor grade, and a deep tumor beyond the subcutaneous fat.

One validity study and three clinical utility studies of DecisionDx-SCC have been published that include data from more than 1,100 patients (see Curr Med Res Opin. 2020 Aug;36[8]:1301-7; Curr Med Res Opin. 2020 Aug;36[8]:1295-1300, and J Drugs Dermatol. 2019 Oct 1;18[10]:980-4). “This is a work in progress,” said Dr. Bar, director of the university’s Mohs micrographic surgery and cutaneous oncology fellowship.

The test was validated in an another study, which was prospectively designed and used archival tissue from 33 independent academic and community centers, including Oregon Health & Science University. All 420 patients in the clinical validation study had one or more high-risk factors, meeting the definition of high risk by NCCN or Mohs Appropriate Use Criteria (AUC). Their mean age was 71 years, 73% were male, 99% were White, and 25% were immune deficient.

Of the 420 patients, 63 had metastasis, and 86% of metastases were located on the head and neck. About 30% of metastasized lesions had perineural involvement, 27% had invasion beyond subcutaneous fat, and metastasized lesions were about 1 cm wider compared with lesions that were not. The overall metastasis rate at 3 years was 15%, “which is similar to that seen in the medical literature for high-risk populations,” Dr. Bar said.

The median time to metastasis was 0.9 years and the 95th percentile was 2.7 years. “This means that the 3-year horizon for identifying events in this study enabled identification of most patients who eventually experienced metastatic events,” she said. In this cohort, approximately half of the metastatic events occurred around 11 months post diagnosis, which “may provide guidance about the timeline and duration of high-intensity follow-up with frequency of clinical visits and imaging for patients at highest risk within the first year.”

The positive predictive value of the DecisionDx-SCC is 52%, meaning that half of class 2B lesions will metastasize. “This compares favorably when you look at the lower positive predictive value of the other staging systems,” Dr. Bar said. “The negative predictive value is 93%, meaning there are not a lot of false negatives. This also compares favorably to the other staging systems.”

Kaplan-Meier analysis of metastasis-free survival showed strong separation between patients with class 1, class 2A, and class 2B results, Dr. Bar said. While the overall risk of metastasis in this patient cohort was 15%, the risk among those with a class 1 result was less than half of that. “Patients with a class 2A result behave similarly to those with traditional risk factors such as deep invasion and poor differentiation, having about a 20% risk of metastasis,” she said. “The class 2B result identifies the most worrisome SCCs, with a greater than 50% risk of metastasis. While the results distribution from routine clinical testing is not yet known, this large validation study of high-risk SCC revealed that approximately half of the patients were class 1, less than half were class 2A, and about 1 in 18 had a class 2B result.”

On univariate analyses with traditional risk factors and use of the Brigham and Women’s staging system, the hazard ratio (HR) for class 2A lesions was 3.2, “which is similar to deep invasion, poor differentiation, or perineural involvement,” Dr. Bar said. At the same time, the HR for class 2B lesions was 11.6, “so class 2B is the strongest predictor of metastasis. The class 2B HR remained statistically significant in the multivariate analysis and is three times higher than that of the next highest HR in this cohort. For example, a high-risk SCC with deep invasion is already two times more likely to metastasize. Adding a class 2B score would be over 14 times more likely to metastasize than a tumor with a class 1 result.”

DecisionDx-SCC test results can inform management decisions within established guidelines. For example, for a high-risk SCC patient who has a class 1 result, or low risk of metastasis, “you may proceed with surgery and clinical nodal exam, and then follow up a couple of times a year,” Dr. Bar said. “For a high-risk patient with a 2A or moderate risk result, you might proceed with surgical treatment plus consider imaging studies such as ultrasound, CT, PET CT, and consider referral to other specialties.”

For a high-risk patient with a 2B or high risk result, she continued, “you may want to proceed with imaging studies right away in addition to surgery and consider consultation with radiation oncology or medical oncology, as well as more frequent follow-up with nodal exams, because the class 2B patients have been shown to have a greater than 50% risk of metastasis.”

Global Academy for Medical Education and this news organization are owned by the same parent company.

Dr. Bar disclosed that Oregon Health & Science University has received research funding from Castle Biosciences.

dbrunk@mdedge.com

Emerging data support the clinical validity and use of DecisionDx-SCC as a prognostic 40-gene expression profile test for patients with high-risk squamous cell carcinoma (SCC), according to Anna A. Bar, MD.

“The incidence of SCC has been growing rapidly, and the disease-related mortality is actually more than that of melanoma,” Dr. Bar, associate professor of dermatology at Oregon Health & Science University, Portland, said during a virtual forum on cutaneous malignancies jointly presented by Postgraduate Institute for Medicine and Global Academy for Medical Education.

“Like many cancers, SCC management plans are guided by the risk of metastasis. The current staging systems, like NCCN, AJCC, or Brigham and Women’s systems, struggle to provide accurate data of the metastatic potential of an individual’s SCC,” she said. “Furthermore, the predictive accuracy of these systems in SCC is variable, and many patients who have high risk factors do not experience poor outcomes, while others initially classified as having less concerning tumors will go on to have metastatic disease. That is where new gene expression tests come into play.”

Developed by and commercially available from Castle Biosciences, DecisionDx-SCC classifies an individual SCC patient’s tumor into one of the categories: low (class 1), moderate (class 2A), or high (class 2B) biologic risk of metastasis. “We’re hoping that DecisionDx results can help make management decisions within established guidelines,” Dr. Bar said. The test is indicated for patients with high-risk features including tumor size greater than 2 cm; tumor location on the head, neck, hands, genitals, feet, or pretibial surface; immunosuppression; a rapidly growing tumor; a tumor with poorly defined borders; a tumor at the site of prior radiation or chronic inflammation; perineural invasion; poorly defined tumor grade, and a deep tumor beyond the subcutaneous fat.

One validity study and three clinical utility studies of DecisionDx-SCC have been published that include data from more than 1,100 patients (see Curr Med Res Opin. 2020 Aug;36[8]:1301-7; Curr Med Res Opin. 2020 Aug;36[8]:1295-1300, and J Drugs Dermatol. 2019 Oct 1;18[10]:980-4). “This is a work in progress,” said Dr. Bar, director of the university’s Mohs micrographic surgery and cutaneous oncology fellowship.

The test was validated in an another study, which was prospectively designed and used archival tissue from 33 independent academic and community centers, including Oregon Health & Science University. All 420 patients in the clinical validation study had one or more high-risk factors, meeting the definition of high risk by NCCN or Mohs Appropriate Use Criteria (AUC). Their mean age was 71 years, 73% were male, 99% were White, and 25% were immune deficient.

Of the 420 patients, 63 had metastasis, and 86% of metastases were located on the head and neck. About 30% of metastasized lesions had perineural involvement, 27% had invasion beyond subcutaneous fat, and metastasized lesions were about 1 cm wider compared with lesions that were not. The overall metastasis rate at 3 years was 15%, “which is similar to that seen in the medical literature for high-risk populations,” Dr. Bar said.

The median time to metastasis was 0.9 years and the 95th percentile was 2.7 years. “This means that the 3-year horizon for identifying events in this study enabled identification of most patients who eventually experienced metastatic events,” she said. In this cohort, approximately half of the metastatic events occurred around 11 months post diagnosis, which “may provide guidance about the timeline and duration of high-intensity follow-up with frequency of clinical visits and imaging for patients at highest risk within the first year.”

The positive predictive value of the DecisionDx-SCC is 52%, meaning that half of class 2B lesions will metastasize. “This compares favorably when you look at the lower positive predictive value of the other staging systems,” Dr. Bar said. “The negative predictive value is 93%, meaning there are not a lot of false negatives. This also compares favorably to the other staging systems.”

Kaplan-Meier analysis of metastasis-free survival showed strong separation between patients with class 1, class 2A, and class 2B results, Dr. Bar said. While the overall risk of metastasis in this patient cohort was 15%, the risk among those with a class 1 result was less than half of that. “Patients with a class 2A result behave similarly to those with traditional risk factors such as deep invasion and poor differentiation, having about a 20% risk of metastasis,” she said. “The class 2B result identifies the most worrisome SCCs, with a greater than 50% risk of metastasis. While the results distribution from routine clinical testing is not yet known, this large validation study of high-risk SCC revealed that approximately half of the patients were class 1, less than half were class 2A, and about 1 in 18 had a class 2B result.”

On univariate analyses with traditional risk factors and use of the Brigham and Women’s staging system, the hazard ratio (HR) for class 2A lesions was 3.2, “which is similar to deep invasion, poor differentiation, or perineural involvement,” Dr. Bar said. At the same time, the HR for class 2B lesions was 11.6, “so class 2B is the strongest predictor of metastasis. The class 2B HR remained statistically significant in the multivariate analysis and is three times higher than that of the next highest HR in this cohort. For example, a high-risk SCC with deep invasion is already two times more likely to metastasize. Adding a class 2B score would be over 14 times more likely to metastasize than a tumor with a class 1 result.”

DecisionDx-SCC test results can inform management decisions within established guidelines. For example, for a high-risk SCC patient who has a class 1 result, or low risk of metastasis, “you may proceed with surgery and clinical nodal exam, and then follow up a couple of times a year,” Dr. Bar said. “For a high-risk patient with a 2A or moderate risk result, you might proceed with surgical treatment plus consider imaging studies such as ultrasound, CT, PET CT, and consider referral to other specialties.”

For a high-risk patient with a 2B or high risk result, she continued, “you may want to proceed with imaging studies right away in addition to surgery and consider consultation with radiation oncology or medical oncology, as well as more frequent follow-up with nodal exams, because the class 2B patients have been shown to have a greater than 50% risk of metastasis.”

Global Academy for Medical Education and this news organization are owned by the same parent company.

Dr. Bar disclosed that Oregon Health & Science University has received research funding from Castle Biosciences.

dbrunk@mdedge.com

Even in the most experienced hands, dermoscopy poses a challenge when the usual pigment clues are lacking to help distinguish melanoma from amelanotic melanoma and pigmented basal cell carcinoma (BCC) from nonpigmented BCC.

Copyright Dr. Jennifer A. Stein

“For me, pink lesions are challenging,” Jennifer A. Stein, MD, PhD, said during the virtual Orlando Dermatology Aesthetic and Clinical Conference. “How can dermoscopy help us distinguish between Spitz nevus, melanoma, clear cell acanthoma, psoriasis, basal cell carcinoma, and squamous cell carcinoma?”

Dr. Stein, professor of dermatology at New York University, offered four tips. First, look for the shiny white perpendicular lines, otherwise known as the chrysalis or crystalline pattern. “You can only see this feature when you’re looking with polarized light,” she said. “This is why you want a dermatoscope that has polarized light, and better yet, one that you’re able to turn on and off, the hybrid kind, because then you can convince yourself that you’re looking at this feature, because it blinks on and off.”

The differential diagnosis for white shiny perpendicular lines includes dermatofibroma/scars (which is most common), Spitz and atypical genital nevi, BCC, and melanoma. “Dermatofibromas sometimes have white circles or rings in the center,” Dr. Stein said. “In BCC, the lines aren’t always perpendicular. Sometimes it’s more of a blotch or strands.”

A second tip for managing a pink lesion on dermoscopy is to look for any brown color. “When you see that combo together you have to worry,” she said. “When you see pigment network on dermoscopy, you have to put melanoma in your differential. If you see shiny white lines in something that is melanocytic, there’s a 98% specificity for melanoma.”

A third tip she offered for managing pink lesions is to check the blood vessels for clues. “For years, I was just naming the vessels based on making the diagnosis and then deciding, ‘that’s a basal cell carcinoma; those must be branching vessels,’ ” said Dr. Stein, who manages NYU’s medical dermatology faculty group practice.

However, blood vessel patterns differ. For example, branching or arborizing vessels are suggestive of BCC. “These vessels are very crisp-looking on dermoscopy,” she said. “They’re all in the same plane of focus and they look like they were drawn in with a fine point marker. That’s different from other blood vessel patterns.” She also pointed out that superficial basal cells have short, fine telangiectasias. “When you put on the polarized light, the clue is the white, shiny structures,” she said.

Dotted vessels, meanwhile, appear on dermoscopy as small red dots aligned perpendicular to the skin surface. The differential includes inflammatory lesions like psoriasis, stasis, and trauma; clear cell acanthoma (characterized by a “string of pearls” arrangement), nevi, and melanoma. “I find dermoscopy most useful in diagnosing SCC – especially squamous cell in situ,” she said. “Important clinical clues suggestive of SCC or melanoma include a solitary lesion, it’s new, it’s growing, and it’s not going away with a topical steroid.”

An additional pattern to be aware of are hairpin vessels, which are looped and feature a sharp bend at one end. These are often seen in seborrheic keratoses. “You can’t count on the hairpin vessels alone, because you can see this in anything keratotic, such as in keratoacanthoma (at the periphery with a yellow keratotic center), warts, SCC, BCC, as well as in dermal nevi and Spitz nevi,” said Dr. Stein, who recommended dermoscopedia.org as resource.

Comma vessels, meanwhile, appear in dermal or compound nevi. She described these as “slightly curved vessels that are much less in focus than branched vessels, because they come in and out of the plane of focus,” she said. “If you put your dermatoscope on top of the nevus and wobble it around you can appreciate the curve. If you look at it from the side, it looks like a curve. If you look at it straight on it will look more like a line. If you look at from the end it will look like a dot.”

Another vessel type she discussed are linear irregular and polymorphous vessels, which she described as “any combination of different types of vessels. We get most worried when we see dotted and linear irregular vessels together. In that case, you worry about melanoma. These can also be seen in nevi and other tumors, such as BCC.”

Dr. Stein’s fourth tip of the presentation was a reminder to consider dermoscopy as one piece of the clinical exam. “Always think about the lesion in context of the rest of the clinical picture and history,” she said. “Don’t get discouraged if it’s hard; just keep practicing. Look for any brown and use your clinical clues to put together to make the right decision.”

She disclosed that NYU receives compensation from MoleSafe for her telemedicine dermoscopic diagnoses.

dbrunk@mdedge.com

Even in the most experienced hands, dermoscopy poses a challenge when the usual pigment clues are lacking to help distinguish melanoma from amelanotic melanoma and pigmented basal cell carcinoma (BCC) from nonpigmented BCC.

Copyright Dr. Jennifer A. Stein

“For me, pink lesions are challenging,” Jennifer A. Stein, MD, PhD, said during the virtual Orlando Dermatology Aesthetic and Clinical Conference. “How can dermoscopy help us distinguish between Spitz nevus, melanoma, clear cell acanthoma, psoriasis, basal cell carcinoma, and squamous cell carcinoma?”

Dr. Stein, professor of dermatology at New York University, offered four tips. First, look for the shiny white perpendicular lines, otherwise known as the chrysalis or crystalline pattern. “You can only see this feature when you’re looking with polarized light,” she said. “This is why you want a dermatoscope that has polarized light, and better yet, one that you’re able to turn on and off, the hybrid kind, because then you can convince yourself that you’re looking at this feature, because it blinks on and off.”

The differential diagnosis for white shiny perpendicular lines includes dermatofibroma/scars (which is most common), Spitz and atypical genital nevi, BCC, and melanoma. “Dermatofibromas sometimes have white circles or rings in the center,” Dr. Stein said. “In BCC, the lines aren’t always perpendicular. Sometimes it’s more of a blotch or strands.”

A second tip for managing a pink lesion on dermoscopy is to look for any brown color. “When you see that combo together you have to worry,” she said. “When you see pigment network on dermoscopy, you have to put melanoma in your differential. If you see shiny white lines in something that is melanocytic, there’s a 98% specificity for melanoma.”

A third tip she offered for managing pink lesions is to check the blood vessels for clues. “For years, I was just naming the vessels based on making the diagnosis and then deciding, ‘that’s a basal cell carcinoma; those must be branching vessels,’ ” said Dr. Stein, who manages NYU’s medical dermatology faculty group practice.

However, blood vessel patterns differ. For example, branching or arborizing vessels are suggestive of BCC. “These vessels are very crisp-looking on dermoscopy,” she said. “They’re all in the same plane of focus and they look like they were drawn in with a fine point marker. That’s different from other blood vessel patterns.” She also pointed out that superficial basal cells have short, fine telangiectasias. “When you put on the polarized light, the clue is the white, shiny structures,” she said.

Dotted vessels, meanwhile, appear on dermoscopy as small red dots aligned perpendicular to the skin surface. The differential includes inflammatory lesions like psoriasis, stasis, and trauma; clear cell acanthoma (characterized by a “string of pearls” arrangement), nevi, and melanoma. “I find dermoscopy most useful in diagnosing SCC – especially squamous cell in situ,” she said. “Important clinical clues suggestive of SCC or melanoma include a solitary lesion, it’s new, it’s growing, and it’s not going away with a topical steroid.”

An additional pattern to be aware of are hairpin vessels, which are looped and feature a sharp bend at one end. These are often seen in seborrheic keratoses. “You can’t count on the hairpin vessels alone, because you can see this in anything keratotic, such as in keratoacanthoma (at the periphery with a yellow keratotic center), warts, SCC, BCC, as well as in dermal nevi and Spitz nevi,” said Dr. Stein, who recommended dermoscopedia.org as resource.

Comma vessels, meanwhile, appear in dermal or compound nevi. She described these as “slightly curved vessels that are much less in focus than branched vessels, because they come in and out of the plane of focus,” she said. “If you put your dermatoscope on top of the nevus and wobble it around you can appreciate the curve. If you look at it from the side, it looks like a curve. If you look at it straight on it will look more like a line. If you look at from the end it will look like a dot.”

Another vessel type she discussed are linear irregular and polymorphous vessels, which she described as “any combination of different types of vessels. We get most worried when we see dotted and linear irregular vessels together. In that case, you worry about melanoma. These can also be seen in nevi and other tumors, such as BCC.”

Dr. Stein’s fourth tip of the presentation was a reminder to consider dermoscopy as one piece of the clinical exam. “Always think about the lesion in context of the rest of the clinical picture and history,” she said. “Don’t get discouraged if it’s hard; just keep practicing. Look for any brown and use your clinical clues to put together to make the right decision.”

She disclosed that NYU receives compensation from MoleSafe for her telemedicine dermoscopic diagnoses.

dbrunk@mdedge.com

Even in the most experienced hands, dermoscopy poses a challenge when the usual pigment clues are lacking to help distinguish melanoma from amelanotic melanoma and pigmented basal cell carcinoma (BCC) from nonpigmented BCC.

Copyright Dr. Jennifer A. Stein

“For me, pink lesions are challenging,” Jennifer A. Stein, MD, PhD, said during the virtual Orlando Dermatology Aesthetic and Clinical Conference. “How can dermoscopy help us distinguish between Spitz nevus, melanoma, clear cell acanthoma, psoriasis, basal cell carcinoma, and squamous cell carcinoma?”

Dr. Stein, professor of dermatology at New York University, offered four tips. First, look for the shiny white perpendicular lines, otherwise known as the chrysalis or crystalline pattern. “You can only see this feature when you’re looking with polarized light,” she said. “This is why you want a dermatoscope that has polarized light, and better yet, one that you’re able to turn on and off, the hybrid kind, because then you can convince yourself that you’re looking at this feature, because it blinks on and off.”

The differential diagnosis for white shiny perpendicular lines includes dermatofibroma/scars (which is most common), Spitz and atypical genital nevi, BCC, and melanoma. “Dermatofibromas sometimes have white circles or rings in the center,” Dr. Stein said. “In BCC, the lines aren’t always perpendicular. Sometimes it’s more of a blotch or strands.”

A second tip for managing a pink lesion on dermoscopy is to look for any brown color. “When you see that combo together you have to worry,” she said. “When you see pigment network on dermoscopy, you have to put melanoma in your differential. If you see shiny white lines in something that is melanocytic, there’s a 98% specificity for melanoma.”

A third tip she offered for managing pink lesions is to check the blood vessels for clues. “For years, I was just naming the vessels based on making the diagnosis and then deciding, ‘that’s a basal cell carcinoma; those must be branching vessels,’ ” said Dr. Stein, who manages NYU’s medical dermatology faculty group practice.

However, blood vessel patterns differ. For example, branching or arborizing vessels are suggestive of BCC. “These vessels are very crisp-looking on dermoscopy,” she said. “They’re all in the same plane of focus and they look like they were drawn in with a fine point marker. That’s different from other blood vessel patterns.” She also pointed out that superficial basal cells have short, fine telangiectasias. “When you put on the polarized light, the clue is the white, shiny structures,” she said.

Dotted vessels, meanwhile, appear on dermoscopy as small red dots aligned perpendicular to the skin surface. The differential includes inflammatory lesions like psoriasis, stasis, and trauma; clear cell acanthoma (characterized by a “string of pearls” arrangement), nevi, and melanoma. “I find dermoscopy most useful in diagnosing SCC – especially squamous cell in situ,” she said. “Important clinical clues suggestive of SCC or melanoma include a solitary lesion, it’s new, it’s growing, and it’s not going away with a topical steroid.”

An additional pattern to be aware of are hairpin vessels, which are looped and feature a sharp bend at one end. These are often seen in seborrheic keratoses. “You can’t count on the hairpin vessels alone, because you can see this in anything keratotic, such as in keratoacanthoma (at the periphery with a yellow keratotic center), warts, SCC, BCC, as well as in dermal nevi and Spitz nevi,” said Dr. Stein, who recommended dermoscopedia.org as resource.

Comma vessels, meanwhile, appear in dermal or compound nevi. She described these as “slightly curved vessels that are much less in focus than branched vessels, because they come in and out of the plane of focus,” she said. “If you put your dermatoscope on top of the nevus and wobble it around you can appreciate the curve. If you look at it from the side, it looks like a curve. If you look at it straight on it will look more like a line. If you look at from the end it will look like a dot.”

Another vessel type she discussed are linear irregular and polymorphous vessels, which she described as “any combination of different types of vessels. We get most worried when we see dotted and linear irregular vessels together. In that case, you worry about melanoma. These can also be seen in nevi and other tumors, such as BCC.”

Dr. Stein’s fourth tip of the presentation was a reminder to consider dermoscopy as one piece of the clinical exam. “Always think about the lesion in context of the rest of the clinical picture and history,” she said. “Don’t get discouraged if it’s hard; just keep practicing. Look for any brown and use your clinical clues to put together to make the right decision.”

She disclosed that NYU receives compensation from MoleSafe for her telemedicine dermoscopic diagnoses.

dbrunk@mdedge.com

Combining transcatheter arterial chemoembolization (TACE) therapy with sorafenib improved progression-free survival (PFS), but not overall survival (OS), when compared with TACE alone in patients with unresectable hepatocellular carcinoma (HCC), final results from the phase 2 TACTICS trial showed.

The lack of a statistically significant difference in OS may have been due to the fact that patients randomized to receive TACE alone had more frequent post-trial therapies compared with patients assigned to TACE plus sorafenib, said study investigator Masatoshi Kudo, MD, PhD, of the Kindai University faculty of medicine in Osaka, Japan.

“These subsequent anticancer procedures and active systemic therapies have potentially diluted OS benefit in TACE plus sorafenib by extending post-progression survival and confounding survival analysis, implying the OS endpoint is not feasible anymore for TACE combination trials in the era of multitargeted agents and immune checkpoint inhibitors,” Dr. Kudo said at the 2021 Gastrointestinal Cancers Symposium (abstract 270).
 

Unresectable HCC

The TACTICS trial was launched in October 2010. Investigators enrolled 156 patients with unresectable HCC, Child-Pugh scores of 7 or less, treatable tumors (10 or fewer nodules of 10 cm or less) and adequate organ function.

Patients were randomized to receive TACE alone or with sorafenib. Sorafenib was delivered at a dose of 400 mg daily starting 2-3 weeks before the first TACE procedure to assess tolerability, followed by 800-mg daily doses. Sorafenib was interrupted for 2 days before and 3 days after each TACE session.

The trial had a gate-keeping design, which specified that OS would be formally analyzed only if PFS results were positive.

As reported in GUT in 2020, the trial met its PFS coprimary endpoint, with a median PFS of 25.2 months for the combination, compared with 13.5 months for TACE alone, at a median follow-up of 122.3 weeks. The hazard ratio (HR) for progression with the combination was 0.59 (P = .006).
 

Updated results

At the symposium, Dr. Kudo presented updated PFS results. At a median follow-up for all randomized patients of 33.4 months, the median PFS with the combination was 22.8 months, compared with 13.5 months for TACE alone (HR, 0.661; P­ = .02).

However, OS did not differ significantly between the groups, with a median of 36.2 months for the combination and 30.8 months for TACE alone (HR, 0.861; P = .40)

In a subgroup analysis of OS, there were small trends in favor of the combination compared with TACE alone in most categories, but the benefit of the combination was statistically significant only for the 12 patients with HCC of hepatitis B virus etiology (HR, 0.72; 95% CI, 0.006-0.808).

There were also trends favoring TACE plus sorafenib for PFS in a subgroup analysis, but none of the differences were statistically significant, except for patients who had received one or two TACE treatments prior to study entry (HR, 0.474; 95% CI, 0.276-0.812).

Treatment-emergent adverse events were consistent with those seen in the primary analysis, with no new safety signals seen at the last follow-up, Dr. Kudo said.

A majority of patients in both arms had subsequent anticancer therapy – 76.3% of the TACE-alone arm and 58.8% of the combination arm.

Patients in the TACE-alone arm were more likely than were those in the combination arm to have ablation (22.4% vs. 14.9%) or additional sorafenib (50% vs. 10.6%). Patients in the TACE-alone arm were also more likely to receive hepatic artery infusion chemotherapy a single time (27.6% vs. 19.1%) but less likely to receive it continuously (10.3% vs. 19.1%).

Dr. Kudo noted that in six trials in which TACE was combined with another agent, the correlation coefficient between PFS and OS was low, and the slope of weighted linear regression was more gentle than that seen in trials of other therapies for advanced HCC, “suggesting that long post-progression survivals strongly affected the OS in TACE combination trials.”

The TACTICS study was funded by the Japan Liver Oncology Group. Dr. Kudo disclosed relationships with Bayer, codeveloper of sorafenib, and multiple other companies.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

Combining transcatheter arterial chemoembolization (TACE) therapy with sorafenib improved progression-free survival (PFS), but not overall survival (OS), when compared with TACE alone in patients with unresectable hepatocellular carcinoma (HCC), final results from the phase 2 TACTICS trial showed.

The lack of a statistically significant difference in OS may have been due to the fact that patients randomized to receive TACE alone had more frequent post-trial therapies compared with patients assigned to TACE plus sorafenib, said study investigator Masatoshi Kudo, MD, PhD, of the Kindai University faculty of medicine in Osaka, Japan.

“These subsequent anticancer procedures and active systemic therapies have potentially diluted OS benefit in TACE plus sorafenib by extending post-progression survival and confounding survival analysis, implying the OS endpoint is not feasible anymore for TACE combination trials in the era of multitargeted agents and immune checkpoint inhibitors,” Dr. Kudo said at the 2021 Gastrointestinal Cancers Symposium (abstract 270).
 

Unresectable HCC

The TACTICS trial was launched in October 2010. Investigators enrolled 156 patients with unresectable HCC, Child-Pugh scores of 7 or less, treatable tumors (10 or fewer nodules of 10 cm or less) and adequate organ function.

Patients were randomized to receive TACE alone or with sorafenib. Sorafenib was delivered at a dose of 400 mg daily starting 2-3 weeks before the first TACE procedure to assess tolerability, followed by 800-mg daily doses. Sorafenib was interrupted for 2 days before and 3 days after each TACE session.

The trial had a gate-keeping design, which specified that OS would be formally analyzed only if PFS results were positive.

As reported in GUT in 2020, the trial met its PFS coprimary endpoint, with a median PFS of 25.2 months for the combination, compared with 13.5 months for TACE alone, at a median follow-up of 122.3 weeks. The hazard ratio (HR) for progression with the combination was 0.59 (P = .006).
 

Updated results

At the symposium, Dr. Kudo presented updated PFS results. At a median follow-up for all randomized patients of 33.4 months, the median PFS with the combination was 22.8 months, compared with 13.5 months for TACE alone (HR, 0.661; P­ = .02).

However, OS did not differ significantly between the groups, with a median of 36.2 months for the combination and 30.8 months for TACE alone (HR, 0.861; P = .40)

In a subgroup analysis of OS, there were small trends in favor of the combination compared with TACE alone in most categories, but the benefit of the combination was statistically significant only for the 12 patients with HCC of hepatitis B virus etiology (HR, 0.72; 95% CI, 0.006-0.808).

There were also trends favoring TACE plus sorafenib for PFS in a subgroup analysis, but none of the differences were statistically significant, except for patients who had received one or two TACE treatments prior to study entry (HR, 0.474; 95% CI, 0.276-0.812).

Treatment-emergent adverse events were consistent with those seen in the primary analysis, with no new safety signals seen at the last follow-up, Dr. Kudo said.

A majority of patients in both arms had subsequent anticancer therapy – 76.3% of the TACE-alone arm and 58.8% of the combination arm.

Patients in the TACE-alone arm were more likely than were those in the combination arm to have ablation (22.4% vs. 14.9%) or additional sorafenib (50% vs. 10.6%). Patients in the TACE-alone arm were also more likely to receive hepatic artery infusion chemotherapy a single time (27.6% vs. 19.1%) but less likely to receive it continuously (10.3% vs. 19.1%).

Dr. Kudo noted that in six trials in which TACE was combined with another agent, the correlation coefficient between PFS and OS was low, and the slope of weighted linear regression was more gentle than that seen in trials of other therapies for advanced HCC, “suggesting that long post-progression survivals strongly affected the OS in TACE combination trials.”

The TACTICS study was funded by the Japan Liver Oncology Group. Dr. Kudo disclosed relationships with Bayer, codeveloper of sorafenib, and multiple other companies.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

Combining transcatheter arterial chemoembolization (TACE) therapy with sorafenib improved progression-free survival (PFS), but not overall survival (OS), when compared with TACE alone in patients with unresectable hepatocellular carcinoma (HCC), final results from the phase 2 TACTICS trial showed.

The lack of a statistically significant difference in OS may have been due to the fact that patients randomized to receive TACE alone had more frequent post-trial therapies compared with patients assigned to TACE plus sorafenib, said study investigator Masatoshi Kudo, MD, PhD, of the Kindai University faculty of medicine in Osaka, Japan.

“These subsequent anticancer procedures and active systemic therapies have potentially diluted OS benefit in TACE plus sorafenib by extending post-progression survival and confounding survival analysis, implying the OS endpoint is not feasible anymore for TACE combination trials in the era of multitargeted agents and immune checkpoint inhibitors,” Dr. Kudo said at the 2021 Gastrointestinal Cancers Symposium (abstract 270).
 

Unresectable HCC

The TACTICS trial was launched in October 2010. Investigators enrolled 156 patients with unresectable HCC, Child-Pugh scores of 7 or less, treatable tumors (10 or fewer nodules of 10 cm or less) and adequate organ function.

Patients were randomized to receive TACE alone or with sorafenib. Sorafenib was delivered at a dose of 400 mg daily starting 2-3 weeks before the first TACE procedure to assess tolerability, followed by 800-mg daily doses. Sorafenib was interrupted for 2 days before and 3 days after each TACE session.

The trial had a gate-keeping design, which specified that OS would be formally analyzed only if PFS results were positive.

As reported in GUT in 2020, the trial met its PFS coprimary endpoint, with a median PFS of 25.2 months for the combination, compared with 13.5 months for TACE alone, at a median follow-up of 122.3 weeks. The hazard ratio (HR) for progression with the combination was 0.59 (P = .006).
 

Updated results

At the symposium, Dr. Kudo presented updated PFS results. At a median follow-up for all randomized patients of 33.4 months, the median PFS with the combination was 22.8 months, compared with 13.5 months for TACE alone (HR, 0.661; P­ = .02).

However, OS did not differ significantly between the groups, with a median of 36.2 months for the combination and 30.8 months for TACE alone (HR, 0.861; P = .40)

In a subgroup analysis of OS, there were small trends in favor of the combination compared with TACE alone in most categories, but the benefit of the combination was statistically significant only for the 12 patients with HCC of hepatitis B virus etiology (HR, 0.72; 95% CI, 0.006-0.808).

There were also trends favoring TACE plus sorafenib for PFS in a subgroup analysis, but none of the differences were statistically significant, except for patients who had received one or two TACE treatments prior to study entry (HR, 0.474; 95% CI, 0.276-0.812).

Treatment-emergent adverse events were consistent with those seen in the primary analysis, with no new safety signals seen at the last follow-up, Dr. Kudo said.

A majority of patients in both arms had subsequent anticancer therapy – 76.3% of the TACE-alone arm and 58.8% of the combination arm.

Patients in the TACE-alone arm were more likely than were those in the combination arm to have ablation (22.4% vs. 14.9%) or additional sorafenib (50% vs. 10.6%). Patients in the TACE-alone arm were also more likely to receive hepatic artery infusion chemotherapy a single time (27.6% vs. 19.1%) but less likely to receive it continuously (10.3% vs. 19.1%).

Dr. Kudo noted that in six trials in which TACE was combined with another agent, the correlation coefficient between PFS and OS was low, and the slope of weighted linear regression was more gentle than that seen in trials of other therapies for advanced HCC, “suggesting that long post-progression survivals strongly affected the OS in TACE combination trials.”

The TACTICS study was funded by the Japan Liver Oncology Group. Dr. Kudo disclosed relationships with Bayer, codeveloper of sorafenib, and multiple other companies.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

Pancreatic enzyme replacement therapy (PERT) is often an essential component of the treatment regimen for patients with pancreatic cancer, but it can be very pricey.

“Out-of-pocket costs for a 30-day supply of enzymes for Medicare beneficiaries can be as high as $1,000,” commented Arjun Gupta, MD, an oncology fellow at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore.

This can contribute to financial toxicity for patients who already have a high symptom burden and distress. The high cost of this supportive care has been underappreciated, he said.

In addition to its use for patients with pancreatic cancer, PERT is also prescribed to patients with chronic pancreatitis and cystic fibrosis. These enzymes can reduce symptoms of indigestion and improve nutrition for patients with exocrine pancreatic insufficiency, he explained.

“Out-of-pocket costs for two large pancreas enzyme capsules, which are often required for a meal, may be $15. And these need to be taken at every meal and may be more expensive than the meal itself,” he said in an interview.

Dr. Gupta led a new study which showed that, among Medicare beneficiaries, the expected out-of-pocket costs for a 30-day supply of optimally dosed PERT averaged $999 across formulations. Patients’ costs, including deductibles and coinsurance, ranged from $853 to $1,536.

The out-of-pocket costs were lower after patients met the deductible ($673; range, $527-$1,210) and continued to decrease after reaching catastrophic coverage ($135; range, $105-$242).

The findings were presented at the 2021 Gastrointestinal Cancers Symposium.

Dr. Gupta noted that there has been a lot of publicity about very expensive anticancer drugs, but little has been said about the costs of products used in supportive care. “While it’s true that many patients cannot afford the drugs, there are patient-assistance programs where they can often get them free of charge,” he said. “But supportive care agents, such as those for constipation or the enzymes – all of those can nickel and dime you and end up being very costly.”

These agents add substantially to the drug cost burden. “Some patients also need insulin, which is also insanely expensive,” he said.

One of the reasons for the high cost of PERT is that there are very few options, and all the available products are brand-name agents. Dr. Gupta noted that clinicians often underprescribe pancreatic enzymes in clinical practice. “Because of this, we wanted to look at what are the estimated out-of-pocket costs for patients directly when they’re prescribed an optimal regimen of pancreatic enzymes,” he said.
 

Study details

For their study, Dr. Gupta and colleagues assessed PERT costs using the Medicare Part D formulary and pricing files for the first quarter of 2020. Point-of-sale and out-of-pocket costs for each PERT formulation were calculated among Part D standalone and Medicare Advantage prescription drug plans.

Costs were then assessed using three scenarios: the standard-benefit design, with a $435 deductible and 25% coinsurance after the deductible is met; 25% coinsurance to fill a prescription after the deductible while in the coverage gap until the patient spends $6,350 out of pocket; and 5% coinsurance once catastrophic coverage is reached.

Across 3,974 plans nationwide, four formulations in 17 different doses were covered by Medicare plans during the study period. Doses ranged from 3,000 to 40,000 lipase units, and the per-unit list price ranged from $1.44 to $13.89.

The point-of-sale price for a 30-day supply of optimally dosed PERT ranged from $2,109 to $4,840.

Dr. Gupta noted that a “good-sized meal often requires 80,000 units of lipase, or two of the very largest pills. Of note, these pills need to be taken meal after meal every meal throughout a patient’s life.”

Prescribers and dietitians try to find the least expensive options, including patient-assistance programs, but in the end, they are sometimes forced to underprescribe. “Some patients will go and buy over-the-counter pancreatic enzyme supplements, and it seems like a good way to cut costs,” said Dr. Gupta, “but it is not recommended for people with pancreatic cancer.”

The problem with these formulations is that they are not regulated. “The enzyme content in them is also minuscule, in the range of hundreds of units instead of the 50,000 units needed per meal,” he said. “Patients end up spending much more for ineffective therapies.”

The study received no outside funding. Dr. Gupta disclosed no relevant financial relationships.

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

Pancreatic enzyme replacement therapy (PERT) is often an essential component of the treatment regimen for patients with pancreatic cancer, but it can be very pricey.

“Out-of-pocket costs for a 30-day supply of enzymes for Medicare beneficiaries can be as high as $1,000,” commented Arjun Gupta, MD, an oncology fellow at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore.

This can contribute to financial toxicity for patients who already have a high symptom burden and distress. The high cost of this supportive care has been underappreciated, he said.

In addition to its use for patients with pancreatic cancer, PERT is also prescribed to patients with chronic pancreatitis and cystic fibrosis. These enzymes can reduce symptoms of indigestion and improve nutrition for patients with exocrine pancreatic insufficiency, he explained.

“Out-of-pocket costs for two large pancreas enzyme capsules, which are often required for a meal, may be $15. And these need to be taken at every meal and may be more expensive than the meal itself,” he said in an interview.

Dr. Gupta led a new study which showed that, among Medicare beneficiaries, the expected out-of-pocket costs for a 30-day supply of optimally dosed PERT averaged $999 across formulations. Patients’ costs, including deductibles and coinsurance, ranged from $853 to $1,536.

The out-of-pocket costs were lower after patients met the deductible ($673; range, $527-$1,210) and continued to decrease after reaching catastrophic coverage ($135; range, $105-$242).

The findings were presented at the 2021 Gastrointestinal Cancers Symposium.

Dr. Gupta noted that there has been a lot of publicity about very expensive anticancer drugs, but little has been said about the costs of products used in supportive care. “While it’s true that many patients cannot afford the drugs, there are patient-assistance programs where they can often get them free of charge,” he said. “But supportive care agents, such as those for constipation or the enzymes – all of those can nickel and dime you and end up being very costly.”

These agents add substantially to the drug cost burden. “Some patients also need insulin, which is also insanely expensive,” he said.

One of the reasons for the high cost of PERT is that there are very few options, and all the available products are brand-name agents. Dr. Gupta noted that clinicians often underprescribe pancreatic enzymes in clinical practice. “Because of this, we wanted to look at what are the estimated out-of-pocket costs for patients directly when they’re prescribed an optimal regimen of pancreatic enzymes,” he said.
 

Study details

For their study, Dr. Gupta and colleagues assessed PERT costs using the Medicare Part D formulary and pricing files for the first quarter of 2020. Point-of-sale and out-of-pocket costs for each PERT formulation were calculated among Part D standalone and Medicare Advantage prescription drug plans.

Costs were then assessed using three scenarios: the standard-benefit design, with a $435 deductible and 25% coinsurance after the deductible is met; 25% coinsurance to fill a prescription after the deductible while in the coverage gap until the patient spends $6,350 out of pocket; and 5% coinsurance once catastrophic coverage is reached.

Across 3,974 plans nationwide, four formulations in 17 different doses were covered by Medicare plans during the study period. Doses ranged from 3,000 to 40,000 lipase units, and the per-unit list price ranged from $1.44 to $13.89.

The point-of-sale price for a 30-day supply of optimally dosed PERT ranged from $2,109 to $4,840.

Dr. Gupta noted that a “good-sized meal often requires 80,000 units of lipase, or two of the very largest pills. Of note, these pills need to be taken meal after meal every meal throughout a patient’s life.”

Prescribers and dietitians try to find the least expensive options, including patient-assistance programs, but in the end, they are sometimes forced to underprescribe. “Some patients will go and buy over-the-counter pancreatic enzyme supplements, and it seems like a good way to cut costs,” said Dr. Gupta, “but it is not recommended for people with pancreatic cancer.”

The problem with these formulations is that they are not regulated. “The enzyme content in them is also minuscule, in the range of hundreds of units instead of the 50,000 units needed per meal,” he said. “Patients end up spending much more for ineffective therapies.”

The study received no outside funding. Dr. Gupta disclosed no relevant financial relationships.

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

Pancreatic enzyme replacement therapy (PERT) is often an essential component of the treatment regimen for patients with pancreatic cancer, but it can be very pricey.

“Out-of-pocket costs for a 30-day supply of enzymes for Medicare beneficiaries can be as high as $1,000,” commented Arjun Gupta, MD, an oncology fellow at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore.

This can contribute to financial toxicity for patients who already have a high symptom burden and distress. The high cost of this supportive care has been underappreciated, he said.

In addition to its use for patients with pancreatic cancer, PERT is also prescribed to patients with chronic pancreatitis and cystic fibrosis. These enzymes can reduce symptoms of indigestion and improve nutrition for patients with exocrine pancreatic insufficiency, he explained.

“Out-of-pocket costs for two large pancreas enzyme capsules, which are often required for a meal, may be $15. And these need to be taken at every meal and may be more expensive than the meal itself,” he said in an interview.

Dr. Gupta led a new study which showed that, among Medicare beneficiaries, the expected out-of-pocket costs for a 30-day supply of optimally dosed PERT averaged $999 across formulations. Patients’ costs, including deductibles and coinsurance, ranged from $853 to $1,536.

The out-of-pocket costs were lower after patients met the deductible ($673; range, $527-$1,210) and continued to decrease after reaching catastrophic coverage ($135; range, $105-$242).

The findings were presented at the 2021 Gastrointestinal Cancers Symposium.

Dr. Gupta noted that there has been a lot of publicity about very expensive anticancer drugs, but little has been said about the costs of products used in supportive care. “While it’s true that many patients cannot afford the drugs, there are patient-assistance programs where they can often get them free of charge,” he said. “But supportive care agents, such as those for constipation or the enzymes – all of those can nickel and dime you and end up being very costly.”

These agents add substantially to the drug cost burden. “Some patients also need insulin, which is also insanely expensive,” he said.

One of the reasons for the high cost of PERT is that there are very few options, and all the available products are brand-name agents. Dr. Gupta noted that clinicians often underprescribe pancreatic enzymes in clinical practice. “Because of this, we wanted to look at what are the estimated out-of-pocket costs for patients directly when they’re prescribed an optimal regimen of pancreatic enzymes,” he said.
 

Study details

For their study, Dr. Gupta and colleagues assessed PERT costs using the Medicare Part D formulary and pricing files for the first quarter of 2020. Point-of-sale and out-of-pocket costs for each PERT formulation were calculated among Part D standalone and Medicare Advantage prescription drug plans.

Costs were then assessed using three scenarios: the standard-benefit design, with a $435 deductible and 25% coinsurance after the deductible is met; 25% coinsurance to fill a prescription after the deductible while in the coverage gap until the patient spends $6,350 out of pocket; and 5% coinsurance once catastrophic coverage is reached.

Across 3,974 plans nationwide, four formulations in 17 different doses were covered by Medicare plans during the study period. Doses ranged from 3,000 to 40,000 lipase units, and the per-unit list price ranged from $1.44 to $13.89.

The point-of-sale price for a 30-day supply of optimally dosed PERT ranged from $2,109 to $4,840.

Dr. Gupta noted that a “good-sized meal often requires 80,000 units of lipase, or two of the very largest pills. Of note, these pills need to be taken meal after meal every meal throughout a patient’s life.”

Prescribers and dietitians try to find the least expensive options, including patient-assistance programs, but in the end, they are sometimes forced to underprescribe. “Some patients will go and buy over-the-counter pancreatic enzyme supplements, and it seems like a good way to cut costs,” said Dr. Gupta, “but it is not recommended for people with pancreatic cancer.”

The problem with these formulations is that they are not regulated. “The enzyme content in them is also minuscule, in the range of hundreds of units instead of the 50,000 units needed per meal,” he said. “Patients end up spending much more for ineffective therapies.”

The study received no outside funding. Dr. Gupta disclosed no relevant financial relationships.

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

Physicians treating patients with IBD typically focus on disease and symptom management along with quality of life measures, but the latter are not the final word on patient well-being. Social well-being is another outcome that can more accurately portray a patient’s satisfaction with their treatment.

That was the message delivered by Laurie Keefer, PhD, at a session on diet, stress, health literacy, and disparities in IBD treatment at the annual congress of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. “When we talk about disease management, we’re talking about these outcomes of mucosal healing, remission, and lack of hospitalizations, but we don’t always talk about wellness,” said Dr. Keefer, director of psychobehavioral research in the department of gastroenterology at Icahn School of Medicine at Mount Sinai, New York.

Dr. Keefer advocated for incorporating measures that focus on the patient’s ability to feel fulfilled, pursue happiness, and contribute to the community. “Wellness is defined as a state of complete physical, mental, and social well-being. It’s a holistic definition, not merely the absence of those things,” she said during her talk.

Social determinants of health, such as income, inequality, health literacy, numeracy, financial stress, social connections, community, place of resonance, and housing coresidents, play important roles.

“Subjective well-being is a state in which an individual feels they are able to do work productively and creatively, have relationships, and contribute to their community. We want them to thrive. We want them to live well. We want them to reach their potential. There’s no reason you cannot reach your potential even though you’re living with IBD,” said Dr. Keefer.

Subjective well-being doesn’t replace quality of life assessment. “Absolutely, quality of life is an important metric, [but I want to] make a plug that maybe we should start to add subjective well-being into these outcome measures,” said Dr. Keefer.

The approach does away with specific measures of health, employment, financial security, or even living situation. “It takes away all of those things we just assume are part of being well. It measures it differently. It measures what makes us happy, divided by the degree of happiness we obtain,” said Dr. Keefer. She presented examples from a study her group is conducting that showed patients’ responses to what made them want to be well. “Some people want to be well to take care of their children or families or a parent, some people want to be well so they can go adventure skydiving, other people just want to be able to exercise and take care of their health. That’s what the target needs to be for wellness. In that sense, wellness is an achievement of best health possible in all domains, not just one. It’s a lifelong pursuit. It forces us to ask not just ‘Are my patient’s symptoms gone? Are they in clinical remission? Are they in histological remission? Are they in deep remission?’ but ‘Is my patient thriving? Are they meeting their potential? Are they getting what they want out of treatment? Are they happy?’ ”

Quality of life measures can provide some insight, but they are limited because they are anchored in physical symptoms, and they focus on a narrow, recent window, usually the past week. “You can imagine that as symptoms improve, those metrics kind of improve, and it looks like quality of life is great. But that’s not always the case, and we’re really missing an opportunity to go deeper. It’s also less sensitive when somebody is in remission, so it’s also very difficult to continue that proactive [approach] of thriving and living well when you’re already coming up positive on quality of life indices,” said Dr. Keefer.

Subjective well-being measures ignore physical symptoms, and focus instead on questions like the patient’s ability to work, socialize, and maintain relationships with family, and whether the patient feels able to contribute meaningfully to society. The measure is insensitive to factors such as inflammation, trauma, or changes to medication. As a result, measures can be used much less frequently – every 6 months, or even once a year.

Subjective well-being can also rely on the patient to define well-being, and that makes it more culturally sensitive. “It can allow for people to be well in whatever way they think they want to be well,” said Dr. Keefer.

There are various resources for measuring subjective well-being. The Organization for Economic Cooperation and Development has guidelines for measuring subjective well-being. The National Institutes of Health PROMIS includes useful measures of psychological well-being, positive affect, and general life satisfaction; they are available for free and include 6-8 items. Other useful measures include the Satisfaction with Life scale, the Positive and Negative Affect scale, and the Harmony in Life scale. “All of those have been well validated and used internationally as measures of well-being,” said Dr. Keefer.

Physicians can also address patients directly, asking them about how satisfied they are with their life. “You’re opening up that discussion to ask them not just, ‘How is your IBD and how is your IBD affecting your work?’ but ‘How is your life going?’ You’re proactively trying to help your patients thrive,” said Dr. Keefer.

Session moderators praised Dr. Keefer’s presentation as an appropriate wrap-up to talks that looked at stress, diet, economic disparities, health literacy, and numeracy.

“We capped it all with a discussion around what is well-being. We often talk about biologics or medicines or surgery when it comes to Crohn’s disease and ulcerative colitis, but what about holistic wellness? It’s all of this. It’s the medication piece, but it’s all of these other pillars involved in the process as well. I think looking at this from many different angles is very important so that patients can achieve the best quality of life possible,” said comoderator Tina Aswani Omprakash, a patient advocate who is pursuing a master’s degree in public health at Mount Sinai’s Icahn School of Medicine.

Physicians treating patients with IBD typically focus on disease and symptom management along with quality of life measures, but the latter are not the final word on patient well-being. Social well-being is another outcome that can more accurately portray a patient’s satisfaction with their treatment.

That was the message delivered by Laurie Keefer, PhD, at a session on diet, stress, health literacy, and disparities in IBD treatment at the annual congress of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. “When we talk about disease management, we’re talking about these outcomes of mucosal healing, remission, and lack of hospitalizations, but we don’t always talk about wellness,” said Dr. Keefer, director of psychobehavioral research in the department of gastroenterology at Icahn School of Medicine at Mount Sinai, New York.

Dr. Keefer advocated for incorporating measures that focus on the patient’s ability to feel fulfilled, pursue happiness, and contribute to the community. “Wellness is defined as a state of complete physical, mental, and social well-being. It’s a holistic definition, not merely the absence of those things,” she said during her talk.

Social determinants of health, such as income, inequality, health literacy, numeracy, financial stress, social connections, community, place of resonance, and housing coresidents, play important roles.

“Subjective well-being is a state in which an individual feels they are able to do work productively and creatively, have relationships, and contribute to their community. We want them to thrive. We want them to live well. We want them to reach their potential. There’s no reason you cannot reach your potential even though you’re living with IBD,” said Dr. Keefer.

Subjective well-being doesn’t replace quality of life assessment. “Absolutely, quality of life is an important metric, [but I want to] make a plug that maybe we should start to add subjective well-being into these outcome measures,” said Dr. Keefer.

The approach does away with specific measures of health, employment, financial security, or even living situation. “It takes away all of those things we just assume are part of being well. It measures it differently. It measures what makes us happy, divided by the degree of happiness we obtain,” said Dr. Keefer. She presented examples from a study her group is conducting that showed patients’ responses to what made them want to be well. “Some people want to be well to take care of their children or families or a parent, some people want to be well so they can go adventure skydiving, other people just want to be able to exercise and take care of their health. That’s what the target needs to be for wellness. In that sense, wellness is an achievement of best health possible in all domains, not just one. It’s a lifelong pursuit. It forces us to ask not just ‘Are my patient’s symptoms gone? Are they in clinical remission? Are they in histological remission? Are they in deep remission?’ but ‘Is my patient thriving? Are they meeting their potential? Are they getting what they want out of treatment? Are they happy?’ ”

Quality of life measures can provide some insight, but they are limited because they are anchored in physical symptoms, and they focus on a narrow, recent window, usually the past week. “You can imagine that as symptoms improve, those metrics kind of improve, and it looks like quality of life is great. But that’s not always the case, and we’re really missing an opportunity to go deeper. It’s also less sensitive when somebody is in remission, so it’s also very difficult to continue that proactive [approach] of thriving and living well when you’re already coming up positive on quality of life indices,” said Dr. Keefer.

Subjective well-being measures ignore physical symptoms, and focus instead on questions like the patient’s ability to work, socialize, and maintain relationships with family, and whether the patient feels able to contribute meaningfully to society. The measure is insensitive to factors such as inflammation, trauma, or changes to medication. As a result, measures can be used much less frequently – every 6 months, or even once a year.

Subjective well-being can also rely on the patient to define well-being, and that makes it more culturally sensitive. “It can allow for people to be well in whatever way they think they want to be well,” said Dr. Keefer.

There are various resources for measuring subjective well-being. The Organization for Economic Cooperation and Development has guidelines for measuring subjective well-being. The National Institutes of Health PROMIS includes useful measures of psychological well-being, positive affect, and general life satisfaction; they are available for free and include 6-8 items. Other useful measures include the Satisfaction with Life scale, the Positive and Negative Affect scale, and the Harmony in Life scale. “All of those have been well validated and used internationally as measures of well-being,” said Dr. Keefer.

Physicians can also address patients directly, asking them about how satisfied they are with their life. “You’re opening up that discussion to ask them not just, ‘How is your IBD and how is your IBD affecting your work?’ but ‘How is your life going?’ You’re proactively trying to help your patients thrive,” said Dr. Keefer.

Session moderators praised Dr. Keefer’s presentation as an appropriate wrap-up to talks that looked at stress, diet, economic disparities, health literacy, and numeracy.

“We capped it all with a discussion around what is well-being. We often talk about biologics or medicines or surgery when it comes to Crohn’s disease and ulcerative colitis, but what about holistic wellness? It’s all of this. It’s the medication piece, but it’s all of these other pillars involved in the process as well. I think looking at this from many different angles is very important so that patients can achieve the best quality of life possible,” said comoderator Tina Aswani Omprakash, a patient advocate who is pursuing a master’s degree in public health at Mount Sinai’s Icahn School of Medicine.

Physicians treating patients with IBD typically focus on disease and symptom management along with quality of life measures, but the latter are not the final word on patient well-being. Social well-being is another outcome that can more accurately portray a patient’s satisfaction with their treatment.

That was the message delivered by Laurie Keefer, PhD, at a session on diet, stress, health literacy, and disparities in IBD treatment at the annual congress of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. “When we talk about disease management, we’re talking about these outcomes of mucosal healing, remission, and lack of hospitalizations, but we don’t always talk about wellness,” said Dr. Keefer, director of psychobehavioral research in the department of gastroenterology at Icahn School of Medicine at Mount Sinai, New York.

Dr. Keefer advocated for incorporating measures that focus on the patient’s ability to feel fulfilled, pursue happiness, and contribute to the community. “Wellness is defined as a state of complete physical, mental, and social well-being. It’s a holistic definition, not merely the absence of those things,” she said during her talk.

Social determinants of health, such as income, inequality, health literacy, numeracy, financial stress, social connections, community, place of resonance, and housing coresidents, play important roles.

“Subjective well-being is a state in which an individual feels they are able to do work productively and creatively, have relationships, and contribute to their community. We want them to thrive. We want them to live well. We want them to reach their potential. There’s no reason you cannot reach your potential even though you’re living with IBD,” said Dr. Keefer.

Subjective well-being doesn’t replace quality of life assessment. “Absolutely, quality of life is an important metric, [but I want to] make a plug that maybe we should start to add subjective well-being into these outcome measures,” said Dr. Keefer.

The approach does away with specific measures of health, employment, financial security, or even living situation. “It takes away all of those things we just assume are part of being well. It measures it differently. It measures what makes us happy, divided by the degree of happiness we obtain,” said Dr. Keefer. She presented examples from a study her group is conducting that showed patients’ responses to what made them want to be well. “Some people want to be well to take care of their children or families or a parent, some people want to be well so they can go adventure skydiving, other people just want to be able to exercise and take care of their health. That’s what the target needs to be for wellness. In that sense, wellness is an achievement of best health possible in all domains, not just one. It’s a lifelong pursuit. It forces us to ask not just ‘Are my patient’s symptoms gone? Are they in clinical remission? Are they in histological remission? Are they in deep remission?’ but ‘Is my patient thriving? Are they meeting their potential? Are they getting what they want out of treatment? Are they happy?’ ”

Quality of life measures can provide some insight, but they are limited because they are anchored in physical symptoms, and they focus on a narrow, recent window, usually the past week. “You can imagine that as symptoms improve, those metrics kind of improve, and it looks like quality of life is great. But that’s not always the case, and we’re really missing an opportunity to go deeper. It’s also less sensitive when somebody is in remission, so it’s also very difficult to continue that proactive [approach] of thriving and living well when you’re already coming up positive on quality of life indices,” said Dr. Keefer.

Subjective well-being measures ignore physical symptoms, and focus instead on questions like the patient’s ability to work, socialize, and maintain relationships with family, and whether the patient feels able to contribute meaningfully to society. The measure is insensitive to factors such as inflammation, trauma, or changes to medication. As a result, measures can be used much less frequently – every 6 months, or even once a year.

Subjective well-being can also rely on the patient to define well-being, and that makes it more culturally sensitive. “It can allow for people to be well in whatever way they think they want to be well,” said Dr. Keefer.

There are various resources for measuring subjective well-being. The Organization for Economic Cooperation and Development has guidelines for measuring subjective well-being. The National Institutes of Health PROMIS includes useful measures of psychological well-being, positive affect, and general life satisfaction; they are available for free and include 6-8 items. Other useful measures include the Satisfaction with Life scale, the Positive and Negative Affect scale, and the Harmony in Life scale. “All of those have been well validated and used internationally as measures of well-being,” said Dr. Keefer.

Physicians can also address patients directly, asking them about how satisfied they are with their life. “You’re opening up that discussion to ask them not just, ‘How is your IBD and how is your IBD affecting your work?’ but ‘How is your life going?’ You’re proactively trying to help your patients thrive,” said Dr. Keefer.

Session moderators praised Dr. Keefer’s presentation as an appropriate wrap-up to talks that looked at stress, diet, economic disparities, health literacy, and numeracy.

“We capped it all with a discussion around what is well-being. We often talk about biologics or medicines or surgery when it comes to Crohn’s disease and ulcerative colitis, but what about holistic wellness? It’s all of this. It’s the medication piece, but it’s all of these other pillars involved in the process as well. I think looking at this from many different angles is very important so that patients can achieve the best quality of life possible,” said comoderator Tina Aswani Omprakash, a patient advocate who is pursuing a master’s degree in public health at Mount Sinai’s Icahn School of Medicine.

A test that uses machine learning may improve the management of patients with pancreatic cysts, sparing some of them unnecessary surgery, a cohort study suggests.

The test, called CompCyst, integrates clinical, imaging, and biomarker data. It proved more accurate than the current standard of care for correctly determining whether patients should be discharged from follow-up, immediately operated on, or monitored.

Rachel Karchin, PhD, of the Johns Hopkins Whiting School of Engineering in Baltimore, reported these results at the AACR Virtual Special Conference: Artificial Intelligence, Diagnosis, and Imaging (Abstract IA-13).

“Preoperative diagnosis of pancreatic cysts and managing patients who present with a cyst are a clinical conundrum because pancreatic cancer is so deadly, while the decision to surgically resect a cyst is complicated by the danger of the surgery, which has high morbidity and mortality,” Dr. Karchin explained. “The challenge of the diagnostic test is to place patients into one of three groups: those who should be discharged, who should be operated on, and who should be monitored.”

High sensitivity is important for the operate and monitor groups to ensure identification of all patients needing these approaches, whereas higher specificity is important for the discharge group to avoid falsely classifying premalignant cysts, Dr. Karchin said.

She and her colleagues applied machine learning to this classification challenge, using data from 862 patients who had undergone resection of pancreatic cysts at 16 centers in the United States, Europe, and Asia. All patients had a known cyst histopathology, which served as the gold standard, and a known clinical management strategy (discharge, operate, or monitor).

The investigators used a multivariate organization of combinatorial alterations algorithm that integrates clinical features, imaging characteristics, cyst fluid genetics, and serum biomarkers to create classifiers. This algorithm can be trained to maximize sensitivity, maximize specificity, or balance these metrics, Dr. Karchin noted.

The resulting test, CompCyst, was trained using data from 436 of the patients and then validated in the remaining 426 patients.

In the validation cohort, for classifying patients who should be discharged from care, the test had a sensitivity of 46% and a specificity of 100%, according to results reported at the conference and published previously (Sci Transl Med. 2019 Jul 19. doi: 10.1126/scitranslmed.aav4772).

For immediately operating, CompCyst had a sensitivity of 91% and a specificity of 54%. And for monitoring the patient, the test had a sensitivity of 99% and a specificity of 30%.

When CompCyst was compared against the standard of care based on conventional clinical and imaging criteria alone, the former was more accurate. CompCyst correctly identified larger shares of patients who should have been discharged (60% vs. 19%) and who should have been monitored (49% vs. 34%), and the test identified a similar share of patients who should have immediately had an operation (91% vs. 89%).

“The takeaway from this is that standard of care is sending too many patients unnecessarily to surgery,” Dr. Karchin commented. “The CompCyst test, with application of the three classifiers sequentially – discharge, operate, or monitor – could reduce unnecessary surgery by 60% or more based on our calculations.”

“While our study was retrospective, it shows promising results in reducing unnecessary surgeries, compared to current standard of care,” she said, adding that a prospective study is planned next.

“In 10-12 weeks, this CompCyst diagnostic test is going to be available at Johns Hopkins for patients. I’m very excited about that,” Dr. Karchin concluded. “We hope that our study shows the potential of combining clinical, imaging, and genetic features with machine learning to improve clinical judgment about many diseases.”

Dr. Karchin disclosed no conflicts of interest. The study was supported by the Lustgarten Foundation for Pancreatic Cancer Research, the Virginia and D.K. Ludwig Fund for Cancer Research, the Sol Goldman Pancreatic Cancer Research Center, the Michael Rolfe Pancreatic Cancer Research Foundation, the Benjamin Baker Scholarship, and the National Institutes of Health.

A test that uses machine learning may improve the management of patients with pancreatic cysts, sparing some of them unnecessary surgery, a cohort study suggests.

The test, called CompCyst, integrates clinical, imaging, and biomarker data. It proved more accurate than the current standard of care for correctly determining whether patients should be discharged from follow-up, immediately operated on, or monitored.

Rachel Karchin, PhD, of the Johns Hopkins Whiting School of Engineering in Baltimore, reported these results at the AACR Virtual Special Conference: Artificial Intelligence, Diagnosis, and Imaging (Abstract IA-13).

“Preoperative diagnosis of pancreatic cysts and managing patients who present with a cyst are a clinical conundrum because pancreatic cancer is so deadly, while the decision to surgically resect a cyst is complicated by the danger of the surgery, which has high morbidity and mortality,” Dr. Karchin explained. “The challenge of the diagnostic test is to place patients into one of three groups: those who should be discharged, who should be operated on, and who should be monitored.”

High sensitivity is important for the operate and monitor groups to ensure identification of all patients needing these approaches, whereas higher specificity is important for the discharge group to avoid falsely classifying premalignant cysts, Dr. Karchin said.

She and her colleagues applied machine learning to this classification challenge, using data from 862 patients who had undergone resection of pancreatic cysts at 16 centers in the United States, Europe, and Asia. All patients had a known cyst histopathology, which served as the gold standard, and a known clinical management strategy (discharge, operate, or monitor).

The investigators used a multivariate organization of combinatorial alterations algorithm that integrates clinical features, imaging characteristics, cyst fluid genetics, and serum biomarkers to create classifiers. This algorithm can be trained to maximize sensitivity, maximize specificity, or balance these metrics, Dr. Karchin noted.

The resulting test, CompCyst, was trained using data from 436 of the patients and then validated in the remaining 426 patients.

In the validation cohort, for classifying patients who should be discharged from care, the test had a sensitivity of 46% and a specificity of 100%, according to results reported at the conference and published previously (Sci Transl Med. 2019 Jul 19. doi: 10.1126/scitranslmed.aav4772).

For immediately operating, CompCyst had a sensitivity of 91% and a specificity of 54%. And for monitoring the patient, the test had a sensitivity of 99% and a specificity of 30%.

When CompCyst was compared against the standard of care based on conventional clinical and imaging criteria alone, the former was more accurate. CompCyst correctly identified larger shares of patients who should have been discharged (60% vs. 19%) and who should have been monitored (49% vs. 34%), and the test identified a similar share of patients who should have immediately had an operation (91% vs. 89%).

“The takeaway from this is that standard of care is sending too many patients unnecessarily to surgery,” Dr. Karchin commented. “The CompCyst test, with application of the three classifiers sequentially – discharge, operate, or monitor – could reduce unnecessary surgery by 60% or more based on our calculations.”

“While our study was retrospective, it shows promising results in reducing unnecessary surgeries, compared to current standard of care,” she said, adding that a prospective study is planned next.

“In 10-12 weeks, this CompCyst diagnostic test is going to be available at Johns Hopkins for patients. I’m very excited about that,” Dr. Karchin concluded. “We hope that our study shows the potential of combining clinical, imaging, and genetic features with machine learning to improve clinical judgment about many diseases.”

Dr. Karchin disclosed no conflicts of interest. The study was supported by the Lustgarten Foundation for Pancreatic Cancer Research, the Virginia and D.K. Ludwig Fund for Cancer Research, the Sol Goldman Pancreatic Cancer Research Center, the Michael Rolfe Pancreatic Cancer Research Foundation, the Benjamin Baker Scholarship, and the National Institutes of Health.

A test that uses machine learning may improve the management of patients with pancreatic cysts, sparing some of them unnecessary surgery, a cohort study suggests.

The test, called CompCyst, integrates clinical, imaging, and biomarker data. It proved more accurate than the current standard of care for correctly determining whether patients should be discharged from follow-up, immediately operated on, or monitored.

Rachel Karchin, PhD, of the Johns Hopkins Whiting School of Engineering in Baltimore, reported these results at the AACR Virtual Special Conference: Artificial Intelligence, Diagnosis, and Imaging (Abstract IA-13).

“Preoperative diagnosis of pancreatic cysts and managing patients who present with a cyst are a clinical conundrum because pancreatic cancer is so deadly, while the decision to surgically resect a cyst is complicated by the danger of the surgery, which has high morbidity and mortality,” Dr. Karchin explained. “The challenge of the diagnostic test is to place patients into one of three groups: those who should be discharged, who should be operated on, and who should be monitored.”

High sensitivity is important for the operate and monitor groups to ensure identification of all patients needing these approaches, whereas higher specificity is important for the discharge group to avoid falsely classifying premalignant cysts, Dr. Karchin said.

She and her colleagues applied machine learning to this classification challenge, using data from 862 patients who had undergone resection of pancreatic cysts at 16 centers in the United States, Europe, and Asia. All patients had a known cyst histopathology, which served as the gold standard, and a known clinical management strategy (discharge, operate, or monitor).

The investigators used a multivariate organization of combinatorial alterations algorithm that integrates clinical features, imaging characteristics, cyst fluid genetics, and serum biomarkers to create classifiers. This algorithm can be trained to maximize sensitivity, maximize specificity, or balance these metrics, Dr. Karchin noted.

The resulting test, CompCyst, was trained using data from 436 of the patients and then validated in the remaining 426 patients.

In the validation cohort, for classifying patients who should be discharged from care, the test had a sensitivity of 46% and a specificity of 100%, according to results reported at the conference and published previously (Sci Transl Med. 2019 Jul 19. doi: 10.1126/scitranslmed.aav4772).

For immediately operating, CompCyst had a sensitivity of 91% and a specificity of 54%. And for monitoring the patient, the test had a sensitivity of 99% and a specificity of 30%.

When CompCyst was compared against the standard of care based on conventional clinical and imaging criteria alone, the former was more accurate. CompCyst correctly identified larger shares of patients who should have been discharged (60% vs. 19%) and who should have been monitored (49% vs. 34%), and the test identified a similar share of patients who should have immediately had an operation (91% vs. 89%).

“The takeaway from this is that standard of care is sending too many patients unnecessarily to surgery,” Dr. Karchin commented. “The CompCyst test, with application of the three classifiers sequentially – discharge, operate, or monitor – could reduce unnecessary surgery by 60% or more based on our calculations.”

“While our study was retrospective, it shows promising results in reducing unnecessary surgeries, compared to current standard of care,” she said, adding that a prospective study is planned next.

“In 10-12 weeks, this CompCyst diagnostic test is going to be available at Johns Hopkins for patients. I’m very excited about that,” Dr. Karchin concluded. “We hope that our study shows the potential of combining clinical, imaging, and genetic features with machine learning to improve clinical judgment about many diseases.”

Dr. Karchin disclosed no conflicts of interest. The study was supported by the Lustgarten Foundation for Pancreatic Cancer Research, the Virginia and D.K. Ludwig Fund for Cancer Research, the Sol Goldman Pancreatic Cancer Research Center, the Michael Rolfe Pancreatic Cancer Research Foundation, the Benjamin Baker Scholarship, and the National Institutes of Health.

Brepocitinib, a first-in-class topical inhibitor of both tyrosine kinase 2 and Janus kinase 1, proved effective for treatment of mild to moderate atopic dermatitis (AD), and with a safety profile essentially indistinguishable from vehicle cream in a phase 2b randomized trial, Megan N. Landis, MD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

The study included 240 adolescents and adults with mild to moderate AD at 70 sites in the United States and nine other countries. Patients’ mean baseline Eczema Area and Severity Index (EASI) score was 7.3, with 9.2% of their body surface area being involved. Participants were equally split between mild and moderate disease. They were randomized to 6 weeks of double-blind treatment in one of eight study arms: once-daily topical brepocitinib at a concentration of 0.1%, 0.3%, 1%, or 3%; twice-daily brepocitinib at 1% or 3%; or once- or twice-daily vehicle cream.

The primary endpoint was change in EASI score from baseline to week 6. Brepocitinib 1% and 3% once daily and 1% twice daily outperformed vehicle, with EASI score reductions of 70.1%, 67.9%, and 75%, respectively, compared with a 44.4% decrease among those in the once-daily vehicle control group and a 47.6% reduction among those in the twice-daily vehicle control group, according to Dr. Landis, a dermatologist at the University of Louisville (Ky).

The key secondary efficacy endpoint was the proportion of patients achieving an Investigator’s Global Assessment (IGA) score of 0 or 1 – clear or almost clear skin – plus at least a 2-point reduction at week 6. This occurred in a dose-dependent fashion in 27.8%-44.4% of patients on once-daily brepocitinib, all significantly better results than the 10.8% rate in once-daily controls. Patients on the TYK2/JAK1 inhibitor at 0.3% twice daily had a 33.3% IGA response rate, versus 13.9% with twice-daily vehicle, also a significant difference.

A 90% reduction in EASI score at week 6, or EASI 90 response, occurred in a dose-dependent fashion in 27.8%-41.7% of patients on 0.3%, 1%, and 3% of patients on once-daily brepocitinib, all significantly better than the 10.8% rate with once-daily vehicle, and in 27% of patients on brepocitinib 1% twice daily, versus 8.3% with twice-daily vehicle.

Improvement in itch was another secondary endpoint. A clinically meaningful week-6 improvement of at least 4 points on the Peak Pruritus Numerical Rating Scale was documented in 45.2% of patients on 1% brepocitinib once daily, 50% on 3% once daily, and 40.7% on 1% brepocitinib twice daily, all significantly better than the roughly 17% itch response rate in controls.

Treatment-emergent adverse events were about one-third more frequent in controls than in brepocitinib-treated patients. These events were overwhelmingly mild and were similar in nature in the two groups. There was no dose-dependent increase in treatment-emergent adverse events in the brepocitinib patients. Moreover, no serious treatment-emergent adverse events occurred during the study, nor were there any cases of herpes zoster or malignancies, and no changes in laboratory parameters or ECG findings.

Pfizer sponsored the phase 2b AD trial of the topical TYK2/JAK1 inhibitor, which is also in phase 2 studies for psoriatic arthritis, psoriasis, lupus, and alopecia areata.

Dr. Landis reported serving as a paid investigator for Pfizer and numerous other pharmaceutical companies.

bjancin@mdedge.com

Brepocitinib, a first-in-class topical inhibitor of both tyrosine kinase 2 and Janus kinase 1, proved effective for treatment of mild to moderate atopic dermatitis (AD), and with a safety profile essentially indistinguishable from vehicle cream in a phase 2b randomized trial, Megan N. Landis, MD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

The study included 240 adolescents and adults with mild to moderate AD at 70 sites in the United States and nine other countries. Patients’ mean baseline Eczema Area and Severity Index (EASI) score was 7.3, with 9.2% of their body surface area being involved. Participants were equally split between mild and moderate disease. They were randomized to 6 weeks of double-blind treatment in one of eight study arms: once-daily topical brepocitinib at a concentration of 0.1%, 0.3%, 1%, or 3%; twice-daily brepocitinib at 1% or 3%; or once- or twice-daily vehicle cream.

The primary endpoint was change in EASI score from baseline to week 6. Brepocitinib 1% and 3% once daily and 1% twice daily outperformed vehicle, with EASI score reductions of 70.1%, 67.9%, and 75%, respectively, compared with a 44.4% decrease among those in the once-daily vehicle control group and a 47.6% reduction among those in the twice-daily vehicle control group, according to Dr. Landis, a dermatologist at the University of Louisville (Ky).

The key secondary efficacy endpoint was the proportion of patients achieving an Investigator’s Global Assessment (IGA) score of 0 or 1 – clear or almost clear skin – plus at least a 2-point reduction at week 6. This occurred in a dose-dependent fashion in 27.8%-44.4% of patients on once-daily brepocitinib, all significantly better results than the 10.8% rate in once-daily controls. Patients on the TYK2/JAK1 inhibitor at 0.3% twice daily had a 33.3% IGA response rate, versus 13.9% with twice-daily vehicle, also a significant difference.

A 90% reduction in EASI score at week 6, or EASI 90 response, occurred in a dose-dependent fashion in 27.8%-41.7% of patients on 0.3%, 1%, and 3% of patients on once-daily brepocitinib, all significantly better than the 10.8% rate with once-daily vehicle, and in 27% of patients on brepocitinib 1% twice daily, versus 8.3% with twice-daily vehicle.

Improvement in itch was another secondary endpoint. A clinically meaningful week-6 improvement of at least 4 points on the Peak Pruritus Numerical Rating Scale was documented in 45.2% of patients on 1% brepocitinib once daily, 50% on 3% once daily, and 40.7% on 1% brepocitinib twice daily, all significantly better than the roughly 17% itch response rate in controls.

Treatment-emergent adverse events were about one-third more frequent in controls than in brepocitinib-treated patients. These events were overwhelmingly mild and were similar in nature in the two groups. There was no dose-dependent increase in treatment-emergent adverse events in the brepocitinib patients. Moreover, no serious treatment-emergent adverse events occurred during the study, nor were there any cases of herpes zoster or malignancies, and no changes in laboratory parameters or ECG findings.

Pfizer sponsored the phase 2b AD trial of the topical TYK2/JAK1 inhibitor, which is also in phase 2 studies for psoriatic arthritis, psoriasis, lupus, and alopecia areata.

Dr. Landis reported serving as a paid investigator for Pfizer and numerous other pharmaceutical companies.

bjancin@mdedge.com

Brepocitinib, a first-in-class topical inhibitor of both tyrosine kinase 2 and Janus kinase 1, proved effective for treatment of mild to moderate atopic dermatitis (AD), and with a safety profile essentially indistinguishable from vehicle cream in a phase 2b randomized trial, Megan N. Landis, MD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

The study included 240 adolescents and adults with mild to moderate AD at 70 sites in the United States and nine other countries. Patients’ mean baseline Eczema Area and Severity Index (EASI) score was 7.3, with 9.2% of their body surface area being involved. Participants were equally split between mild and moderate disease. They were randomized to 6 weeks of double-blind treatment in one of eight study arms: once-daily topical brepocitinib at a concentration of 0.1%, 0.3%, 1%, or 3%; twice-daily brepocitinib at 1% or 3%; or once- or twice-daily vehicle cream.

The primary endpoint was change in EASI score from baseline to week 6. Brepocitinib 1% and 3% once daily and 1% twice daily outperformed vehicle, with EASI score reductions of 70.1%, 67.9%, and 75%, respectively, compared with a 44.4% decrease among those in the once-daily vehicle control group and a 47.6% reduction among those in the twice-daily vehicle control group, according to Dr. Landis, a dermatologist at the University of Louisville (Ky).

The key secondary efficacy endpoint was the proportion of patients achieving an Investigator’s Global Assessment (IGA) score of 0 or 1 – clear or almost clear skin – plus at least a 2-point reduction at week 6. This occurred in a dose-dependent fashion in 27.8%-44.4% of patients on once-daily brepocitinib, all significantly better results than the 10.8% rate in once-daily controls. Patients on the TYK2/JAK1 inhibitor at 0.3% twice daily had a 33.3% IGA response rate, versus 13.9% with twice-daily vehicle, also a significant difference.

A 90% reduction in EASI score at week 6, or EASI 90 response, occurred in a dose-dependent fashion in 27.8%-41.7% of patients on 0.3%, 1%, and 3% of patients on once-daily brepocitinib, all significantly better than the 10.8% rate with once-daily vehicle, and in 27% of patients on brepocitinib 1% twice daily, versus 8.3% with twice-daily vehicle.

Improvement in itch was another secondary endpoint. A clinically meaningful week-6 improvement of at least 4 points on the Peak Pruritus Numerical Rating Scale was documented in 45.2% of patients on 1% brepocitinib once daily, 50% on 3% once daily, and 40.7% on 1% brepocitinib twice daily, all significantly better than the roughly 17% itch response rate in controls.

Treatment-emergent adverse events were about one-third more frequent in controls than in brepocitinib-treated patients. These events were overwhelmingly mild and were similar in nature in the two groups. There was no dose-dependent increase in treatment-emergent adverse events in the brepocitinib patients. Moreover, no serious treatment-emergent adverse events occurred during the study, nor were there any cases of herpes zoster or malignancies, and no changes in laboratory parameters or ECG findings.

Pfizer sponsored the phase 2b AD trial of the topical TYK2/JAK1 inhibitor, which is also in phase 2 studies for psoriatic arthritis, psoriasis, lupus, and alopecia areata.

Dr. Landis reported serving as a paid investigator for Pfizer and numerous other pharmaceutical companies.

bjancin@mdedge.com

First-line trifluridine/tipiracil plus bevacizumab (TT-B) offered a slight survival benefit over capecitabine plus bevacizumab (C-B) in patients with unresectable metastatic colorectal cancer in the final analysis of the TASCO1 trial.

The median progression-free survival (PFS) in the phase 2 trial showed a difference of 1.41 months favoring TT-B over C-B, but this difference was not statistically significant.

The median overall survival was 4.64 months longer with TT-B than with C-B. However, the final analysis of TASCO1 was not designed to be comparative for overall survival, “so no formal statistical analysis is presented, and survival is a secondary endpoint,” noted investigator Eric Van Cutsem, MD, PhD, of University Hospital Gasthuisberg in Leuven, Belgium.

Dr. Van Cutsem presented the final results of TASCO1 at the 2021 Gastrointestinal Cancers Symposium (abstract 14).

Prior results from the trial were reported last year (Ann Oncol. 2020 Sep;31[9]:1160-68).
 

About trifluridine/tipiracil

Trifluridine/tipiracil is an oral drug combining the thymidine analogue trifluridine with tipiracil, an inhibitor of trifluridine degradation. The drug was approved by the Food and Drug Administration in 2015 under the trade name Lonsurf for the treatment of refractory metastatic colorectal cancer, and in 2019 for patients with metastatic gastric cancer or gastroesophageal junction cancer that had been treated with at least two lines of chemotherapy.

Trifluridine/tipiracil was associated with a brief but statistically significant survival benefit when compared with placebo in patients with heavily pretreated metastatic gastric cancer in the TAS-102 Gastric Study (Lancet Oncol. 2018 Nov;19[11]:1437-48).

In a separate analysis of the study, trifluridine/tipiracil was associated with significantly better overall survival and PFS than placebo in patients who had undergone gastrectomy (JAMA Oncol. 2019 Oct 10;6[1]:e193531).
 

TASCO1 details

In TASCO1, investigators enrolled patients with colorectal cancer who had never received systemic therapy for unresectable metastatic disease, and who were judged to be ineligible for intensive therapy due to advanced age, low tumor burden, poor performance status, comorbidities, or other clinical reasons.

After stratification by RAS status, performance status, and region, patients were randomly assigned to receive TT-B (n = 77) or C-B (n = 76).

TT-B consisted of oral trifluridine/tipiracil at 35 mg/m² twice daily on days 1-5 and 8-12 every 4 weeks plus bevacizumab at 5 mg/kg intravenously on days 1 and 15 every 4 weeks.

C-B consisted of oral capecitabine at 1,250 or 1,000 mg/m² twice a day on days 1-14 every 3 weeks plus bevacizumab at 7.5 mg/kg IV on day 1 every 3 weeks.
 

Final results

The median PFS, the primary endpoint, was 9.23 months with TT-B and 7.82 months with C-B. The difference was not statistically significant, with the upper limit of the 95% confidence interval crossing 1.

The median overall survival was 22.31 months with TT-B and 17.67 months with C-B (hazard ratio, 0.78; 95% CI, 0.55-1.10).

Dr. Van Cutsem pointed out that more patients in the TT-B arm had subsequent therapies compared with patients in the C-B arm – 59.7% vs. 40.8%.

He also noted that the safety profile of TT-B “remains unchanged from the initial analysis.”

Grade 3 or greater neutropenia, decreased neutrophil count, anemia, and decreased white blood cell count were all higher among patients on TT-B, but grade 3 or greater febrile neutropenia was similar between the groups.

Patients in the TT-B arm had more frequent grade 3 or greater nausea, vomiting, and hypertension. Grade 3 or higher hand-foot syndrome and diarrhea were both more common with C-B.

At the study cutoff date in September 2020, 66 patients in each arm had died.

Dr. Van Cutsem said more data on the efficacy of TT-B vs. C-B will come from the ongoing phase 3 SOLSTICE trial. Results from this trial are expected in late 2022.
 

‘The jury is still out’

The final results from TASCO1 suggest there may be some benefit from TT-B in patients with treatment-naive metastatic colorectal cancer, “but we don’t use it in the first line,” said Jeffery Clark, MD, an oncologist who was not involved in the study.

The trial supports the benefit of combining trifluridine/tipiracil with bevacizumab, and the results were “somewhat better” than he had expected, said Dr. Clark, director of clinical trials support at Mass General Cancer Center in Boston.

“Even though the results are encouraging, there were a couple of things about the trial that one has to at least think about,” Dr. Clark said in an interview.

He noted, for example, that a higher proportion of patients assigned to TT-B had prior adjuvant therapy (27.3% vs. 19.7%), and patients in the TT-B arm were also more likely to have second lines of systemic therapy, which could have skewed the results in favor of the experimental arm.

“I think, basically, the jury is still out until we see the results of the SOLSTICE trial,” he said.

The TASCO1 study was funded by Servier and Taiho. Dr. Van Cutsem has received research funding and served on an advisory board for Servier and other companies. Dr. Clark reported no relevant disclosures.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

First-line trifluridine/tipiracil plus bevacizumab (TT-B) offered a slight survival benefit over capecitabine plus bevacizumab (C-B) in patients with unresectable metastatic colorectal cancer in the final analysis of the TASCO1 trial.

The median progression-free survival (PFS) in the phase 2 trial showed a difference of 1.41 months favoring TT-B over C-B, but this difference was not statistically significant.

The median overall survival was 4.64 months longer with TT-B than with C-B. However, the final analysis of TASCO1 was not designed to be comparative for overall survival, “so no formal statistical analysis is presented, and survival is a secondary endpoint,” noted investigator Eric Van Cutsem, MD, PhD, of University Hospital Gasthuisberg in Leuven, Belgium.

Dr. Van Cutsem presented the final results of TASCO1 at the 2021 Gastrointestinal Cancers Symposium (abstract 14).

Prior results from the trial were reported last year (Ann Oncol. 2020 Sep;31[9]:1160-68).
 

About trifluridine/tipiracil

Trifluridine/tipiracil is an oral drug combining the thymidine analogue trifluridine with tipiracil, an inhibitor of trifluridine degradation. The drug was approved by the Food and Drug Administration in 2015 under the trade name Lonsurf for the treatment of refractory metastatic colorectal cancer, and in 2019 for patients with metastatic gastric cancer or gastroesophageal junction cancer that had been treated with at least two lines of chemotherapy.

Trifluridine/tipiracil was associated with a brief but statistically significant survival benefit when compared with placebo in patients with heavily pretreated metastatic gastric cancer in the TAS-102 Gastric Study (Lancet Oncol. 2018 Nov;19[11]:1437-48).

In a separate analysis of the study, trifluridine/tipiracil was associated with significantly better overall survival and PFS than placebo in patients who had undergone gastrectomy (JAMA Oncol. 2019 Oct 10;6[1]:e193531).
 

TASCO1 details

In TASCO1, investigators enrolled patients with colorectal cancer who had never received systemic therapy for unresectable metastatic disease, and who were judged to be ineligible for intensive therapy due to advanced age, low tumor burden, poor performance status, comorbidities, or other clinical reasons.

After stratification by RAS status, performance status, and region, patients were randomly assigned to receive TT-B (n = 77) or C-B (n = 76).

TT-B consisted of oral trifluridine/tipiracil at 35 mg/m² twice daily on days 1-5 and 8-12 every 4 weeks plus bevacizumab at 5 mg/kg intravenously on days 1 and 15 every 4 weeks.

C-B consisted of oral capecitabine at 1,250 or 1,000 mg/m² twice a day on days 1-14 every 3 weeks plus bevacizumab at 7.5 mg/kg IV on day 1 every 3 weeks.
 

Final results

The median PFS, the primary endpoint, was 9.23 months with TT-B and 7.82 months with C-B. The difference was not statistically significant, with the upper limit of the 95% confidence interval crossing 1.

The median overall survival was 22.31 months with TT-B and 17.67 months with C-B (hazard ratio, 0.78; 95% CI, 0.55-1.10).

Dr. Van Cutsem pointed out that more patients in the TT-B arm had subsequent therapies compared with patients in the C-B arm – 59.7% vs. 40.8%.

He also noted that the safety profile of TT-B “remains unchanged from the initial analysis.”

Grade 3 or greater neutropenia, decreased neutrophil count, anemia, and decreased white blood cell count were all higher among patients on TT-B, but grade 3 or greater febrile neutropenia was similar between the groups.

Patients in the TT-B arm had more frequent grade 3 or greater nausea, vomiting, and hypertension. Grade 3 or higher hand-foot syndrome and diarrhea were both more common with C-B.

At the study cutoff date in September 2020, 66 patients in each arm had died.

Dr. Van Cutsem said more data on the efficacy of TT-B vs. C-B will come from the ongoing phase 3 SOLSTICE trial. Results from this trial are expected in late 2022.
 

‘The jury is still out’

The final results from TASCO1 suggest there may be some benefit from TT-B in patients with treatment-naive metastatic colorectal cancer, “but we don’t use it in the first line,” said Jeffery Clark, MD, an oncologist who was not involved in the study.

The trial supports the benefit of combining trifluridine/tipiracil with bevacizumab, and the results were “somewhat better” than he had expected, said Dr. Clark, director of clinical trials support at Mass General Cancer Center in Boston.

“Even though the results are encouraging, there were a couple of things about the trial that one has to at least think about,” Dr. Clark said in an interview.

He noted, for example, that a higher proportion of patients assigned to TT-B had prior adjuvant therapy (27.3% vs. 19.7%), and patients in the TT-B arm were also more likely to have second lines of systemic therapy, which could have skewed the results in favor of the experimental arm.

“I think, basically, the jury is still out until we see the results of the SOLSTICE trial,” he said.

The TASCO1 study was funded by Servier and Taiho. Dr. Van Cutsem has received research funding and served on an advisory board for Servier and other companies. Dr. Clark reported no relevant disclosures.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

First-line trifluridine/tipiracil plus bevacizumab (TT-B) offered a slight survival benefit over capecitabine plus bevacizumab (C-B) in patients with unresectable metastatic colorectal cancer in the final analysis of the TASCO1 trial.

The median progression-free survival (PFS) in the phase 2 trial showed a difference of 1.41 months favoring TT-B over C-B, but this difference was not statistically significant.

The median overall survival was 4.64 months longer with TT-B than with C-B. However, the final analysis of TASCO1 was not designed to be comparative for overall survival, “so no formal statistical analysis is presented, and survival is a secondary endpoint,” noted investigator Eric Van Cutsem, MD, PhD, of University Hospital Gasthuisberg in Leuven, Belgium.

Dr. Van Cutsem presented the final results of TASCO1 at the 2021 Gastrointestinal Cancers Symposium (abstract 14).

Prior results from the trial were reported last year (Ann Oncol. 2020 Sep;31[9]:1160-68).
 

About trifluridine/tipiracil

Trifluridine/tipiracil is an oral drug combining the thymidine analogue trifluridine with tipiracil, an inhibitor of trifluridine degradation. The drug was approved by the Food and Drug Administration in 2015 under the trade name Lonsurf for the treatment of refractory metastatic colorectal cancer, and in 2019 for patients with metastatic gastric cancer or gastroesophageal junction cancer that had been treated with at least two lines of chemotherapy.

Trifluridine/tipiracil was associated with a brief but statistically significant survival benefit when compared with placebo in patients with heavily pretreated metastatic gastric cancer in the TAS-102 Gastric Study (Lancet Oncol. 2018 Nov;19[11]:1437-48).

In a separate analysis of the study, trifluridine/tipiracil was associated with significantly better overall survival and PFS than placebo in patients who had undergone gastrectomy (JAMA Oncol. 2019 Oct 10;6[1]:e193531).
 

TASCO1 details

In TASCO1, investigators enrolled patients with colorectal cancer who had never received systemic therapy for unresectable metastatic disease, and who were judged to be ineligible for intensive therapy due to advanced age, low tumor burden, poor performance status, comorbidities, or other clinical reasons.

After stratification by RAS status, performance status, and region, patients were randomly assigned to receive TT-B (n = 77) or C-B (n = 76).

TT-B consisted of oral trifluridine/tipiracil at 35 mg/m² twice daily on days 1-5 and 8-12 every 4 weeks plus bevacizumab at 5 mg/kg intravenously on days 1 and 15 every 4 weeks.

C-B consisted of oral capecitabine at 1,250 or 1,000 mg/m² twice a day on days 1-14 every 3 weeks plus bevacizumab at 7.5 mg/kg IV on day 1 every 3 weeks.
 

Final results

The median PFS, the primary endpoint, was 9.23 months with TT-B and 7.82 months with C-B. The difference was not statistically significant, with the upper limit of the 95% confidence interval crossing 1.

The median overall survival was 22.31 months with TT-B and 17.67 months with C-B (hazard ratio, 0.78; 95% CI, 0.55-1.10).

Dr. Van Cutsem pointed out that more patients in the TT-B arm had subsequent therapies compared with patients in the C-B arm – 59.7% vs. 40.8%.

He also noted that the safety profile of TT-B “remains unchanged from the initial analysis.”

Grade 3 or greater neutropenia, decreased neutrophil count, anemia, and decreased white blood cell count were all higher among patients on TT-B, but grade 3 or greater febrile neutropenia was similar between the groups.

Patients in the TT-B arm had more frequent grade 3 or greater nausea, vomiting, and hypertension. Grade 3 or higher hand-foot syndrome and diarrhea were both more common with C-B.

At the study cutoff date in September 2020, 66 patients in each arm had died.

Dr. Van Cutsem said more data on the efficacy of TT-B vs. C-B will come from the ongoing phase 3 SOLSTICE trial. Results from this trial are expected in late 2022.
 

‘The jury is still out’

The final results from TASCO1 suggest there may be some benefit from TT-B in patients with treatment-naive metastatic colorectal cancer, “but we don’t use it in the first line,” said Jeffery Clark, MD, an oncologist who was not involved in the study.

The trial supports the benefit of combining trifluridine/tipiracil with bevacizumab, and the results were “somewhat better” than he had expected, said Dr. Clark, director of clinical trials support at Mass General Cancer Center in Boston.

“Even though the results are encouraging, there were a couple of things about the trial that one has to at least think about,” Dr. Clark said in an interview.

He noted, for example, that a higher proportion of patients assigned to TT-B had prior adjuvant therapy (27.3% vs. 19.7%), and patients in the TT-B arm were also more likely to have second lines of systemic therapy, which could have skewed the results in favor of the experimental arm.

“I think, basically, the jury is still out until we see the results of the SOLSTICE trial,” he said.

The TASCO1 study was funded by Servier and Taiho. Dr. Van Cutsem has received research funding and served on an advisory board for Servier and other companies. Dr. Clark reported no relevant disclosures.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.