AVAHO

The incidence of colorectal cancer (CRC) is rapidly increasing among younger individuals, and the disease is also being diagnosed at more advanced stages in all ages, according to a new report from the American Cancer Society.

Diagnoses in people younger than 55 years doubled from 11% (1 in 10) in 1995 to 20% (1 in 5) in 2019.

In addition, more advanced disease is being diagnosed; the proportion of individuals of all ages presenting with advanced-stage CRC increased from 52% in the mid-2000s to 60% in 2019.

“We know rates are increasing in young people, but it’s alarming to see how rapidly the whole patient population is shifting younger, despite shrinking numbers in the overall population,” said Rebecca Siegel, MPH, senior scientific director of surveillance research at the American Cancer Society and lead author of the report.

“The trend toward more advanced disease in people of all ages is also surprising and should motivate everyone 45 and older to get screened,” she added.

The report was published online in CA: A Cancer Journal for Clinicians.

CRC is the third most commonly diagnosed cancer and the third leading cause of cancer death of both men and women in the United States. It is estimated that there will be 153,020 new cases of CRC in the U.S. in 2023, including 106,970 tumors in the colon and 46,050 in the rectum.

Overall, in 2023, an estimated 153,020 people will be diagnosed with CRC in the U.S., and of those, 52,550 people will die from the disease.

The incidence of CRC rapidly decreased during the 2000s among people aged 50 and older, largely because of an increase in cancer screening with colonoscopy. But progress slowed during the past decade, and now the trends toward declining incidence is largely confined to those aged 65 and older.

The authors point out that more than half of all cases and deaths are associated with modifiable risk factors, including smoking, an unhealthy diet, high alcohol consumption, physical inactivity, and excess body weight. A large proportion of CRC incidence and mortality is preventable through recommended screening, surveillance, and high-quality treatment.

But it remains unclear why rates are rising among younger adults and why there is a trend toward the disase being initially diagnosed at more advanced stages.

“We have to address why the rates in young adults continue to trend in the wrong direction,” said Ahmedin Jemal, DVM, PhD, senior vice president of surveillance and health equity science at the American Cancer Society and senior author of the study. “We need to invest more in research to uncover the causes of the rising trends and to discover new treatment for advanced-stage diseases to reduce the morbidity and mortality associated with this disease in this young population, who are raising families and supporting other family members.”

For their report, Ms. Siegel and colleagues used incidence data from 1995 to 2019 from 50 states and the District of Columbia. The data came from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute and the National Program of Cancer Registries of the U.S. Centers for Disease Control and Prevention, as provided by the North American Association of Central Cancer Registries. National mortality data through 2020 were provided by the National Center for Health Statistics.

The authors note that while overall, deaths from CRC are continuing to fall, “this progress is tempered by a rapidly changing landscape of disease that foreshadows less favorable trends ahead.”

The incidence rates have increased by 2% per year among people younger than 50 years as well as among those aged 50-54 years while, for the past decade, the rates have declined among those aged 65 and older. Incidence rates have stabilized among persons aged 50-64 years.

Although the majority of diagnoses continue to occur among people aged 65 years and older, 19,550 cases (13%) will occur in those younger than age 50 years, and one-third will be diagnosed in those aged 50-64 years.

Other key findings include the following.

• Declines in incidence and mortality have slowed, from 3% to 4% per year during the 2000s to 1% per year for incidence and 2% per year for mortality during the past decade.
• The incidence rate was 33% higher among men than women from 2015 to 2019, which may reflect differences in risk factors, such as excess body weight, processed meat consumption, and a history of smoking.
• The percentage of patients who present with advanced-stage disease has increased from a low of 52% in the mid-2000s to 60% in 2019 despite an increase in the use of screening.
• Death rates from CRC have risen since around 2005 by 1% annually among those younger than 50 years and by 0.6% in people aged 50-54.
• The report also identified racial/ethnic differences in incidence and mortality: Incidence was highest among Alaska Natives (88.5 per 100,000), American Indians (46.0 per 100,000), and Black persons, compared with White persons (41.7 per 100,000 vs. 35.7 per 100,000). Mortality followed a similar pattern; the highest rates were observed among Alaska Natives (50.5 per 100,000), American Indians (17.5 per 100,000), and Black persons, compared with White persons (17.6 per 100,000 vs. 13.1 per 100,000).
• There was also a shift to left-sided tumors, despite greater efficacy of screening for preventing left-sided lesions. The proportion of CRCs occurring in the rectum has steadily risen from 27% in 1995 to 31% in 2019.

“These highly concerning data illustrate the urgent need to invest in targeted cancer research studies dedicated to understanding and preventing early-onset colorectal cancer,” said Karen E. Knudsen, MBA, PhD, and CEO of the American Cancer Society. “The shift to diagnosis of more advanced disease also underscores the importance of screening and early detection, which saves lives.”

The study was supported by the American Cancer Society.

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

The incidence of colorectal cancer (CRC) is rapidly increasing among younger individuals, and the disease is also being diagnosed at more advanced stages in all ages, according to a new report from the American Cancer Society.

Diagnoses in people younger than 55 years doubled from 11% (1 in 10) in 1995 to 20% (1 in 5) in 2019.

In addition, more advanced disease is being diagnosed; the proportion of individuals of all ages presenting with advanced-stage CRC increased from 52% in the mid-2000s to 60% in 2019.

“We know rates are increasing in young people, but it’s alarming to see how rapidly the whole patient population is shifting younger, despite shrinking numbers in the overall population,” said Rebecca Siegel, MPH, senior scientific director of surveillance research at the American Cancer Society and lead author of the report.

“The trend toward more advanced disease in people of all ages is also surprising and should motivate everyone 45 and older to get screened,” she added.

The report was published online in CA: A Cancer Journal for Clinicians.

CRC is the third most commonly diagnosed cancer and the third leading cause of cancer death of both men and women in the United States. It is estimated that there will be 153,020 new cases of CRC in the U.S. in 2023, including 106,970 tumors in the colon and 46,050 in the rectum.

Overall, in 2023, an estimated 153,020 people will be diagnosed with CRC in the U.S., and of those, 52,550 people will die from the disease.

The incidence of CRC rapidly decreased during the 2000s among people aged 50 and older, largely because of an increase in cancer screening with colonoscopy. But progress slowed during the past decade, and now the trends toward declining incidence is largely confined to those aged 65 and older.

The authors point out that more than half of all cases and deaths are associated with modifiable risk factors, including smoking, an unhealthy diet, high alcohol consumption, physical inactivity, and excess body weight. A large proportion of CRC incidence and mortality is preventable through recommended screening, surveillance, and high-quality treatment.

But it remains unclear why rates are rising among younger adults and why there is a trend toward the disase being initially diagnosed at more advanced stages.

“We have to address why the rates in young adults continue to trend in the wrong direction,” said Ahmedin Jemal, DVM, PhD, senior vice president of surveillance and health equity science at the American Cancer Society and senior author of the study. “We need to invest more in research to uncover the causes of the rising trends and to discover new treatment for advanced-stage diseases to reduce the morbidity and mortality associated with this disease in this young population, who are raising families and supporting other family members.”

For their report, Ms. Siegel and colleagues used incidence data from 1995 to 2019 from 50 states and the District of Columbia. The data came from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute and the National Program of Cancer Registries of the U.S. Centers for Disease Control and Prevention, as provided by the North American Association of Central Cancer Registries. National mortality data through 2020 were provided by the National Center for Health Statistics.

The authors note that while overall, deaths from CRC are continuing to fall, “this progress is tempered by a rapidly changing landscape of disease that foreshadows less favorable trends ahead.”

The incidence rates have increased by 2% per year among people younger than 50 years as well as among those aged 50-54 years while, for the past decade, the rates have declined among those aged 65 and older. Incidence rates have stabilized among persons aged 50-64 years.

Although the majority of diagnoses continue to occur among people aged 65 years and older, 19,550 cases (13%) will occur in those younger than age 50 years, and one-third will be diagnosed in those aged 50-64 years.

Other key findings include the following.

• Declines in incidence and mortality have slowed, from 3% to 4% per year during the 2000s to 1% per year for incidence and 2% per year for mortality during the past decade.
• The incidence rate was 33% higher among men than women from 2015 to 2019, which may reflect differences in risk factors, such as excess body weight, processed meat consumption, and a history of smoking.
• The percentage of patients who present with advanced-stage disease has increased from a low of 52% in the mid-2000s to 60% in 2019 despite an increase in the use of screening.
• Death rates from CRC have risen since around 2005 by 1% annually among those younger than 50 years and by 0.6% in people aged 50-54.
• The report also identified racial/ethnic differences in incidence and mortality: Incidence was highest among Alaska Natives (88.5 per 100,000), American Indians (46.0 per 100,000), and Black persons, compared with White persons (41.7 per 100,000 vs. 35.7 per 100,000). Mortality followed a similar pattern; the highest rates were observed among Alaska Natives (50.5 per 100,000), American Indians (17.5 per 100,000), and Black persons, compared with White persons (17.6 per 100,000 vs. 13.1 per 100,000).
• There was also a shift to left-sided tumors, despite greater efficacy of screening for preventing left-sided lesions. The proportion of CRCs occurring in the rectum has steadily risen from 27% in 1995 to 31% in 2019.

“These highly concerning data illustrate the urgent need to invest in targeted cancer research studies dedicated to understanding and preventing early-onset colorectal cancer,” said Karen E. Knudsen, MBA, PhD, and CEO of the American Cancer Society. “The shift to diagnosis of more advanced disease also underscores the importance of screening and early detection, which saves lives.”

The study was supported by the American Cancer Society.

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

The incidence of colorectal cancer (CRC) is rapidly increasing among younger individuals, and the disease is also being diagnosed at more advanced stages in all ages, according to a new report from the American Cancer Society.

Diagnoses in people younger than 55 years doubled from 11% (1 in 10) in 1995 to 20% (1 in 5) in 2019.

In addition, more advanced disease is being diagnosed; the proportion of individuals of all ages presenting with advanced-stage CRC increased from 52% in the mid-2000s to 60% in 2019.

“We know rates are increasing in young people, but it’s alarming to see how rapidly the whole patient population is shifting younger, despite shrinking numbers in the overall population,” said Rebecca Siegel, MPH, senior scientific director of surveillance research at the American Cancer Society and lead author of the report.

“The trend toward more advanced disease in people of all ages is also surprising and should motivate everyone 45 and older to get screened,” she added.

The report was published online in CA: A Cancer Journal for Clinicians.

CRC is the third most commonly diagnosed cancer and the third leading cause of cancer death of both men and women in the United States. It is estimated that there will be 153,020 new cases of CRC in the U.S. in 2023, including 106,970 tumors in the colon and 46,050 in the rectum.

Overall, in 2023, an estimated 153,020 people will be diagnosed with CRC in the U.S., and of those, 52,550 people will die from the disease.

The incidence of CRC rapidly decreased during the 2000s among people aged 50 and older, largely because of an increase in cancer screening with colonoscopy. But progress slowed during the past decade, and now the trends toward declining incidence is largely confined to those aged 65 and older.

The authors point out that more than half of all cases and deaths are associated with modifiable risk factors, including smoking, an unhealthy diet, high alcohol consumption, physical inactivity, and excess body weight. A large proportion of CRC incidence and mortality is preventable through recommended screening, surveillance, and high-quality treatment.

But it remains unclear why rates are rising among younger adults and why there is a trend toward the disase being initially diagnosed at more advanced stages.

“We have to address why the rates in young adults continue to trend in the wrong direction,” said Ahmedin Jemal, DVM, PhD, senior vice president of surveillance and health equity science at the American Cancer Society and senior author of the study. “We need to invest more in research to uncover the causes of the rising trends and to discover new treatment for advanced-stage diseases to reduce the morbidity and mortality associated with this disease in this young population, who are raising families and supporting other family members.”

For their report, Ms. Siegel and colleagues used incidence data from 1995 to 2019 from 50 states and the District of Columbia. The data came from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute and the National Program of Cancer Registries of the U.S. Centers for Disease Control and Prevention, as provided by the North American Association of Central Cancer Registries. National mortality data through 2020 were provided by the National Center for Health Statistics.

The authors note that while overall, deaths from CRC are continuing to fall, “this progress is tempered by a rapidly changing landscape of disease that foreshadows less favorable trends ahead.”

The incidence rates have increased by 2% per year among people younger than 50 years as well as among those aged 50-54 years while, for the past decade, the rates have declined among those aged 65 and older. Incidence rates have stabilized among persons aged 50-64 years.

Although the majority of diagnoses continue to occur among people aged 65 years and older, 19,550 cases (13%) will occur in those younger than age 50 years, and one-third will be diagnosed in those aged 50-64 years.

Other key findings include the following.

• Declines in incidence and mortality have slowed, from 3% to 4% per year during the 2000s to 1% per year for incidence and 2% per year for mortality during the past decade.
• The incidence rate was 33% higher among men than women from 2015 to 2019, which may reflect differences in risk factors, such as excess body weight, processed meat consumption, and a history of smoking.
• The percentage of patients who present with advanced-stage disease has increased from a low of 52% in the mid-2000s to 60% in 2019 despite an increase in the use of screening.
• Death rates from CRC have risen since around 2005 by 1% annually among those younger than 50 years and by 0.6% in people aged 50-54.
• The report also identified racial/ethnic differences in incidence and mortality: Incidence was highest among Alaska Natives (88.5 per 100,000), American Indians (46.0 per 100,000), and Black persons, compared with White persons (41.7 per 100,000 vs. 35.7 per 100,000). Mortality followed a similar pattern; the highest rates were observed among Alaska Natives (50.5 per 100,000), American Indians (17.5 per 100,000), and Black persons, compared with White persons (17.6 per 100,000 vs. 13.1 per 100,000).
• There was also a shift to left-sided tumors, despite greater efficacy of screening for preventing left-sided lesions. The proportion of CRCs occurring in the rectum has steadily risen from 27% in 1995 to 31% in 2019.

“These highly concerning data illustrate the urgent need to invest in targeted cancer research studies dedicated to understanding and preventing early-onset colorectal cancer,” said Karen E. Knudsen, MBA, PhD, and CEO of the American Cancer Society. “The shift to diagnosis of more advanced disease also underscores the importance of screening and early detection, which saves lives.”

The study was supported by the American Cancer Society.

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

SAN FRANCISCO – For patients with prostate cancer who have unfavorable features and a detectable PSA following a radical prostatectomy, the standard of care is treatment with 6 months of a gonadotropin-releasing hormone (GnRH) agonist with salvage radiation therapy (SRT), as established by the GETUG-AFU 16 trial.

A new trial, dubbed FORMULA-509, explored whether outcomes could be improved by intensifying the drug treatment by adding 6 months of abiraterone acetate plus prednisone as well as apalutamide on top of the GnRH agonist alongside the salvage radiotherapy.

This approach did not provide a significant improvement in progression-free survival (PFS) or metastasis-free survival (MFS) in the overall study population.

However, the combination did significantly improve PFS and MFS in a subset of men with PSA levels greater than 0.5 ng/mL.

“Although this primary analysis did not meet the prespecified threshold for statistical significance, it does strongly suggest that the addition of abiraterone acetate/prednisone/apalutamide to salvage radiotherapy plus 6 months of ADT [androgen deprivation therapy] may improve progression-free survival and metastasis-free survival,” said lead author Paul L. Nguyen, MD, of the Dana-Farber Cancer Institute in Boston, and professor of radiation oncology at Harvard Medical School.

“This may be particularly evident in the subgroup of patients with PSA greater that 0.5 ng/mL where a preplanned subgroup analysis by stratification factors observed a statistically significant benefit for both progression-free survival and metastasis-free survival,” he said. “Six months of intensified ADT with next generation anti-androgens may provide an attractive alternative to lengthening ADT for patients with rising PSA and unfavorable features after radical prostatectomy.”

The study results were presented at the ASCO Genitourinary Cancers Symposium.
 

Benefit in subset

The FORMULA-509 trial included 305 patients with PSA ≥ 0.1 ng/mL who had undergone a radical prostatectomy, and who had one or more unfavorable risk features (Gleason 8-10 disease, PSA > 0.5 ng/mL, pT3/T4, pN1 or radiographic N1, PSA doubling time < 10 months, negative margins, persistent PSA, gross local/regional disease).

“This was a pretty high-risk population,” Dr. Nguyen emphasized, as 35% had Gleason score of 9, about a third (31%) a PSA >0.5, and 29% were pathologic node positive.

All patients received salvage radiotherapy plus 6 months of GnRH agonist (bicalutamide 50 mg), and half were randomly assigned to also receive abiraterone acetate/prednisone 1,000 mg/5 mg + apalutamide 240 mg daily.

At a median follow-up of 34 months, the 3-year PFS rate was 74.9% in the AAP-apalutamide arm vs. 68.5% for the control group (hazard ratio [HR], 0.71; P = .06), and the 3-year MFS rate was 90.6% vs. 87.2%, respectively (HR, 0.57; P = .05).

In the subset of patients with a PSA greater than 0.5 ng/mL, the 3-year PFS and MFS rates were significantly higher with in the AAP-apalutamide group: the 3-year PFS rate was 67.2% vs. 46.8% (HR, 0.50; P = .03), and the 3-year MFS rate was 84.3% vs. 66.1% (HR, 0.32; P = .02).

Adverse events were consistent with the known safety profiles of the agents being studied, Dr. Nguyen noted. The most common toxicities for AAP-apalutamide vs. controls were hypertension (21.8% vs. 13.3%), maculopapular rash (11.5% vs. 0.6%), diarrhea (8.5% vs. 4.8%), and fatigue (7.9% vs. 6.1%).

Dr. Nguyen noted that even though “we’re not supposed to compare clinical trials,” the results of this study appeared to compare favorably with those of another trial, RADICALS-HD, which was presented at the 2022 European Society of Medical Oncology Congress. That study showed that in patients undergoing postoperative radiation therapy, 24 months of ADT was superior to 6 months of ADT in improving both time to salvage ADT and MFS.

However, Dr. Nguyen emphasized that it would have to be formally tested, to see if “FORMULA-509 is performing in the ballpark of what 24 months of ADT would do.

“And I think that compared to 6 months of ADT, we can say it is certainly performing in the ballpark,” he said. “So, for patients with higher risk features, intensifying 6 months of ADT, I think, may be an appealing alternative to lengthening the ADT duration to 24 months.”

He added that this concept would be formally tested in the upcoming PROSTATE IQ study.
 

Strong evidence, standardization needed

In a discussion of the paper, Tyler Seibert, MD, PhD, of the University of California San Diego, said that “escalation by 24 months has the strongest evidence today, specifically from the RADICALS-HD trial, with more than 1,500 men with 10 years of  follow-up and a clear statistically significant result.

“Intensification for 6 months is a very compelling concept, as most patients are not getting 2 years of androgen deprivation therapy at this point post prostatectomy,” he continued. “While we await the long term follow-up of this study and the pending PROSTATE IQ trial, and if only 6 months of therapy is acceptable or feasible, the FORMULA-509 [trial] provides convincing evidence that select patients would benefit from intensification with AAP and apalutamide.”

Another expert weighed in on the data. Approached by this news organization for an independent comment, Jeff M. Michalski, MD, MBA, professor of radiation oncology at Washington University, St Louis, and president of the American Society of Radiation Oncology, noted a few issues in the study.

He said that standards had changed since this study was first approved and had begun accrual several years ago. “In context of today’s era, the current standard is to do a PET scan if patients have a chemical failure after surgery,” he said. “The PSA levels of patients who were treated [in this trial] were very high, and many patients do not want to wait until they reach that level.”

Dr. Michalski also pointed out the number of patients getting radiation was less than the number who had node-positive disease. “This shows that patients had received suboptimal therapy late in the disease,” he said.

Overall, most patients in the study did not receive lymph node radiation, even though they had high-risk features. “A recent study of almost 1,800 patients that was published in The Lancet found that there is a benefit to pelvic lymph node radiation,” he said. “Because it wasn’t mandated, most of the patients did not receive pelvic lymph node radiation, which we now understand offers some benefit.”

The reasons for not giving pelvic radiation to these men is unclear. “Treatment was left at the discretion of the physician and this could create bias,” Dr. Michalski said. “It could drive one arm more than another.”

The study also wasn’t controlled for pelvic radiation. “Most of the nodal positive patients received it, but the other patients were undertreated,” he noted.

Dr. Michalski added that he hopes that in the forthcoming PROSTATE IQ study, lymph node radiation and imaging are standardized.

The trial was supported by Janssen Oncology. Dr. Nguyen disclosed relationships with, and/or support from, Volatilyx, Bayer, Blue Earth Diagnostics, Boston Scientific, Janssen Oncology, Myovant Sciences, Astellas Pharma, and Janssen. Dr. Seibert disclosed relationships with, and/or support from, CorTechs Labs, Varian Medical Systems, and GE Healthcare.

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

SAN FRANCISCO – For patients with prostate cancer who have unfavorable features and a detectable PSA following a radical prostatectomy, the standard of care is treatment with 6 months of a gonadotropin-releasing hormone (GnRH) agonist with salvage radiation therapy (SRT), as established by the GETUG-AFU 16 trial.

A new trial, dubbed FORMULA-509, explored whether outcomes could be improved by intensifying the drug treatment by adding 6 months of abiraterone acetate plus prednisone as well as apalutamide on top of the GnRH agonist alongside the salvage radiotherapy.

This approach did not provide a significant improvement in progression-free survival (PFS) or metastasis-free survival (MFS) in the overall study population.

However, the combination did significantly improve PFS and MFS in a subset of men with PSA levels greater than 0.5 ng/mL.

“Although this primary analysis did not meet the prespecified threshold for statistical significance, it does strongly suggest that the addition of abiraterone acetate/prednisone/apalutamide to salvage radiotherapy plus 6 months of ADT [androgen deprivation therapy] may improve progression-free survival and metastasis-free survival,” said lead author Paul L. Nguyen, MD, of the Dana-Farber Cancer Institute in Boston, and professor of radiation oncology at Harvard Medical School.

“This may be particularly evident in the subgroup of patients with PSA greater that 0.5 ng/mL where a preplanned subgroup analysis by stratification factors observed a statistically significant benefit for both progression-free survival and metastasis-free survival,” he said. “Six months of intensified ADT with next generation anti-androgens may provide an attractive alternative to lengthening ADT for patients with rising PSA and unfavorable features after radical prostatectomy.”

The study results were presented at the ASCO Genitourinary Cancers Symposium.
 

Benefit in subset

The FORMULA-509 trial included 305 patients with PSA ≥ 0.1 ng/mL who had undergone a radical prostatectomy, and who had one or more unfavorable risk features (Gleason 8-10 disease, PSA > 0.5 ng/mL, pT3/T4, pN1 or radiographic N1, PSA doubling time < 10 months, negative margins, persistent PSA, gross local/regional disease).

“This was a pretty high-risk population,” Dr. Nguyen emphasized, as 35% had Gleason score of 9, about a third (31%) a PSA >0.5, and 29% were pathologic node positive.

All patients received salvage radiotherapy plus 6 months of GnRH agonist (bicalutamide 50 mg), and half were randomly assigned to also receive abiraterone acetate/prednisone 1,000 mg/5 mg + apalutamide 240 mg daily.

At a median follow-up of 34 months, the 3-year PFS rate was 74.9% in the AAP-apalutamide arm vs. 68.5% for the control group (hazard ratio [HR], 0.71; P = .06), and the 3-year MFS rate was 90.6% vs. 87.2%, respectively (HR, 0.57; P = .05).

In the subset of patients with a PSA greater than 0.5 ng/mL, the 3-year PFS and MFS rates were significantly higher with in the AAP-apalutamide group: the 3-year PFS rate was 67.2% vs. 46.8% (HR, 0.50; P = .03), and the 3-year MFS rate was 84.3% vs. 66.1% (HR, 0.32; P = .02).

Adverse events were consistent with the known safety profiles of the agents being studied, Dr. Nguyen noted. The most common toxicities for AAP-apalutamide vs. controls were hypertension (21.8% vs. 13.3%), maculopapular rash (11.5% vs. 0.6%), diarrhea (8.5% vs. 4.8%), and fatigue (7.9% vs. 6.1%).

Dr. Nguyen noted that even though “we’re not supposed to compare clinical trials,” the results of this study appeared to compare favorably with those of another trial, RADICALS-HD, which was presented at the 2022 European Society of Medical Oncology Congress. That study showed that in patients undergoing postoperative radiation therapy, 24 months of ADT was superior to 6 months of ADT in improving both time to salvage ADT and MFS.

However, Dr. Nguyen emphasized that it would have to be formally tested, to see if “FORMULA-509 is performing in the ballpark of what 24 months of ADT would do.

“And I think that compared to 6 months of ADT, we can say it is certainly performing in the ballpark,” he said. “So, for patients with higher risk features, intensifying 6 months of ADT, I think, may be an appealing alternative to lengthening the ADT duration to 24 months.”

He added that this concept would be formally tested in the upcoming PROSTATE IQ study.
 

Strong evidence, standardization needed

In a discussion of the paper, Tyler Seibert, MD, PhD, of the University of California San Diego, said that “escalation by 24 months has the strongest evidence today, specifically from the RADICALS-HD trial, with more than 1,500 men with 10 years of  follow-up and a clear statistically significant result.

“Intensification for 6 months is a very compelling concept, as most patients are not getting 2 years of androgen deprivation therapy at this point post prostatectomy,” he continued. “While we await the long term follow-up of this study and the pending PROSTATE IQ trial, and if only 6 months of therapy is acceptable or feasible, the FORMULA-509 [trial] provides convincing evidence that select patients would benefit from intensification with AAP and apalutamide.”

Another expert weighed in on the data. Approached by this news organization for an independent comment, Jeff M. Michalski, MD, MBA, professor of radiation oncology at Washington University, St Louis, and president of the American Society of Radiation Oncology, noted a few issues in the study.

He said that standards had changed since this study was first approved and had begun accrual several years ago. “In context of today’s era, the current standard is to do a PET scan if patients have a chemical failure after surgery,” he said. “The PSA levels of patients who were treated [in this trial] were very high, and many patients do not want to wait until they reach that level.”

Dr. Michalski also pointed out the number of patients getting radiation was less than the number who had node-positive disease. “This shows that patients had received suboptimal therapy late in the disease,” he said.

Overall, most patients in the study did not receive lymph node radiation, even though they had high-risk features. “A recent study of almost 1,800 patients that was published in The Lancet found that there is a benefit to pelvic lymph node radiation,” he said. “Because it wasn’t mandated, most of the patients did not receive pelvic lymph node radiation, which we now understand offers some benefit.”

The reasons for not giving pelvic radiation to these men is unclear. “Treatment was left at the discretion of the physician and this could create bias,” Dr. Michalski said. “It could drive one arm more than another.”

The study also wasn’t controlled for pelvic radiation. “Most of the nodal positive patients received it, but the other patients were undertreated,” he noted.

Dr. Michalski added that he hopes that in the forthcoming PROSTATE IQ study, lymph node radiation and imaging are standardized.

The trial was supported by Janssen Oncology. Dr. Nguyen disclosed relationships with, and/or support from, Volatilyx, Bayer, Blue Earth Diagnostics, Boston Scientific, Janssen Oncology, Myovant Sciences, Astellas Pharma, and Janssen. Dr. Seibert disclosed relationships with, and/or support from, CorTechs Labs, Varian Medical Systems, and GE Healthcare.

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

SAN FRANCISCO – For patients with prostate cancer who have unfavorable features and a detectable PSA following a radical prostatectomy, the standard of care is treatment with 6 months of a gonadotropin-releasing hormone (GnRH) agonist with salvage radiation therapy (SRT), as established by the GETUG-AFU 16 trial.

A new trial, dubbed FORMULA-509, explored whether outcomes could be improved by intensifying the drug treatment by adding 6 months of abiraterone acetate plus prednisone as well as apalutamide on top of the GnRH agonist alongside the salvage radiotherapy.

This approach did not provide a significant improvement in progression-free survival (PFS) or metastasis-free survival (MFS) in the overall study population.

However, the combination did significantly improve PFS and MFS in a subset of men with PSA levels greater than 0.5 ng/mL.

“Although this primary analysis did not meet the prespecified threshold for statistical significance, it does strongly suggest that the addition of abiraterone acetate/prednisone/apalutamide to salvage radiotherapy plus 6 months of ADT [androgen deprivation therapy] may improve progression-free survival and metastasis-free survival,” said lead author Paul L. Nguyen, MD, of the Dana-Farber Cancer Institute in Boston, and professor of radiation oncology at Harvard Medical School.

“This may be particularly evident in the subgroup of patients with PSA greater that 0.5 ng/mL where a preplanned subgroup analysis by stratification factors observed a statistically significant benefit for both progression-free survival and metastasis-free survival,” he said. “Six months of intensified ADT with next generation anti-androgens may provide an attractive alternative to lengthening ADT for patients with rising PSA and unfavorable features after radical prostatectomy.”

The study results were presented at the ASCO Genitourinary Cancers Symposium.
 

Benefit in subset

The FORMULA-509 trial included 305 patients with PSA ≥ 0.1 ng/mL who had undergone a radical prostatectomy, and who had one or more unfavorable risk features (Gleason 8-10 disease, PSA > 0.5 ng/mL, pT3/T4, pN1 or radiographic N1, PSA doubling time < 10 months, negative margins, persistent PSA, gross local/regional disease).

“This was a pretty high-risk population,” Dr. Nguyen emphasized, as 35% had Gleason score of 9, about a third (31%) a PSA >0.5, and 29% were pathologic node positive.

All patients received salvage radiotherapy plus 6 months of GnRH agonist (bicalutamide 50 mg), and half were randomly assigned to also receive abiraterone acetate/prednisone 1,000 mg/5 mg + apalutamide 240 mg daily.

At a median follow-up of 34 months, the 3-year PFS rate was 74.9% in the AAP-apalutamide arm vs. 68.5% for the control group (hazard ratio [HR], 0.71; P = .06), and the 3-year MFS rate was 90.6% vs. 87.2%, respectively (HR, 0.57; P = .05).

In the subset of patients with a PSA greater than 0.5 ng/mL, the 3-year PFS and MFS rates were significantly higher with in the AAP-apalutamide group: the 3-year PFS rate was 67.2% vs. 46.8% (HR, 0.50; P = .03), and the 3-year MFS rate was 84.3% vs. 66.1% (HR, 0.32; P = .02).

Adverse events were consistent with the known safety profiles of the agents being studied, Dr. Nguyen noted. The most common toxicities for AAP-apalutamide vs. controls were hypertension (21.8% vs. 13.3%), maculopapular rash (11.5% vs. 0.6%), diarrhea (8.5% vs. 4.8%), and fatigue (7.9% vs. 6.1%).

Dr. Nguyen noted that even though “we’re not supposed to compare clinical trials,” the results of this study appeared to compare favorably with those of another trial, RADICALS-HD, which was presented at the 2022 European Society of Medical Oncology Congress. That study showed that in patients undergoing postoperative radiation therapy, 24 months of ADT was superior to 6 months of ADT in improving both time to salvage ADT and MFS.

However, Dr. Nguyen emphasized that it would have to be formally tested, to see if “FORMULA-509 is performing in the ballpark of what 24 months of ADT would do.

“And I think that compared to 6 months of ADT, we can say it is certainly performing in the ballpark,” he said. “So, for patients with higher risk features, intensifying 6 months of ADT, I think, may be an appealing alternative to lengthening the ADT duration to 24 months.”

He added that this concept would be formally tested in the upcoming PROSTATE IQ study.
 

Strong evidence, standardization needed

In a discussion of the paper, Tyler Seibert, MD, PhD, of the University of California San Diego, said that “escalation by 24 months has the strongest evidence today, specifically from the RADICALS-HD trial, with more than 1,500 men with 10 years of  follow-up and a clear statistically significant result.

“Intensification for 6 months is a very compelling concept, as most patients are not getting 2 years of androgen deprivation therapy at this point post prostatectomy,” he continued. “While we await the long term follow-up of this study and the pending PROSTATE IQ trial, and if only 6 months of therapy is acceptable or feasible, the FORMULA-509 [trial] provides convincing evidence that select patients would benefit from intensification with AAP and apalutamide.”

Another expert weighed in on the data. Approached by this news organization for an independent comment, Jeff M. Michalski, MD, MBA, professor of radiation oncology at Washington University, St Louis, and president of the American Society of Radiation Oncology, noted a few issues in the study.

He said that standards had changed since this study was first approved and had begun accrual several years ago. “In context of today’s era, the current standard is to do a PET scan if patients have a chemical failure after surgery,” he said. “The PSA levels of patients who were treated [in this trial] were very high, and many patients do not want to wait until they reach that level.”

Dr. Michalski also pointed out the number of patients getting radiation was less than the number who had node-positive disease. “This shows that patients had received suboptimal therapy late in the disease,” he said.

Overall, most patients in the study did not receive lymph node radiation, even though they had high-risk features. “A recent study of almost 1,800 patients that was published in The Lancet found that there is a benefit to pelvic lymph node radiation,” he said. “Because it wasn’t mandated, most of the patients did not receive pelvic lymph node radiation, which we now understand offers some benefit.”

The reasons for not giving pelvic radiation to these men is unclear. “Treatment was left at the discretion of the physician and this could create bias,” Dr. Michalski said. “It could drive one arm more than another.”

The study also wasn’t controlled for pelvic radiation. “Most of the nodal positive patients received it, but the other patients were undertreated,” he noted.

Dr. Michalski added that he hopes that in the forthcoming PROSTATE IQ study, lymph node radiation and imaging are standardized.

The trial was supported by Janssen Oncology. Dr. Nguyen disclosed relationships with, and/or support from, Volatilyx, Bayer, Blue Earth Diagnostics, Boston Scientific, Janssen Oncology, Myovant Sciences, Astellas Pharma, and Janssen. Dr. Seibert disclosed relationships with, and/or support from, CorTechs Labs, Varian Medical Systems, and GE Healthcare.

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

When it comes to a woman’s risk for a breast cancer recurrence, hormone status appears to matter.

New research shows that patients with ER-negative disease have a higher risk of a second breast cancer within a 5-year window post diagnosis, compared with patients with ER-positive disease.

“Our findings suggest that primary breast cancer ER status could be used to identify women at highest risk of second breast cancer events during the early post-treatment period and should be a consideration for guidelines and decision-making regarding surveillance imaging regimens for breast cancer survivors,” the study authors, led by Kathryn P. Lowry, MD, of Fred Hutchinson Cancer Center in Seattle, concluded.

The study was published online in Cancer.

Breast cancer survivors are at risk for a second breast cancer, making ongoing surveillance essential. Surveillance could be informed by better understanding an individual’s recurrence risk, but whether differences exist for women with ER‐positive vs. ER‐negative cancers remains unclear.

Dr. Lowry and colleagues analyzed women diagnosed with stage I-III breast cancer between 2000 and 2017, drawing from six Breast Cancer Surveillance Consortium registries. The team collected information on patients’ ER status as well as second breast cancer events detectable by surveillance imaging. Second breast cancer rates were assessed 1-5 years and 6-10 years after diagnosis. The final study cohort included 23,139 women with ER-positive disease and 4,605 with ER-negative disease.

The researchers found that, at the 5-year mark, the cumulative breast cancer incidence was 7.1% for ER‐negative disease and 3.6% for ER‐positive disease. At the 10-year mark, the cumulative breast cancer incidence was still higher for women with ER-negative disease – 11.8% vs. 7.5% among those with ER-positive disease. 

Patients with ER-negative disease also had higher rates of second breast cancers within the first 5 years of follow-ups – 16.0 per 1,000 person‐years vs. 7.8 per 1,000 person‐years for those with ER‐positive breast cancer – though after 5 years, the rates by ER status were similar among the two groups (12.1 per 1,000 vs. 9.3 per 1,000 person‐years, respectively).

Overall, the findings indicate that the “ER status of the primary invasive cancer was an important prognostic factor for both the magnitude and the timing of second breast cancer events,” the authors concluded.

The team noted several limitations to their study, including that information on the presence of pathogenic variants, such as BRCA1 and BRCA2, were not available. Given that these variants tend to be more common among women with ER-negative breast cancers, this could represent a confounder.

Marisa C. Weiss, MD, chief medical officer and founder of Breastcancer.org, who was not involved in the research, highlighted two important details to keep in mind.

“We do know that triple negative breast cancers are associated with a higher risk of having an inherited genetic abnormality like BRCA1, which predicts a higher risk of second malignancies,” said Dr. Weiss, a breast oncologist at Lankenau Medical Center in Wynnewood, Pa. “Also, it should be noted that patients with HR-positive breast cancer have a higher incidence of local recurrence spread out over 10-plus years.”

What might these results mean for practice and following patients over the long term?

According to the researchers, “further study is needed to evaluate whether women with ER‐negative primary cancers may potentially benefit from more intensive surveillance in the early postdiagnosis period.”

Dr. Weiss noted as well that “each person’s situation is unique,” and it is “very important to develop a customized survivorship care plan with close surveillance,” which includes genetic testing.

Dr. Lowry reported grants from the American Cancer Society and personal fees from the Radiological Society of North America outside the submitted work. Several coauthors also reported disclosures. Dr. Weiss reported no relevant financial relationships.

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

When it comes to a woman’s risk for a breast cancer recurrence, hormone status appears to matter.

New research shows that patients with ER-negative disease have a higher risk of a second breast cancer within a 5-year window post diagnosis, compared with patients with ER-positive disease.

“Our findings suggest that primary breast cancer ER status could be used to identify women at highest risk of second breast cancer events during the early post-treatment period and should be a consideration for guidelines and decision-making regarding surveillance imaging regimens for breast cancer survivors,” the study authors, led by Kathryn P. Lowry, MD, of Fred Hutchinson Cancer Center in Seattle, concluded.

The study was published online in Cancer.

Breast cancer survivors are at risk for a second breast cancer, making ongoing surveillance essential. Surveillance could be informed by better understanding an individual’s recurrence risk, but whether differences exist for women with ER‐positive vs. ER‐negative cancers remains unclear.

Dr. Lowry and colleagues analyzed women diagnosed with stage I-III breast cancer between 2000 and 2017, drawing from six Breast Cancer Surveillance Consortium registries. The team collected information on patients’ ER status as well as second breast cancer events detectable by surveillance imaging. Second breast cancer rates were assessed 1-5 years and 6-10 years after diagnosis. The final study cohort included 23,139 women with ER-positive disease and 4,605 with ER-negative disease.

The researchers found that, at the 5-year mark, the cumulative breast cancer incidence was 7.1% for ER‐negative disease and 3.6% for ER‐positive disease. At the 10-year mark, the cumulative breast cancer incidence was still higher for women with ER-negative disease – 11.8% vs. 7.5% among those with ER-positive disease. 

Patients with ER-negative disease also had higher rates of second breast cancers within the first 5 years of follow-ups – 16.0 per 1,000 person‐years vs. 7.8 per 1,000 person‐years for those with ER‐positive breast cancer – though after 5 years, the rates by ER status were similar among the two groups (12.1 per 1,000 vs. 9.3 per 1,000 person‐years, respectively).

Overall, the findings indicate that the “ER status of the primary invasive cancer was an important prognostic factor for both the magnitude and the timing of second breast cancer events,” the authors concluded.

The team noted several limitations to their study, including that information on the presence of pathogenic variants, such as BRCA1 and BRCA2, were not available. Given that these variants tend to be more common among women with ER-negative breast cancers, this could represent a confounder.

Marisa C. Weiss, MD, chief medical officer and founder of Breastcancer.org, who was not involved in the research, highlighted two important details to keep in mind.

“We do know that triple negative breast cancers are associated with a higher risk of having an inherited genetic abnormality like BRCA1, which predicts a higher risk of second malignancies,” said Dr. Weiss, a breast oncologist at Lankenau Medical Center in Wynnewood, Pa. “Also, it should be noted that patients with HR-positive breast cancer have a higher incidence of local recurrence spread out over 10-plus years.”

What might these results mean for practice and following patients over the long term?

According to the researchers, “further study is needed to evaluate whether women with ER‐negative primary cancers may potentially benefit from more intensive surveillance in the early postdiagnosis period.”

Dr. Weiss noted as well that “each person’s situation is unique,” and it is “very important to develop a customized survivorship care plan with close surveillance,” which includes genetic testing.

Dr. Lowry reported grants from the American Cancer Society and personal fees from the Radiological Society of North America outside the submitted work. Several coauthors also reported disclosures. Dr. Weiss reported no relevant financial relationships.

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

When it comes to a woman’s risk for a breast cancer recurrence, hormone status appears to matter.

New research shows that patients with ER-negative disease have a higher risk of a second breast cancer within a 5-year window post diagnosis, compared with patients with ER-positive disease.

“Our findings suggest that primary breast cancer ER status could be used to identify women at highest risk of second breast cancer events during the early post-treatment period and should be a consideration for guidelines and decision-making regarding surveillance imaging regimens for breast cancer survivors,” the study authors, led by Kathryn P. Lowry, MD, of Fred Hutchinson Cancer Center in Seattle, concluded.

The study was published online in Cancer.

Breast cancer survivors are at risk for a second breast cancer, making ongoing surveillance essential. Surveillance could be informed by better understanding an individual’s recurrence risk, but whether differences exist for women with ER‐positive vs. ER‐negative cancers remains unclear.

Dr. Lowry and colleagues analyzed women diagnosed with stage I-III breast cancer between 2000 and 2017, drawing from six Breast Cancer Surveillance Consortium registries. The team collected information on patients’ ER status as well as second breast cancer events detectable by surveillance imaging. Second breast cancer rates were assessed 1-5 years and 6-10 years after diagnosis. The final study cohort included 23,139 women with ER-positive disease and 4,605 with ER-negative disease.

The researchers found that, at the 5-year mark, the cumulative breast cancer incidence was 7.1% for ER‐negative disease and 3.6% for ER‐positive disease. At the 10-year mark, the cumulative breast cancer incidence was still higher for women with ER-negative disease – 11.8% vs. 7.5% among those with ER-positive disease. 

Patients with ER-negative disease also had higher rates of second breast cancers within the first 5 years of follow-ups – 16.0 per 1,000 person‐years vs. 7.8 per 1,000 person‐years for those with ER‐positive breast cancer – though after 5 years, the rates by ER status were similar among the two groups (12.1 per 1,000 vs. 9.3 per 1,000 person‐years, respectively).

Overall, the findings indicate that the “ER status of the primary invasive cancer was an important prognostic factor for both the magnitude and the timing of second breast cancer events,” the authors concluded.

The team noted several limitations to their study, including that information on the presence of pathogenic variants, such as BRCA1 and BRCA2, were not available. Given that these variants tend to be more common among women with ER-negative breast cancers, this could represent a confounder.

Marisa C. Weiss, MD, chief medical officer and founder of Breastcancer.org, who was not involved in the research, highlighted two important details to keep in mind.

“We do know that triple negative breast cancers are associated with a higher risk of having an inherited genetic abnormality like BRCA1, which predicts a higher risk of second malignancies,” said Dr. Weiss, a breast oncologist at Lankenau Medical Center in Wynnewood, Pa. “Also, it should be noted that patients with HR-positive breast cancer have a higher incidence of local recurrence spread out over 10-plus years.”

What might these results mean for practice and following patients over the long term?

According to the researchers, “further study is needed to evaluate whether women with ER‐negative primary cancers may potentially benefit from more intensive surveillance in the early postdiagnosis period.”

Dr. Weiss noted as well that “each person’s situation is unique,” and it is “very important to develop a customized survivorship care plan with close surveillance,” which includes genetic testing.

Dr. Lowry reported grants from the American Cancer Society and personal fees from the Radiological Society of North America outside the submitted work. Several coauthors also reported disclosures. Dr. Weiss reported no relevant financial relationships.

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

The age-adjusted incidence rate of pancreatic cancer is increasing in young women in the United States, and it doesn’t show signs of slowing down, according to a new study published in Gastroenterology.

Cedars-Sinai Medical Center

Between 2001 and 2018, there was a greater than 200% difference in the incidence trend between men and women for ages 15-34, wrote Yazan Abboud, MD, a postdoctoral research fellow in the pancreaticobiliary department of the Karsh Division of Gastroenterology and Hepatology at Cedars-Sinai Medical Center, Los Angeles, and colleagues.

“The exact cause of the trend among younger women is unclear and may be driven by sex-based disproportional exposure or response to known or yet-to-be-explored risk factors,” they wrote. “Future efforts should aim to elucidate the causes of such a trend with the goal to formulate possible preventive measures.”

Although previous studies have found increasing pancreatic cancer incidence rates, especially in younger women, the data haven’t been externally validated outside of the National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) data, they wrote. In addition, there are limited data about the contributing factors, such as race, histopathological subtype, tumor location, and stage at diagnosis.

Using SEER-excluded data from the Centers for Disease Control and Prevention’s National Program of Cancer Registries (NPCR), Dr. Abboud and colleagues conducted a population-based time-trend analysis of pancreatic cancer incidence rates from 2001 to 2018 in younger adults under age 55, including the role of demographics and tumor characteristics. They analyzed age-adjusted incidence rates (aIR), mortality rates, annual percentage change (APC), and average annual percentage change (AAPC) for ages 55 and older and ages 55 and younger. In addition, the research team evaluated the impact of incidence trends on sex-specific mortality trends in younger adults using the CDC’s National Center of Health Statistics database.

Between 2001 and 2018, 748,132 patients were diagnosed with pancreatic cancer. After excluding SEER data, 454,611 patients met the inclusion criteria. About 48.9% were women.

The overall aIR of pancreatic cancer during that time was 12.18 per 100,000 people. Women had a significantly lower aIR, at 10.69 per 100,000, compared with men at 13.95 per 100,000.

In general, pancreatic cancer aIR significantly increased during that time (AAPC = 1.17%). Sex-specific trends increased among both women (AAPC = 1.27%) and men (AAPC = 1.14%), though they showed no significant difference and were parallel.

In ages 55 and older, 401,419 patients (49.7% women) were diagnosed with pancreatic cancer. The aIR significantly increased during the study period (AAPC = 1.11%), with sex-specific aIR increasing in both women (AAPC = 1.11%) and men (AAPC = 1.17%), without a significant difference.

However, a difference appeared in the 53,051 patients (42.9% women) who were ages 55 and younger. The aIR relatively increased (AAPC = 1.29%), with faster jumps in women (AAPC = 2.36%), compared with men (AAPC = .62%). There was an absolute significant difference of 1.74%.

The trends continued in breakdowns by age. For 50,599 patients (42.2% women) between ages 35 and 54, the aIR relatively increased (AAPC = 1.10%). Sex-specific aIR increased among women (AAPC = 2.09%) but remained stable among men (AAPC = 0.54%), with an absolute significant difference of 1.55%.

In the youngest cohort of 2,452 patients (57.3% women) between ages 15 and 34, aIR relatively increased (AAPC = 4.93). Sex-specific aIR also increased in both women (AAPC = 6.45%) and men (AAPC = 2.97%), with an absolute significant difference of 3.48%.

By race, although White women under age 55 experienced increasing aIR at a greater rate than men (AAPC difference = 1.59%), an even more dramatic increase was seen in Black women, as compared to counterpart men (AAPC difference = 2.23%). Sex-specific trends in people of other races were parallel.

Based on tumor characteristics in ages 55 and younger, the pancreatic ductal adenocarcinoma histopathological subtype had an AAPC difference of 0.89%, and a tumor location in the head-of-pancreas had an AAPC difference of 1.64%.

When evaluating tumors based on stage-at-diagnosis, the AAPC difference was nonsignificant in all subgroups. However, sex-specific trends differed in tumors diagnosed at localized stages, suggesting that aIR in women may be increasing at a greater rate than in men (AAPC difference = 1.64%).

Among 64,239 patients (39.3% women) who died from pancreatic cancer under age 55, the mortality rates were unchanged in women (AAPC = –0.09%) but declined in men (AAPC = –0.64%), with an absolute significant AAPC difference of 0.54%.

UCLA

“Pancreatic cancer has a very poor overall survival, accounting for 7% of cancer-related deaths. The incidence of cancers, in general, is expected to rise as life expectancy increases in the United States,” said Danny Issa, MD, a gastroenterologist at the University of California, Los Angeles, who wasn’t involved with this study.

“Recently, noncomparative studies showed a possible increase in the incidence of pancreatic cancer in younger White women and in older White men and women. These reports had limitations,” he said. “The findings of this study are monumental as they confirmed that age-adjusted incidence rates have been increasing at a higher rate in younger women compared to younger men.”

In addition, Dr. Issa said, the significant increases among Black women for adenocarcinoma and for cancers located in the head of the pancreas are notable and should be studied further.

“Over the past few decades, research studies have helped improve cancer treatment by uncovering risk factors and identifying the most affected (or protected) population,” he said. “Therefore, epidemiologic studies are crucial, especially for hard-to-treat cancers such as pancreatic cancer.”

The study was supported in part by a philanthropic grant from The Widjaja Family Fund for Pancreatic Cancer Research. The authors disclosed no conflicts of interest. Dr. Issa reported no relevant disclosures.

The age-adjusted incidence rate of pancreatic cancer is increasing in young women in the United States, and it doesn’t show signs of slowing down, according to a new study published in Gastroenterology.

Cedars-Sinai Medical Center

Between 2001 and 2018, there was a greater than 200% difference in the incidence trend between men and women for ages 15-34, wrote Yazan Abboud, MD, a postdoctoral research fellow in the pancreaticobiliary department of the Karsh Division of Gastroenterology and Hepatology at Cedars-Sinai Medical Center, Los Angeles, and colleagues.

“The exact cause of the trend among younger women is unclear and may be driven by sex-based disproportional exposure or response to known or yet-to-be-explored risk factors,” they wrote. “Future efforts should aim to elucidate the causes of such a trend with the goal to formulate possible preventive measures.”

Although previous studies have found increasing pancreatic cancer incidence rates, especially in younger women, the data haven’t been externally validated outside of the National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) data, they wrote. In addition, there are limited data about the contributing factors, such as race, histopathological subtype, tumor location, and stage at diagnosis.

Using SEER-excluded data from the Centers for Disease Control and Prevention’s National Program of Cancer Registries (NPCR), Dr. Abboud and colleagues conducted a population-based time-trend analysis of pancreatic cancer incidence rates from 2001 to 2018 in younger adults under age 55, including the role of demographics and tumor characteristics. They analyzed age-adjusted incidence rates (aIR), mortality rates, annual percentage change (APC), and average annual percentage change (AAPC) for ages 55 and older and ages 55 and younger. In addition, the research team evaluated the impact of incidence trends on sex-specific mortality trends in younger adults using the CDC’s National Center of Health Statistics database.

Between 2001 and 2018, 748,132 patients were diagnosed with pancreatic cancer. After excluding SEER data, 454,611 patients met the inclusion criteria. About 48.9% were women.

The overall aIR of pancreatic cancer during that time was 12.18 per 100,000 people. Women had a significantly lower aIR, at 10.69 per 100,000, compared with men at 13.95 per 100,000.

In general, pancreatic cancer aIR significantly increased during that time (AAPC = 1.17%). Sex-specific trends increased among both women (AAPC = 1.27%) and men (AAPC = 1.14%), though they showed no significant difference and were parallel.

In ages 55 and older, 401,419 patients (49.7% women) were diagnosed with pancreatic cancer. The aIR significantly increased during the study period (AAPC = 1.11%), with sex-specific aIR increasing in both women (AAPC = 1.11%) and men (AAPC = 1.17%), without a significant difference.

However, a difference appeared in the 53,051 patients (42.9% women) who were ages 55 and younger. The aIR relatively increased (AAPC = 1.29%), with faster jumps in women (AAPC = 2.36%), compared with men (AAPC = .62%). There was an absolute significant difference of 1.74%.

The trends continued in breakdowns by age. For 50,599 patients (42.2% women) between ages 35 and 54, the aIR relatively increased (AAPC = 1.10%). Sex-specific aIR increased among women (AAPC = 2.09%) but remained stable among men (AAPC = 0.54%), with an absolute significant difference of 1.55%.

In the youngest cohort of 2,452 patients (57.3% women) between ages 15 and 34, aIR relatively increased (AAPC = 4.93). Sex-specific aIR also increased in both women (AAPC = 6.45%) and men (AAPC = 2.97%), with an absolute significant difference of 3.48%.

By race, although White women under age 55 experienced increasing aIR at a greater rate than men (AAPC difference = 1.59%), an even more dramatic increase was seen in Black women, as compared to counterpart men (AAPC difference = 2.23%). Sex-specific trends in people of other races were parallel.

Based on tumor characteristics in ages 55 and younger, the pancreatic ductal adenocarcinoma histopathological subtype had an AAPC difference of 0.89%, and a tumor location in the head-of-pancreas had an AAPC difference of 1.64%.

When evaluating tumors based on stage-at-diagnosis, the AAPC difference was nonsignificant in all subgroups. However, sex-specific trends differed in tumors diagnosed at localized stages, suggesting that aIR in women may be increasing at a greater rate than in men (AAPC difference = 1.64%).

Among 64,239 patients (39.3% women) who died from pancreatic cancer under age 55, the mortality rates were unchanged in women (AAPC = –0.09%) but declined in men (AAPC = –0.64%), with an absolute significant AAPC difference of 0.54%.

UCLA

“Pancreatic cancer has a very poor overall survival, accounting for 7% of cancer-related deaths. The incidence of cancers, in general, is expected to rise as life expectancy increases in the United States,” said Danny Issa, MD, a gastroenterologist at the University of California, Los Angeles, who wasn’t involved with this study.

“Recently, noncomparative studies showed a possible increase in the incidence of pancreatic cancer in younger White women and in older White men and women. These reports had limitations,” he said. “The findings of this study are monumental as they confirmed that age-adjusted incidence rates have been increasing at a higher rate in younger women compared to younger men.”

In addition, Dr. Issa said, the significant increases among Black women for adenocarcinoma and for cancers located in the head of the pancreas are notable and should be studied further.

“Over the past few decades, research studies have helped improve cancer treatment by uncovering risk factors and identifying the most affected (or protected) population,” he said. “Therefore, epidemiologic studies are crucial, especially for hard-to-treat cancers such as pancreatic cancer.”

The study was supported in part by a philanthropic grant from The Widjaja Family Fund for Pancreatic Cancer Research. The authors disclosed no conflicts of interest. Dr. Issa reported no relevant disclosures.

The age-adjusted incidence rate of pancreatic cancer is increasing in young women in the United States, and it doesn’t show signs of slowing down, according to a new study published in Gastroenterology.

Cedars-Sinai Medical Center

Between 2001 and 2018, there was a greater than 200% difference in the incidence trend between men and women for ages 15-34, wrote Yazan Abboud, MD, a postdoctoral research fellow in the pancreaticobiliary department of the Karsh Division of Gastroenterology and Hepatology at Cedars-Sinai Medical Center, Los Angeles, and colleagues.

“The exact cause of the trend among younger women is unclear and may be driven by sex-based disproportional exposure or response to known or yet-to-be-explored risk factors,” they wrote. “Future efforts should aim to elucidate the causes of such a trend with the goal to formulate possible preventive measures.”

Although previous studies have found increasing pancreatic cancer incidence rates, especially in younger women, the data haven’t been externally validated outside of the National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) data, they wrote. In addition, there are limited data about the contributing factors, such as race, histopathological subtype, tumor location, and stage at diagnosis.

Using SEER-excluded data from the Centers for Disease Control and Prevention’s National Program of Cancer Registries (NPCR), Dr. Abboud and colleagues conducted a population-based time-trend analysis of pancreatic cancer incidence rates from 2001 to 2018 in younger adults under age 55, including the role of demographics and tumor characteristics. They analyzed age-adjusted incidence rates (aIR), mortality rates, annual percentage change (APC), and average annual percentage change (AAPC) for ages 55 and older and ages 55 and younger. In addition, the research team evaluated the impact of incidence trends on sex-specific mortality trends in younger adults using the CDC’s National Center of Health Statistics database.

Between 2001 and 2018, 748,132 patients were diagnosed with pancreatic cancer. After excluding SEER data, 454,611 patients met the inclusion criteria. About 48.9% were women.

The overall aIR of pancreatic cancer during that time was 12.18 per 100,000 people. Women had a significantly lower aIR, at 10.69 per 100,000, compared with men at 13.95 per 100,000.

In general, pancreatic cancer aIR significantly increased during that time (AAPC = 1.17%). Sex-specific trends increased among both women (AAPC = 1.27%) and men (AAPC = 1.14%), though they showed no significant difference and were parallel.

In ages 55 and older, 401,419 patients (49.7% women) were diagnosed with pancreatic cancer. The aIR significantly increased during the study period (AAPC = 1.11%), with sex-specific aIR increasing in both women (AAPC = 1.11%) and men (AAPC = 1.17%), without a significant difference.

However, a difference appeared in the 53,051 patients (42.9% women) who were ages 55 and younger. The aIR relatively increased (AAPC = 1.29%), with faster jumps in women (AAPC = 2.36%), compared with men (AAPC = .62%). There was an absolute significant difference of 1.74%.

The trends continued in breakdowns by age. For 50,599 patients (42.2% women) between ages 35 and 54, the aIR relatively increased (AAPC = 1.10%). Sex-specific aIR increased among women (AAPC = 2.09%) but remained stable among men (AAPC = 0.54%), with an absolute significant difference of 1.55%.

In the youngest cohort of 2,452 patients (57.3% women) between ages 15 and 34, aIR relatively increased (AAPC = 4.93). Sex-specific aIR also increased in both women (AAPC = 6.45%) and men (AAPC = 2.97%), with an absolute significant difference of 3.48%.

By race, although White women under age 55 experienced increasing aIR at a greater rate than men (AAPC difference = 1.59%), an even more dramatic increase was seen in Black women, as compared to counterpart men (AAPC difference = 2.23%). Sex-specific trends in people of other races were parallel.

Based on tumor characteristics in ages 55 and younger, the pancreatic ductal adenocarcinoma histopathological subtype had an AAPC difference of 0.89%, and a tumor location in the head-of-pancreas had an AAPC difference of 1.64%.

When evaluating tumors based on stage-at-diagnosis, the AAPC difference was nonsignificant in all subgroups. However, sex-specific trends differed in tumors diagnosed at localized stages, suggesting that aIR in women may be increasing at a greater rate than in men (AAPC difference = 1.64%).

Among 64,239 patients (39.3% women) who died from pancreatic cancer under age 55, the mortality rates were unchanged in women (AAPC = –0.09%) but declined in men (AAPC = –0.64%), with an absolute significant AAPC difference of 0.54%.

UCLA

“Pancreatic cancer has a very poor overall survival, accounting for 7% of cancer-related deaths. The incidence of cancers, in general, is expected to rise as life expectancy increases in the United States,” said Danny Issa, MD, a gastroenterologist at the University of California, Los Angeles, who wasn’t involved with this study.

“Recently, noncomparative studies showed a possible increase in the incidence of pancreatic cancer in younger White women and in older White men and women. These reports had limitations,” he said. “The findings of this study are monumental as they confirmed that age-adjusted incidence rates have been increasing at a higher rate in younger women compared to younger men.”

In addition, Dr. Issa said, the significant increases among Black women for adenocarcinoma and for cancers located in the head of the pancreas are notable and should be studied further.

“Over the past few decades, research studies have helped improve cancer treatment by uncovering risk factors and identifying the most affected (or protected) population,” he said. “Therefore, epidemiologic studies are crucial, especially for hard-to-treat cancers such as pancreatic cancer.”

The study was supported in part by a philanthropic grant from The Widjaja Family Fund for Pancreatic Cancer Research. The authors disclosed no conflicts of interest. Dr. Issa reported no relevant disclosures.

FRANCE – Conducted every 5 years since 2005, the Cancer Survey documents the knowledge, perceptions, and way of life of the French people in relation to cancer. The French National Cancer Institute (InCA), in partnership with Public Health France (SPF), has published the results of its 2021 survey. The researchers analyzed responses to telephone interviews of a representative sample of almost 5,000 individuals aged 15-85 years.

This study shows how thinking has changed over time and how difficult it is to alter preconceived notions.
 

Is cancer hereditary?

The report shows that 67.7% of respondents believe that cancer is a hereditary disease. Respondents were asked to explain their answer. “Data show that medical practices for cancer treatment substantiate this belief [that cancer is hereditary],” wrote the authors of the report.

“Indeed, health care professionals almost systematically ask questions about family history of breast cancer and, when a family member has been diagnosed with cancer, medical monitoring of other family members is often sought out, thus reinforcing the belief that cancer is hereditary,” they said.

Furthermore, there seems to be confusion regarding the role of genes in the development of cancer. A person can inherit cancer-predisposing genes, not cancer itself. The authors highlighted their concern that this confusion may “lead people to think that prevention measures are unnecessary because cancer is inherited.”
 

Misconceptions about smoking

About 41% of smokers think that the length of time one has been smoking is the biggest determining factor for developing cancer; 58.1% think the number of cigarettes smoked per day has a bigger impact.

Experts at InCA and SPF put the debate to rest, stating that prolonged exposure to carcinogenic substances is far more toxic. As for the danger threshold concerning the number of cigarettes smoked per day, respondents believed this to be 9.2 cigarettes per day, on average. They believed that the danger threshold for the number of years as an active smoker is 13.4, on average.

“The [survey] respondents clearly understand that smoking carries a risk, but many smokers think that light smoking or smoking for a short period of time doesn’t carry any risks.” Yet it is understood that even occasional tobacco consumption increases mortality.

This was not the only misconception regarding smoking and its relationship with cancer. About 34% of survey respondents agreed with the following statement: “Smoking doesn’t cause cancer unless you’re a heavy smoker and have smoked for a long time.” Furthermore, 43.3% agreed with the statement, “Pollution is more likely to cause cancer than smoking,” 54.6% think that “exercising cleans your lungs of tobacco,” and 61.6% think that “a smoker can prevent developing cancer caused by smoking if they know to quit on time.”
 

Overweight and obesity

Although diet and excess weight represent the third and fourth biggest avoidable cancer risk factors, after smoking and alcohol, only 30% of survey respondents knew of this link.

“Among the causes of cancer known and cited by respondents without prompting, excessive weight and obesity were mentioned only 100 times out of 12,558 responses,” highlighted the authors of the report. The explanation put forward by the authors is that discourse about diet has been more focused on diet as a protective health factor, especially in preventing cardiovascular diseases. “The link between cancer and diet is less prominent in the public space,” they noted.
 

Breastfeeding and cancer

About 63% of survey respondents, which for the first time included both women and men, believe that breastfeeding does not affect mothers’ risk of breast cancer, but this is a misconception. And almost 1 in 3 respondents said that breastfeeding provides health benefits for the mother.

Artificial UV rays

Exposure to UV rays, whether of natural or artificial origin, is a major risk factor for skin cancer. However, 1 in 5 people (20.9%) think that a session in a tanning bed is less harmful than sun exposure.

Daily stress

Regarding psychological factors linked to cancer, the authors noted that risk factors not supported by scientific evidence were, ironically, cited more often by respondents than proven risk factors. There is a real knowledge gap between scientific data and the beliefs of the French people. For example, “working at night” is largely not seen as a risk factor, but data show that it presents a clear risk. However, “not being able to express one’s feelings,” “having been weakened by traumatic experiences,” and “being exposed to the stress of modern life” are seen as risk factors of cancer, without any scientific evidence.

Cigarettes and e-cigarettes

About 53% of respondents agreed that “e-cigarettes are just as harmful or more harmful than traditional cigarettes.” Nicotine and the flavors in e-cigarettes are largely perceived as “very” or “extremely” harmful to the health of a person. However, the authors note that “no published study on nicotine substitutes has shown harmful effects on the health of a person, let alone determined it a risk factor for cancer. The nicotine doses in e-cigarettes are similar to traditional nicotine substitutes, and no cytotoxic effect of nicotine in its inhaled form has been found.” There seems to be confusion between dependence and risk of cancer.

Alcohol consumption

Eight of 10 respondents believe that “some people can drink a lot of alcohol all their life without ever getting cancer,” which goes against the scientific literature. The authors of the report state that the negative effects of alcohol on health seem poorly understood. Although alcohol is the second biggest cause of cancer, only a third of survey respondents cited it without having been prompted as one of the main causes of cancer. And 23.5% even think that “in terms of decreasing your risk of cancer, it’s better to drink a little wine than to drink no wine at all.”

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

FRANCE – Conducted every 5 years since 2005, the Cancer Survey documents the knowledge, perceptions, and way of life of the French people in relation to cancer. The French National Cancer Institute (InCA), in partnership with Public Health France (SPF), has published the results of its 2021 survey. The researchers analyzed responses to telephone interviews of a representative sample of almost 5,000 individuals aged 15-85 years.

This study shows how thinking has changed over time and how difficult it is to alter preconceived notions.
 

Is cancer hereditary?

The report shows that 67.7% of respondents believe that cancer is a hereditary disease. Respondents were asked to explain their answer. “Data show that medical practices for cancer treatment substantiate this belief [that cancer is hereditary],” wrote the authors of the report.

“Indeed, health care professionals almost systematically ask questions about family history of breast cancer and, when a family member has been diagnosed with cancer, medical monitoring of other family members is often sought out, thus reinforcing the belief that cancer is hereditary,” they said.

Furthermore, there seems to be confusion regarding the role of genes in the development of cancer. A person can inherit cancer-predisposing genes, not cancer itself. The authors highlighted their concern that this confusion may “lead people to think that prevention measures are unnecessary because cancer is inherited.”
 

Misconceptions about smoking

About 41% of smokers think that the length of time one has been smoking is the biggest determining factor for developing cancer; 58.1% think the number of cigarettes smoked per day has a bigger impact.

Experts at InCA and SPF put the debate to rest, stating that prolonged exposure to carcinogenic substances is far more toxic. As for the danger threshold concerning the number of cigarettes smoked per day, respondents believed this to be 9.2 cigarettes per day, on average. They believed that the danger threshold for the number of years as an active smoker is 13.4, on average.

“The [survey] respondents clearly understand that smoking carries a risk, but many smokers think that light smoking or smoking for a short period of time doesn’t carry any risks.” Yet it is understood that even occasional tobacco consumption increases mortality.

This was not the only misconception regarding smoking and its relationship with cancer. About 34% of survey respondents agreed with the following statement: “Smoking doesn’t cause cancer unless you’re a heavy smoker and have smoked for a long time.” Furthermore, 43.3% agreed with the statement, “Pollution is more likely to cause cancer than smoking,” 54.6% think that “exercising cleans your lungs of tobacco,” and 61.6% think that “a smoker can prevent developing cancer caused by smoking if they know to quit on time.”
 

Overweight and obesity

Although diet and excess weight represent the third and fourth biggest avoidable cancer risk factors, after smoking and alcohol, only 30% of survey respondents knew of this link.

“Among the causes of cancer known and cited by respondents without prompting, excessive weight and obesity were mentioned only 100 times out of 12,558 responses,” highlighted the authors of the report. The explanation put forward by the authors is that discourse about diet has been more focused on diet as a protective health factor, especially in preventing cardiovascular diseases. “The link between cancer and diet is less prominent in the public space,” they noted.
 

Breastfeeding and cancer

About 63% of survey respondents, which for the first time included both women and men, believe that breastfeeding does not affect mothers’ risk of breast cancer, but this is a misconception. And almost 1 in 3 respondents said that breastfeeding provides health benefits for the mother.

Artificial UV rays

Exposure to UV rays, whether of natural or artificial origin, is a major risk factor for skin cancer. However, 1 in 5 people (20.9%) think that a session in a tanning bed is less harmful than sun exposure.

Daily stress

Regarding psychological factors linked to cancer, the authors noted that risk factors not supported by scientific evidence were, ironically, cited more often by respondents than proven risk factors. There is a real knowledge gap between scientific data and the beliefs of the French people. For example, “working at night” is largely not seen as a risk factor, but data show that it presents a clear risk. However, “not being able to express one’s feelings,” “having been weakened by traumatic experiences,” and “being exposed to the stress of modern life” are seen as risk factors of cancer, without any scientific evidence.

Cigarettes and e-cigarettes

About 53% of respondents agreed that “e-cigarettes are just as harmful or more harmful than traditional cigarettes.” Nicotine and the flavors in e-cigarettes are largely perceived as “very” or “extremely” harmful to the health of a person. However, the authors note that “no published study on nicotine substitutes has shown harmful effects on the health of a person, let alone determined it a risk factor for cancer. The nicotine doses in e-cigarettes are similar to traditional nicotine substitutes, and no cytotoxic effect of nicotine in its inhaled form has been found.” There seems to be confusion between dependence and risk of cancer.

Alcohol consumption

Eight of 10 respondents believe that “some people can drink a lot of alcohol all their life without ever getting cancer,” which goes against the scientific literature. The authors of the report state that the negative effects of alcohol on health seem poorly understood. Although alcohol is the second biggest cause of cancer, only a third of survey respondents cited it without having been prompted as one of the main causes of cancer. And 23.5% even think that “in terms of decreasing your risk of cancer, it’s better to drink a little wine than to drink no wine at all.”

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

FRANCE – Conducted every 5 years since 2005, the Cancer Survey documents the knowledge, perceptions, and way of life of the French people in relation to cancer. The French National Cancer Institute (InCA), in partnership with Public Health France (SPF), has published the results of its 2021 survey. The researchers analyzed responses to telephone interviews of a representative sample of almost 5,000 individuals aged 15-85 years.

This study shows how thinking has changed over time and how difficult it is to alter preconceived notions.
 

Is cancer hereditary?

The report shows that 67.7% of respondents believe that cancer is a hereditary disease. Respondents were asked to explain their answer. “Data show that medical practices for cancer treatment substantiate this belief [that cancer is hereditary],” wrote the authors of the report.

“Indeed, health care professionals almost systematically ask questions about family history of breast cancer and, when a family member has been diagnosed with cancer, medical monitoring of other family members is often sought out, thus reinforcing the belief that cancer is hereditary,” they said.

Furthermore, there seems to be confusion regarding the role of genes in the development of cancer. A person can inherit cancer-predisposing genes, not cancer itself. The authors highlighted their concern that this confusion may “lead people to think that prevention measures are unnecessary because cancer is inherited.”
 

Misconceptions about smoking

About 41% of smokers think that the length of time one has been smoking is the biggest determining factor for developing cancer; 58.1% think the number of cigarettes smoked per day has a bigger impact.

Experts at InCA and SPF put the debate to rest, stating that prolonged exposure to carcinogenic substances is far more toxic. As for the danger threshold concerning the number of cigarettes smoked per day, respondents believed this to be 9.2 cigarettes per day, on average. They believed that the danger threshold for the number of years as an active smoker is 13.4, on average.

“The [survey] respondents clearly understand that smoking carries a risk, but many smokers think that light smoking or smoking for a short period of time doesn’t carry any risks.” Yet it is understood that even occasional tobacco consumption increases mortality.

This was not the only misconception regarding smoking and its relationship with cancer. About 34% of survey respondents agreed with the following statement: “Smoking doesn’t cause cancer unless you’re a heavy smoker and have smoked for a long time.” Furthermore, 43.3% agreed with the statement, “Pollution is more likely to cause cancer than smoking,” 54.6% think that “exercising cleans your lungs of tobacco,” and 61.6% think that “a smoker can prevent developing cancer caused by smoking if they know to quit on time.”
 

Overweight and obesity

Although diet and excess weight represent the third and fourth biggest avoidable cancer risk factors, after smoking and alcohol, only 30% of survey respondents knew of this link.

“Among the causes of cancer known and cited by respondents without prompting, excessive weight and obesity were mentioned only 100 times out of 12,558 responses,” highlighted the authors of the report. The explanation put forward by the authors is that discourse about diet has been more focused on diet as a protective health factor, especially in preventing cardiovascular diseases. “The link between cancer and diet is less prominent in the public space,” they noted.
 

Breastfeeding and cancer

About 63% of survey respondents, which for the first time included both women and men, believe that breastfeeding does not affect mothers’ risk of breast cancer, but this is a misconception. And almost 1 in 3 respondents said that breastfeeding provides health benefits for the mother.

Artificial UV rays

Exposure to UV rays, whether of natural or artificial origin, is a major risk factor for skin cancer. However, 1 in 5 people (20.9%) think that a session in a tanning bed is less harmful than sun exposure.

Daily stress

Regarding psychological factors linked to cancer, the authors noted that risk factors not supported by scientific evidence were, ironically, cited more often by respondents than proven risk factors. There is a real knowledge gap between scientific data and the beliefs of the French people. For example, “working at night” is largely not seen as a risk factor, but data show that it presents a clear risk. However, “not being able to express one’s feelings,” “having been weakened by traumatic experiences,” and “being exposed to the stress of modern life” are seen as risk factors of cancer, without any scientific evidence.

Cigarettes and e-cigarettes

About 53% of respondents agreed that “e-cigarettes are just as harmful or more harmful than traditional cigarettes.” Nicotine and the flavors in e-cigarettes are largely perceived as “very” or “extremely” harmful to the health of a person. However, the authors note that “no published study on nicotine substitutes has shown harmful effects on the health of a person, let alone determined it a risk factor for cancer. The nicotine doses in e-cigarettes are similar to traditional nicotine substitutes, and no cytotoxic effect of nicotine in its inhaled form has been found.” There seems to be confusion between dependence and risk of cancer.

Alcohol consumption

Eight of 10 respondents believe that “some people can drink a lot of alcohol all their life without ever getting cancer,” which goes against the scientific literature. The authors of the report state that the negative effects of alcohol on health seem poorly understood. Although alcohol is the second biggest cause of cancer, only a third of survey respondents cited it without having been prompted as one of the main causes of cancer. And 23.5% even think that “in terms of decreasing your risk of cancer, it’s better to drink a little wine than to drink no wine at all.”

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at New York University’s Grossman School of Medicine, where I’m the director.

It’s flu season, yet again. For many parts of the country, we’re already in the thick of it, and for other places, we’re going to have flu outbreaks continuing and intensifying. I’ve long believed that every health care institution – nursing homes, hospitals, clinics, home care, hospice – should require flu shots for all doctors and all nurses because it is the easiest, cheapest, and most ethical way to protect the workforce, who you need to be in there when flu outbreaks take place, and to protect patients against getting the flu when they come into hospital settings and get exposed to health care workers who may have the flu already but don’t know it.

In a recent poll, I was happy to see that the majority of physicians surveyed agreed with me: 65% said they supported mandatory flu vaccination in hospitals and only 23% said they did not. I think flu vaccination is something that has already been shown to be useful and important, not only in stopping people from getting the flu but also in making sure that they don’t get as sick when they get the flu.

Just like COVID-19 vaccination, it doesn’t always prevent somebody from getting infected, but if you get it, it keeps you from winding up sick at home, or worse – from dying and winding up in the morgue. Flu kills many, many people every year. We don’t want that to happen. A flu vaccine will really help prevent deaths, help prevent the number of symptoms that somebody gets, and will get people back to work. The benefits are pretty clear.

Does the flu vaccine work equally well every year? It does not. Some years, the strains that are picked for the vaccine don’t match the ones that circulate, and we don’t get as much protection as we hoped for. I think the safety side is so strong that it’s worth making the investment and the effort to promote mandatory flu vaccination.

Can you opt out on religious grounds? Well, some hospitals permit that at New York University. You have to go before a committee and make a case that your exemption on religious grounds is based on an authentic set of beliefs that are deeply held, and not just something you thought up the day before flu vaccine requirements went into effect.

There may be room for some exemptions – obviously, for health reasons. If people think that the flu vaccine is dangerous to them and can get a physician to agree and sign off that they are not appropriate to vaccinate, okay.

On the other hand, if you’re working with an especially vulnerable population – newborns, people who are immunosuppressed – then I think you’ve got to be vaccinated and you shouldn’t be working around people who are at huge risk of getting the flu if you refuse to be vaccinated or, for that matter, can’t be vaccinated.

Would I extend these mandates? Yes, I would. I’d extend them to COVID-19 vaccination and to measles vaccination. I think physicians and nurses should be good role models. They should get vaccinated. We know that the best available evidence says that vaccination for infectious disease is safe. It is really the best thing we can do to combat a variety of diseases such as the flu and COVID-19.

It seems to me that, in addition, the data that are out there in terms of risks from flu and COVID-19 – deaths in places like nursing homes – are overwhelming about the importance of trying to get staff vaccinated so they don’t bring flu into an institutionalized population. This is similar for prison health and many other settings where people are kept close together and staff may move from place to place, rotating from institution to institution, spreading infectious disease.

I’m going to go with the poll. Let’s keep pushing for health care workers to do the right thing and to be good role models. Let’s get everybody a flu vaccination. Let’s extend it to a COVID-19 vaccination and its boosters.

Let’s try to show the nation that health care is going to be guided by good science, a duty to one’s own health, and a duty to one’s patients. It shouldn’t be political. It should be based on what works best for the interests of health care providers and those they care for.

I’m Art Caplan at the New York University Grossman School of Medicine. Thanks for watching.
 

Dr. Caplan has disclosed the following relevant financial relationships: Served as a director, officer, partner, employee, advisor, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position). Serves as a contributing author and advisor for Medscape. A version of this article originally appeared on Medscape.com.

This transcript has been edited for clarity.

Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at New York University’s Grossman School of Medicine, where I’m the director.

It’s flu season, yet again. For many parts of the country, we’re already in the thick of it, and for other places, we’re going to have flu outbreaks continuing and intensifying. I’ve long believed that every health care institution – nursing homes, hospitals, clinics, home care, hospice – should require flu shots for all doctors and all nurses because it is the easiest, cheapest, and most ethical way to protect the workforce, who you need to be in there when flu outbreaks take place, and to protect patients against getting the flu when they come into hospital settings and get exposed to health care workers who may have the flu already but don’t know it.

In a recent poll, I was happy to see that the majority of physicians surveyed agreed with me: 65% said they supported mandatory flu vaccination in hospitals and only 23% said they did not. I think flu vaccination is something that has already been shown to be useful and important, not only in stopping people from getting the flu but also in making sure that they don’t get as sick when they get the flu.

Just like COVID-19 vaccination, it doesn’t always prevent somebody from getting infected, but if you get it, it keeps you from winding up sick at home, or worse – from dying and winding up in the morgue. Flu kills many, many people every year. We don’t want that to happen. A flu vaccine will really help prevent deaths, help prevent the number of symptoms that somebody gets, and will get people back to work. The benefits are pretty clear.

Does the flu vaccine work equally well every year? It does not. Some years, the strains that are picked for the vaccine don’t match the ones that circulate, and we don’t get as much protection as we hoped for. I think the safety side is so strong that it’s worth making the investment and the effort to promote mandatory flu vaccination.

Can you opt out on religious grounds? Well, some hospitals permit that at New York University. You have to go before a committee and make a case that your exemption on religious grounds is based on an authentic set of beliefs that are deeply held, and not just something you thought up the day before flu vaccine requirements went into effect.

There may be room for some exemptions – obviously, for health reasons. If people think that the flu vaccine is dangerous to them and can get a physician to agree and sign off that they are not appropriate to vaccinate, okay.

On the other hand, if you’re working with an especially vulnerable population – newborns, people who are immunosuppressed – then I think you’ve got to be vaccinated and you shouldn’t be working around people who are at huge risk of getting the flu if you refuse to be vaccinated or, for that matter, can’t be vaccinated.

Would I extend these mandates? Yes, I would. I’d extend them to COVID-19 vaccination and to measles vaccination. I think physicians and nurses should be good role models. They should get vaccinated. We know that the best available evidence says that vaccination for infectious disease is safe. It is really the best thing we can do to combat a variety of diseases such as the flu and COVID-19.

It seems to me that, in addition, the data that are out there in terms of risks from flu and COVID-19 – deaths in places like nursing homes – are overwhelming about the importance of trying to get staff vaccinated so they don’t bring flu into an institutionalized population. This is similar for prison health and many other settings where people are kept close together and staff may move from place to place, rotating from institution to institution, spreading infectious disease.

I’m going to go with the poll. Let’s keep pushing for health care workers to do the right thing and to be good role models. Let’s get everybody a flu vaccination. Let’s extend it to a COVID-19 vaccination and its boosters.

Let’s try to show the nation that health care is going to be guided by good science, a duty to one’s own health, and a duty to one’s patients. It shouldn’t be political. It should be based on what works best for the interests of health care providers and those they care for.

I’m Art Caplan at the New York University Grossman School of Medicine. Thanks for watching.
 

Dr. Caplan has disclosed the following relevant financial relationships: Served as a director, officer, partner, employee, advisor, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position). Serves as a contributing author and advisor for Medscape. A version of this article originally appeared on Medscape.com.

This transcript has been edited for clarity.

Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at New York University’s Grossman School of Medicine, where I’m the director.

It’s flu season, yet again. For many parts of the country, we’re already in the thick of it, and for other places, we’re going to have flu outbreaks continuing and intensifying. I’ve long believed that every health care institution – nursing homes, hospitals, clinics, home care, hospice – should require flu shots for all doctors and all nurses because it is the easiest, cheapest, and most ethical way to protect the workforce, who you need to be in there when flu outbreaks take place, and to protect patients against getting the flu when they come into hospital settings and get exposed to health care workers who may have the flu already but don’t know it.

In a recent poll, I was happy to see that the majority of physicians surveyed agreed with me: 65% said they supported mandatory flu vaccination in hospitals and only 23% said they did not. I think flu vaccination is something that has already been shown to be useful and important, not only in stopping people from getting the flu but also in making sure that they don’t get as sick when they get the flu.

Just like COVID-19 vaccination, it doesn’t always prevent somebody from getting infected, but if you get it, it keeps you from winding up sick at home, or worse – from dying and winding up in the morgue. Flu kills many, many people every year. We don’t want that to happen. A flu vaccine will really help prevent deaths, help prevent the number of symptoms that somebody gets, and will get people back to work. The benefits are pretty clear.

Does the flu vaccine work equally well every year? It does not. Some years, the strains that are picked for the vaccine don’t match the ones that circulate, and we don’t get as much protection as we hoped for. I think the safety side is so strong that it’s worth making the investment and the effort to promote mandatory flu vaccination.

Can you opt out on religious grounds? Well, some hospitals permit that at New York University. You have to go before a committee and make a case that your exemption on religious grounds is based on an authentic set of beliefs that are deeply held, and not just something you thought up the day before flu vaccine requirements went into effect.

There may be room for some exemptions – obviously, for health reasons. If people think that the flu vaccine is dangerous to them and can get a physician to agree and sign off that they are not appropriate to vaccinate, okay.

On the other hand, if you’re working with an especially vulnerable population – newborns, people who are immunosuppressed – then I think you’ve got to be vaccinated and you shouldn’t be working around people who are at huge risk of getting the flu if you refuse to be vaccinated or, for that matter, can’t be vaccinated.

Would I extend these mandates? Yes, I would. I’d extend them to COVID-19 vaccination and to measles vaccination. I think physicians and nurses should be good role models. They should get vaccinated. We know that the best available evidence says that vaccination for infectious disease is safe. It is really the best thing we can do to combat a variety of diseases such as the flu and COVID-19.

It seems to me that, in addition, the data that are out there in terms of risks from flu and COVID-19 – deaths in places like nursing homes – are overwhelming about the importance of trying to get staff vaccinated so they don’t bring flu into an institutionalized population. This is similar for prison health and many other settings where people are kept close together and staff may move from place to place, rotating from institution to institution, spreading infectious disease.

I’m going to go with the poll. Let’s keep pushing for health care workers to do the right thing and to be good role models. Let’s get everybody a flu vaccination. Let’s extend it to a COVID-19 vaccination and its boosters.

Let’s try to show the nation that health care is going to be guided by good science, a duty to one’s own health, and a duty to one’s patients. It shouldn’t be political. It should be based on what works best for the interests of health care providers and those they care for.

I’m Art Caplan at the New York University Grossman School of Medicine. Thanks for watching.
 

Dr. Caplan has disclosed the following relevant financial relationships: Served as a director, officer, partner, employee, advisor, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position). Serves as a contributing author and advisor for Medscape. A version of this article originally appeared on Medscape.com.

A real-world analysis shows “meaningful” overall survival benefits when a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor is added to endocrine therapy for older women with hormone receptor (HR)–positive/HER2-negative metastatic breast cancer (MBC).

Three years after starting first-line treatment, overall survival rates were 49% with endocrine therapy alone versus 73% with endocrine therapy plus a CDK4/6 inhibitor – findings largely consistent with clinical trial data.

Treatment with endocrine therapy alone “should have a limited role in early lines of therapy for patients with HR-positive/HER2-negative MBC,” the researchers concluded.

The study was published online in the journal Cancer.

The Food and Drug Administration has approved the CDK4/6 inhibitors palbociclib, abemaciclib, and ribociclib for HR-positive/HER2-negative MBC in first and advanced therapy lines. The approval was based on phase 3, randomized, controlled trial data.

Yet gaps in evidence remain regarding survival outcomes in real-world settings for patients starting treatment with a CDK4/6 inhibitor, particularly for patients aged 65 and older, who typically aren’t included in randomized clinical trials.

To address these gaps, Ravi Goyal, PhD, with the University of Houston, and colleagues conducted a retrospective cohort study using the Survey Epidemiology and End Results Medicare database.

Dr. Goyal and coauthors identified 630 Medicare patients with HR-positive/HER2-negative MBC for whom first-line treatment was initiated within 12 months of diagnosis. Patients received either endocrine therapy alone (461 patients) or endocrine therapy plus a CDK4/6 inhibitor (169 patients), most commonly palbociclib.

The median duration of follow-up from the start of treatment was 24 months in the endocrine therapy–alone group and 30 months in the combination therapy group.

In a Kaplan-Meier analysis, the overall survival rate at 3 years after starting first-line treatment was 73% for the combination therapy group versus49% for the endocrine therapy group (P < .0001). Median overall survival from first-line therapy was not estimable in the endocrine therapy plus CDK4/6 inhibitor group; it was 34.8 months in the endocrine therapy–only group.

In multivariable Cox regression models, first-line dual therapy was independently associated with 41% lower rate of death in comparison with endocrine therapy alone (adjusted hazard ratio, 0.59).

Dr. Goyal and colleagues also performed a separate analysis of 206 patients for whom treatment was initiated in the second line; 88 received endocrine therapy alone, and 118 received endocrine therapy plus CDK4/6 inhibitor therapy.

In this setting, a similar benefit of dual therapy was observed. The 3-year overall survival rate was 68% for the combination group versus 50% for endocrine therapy alone (P = .0051). Median overall survival with second-line therapy was not estimable for the combination group; it was 30.9 months for the endocrine therapy group.

In the second line, multivariable Cox regression analysis showed that combination therapy was associated with a nearly 58% lower rate of death in comparison with endocrine therapy alone (aHR, 0.42).

The coauthors of an editorial in Cancer explain that the combination of a CDK4/6 inhibitor and endocrine therapy has become the “preferred first-line approach” in the management of HR-positive/HER2-negative MBC.

Dario Trapani, MD, and Erica Mayer, MD, with Dana-Farber Cancer Institute, Boston, noted that an overall survival benefit of similar magnitude from endocrine therapy plus a CDK4/6 inhibitor has also been reported in a recent real-world study of palbociclib and letrozole.

The work of Dr. Goyal and colleagues provides “confirmatory real-world evidence observed in clinical trials for endocrine sensitive, de novo, metastatic [breast cancer] in an older population,” Dr. Trapani and Dr. Mayer wrote.

The study had no specific funding. The authors and Dr. Trapani disclosed no relevant financial relaitonships. Dr. Mayer has consulted for Lilly, Novartis, Gilead, AstraZeneca, and Diaccurate.

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

A real-world analysis shows “meaningful” overall survival benefits when a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor is added to endocrine therapy for older women with hormone receptor (HR)–positive/HER2-negative metastatic breast cancer (MBC).

Three years after starting first-line treatment, overall survival rates were 49% with endocrine therapy alone versus 73% with endocrine therapy plus a CDK4/6 inhibitor – findings largely consistent with clinical trial data.

Treatment with endocrine therapy alone “should have a limited role in early lines of therapy for patients with HR-positive/HER2-negative MBC,” the researchers concluded.

The study was published online in the journal Cancer.

The Food and Drug Administration has approved the CDK4/6 inhibitors palbociclib, abemaciclib, and ribociclib for HR-positive/HER2-negative MBC in first and advanced therapy lines. The approval was based on phase 3, randomized, controlled trial data.

Yet gaps in evidence remain regarding survival outcomes in real-world settings for patients starting treatment with a CDK4/6 inhibitor, particularly for patients aged 65 and older, who typically aren’t included in randomized clinical trials.

To address these gaps, Ravi Goyal, PhD, with the University of Houston, and colleagues conducted a retrospective cohort study using the Survey Epidemiology and End Results Medicare database.

Dr. Goyal and coauthors identified 630 Medicare patients with HR-positive/HER2-negative MBC for whom first-line treatment was initiated within 12 months of diagnosis. Patients received either endocrine therapy alone (461 patients) or endocrine therapy plus a CDK4/6 inhibitor (169 patients), most commonly palbociclib.

The median duration of follow-up from the start of treatment was 24 months in the endocrine therapy–alone group and 30 months in the combination therapy group.

In a Kaplan-Meier analysis, the overall survival rate at 3 years after starting first-line treatment was 73% for the combination therapy group versus49% for the endocrine therapy group (P < .0001). Median overall survival from first-line therapy was not estimable in the endocrine therapy plus CDK4/6 inhibitor group; it was 34.8 months in the endocrine therapy–only group.

In multivariable Cox regression models, first-line dual therapy was independently associated with 41% lower rate of death in comparison with endocrine therapy alone (adjusted hazard ratio, 0.59).

Dr. Goyal and colleagues also performed a separate analysis of 206 patients for whom treatment was initiated in the second line; 88 received endocrine therapy alone, and 118 received endocrine therapy plus CDK4/6 inhibitor therapy.

In this setting, a similar benefit of dual therapy was observed. The 3-year overall survival rate was 68% for the combination group versus 50% for endocrine therapy alone (P = .0051). Median overall survival with second-line therapy was not estimable for the combination group; it was 30.9 months for the endocrine therapy group.

In the second line, multivariable Cox regression analysis showed that combination therapy was associated with a nearly 58% lower rate of death in comparison with endocrine therapy alone (aHR, 0.42).

The coauthors of an editorial in Cancer explain that the combination of a CDK4/6 inhibitor and endocrine therapy has become the “preferred first-line approach” in the management of HR-positive/HER2-negative MBC.

Dario Trapani, MD, and Erica Mayer, MD, with Dana-Farber Cancer Institute, Boston, noted that an overall survival benefit of similar magnitude from endocrine therapy plus a CDK4/6 inhibitor has also been reported in a recent real-world study of palbociclib and letrozole.

The work of Dr. Goyal and colleagues provides “confirmatory real-world evidence observed in clinical trials for endocrine sensitive, de novo, metastatic [breast cancer] in an older population,” Dr. Trapani and Dr. Mayer wrote.

The study had no specific funding. The authors and Dr. Trapani disclosed no relevant financial relaitonships. Dr. Mayer has consulted for Lilly, Novartis, Gilead, AstraZeneca, and Diaccurate.

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

A real-world analysis shows “meaningful” overall survival benefits when a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor is added to endocrine therapy for older women with hormone receptor (HR)–positive/HER2-negative metastatic breast cancer (MBC).

Three years after starting first-line treatment, overall survival rates were 49% with endocrine therapy alone versus 73% with endocrine therapy plus a CDK4/6 inhibitor – findings largely consistent with clinical trial data.

Treatment with endocrine therapy alone “should have a limited role in early lines of therapy for patients with HR-positive/HER2-negative MBC,” the researchers concluded.

The study was published online in the journal Cancer.

The Food and Drug Administration has approved the CDK4/6 inhibitors palbociclib, abemaciclib, and ribociclib for HR-positive/HER2-negative MBC in first and advanced therapy lines. The approval was based on phase 3, randomized, controlled trial data.

Yet gaps in evidence remain regarding survival outcomes in real-world settings for patients starting treatment with a CDK4/6 inhibitor, particularly for patients aged 65 and older, who typically aren’t included in randomized clinical trials.

To address these gaps, Ravi Goyal, PhD, with the University of Houston, and colleagues conducted a retrospective cohort study using the Survey Epidemiology and End Results Medicare database.

Dr. Goyal and coauthors identified 630 Medicare patients with HR-positive/HER2-negative MBC for whom first-line treatment was initiated within 12 months of diagnosis. Patients received either endocrine therapy alone (461 patients) or endocrine therapy plus a CDK4/6 inhibitor (169 patients), most commonly palbociclib.

The median duration of follow-up from the start of treatment was 24 months in the endocrine therapy–alone group and 30 months in the combination therapy group.

In a Kaplan-Meier analysis, the overall survival rate at 3 years after starting first-line treatment was 73% for the combination therapy group versus49% for the endocrine therapy group (P < .0001). Median overall survival from first-line therapy was not estimable in the endocrine therapy plus CDK4/6 inhibitor group; it was 34.8 months in the endocrine therapy–only group.

In multivariable Cox regression models, first-line dual therapy was independently associated with 41% lower rate of death in comparison with endocrine therapy alone (adjusted hazard ratio, 0.59).

Dr. Goyal and colleagues also performed a separate analysis of 206 patients for whom treatment was initiated in the second line; 88 received endocrine therapy alone, and 118 received endocrine therapy plus CDK4/6 inhibitor therapy.

In this setting, a similar benefit of dual therapy was observed. The 3-year overall survival rate was 68% for the combination group versus 50% for endocrine therapy alone (P = .0051). Median overall survival with second-line therapy was not estimable for the combination group; it was 30.9 months for the endocrine therapy group.

In the second line, multivariable Cox regression analysis showed that combination therapy was associated with a nearly 58% lower rate of death in comparison with endocrine therapy alone (aHR, 0.42).

The coauthors of an editorial in Cancer explain that the combination of a CDK4/6 inhibitor and endocrine therapy has become the “preferred first-line approach” in the management of HR-positive/HER2-negative MBC.

Dario Trapani, MD, and Erica Mayer, MD, with Dana-Farber Cancer Institute, Boston, noted that an overall survival benefit of similar magnitude from endocrine therapy plus a CDK4/6 inhibitor has also been reported in a recent real-world study of palbociclib and letrozole.

The work of Dr. Goyal and colleagues provides “confirmatory real-world evidence observed in clinical trials for endocrine sensitive, de novo, metastatic [breast cancer] in an older population,” Dr. Trapani and Dr. Mayer wrote.

The study had no specific funding. The authors and Dr. Trapani disclosed no relevant financial relaitonships. Dr. Mayer has consulted for Lilly, Novartis, Gilead, AstraZeneca, and Diaccurate.

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

Advanced imaging technology that uses artificial intelligence can potentially predict which patients with lung cancer are likely to experience cancer progression after surgery, according to new data.

The technology, known as highly multiplexed imaging mass cytometry (IMC), can provide cellular-level detail of the tumor immune microenvironment, which may allow clinicians to identify patients who need additional treatment, as well as those who don’t.

“It is well known that the frequency of certain cell populations within the tumor microenvironment correlates with clinical outcomes. These observations help us understand the biology underlying cancer progression,” senior author Logan Walsh, PhD, assistant professor of human genetics and the Rosalind Goodman Chair in Lung Cancer Research at McGill University’s Rosalind and Morris Goodman Cancer Institute, Montreal, said in an interview.

“We wanted to test whether using completely unbiased AI could find and use the spatial topography of the tumor microenvironment from IMC data to predict clinical outcomes,” he said. “It turns out the answer is yes! AI can predict clinical outcomes when combined with IMC with extremely high accuracy from a single 1-mm² tumor core.”

The study was published on in Nature.
 

The immune landscape

Lung cancer is the leading cause of cancer-related death in Canada, surpassing breast, colon, and prostate cancer deaths combined, the study authors write.

Lung adenocarcinoma, a non–small cell lung cancer, is the most common subtype and is characterized by distinct cellular and molecular features. The tumor immune microenvironment influences disease progression and therapy response, the authors write. Understanding the spatial landscape of the microenvironment could provide insight into disease progression, therapeutic vulnerabilities, and biomarkers of response to existing treatments.

In a collaborative study, Dr. Walsh and colleagues from McGill University and Université Laval profiled the cellular composition and spatial organization of the tumor immune microenvironment in tumors from 416 patients with lung adenocarcinoma across five histologic patterns. They used IMC to assess at samples from the universities’ biobanks that patients had provided for research purposes.

The research team detected more than 1.6 million cells, which allowed spatial analysis of immune lineages and activation states with distinct clinical correlates, including survival. They used a supervised lineage assignment approach to classify 14 distinct immune cell populations, along with tumor cells and endothelial cells.

High-grade solid tumors had the greatest immune infiltrate (44.6%), compared with micropapillary (37%), acinar (39.7%), papillary (32.8%), and lepidic architectures (32.7%). Macrophages were the most frequent cell population in the tumor immune microenvironment, representing 12.3% of total cells and 34.1% of immune cells.

The prevalence of CD163+ macrophages was strongly correlated with FOXP3+ immunoregulatory T cells in the solid pattern. This relationship was less pronounced in low-grade lepidic and papillary architectures. This finding could suggest an interplay between macrophage and T-cell populations in the tumor immune microenvironment across lung adenocarcinoma patterns.

Using a deep neural network model, the researchers also analyzed the relationship between immune populations and clinical or pathologic variables by examining the frequency of individual cell types as a percentage of total cells in each image. Each image was cross-referenced with clinical data from patients, including sex, age, body mass index, smoking status, stage, progression, survival, and histologic subtype.

Overall, the researchers found that various clinical outcomes, including cancer progression, could be predicted with high accuracy using a single 1-mm² tumor core. For instance, they could predict progression in stage IA and IB resected lung cancer with 95.9% accuracy.
 

Additional applications

“We were not surprised that AI was able to predict clinical outcomes, but we were surprised that it was able to do so with such high accuracy and precision,” said Dr. Walsh. “We were also surprised to learn that our predictions were equally accurate using only six-plex data, compared with 35-plex. This hinted to us that we could potentially scale down the number of markers to a practical number that would be amenable to technologies available in routine pathology labs.”

Dr. Walsh and colleagues are now validating the predictive tool using a lower-plex technology. In addition, they are investigating the immune landscapes of primary and metastatic brain tumors.

“This study is important, as it helps us to understand and appreciate the biological and mechanistic factors that may influence treatment outcomes. Our standard clinical predictors for predicting risk of recurrence and probability of response to therapy are not optimal,” Yee Ung, MD, an associate professor of radiation oncology at Sunnybrook Health Sciences Centre, Toronto, said in an interview.

Dr. Ung, who wasn’t involved with this study, has researched noninvasive hypoxia imaging and targeting in lung cancer. Ideally, he said, future studies should incorporate the use of noninvasive imaging predictive factors, in addition to the tumor immune microenvironment and clinical factors, to predict outcomes and provide personalized treatment.

“As we begin to investigate and understand more about cancer biology down to the cellular and molecular level, we need to strategically use AI methodologies in the processing and analysis of data,” he said.

The study was supported by the McGill Interdisciplinary Initiative in Infection and Immunity, the Brain Tumour Funders’ Collaborative, the Canadian Institutes of Health Research, and the Canadian Foundation for Innovation. Dr. Walsh and Dr. Ung have disclosed no relevant financial relationships.

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

Advanced imaging technology that uses artificial intelligence can potentially predict which patients with lung cancer are likely to experience cancer progression after surgery, according to new data.

The technology, known as highly multiplexed imaging mass cytometry (IMC), can provide cellular-level detail of the tumor immune microenvironment, which may allow clinicians to identify patients who need additional treatment, as well as those who don’t.

“It is well known that the frequency of certain cell populations within the tumor microenvironment correlates with clinical outcomes. These observations help us understand the biology underlying cancer progression,” senior author Logan Walsh, PhD, assistant professor of human genetics and the Rosalind Goodman Chair in Lung Cancer Research at McGill University’s Rosalind and Morris Goodman Cancer Institute, Montreal, said in an interview.

“We wanted to test whether using completely unbiased AI could find and use the spatial topography of the tumor microenvironment from IMC data to predict clinical outcomes,” he said. “It turns out the answer is yes! AI can predict clinical outcomes when combined with IMC with extremely high accuracy from a single 1-mm² tumor core.”

The study was published on in Nature.
 

The immune landscape

Lung cancer is the leading cause of cancer-related death in Canada, surpassing breast, colon, and prostate cancer deaths combined, the study authors write.

Lung adenocarcinoma, a non–small cell lung cancer, is the most common subtype and is characterized by distinct cellular and molecular features. The tumor immune microenvironment influences disease progression and therapy response, the authors write. Understanding the spatial landscape of the microenvironment could provide insight into disease progression, therapeutic vulnerabilities, and biomarkers of response to existing treatments.

In a collaborative study, Dr. Walsh and colleagues from McGill University and Université Laval profiled the cellular composition and spatial organization of the tumor immune microenvironment in tumors from 416 patients with lung adenocarcinoma across five histologic patterns. They used IMC to assess at samples from the universities’ biobanks that patients had provided for research purposes.

The research team detected more than 1.6 million cells, which allowed spatial analysis of immune lineages and activation states with distinct clinical correlates, including survival. They used a supervised lineage assignment approach to classify 14 distinct immune cell populations, along with tumor cells and endothelial cells.

High-grade solid tumors had the greatest immune infiltrate (44.6%), compared with micropapillary (37%), acinar (39.7%), papillary (32.8%), and lepidic architectures (32.7%). Macrophages were the most frequent cell population in the tumor immune microenvironment, representing 12.3% of total cells and 34.1% of immune cells.

The prevalence of CD163+ macrophages was strongly correlated with FOXP3+ immunoregulatory T cells in the solid pattern. This relationship was less pronounced in low-grade lepidic and papillary architectures. This finding could suggest an interplay between macrophage and T-cell populations in the tumor immune microenvironment across lung adenocarcinoma patterns.

Using a deep neural network model, the researchers also analyzed the relationship between immune populations and clinical or pathologic variables by examining the frequency of individual cell types as a percentage of total cells in each image. Each image was cross-referenced with clinical data from patients, including sex, age, body mass index, smoking status, stage, progression, survival, and histologic subtype.

Overall, the researchers found that various clinical outcomes, including cancer progression, could be predicted with high accuracy using a single 1-mm² tumor core. For instance, they could predict progression in stage IA and IB resected lung cancer with 95.9% accuracy.
 

Additional applications

“We were not surprised that AI was able to predict clinical outcomes, but we were surprised that it was able to do so with such high accuracy and precision,” said Dr. Walsh. “We were also surprised to learn that our predictions were equally accurate using only six-plex data, compared with 35-plex. This hinted to us that we could potentially scale down the number of markers to a practical number that would be amenable to technologies available in routine pathology labs.”

Dr. Walsh and colleagues are now validating the predictive tool using a lower-plex technology. In addition, they are investigating the immune landscapes of primary and metastatic brain tumors.

“This study is important, as it helps us to understand and appreciate the biological and mechanistic factors that may influence treatment outcomes. Our standard clinical predictors for predicting risk of recurrence and probability of response to therapy are not optimal,” Yee Ung, MD, an associate professor of radiation oncology at Sunnybrook Health Sciences Centre, Toronto, said in an interview.

Dr. Ung, who wasn’t involved with this study, has researched noninvasive hypoxia imaging and targeting in lung cancer. Ideally, he said, future studies should incorporate the use of noninvasive imaging predictive factors, in addition to the tumor immune microenvironment and clinical factors, to predict outcomes and provide personalized treatment.

“As we begin to investigate and understand more about cancer biology down to the cellular and molecular level, we need to strategically use AI methodologies in the processing and analysis of data,” he said.

The study was supported by the McGill Interdisciplinary Initiative in Infection and Immunity, the Brain Tumour Funders’ Collaborative, the Canadian Institutes of Health Research, and the Canadian Foundation for Innovation. Dr. Walsh and Dr. Ung have disclosed no relevant financial relationships.

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

Advanced imaging technology that uses artificial intelligence can potentially predict which patients with lung cancer are likely to experience cancer progression after surgery, according to new data.

The technology, known as highly multiplexed imaging mass cytometry (IMC), can provide cellular-level detail of the tumor immune microenvironment, which may allow clinicians to identify patients who need additional treatment, as well as those who don’t.

“It is well known that the frequency of certain cell populations within the tumor microenvironment correlates with clinical outcomes. These observations help us understand the biology underlying cancer progression,” senior author Logan Walsh, PhD, assistant professor of human genetics and the Rosalind Goodman Chair in Lung Cancer Research at McGill University’s Rosalind and Morris Goodman Cancer Institute, Montreal, said in an interview.

“We wanted to test whether using completely unbiased AI could find and use the spatial topography of the tumor microenvironment from IMC data to predict clinical outcomes,” he said. “It turns out the answer is yes! AI can predict clinical outcomes when combined with IMC with extremely high accuracy from a single 1-mm² tumor core.”

The study was published on in Nature.
 

The immune landscape

Lung cancer is the leading cause of cancer-related death in Canada, surpassing breast, colon, and prostate cancer deaths combined, the study authors write.

Lung adenocarcinoma, a non–small cell lung cancer, is the most common subtype and is characterized by distinct cellular and molecular features. The tumor immune microenvironment influences disease progression and therapy response, the authors write. Understanding the spatial landscape of the microenvironment could provide insight into disease progression, therapeutic vulnerabilities, and biomarkers of response to existing treatments.

In a collaborative study, Dr. Walsh and colleagues from McGill University and Université Laval profiled the cellular composition and spatial organization of the tumor immune microenvironment in tumors from 416 patients with lung adenocarcinoma across five histologic patterns. They used IMC to assess at samples from the universities’ biobanks that patients had provided for research purposes.

The research team detected more than 1.6 million cells, which allowed spatial analysis of immune lineages and activation states with distinct clinical correlates, including survival. They used a supervised lineage assignment approach to classify 14 distinct immune cell populations, along with tumor cells and endothelial cells.

High-grade solid tumors had the greatest immune infiltrate (44.6%), compared with micropapillary (37%), acinar (39.7%), papillary (32.8%), and lepidic architectures (32.7%). Macrophages were the most frequent cell population in the tumor immune microenvironment, representing 12.3% of total cells and 34.1% of immune cells.

The prevalence of CD163+ macrophages was strongly correlated with FOXP3+ immunoregulatory T cells in the solid pattern. This relationship was less pronounced in low-grade lepidic and papillary architectures. This finding could suggest an interplay between macrophage and T-cell populations in the tumor immune microenvironment across lung adenocarcinoma patterns.

Using a deep neural network model, the researchers also analyzed the relationship between immune populations and clinical or pathologic variables by examining the frequency of individual cell types as a percentage of total cells in each image. Each image was cross-referenced with clinical data from patients, including sex, age, body mass index, smoking status, stage, progression, survival, and histologic subtype.

Overall, the researchers found that various clinical outcomes, including cancer progression, could be predicted with high accuracy using a single 1-mm² tumor core. For instance, they could predict progression in stage IA and IB resected lung cancer with 95.9% accuracy.
 

Additional applications

“We were not surprised that AI was able to predict clinical outcomes, but we were surprised that it was able to do so with such high accuracy and precision,” said Dr. Walsh. “We were also surprised to learn that our predictions were equally accurate using only six-plex data, compared with 35-plex. This hinted to us that we could potentially scale down the number of markers to a practical number that would be amenable to technologies available in routine pathology labs.”

Dr. Walsh and colleagues are now validating the predictive tool using a lower-plex technology. In addition, they are investigating the immune landscapes of primary and metastatic brain tumors.

“This study is important, as it helps us to understand and appreciate the biological and mechanistic factors that may influence treatment outcomes. Our standard clinical predictors for predicting risk of recurrence and probability of response to therapy are not optimal,” Yee Ung, MD, an associate professor of radiation oncology at Sunnybrook Health Sciences Centre, Toronto, said in an interview.

Dr. Ung, who wasn’t involved with this study, has researched noninvasive hypoxia imaging and targeting in lung cancer. Ideally, he said, future studies should incorporate the use of noninvasive imaging predictive factors, in addition to the tumor immune microenvironment and clinical factors, to predict outcomes and provide personalized treatment.

“As we begin to investigate and understand more about cancer biology down to the cellular and molecular level, we need to strategically use AI methodologies in the processing and analysis of data,” he said.

The study was supported by the McGill Interdisciplinary Initiative in Infection and Immunity, the Brain Tumour Funders’ Collaborative, the Canadian Institutes of Health Research, and the Canadian Foundation for Innovation. Dr. Walsh and Dr. Ung have disclosed no relevant financial relationships.

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

This transcript has been edited for clarity.

I’m Mark Kris from Memorial Sloan Kettering, speaking today about a topic that’s become quite controversial, which is the use of postoperative radiation therapy (PORT) in patients who have complete resections of lung cancers and who show evidence of spread to mediastinal lymph nodes, so-called N2 disease.

Data from clinical trials and data from a SEER study showed approximately 7% improvement in overall survival in patients with N2 disease who received PORT. There has been a very clear demonstration of an improved local control rate in every trial that’s ever looked at PORT.

However, there was a randomized trial, the Lung ART trial, where patients were randomized to get PORT or not. PORT was delivered in a way that is not routinely used now. In that trial, the benefit of PORT was found in terms of local control, almost doubling control within the mediastinum.

The difference in overall survival was less than 12%. Again, I’m not surprised to see that because the improvement in overall survival is probably somewhere between 5% and 10%. They also found an excess of deaths, probably due to cardiac causes from the radiation in the radiation arm.

However, the trial used a type of radiation not used at this point – it used conformal, but now we would use 3D. And its ability at the time of the trial to estimate and lower cardiac risk was not what it is today. Owing to the design of the trial, it was not a significant difference and has largely been interpreted as saying that the PORT doesn’t work.

First, let’s please go to the guidelines. I’m going to the ASCO guidelines, which say that patients with mediastinal disease should not routinely get PORT, but they should be routinely referred to a radiation oncologist for consideration of PORT. I don’t think anything that’s been published so far changes that.

I think each case needs to be individualized and requires the specialty care of a radiation oncologist to weigh the pros and cons of PORT. It also depends upon the treatment plan. Can the heart be spared? Are there radiation techniques available that would eliminate or lessen heart exposure, such as using protons? The point is that PORT is still needed.

When we look at the trials of patients receiving adjuvant therapy – and I’m looking particularly at the ADAURA trial where patients received adjuvant osimertinib – the greatest number of failures now is in the chest. We have to look for good ways to cut down on failure in the chest. Unfortunately, failure in the chest means ultimately failure and lack of cure, and we have to do a better job at that. I think PORT can play a role there.

Please, when you have patients with N2 disease, after the completion of systemic therapies, think about the use of PORT and get the advice of a radiation oncologist to meet with the patient, review their clinical situation, and assess whether or not PORT could be useful for that patient.

That is following the NCCN guidelines, which were not changed on the basis of the Lung ART paper. I think we owe it to our patients to make sure that those who could benefit from this additional therapy receive it.

I’ll put it to you that radiation delivered in the most innovative way – taking very careful account of the effects on the heart – can improve local control. There’s no question about that. I think PORT has the ability to improve survival by a small amount – probably less than 12%, which I will agree the Lung ART trial showed – but still an important amount for patients with this condition.

Mark G. Kris, MD, is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York City. He reported conflicts of interest with Arial Pharmaceuticals, Pfizer, PUMA, and Roche/Genentech. A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

I’m Mark Kris from Memorial Sloan Kettering, speaking today about a topic that’s become quite controversial, which is the use of postoperative radiation therapy (PORT) in patients who have complete resections of lung cancers and who show evidence of spread to mediastinal lymph nodes, so-called N2 disease.

Data from clinical trials and data from a SEER study showed approximately 7% improvement in overall survival in patients with N2 disease who received PORT. There has been a very clear demonstration of an improved local control rate in every trial that’s ever looked at PORT.

However, there was a randomized trial, the Lung ART trial, where patients were randomized to get PORT or not. PORT was delivered in a way that is not routinely used now. In that trial, the benefit of PORT was found in terms of local control, almost doubling control within the mediastinum.

The difference in overall survival was less than 12%. Again, I’m not surprised to see that because the improvement in overall survival is probably somewhere between 5% and 10%. They also found an excess of deaths, probably due to cardiac causes from the radiation in the radiation arm.

However, the trial used a type of radiation not used at this point – it used conformal, but now we would use 3D. And its ability at the time of the trial to estimate and lower cardiac risk was not what it is today. Owing to the design of the trial, it was not a significant difference and has largely been interpreted as saying that the PORT doesn’t work.

First, let’s please go to the guidelines. I’m going to the ASCO guidelines, which say that patients with mediastinal disease should not routinely get PORT, but they should be routinely referred to a radiation oncologist for consideration of PORT. I don’t think anything that’s been published so far changes that.

I think each case needs to be individualized and requires the specialty care of a radiation oncologist to weigh the pros and cons of PORT. It also depends upon the treatment plan. Can the heart be spared? Are there radiation techniques available that would eliminate or lessen heart exposure, such as using protons? The point is that PORT is still needed.

When we look at the trials of patients receiving adjuvant therapy – and I’m looking particularly at the ADAURA trial where patients received adjuvant osimertinib – the greatest number of failures now is in the chest. We have to look for good ways to cut down on failure in the chest. Unfortunately, failure in the chest means ultimately failure and lack of cure, and we have to do a better job at that. I think PORT can play a role there.

Please, when you have patients with N2 disease, after the completion of systemic therapies, think about the use of PORT and get the advice of a radiation oncologist to meet with the patient, review their clinical situation, and assess whether or not PORT could be useful for that patient.

That is following the NCCN guidelines, which were not changed on the basis of the Lung ART paper. I think we owe it to our patients to make sure that those who could benefit from this additional therapy receive it.

I’ll put it to you that radiation delivered in the most innovative way – taking very careful account of the effects on the heart – can improve local control. There’s no question about that. I think PORT has the ability to improve survival by a small amount – probably less than 12%, which I will agree the Lung ART trial showed – but still an important amount for patients with this condition.

Mark G. Kris, MD, is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York City. He reported conflicts of interest with Arial Pharmaceuticals, Pfizer, PUMA, and Roche/Genentech. A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

I’m Mark Kris from Memorial Sloan Kettering, speaking today about a topic that’s become quite controversial, which is the use of postoperative radiation therapy (PORT) in patients who have complete resections of lung cancers and who show evidence of spread to mediastinal lymph nodes, so-called N2 disease.

Data from clinical trials and data from a SEER study showed approximately 7% improvement in overall survival in patients with N2 disease who received PORT. There has been a very clear demonstration of an improved local control rate in every trial that’s ever looked at PORT.

However, there was a randomized trial, the Lung ART trial, where patients were randomized to get PORT or not. PORT was delivered in a way that is not routinely used now. In that trial, the benefit of PORT was found in terms of local control, almost doubling control within the mediastinum.

The difference in overall survival was less than 12%. Again, I’m not surprised to see that because the improvement in overall survival is probably somewhere between 5% and 10%. They also found an excess of deaths, probably due to cardiac causes from the radiation in the radiation arm.

However, the trial used a type of radiation not used at this point – it used conformal, but now we would use 3D. And its ability at the time of the trial to estimate and lower cardiac risk was not what it is today. Owing to the design of the trial, it was not a significant difference and has largely been interpreted as saying that the PORT doesn’t work.

First, let’s please go to the guidelines. I’m going to the ASCO guidelines, which say that patients with mediastinal disease should not routinely get PORT, but they should be routinely referred to a radiation oncologist for consideration of PORT. I don’t think anything that’s been published so far changes that.

I think each case needs to be individualized and requires the specialty care of a radiation oncologist to weigh the pros and cons of PORT. It also depends upon the treatment plan. Can the heart be spared? Are there radiation techniques available that would eliminate or lessen heart exposure, such as using protons? The point is that PORT is still needed.

When we look at the trials of patients receiving adjuvant therapy – and I’m looking particularly at the ADAURA trial where patients received adjuvant osimertinib – the greatest number of failures now is in the chest. We have to look for good ways to cut down on failure in the chest. Unfortunately, failure in the chest means ultimately failure and lack of cure, and we have to do a better job at that. I think PORT can play a role there.

Please, when you have patients with N2 disease, after the completion of systemic therapies, think about the use of PORT and get the advice of a radiation oncologist to meet with the patient, review their clinical situation, and assess whether or not PORT could be useful for that patient.

That is following the NCCN guidelines, which were not changed on the basis of the Lung ART paper. I think we owe it to our patients to make sure that those who could benefit from this additional therapy receive it.

I’ll put it to you that radiation delivered in the most innovative way – taking very careful account of the effects on the heart – can improve local control. There’s no question about that. I think PORT has the ability to improve survival by a small amount – probably less than 12%, which I will agree the Lung ART trial showed – but still an important amount for patients with this condition.

Mark G. Kris, MD, is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York City. He reported conflicts of interest with Arial Pharmaceuticals, Pfizer, PUMA, and Roche/Genentech. A version of this article first appeared on Medscape.com.

A number of new studies in lung cancer have started in recent months. Could one of your patients benefit from participating?

Untreated advanced non–small cell lung cancer (NSCLC). Adult patients with stage IIIB, IIIC, or IV disease without actionable genomic alterations can join a randomized, open-label, phase 3 study testing the survival advantage of datopotamab deruxtecan (Dato-DXd) (AstraZeneca/Daiichi Sankyo). Dato-DXd is one of a half dozen experimental antibody-drug conjugates that target TROP2, a transmembrane glycoprotein that is overexpressed in several solid tumors, including NSCLC. One group of participants will receive an intravenous (IV) infusion of Dato-DXd plus durvalumab (Imfinzi) for up to 4 years, and over the first 12 weeks, they will receive four rounds of IV carboplatin (Paraplatin). The other group will receive IV infusions of pembrolizumab (Keytruda) every 3 weeks plus a combination of standard IV chemotherapy appropriate for the patient’s histology (nonsquamous or squamous NSCLC). In the United States, centers in Arkansas, Nebraska, Ohio, and Texas started recruiting in December 2020; trial sites are planned in 16 other states and 23 other countries. The trialists plan to enroll 1,000 participants. Overall survival (OS) and progression-free survival (PFS) are the primary endpoints; quality of life (QoL) is not being tracked. More details at clinicaltrials.gov.

Untreated advanced or metastatic NSCLC. Adult patients in this clinical situation without actionable genomic alterations as well as those with a PD-L1 tumor proportion score (TPS) of < 50% are eligible to participate in a randomized, open-label, phase 3 trial of Dato-DXd in combination with pembrolizumab, with or without chemotherapy. One group of participants will receive IV Dato-DXd and pembrolizumab every 3 weeks. For the second group of patients, IV platinum chemotherapy will be added to the Dato-DXd and pembrolizumab for the first four rounds of treatment. The third group of individuals make up the comparator arm and will receive thrice-weekly IV pembrolizumab, pemetrexed (Alimta), plus platinum chemotherapy. All participants will be treated for approximately 2.5 years or until disease progression or death. The trial began recruiting 975 participants in Arizona, Florida, Maryland, and New Jersey, and in Japan in January 2023. The primary endpoints are OS and PFS; QoL will not be assessed. More details at clinicaltrials.gov.

Metastatic NSCLC. Individuals with this cancer who have a TPS of > 50% can also receive an antibody-drug conjugate targeting TROP2 in combination with pembrolizumab. This time, the product is sacituzumab govitecan (Trodelvy). The randomized, open-label phase 3 trial is testing whether the two drugs in combination improve survival and slow progression better than pembrolizumab alone. For approximately 2 years, one group of people in the trial will receive IV pembrolizumab every 3 weeks. The other group, in addition to the pembrolizumab, will receive IV sacituzumab govitecan weekly for 2 weeks then 1 week off until unacceptable toxicity, disease progression, withdrawal of consent, or death. Study sites in the states of Florida and Georgia, and in Australia, Taiwan, and Turkey, opened in February 2023 with the aim of recruiting 614 participants. Overall survival over 4 years and PFS are the primary outcomes. QoL is a secondary outcome. More details at clinicaltrials.gov.

Unresectable metastatic NSCLC. Individuals with this type of lung cancer are being recruited for a nonrandomized, phase 1/2 study to determine whether a combination of amivantamab (Rybrevant) and capmatinib (Tabrecta) is tolerable and more effective than either therapy alone. The two drugs inhibit different stages of mesenchymal-epithelial transition (MET), a step in cell development that is crucial for metastasis because it enhances cell mobility, invasion, and resistance to apoptosis. In the phase 1 study, participants will start with twice-daily tablets of capmatinib and IV amivantamab once weekly for 4 weeks then every 2 weeks. Doses will be adjusted on the basis of toxicities. In phase 2, a new group of participants will receive the refined doses for up to 2 years until progression or death. The study opened at the Oncology Institute of Hope and Innovation in Whittier, Calif., in December 2020 with the aim of recruiting 161 participants. Sites are gearing up in five more U.S. states and in Canada, Europe, and Asia. Objective response rate is the primary outcome of the phase 2 study, with OS and QoL as secondary endpoints. More details at clinicaltrials.gov.

Locally advanced or metastatic NSCLC with EGFR-exon-20 insertion mutations. Adults with this diagnosis who have not yet been treated and are not amenable to curative surgery or radiotherapy are sought for a randomized, open-label phase 3 trial testing whether investigational EGFR tyrosine-kinase inhibitor furmonertinib (from ArriVent) is more effective than chemotherapy for first-line treatment. Chemotherapy is currently standard of care in this indication with targeted therapies amivantamab-vmjw (Rybrevant) and mobocertinib succinate (Exkivity) as second-line options. Individuals in the trial will take daily tablets of furmonertinib or platinum-based IV chemotherapy for 32 months or until disease progression, whichever comes first. The study opened in December in sites across 15 U.S. states. Centers in a further nine states are gearing up, with the aim of enrolling a total of 375 people. The primary outcome is PFS. QoL and OS at 5 years are secondary outcomes. More details at clinicaltrials.gov.

NSCLC previously treated with at least one platinum chemotherapy and at least one targeted treatment. Adults aged 70 or younger with this type of lung cancer are eligible for a National Cancer Institute phase 2 investigation of autologous T-cell receptor (TCR) gene therapy. Unlike CAR T-cell therapy, which only reaches the 20% of cancer neoantigens that are expressed extracellularly, TCR technology can target the 80% of abnormal proteins that are expressed inside cancer cells. Participants will receive a single infusion of their own engineered T cells. They will attend follow-up visits every 3-6 months for 3 years, then join a long-term study in which they will be followed for 12 more years. The National Institutes of Health Clinical Center in Bethesda, Md., started recruiting for the trial’s 210 participants with one of a selection of solid cancers in February 2023. Response rate measured by objective tumor regression is the primary endpoint. OS and QoL will not be tracked. More details at clinicaltrials.gov.

All trial information is from the National Institutes of Health U.S. National Library of Medicine (online at clinicaltrials.gov).

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

Editor’s note: This article was changed on 24 February to remove an incorrect reference to osimertinib.

A number of new studies in lung cancer have started in recent months. Could one of your patients benefit from participating?

Untreated advanced non–small cell lung cancer (NSCLC). Adult patients with stage IIIB, IIIC, or IV disease without actionable genomic alterations can join a randomized, open-label, phase 3 study testing the survival advantage of datopotamab deruxtecan (Dato-DXd) (AstraZeneca/Daiichi Sankyo). Dato-DXd is one of a half dozen experimental antibody-drug conjugates that target TROP2, a transmembrane glycoprotein that is overexpressed in several solid tumors, including NSCLC. One group of participants will receive an intravenous (IV) infusion of Dato-DXd plus durvalumab (Imfinzi) for up to 4 years, and over the first 12 weeks, they will receive four rounds of IV carboplatin (Paraplatin). The other group will receive IV infusions of pembrolizumab (Keytruda) every 3 weeks plus a combination of standard IV chemotherapy appropriate for the patient’s histology (nonsquamous or squamous NSCLC). In the United States, centers in Arkansas, Nebraska, Ohio, and Texas started recruiting in December 2020; trial sites are planned in 16 other states and 23 other countries. The trialists plan to enroll 1,000 participants. Overall survival (OS) and progression-free survival (PFS) are the primary endpoints; quality of life (QoL) is not being tracked. More details at clinicaltrials.gov.

Untreated advanced or metastatic NSCLC. Adult patients in this clinical situation without actionable genomic alterations as well as those with a PD-L1 tumor proportion score (TPS) of < 50% are eligible to participate in a randomized, open-label, phase 3 trial of Dato-DXd in combination with pembrolizumab, with or without chemotherapy. One group of participants will receive IV Dato-DXd and pembrolizumab every 3 weeks. For the second group of patients, IV platinum chemotherapy will be added to the Dato-DXd and pembrolizumab for the first four rounds of treatment. The third group of individuals make up the comparator arm and will receive thrice-weekly IV pembrolizumab, pemetrexed (Alimta), plus platinum chemotherapy. All participants will be treated for approximately 2.5 years or until disease progression or death. The trial began recruiting 975 participants in Arizona, Florida, Maryland, and New Jersey, and in Japan in January 2023. The primary endpoints are OS and PFS; QoL will not be assessed. More details at clinicaltrials.gov.

Metastatic NSCLC. Individuals with this cancer who have a TPS of > 50% can also receive an antibody-drug conjugate targeting TROP2 in combination with pembrolizumab. This time, the product is sacituzumab govitecan (Trodelvy). The randomized, open-label phase 3 trial is testing whether the two drugs in combination improve survival and slow progression better than pembrolizumab alone. For approximately 2 years, one group of people in the trial will receive IV pembrolizumab every 3 weeks. The other group, in addition to the pembrolizumab, will receive IV sacituzumab govitecan weekly for 2 weeks then 1 week off until unacceptable toxicity, disease progression, withdrawal of consent, or death. Study sites in the states of Florida and Georgia, and in Australia, Taiwan, and Turkey, opened in February 2023 with the aim of recruiting 614 participants. Overall survival over 4 years and PFS are the primary outcomes. QoL is a secondary outcome. More details at clinicaltrials.gov.

Unresectable metastatic NSCLC. Individuals with this type of lung cancer are being recruited for a nonrandomized, phase 1/2 study to determine whether a combination of amivantamab (Rybrevant) and capmatinib (Tabrecta) is tolerable and more effective than either therapy alone. The two drugs inhibit different stages of mesenchymal-epithelial transition (MET), a step in cell development that is crucial for metastasis because it enhances cell mobility, invasion, and resistance to apoptosis. In the phase 1 study, participants will start with twice-daily tablets of capmatinib and IV amivantamab once weekly for 4 weeks then every 2 weeks. Doses will be adjusted on the basis of toxicities. In phase 2, a new group of participants will receive the refined doses for up to 2 years until progression or death. The study opened at the Oncology Institute of Hope and Innovation in Whittier, Calif., in December 2020 with the aim of recruiting 161 participants. Sites are gearing up in five more U.S. states and in Canada, Europe, and Asia. Objective response rate is the primary outcome of the phase 2 study, with OS and QoL as secondary endpoints. More details at clinicaltrials.gov.

Locally advanced or metastatic NSCLC with EGFR-exon-20 insertion mutations. Adults with this diagnosis who have not yet been treated and are not amenable to curative surgery or radiotherapy are sought for a randomized, open-label phase 3 trial testing whether investigational EGFR tyrosine-kinase inhibitor furmonertinib (from ArriVent) is more effective than chemotherapy for first-line treatment. Chemotherapy is currently standard of care in this indication with targeted therapies amivantamab-vmjw (Rybrevant) and mobocertinib succinate (Exkivity) as second-line options. Individuals in the trial will take daily tablets of furmonertinib or platinum-based IV chemotherapy for 32 months or until disease progression, whichever comes first. The study opened in December in sites across 15 U.S. states. Centers in a further nine states are gearing up, with the aim of enrolling a total of 375 people. The primary outcome is PFS. QoL and OS at 5 years are secondary outcomes. More details at clinicaltrials.gov.

NSCLC previously treated with at least one platinum chemotherapy and at least one targeted treatment. Adults aged 70 or younger with this type of lung cancer are eligible for a National Cancer Institute phase 2 investigation of autologous T-cell receptor (TCR) gene therapy. Unlike CAR T-cell therapy, which only reaches the 20% of cancer neoantigens that are expressed extracellularly, TCR technology can target the 80% of abnormal proteins that are expressed inside cancer cells. Participants will receive a single infusion of their own engineered T cells. They will attend follow-up visits every 3-6 months for 3 years, then join a long-term study in which they will be followed for 12 more years. The National Institutes of Health Clinical Center in Bethesda, Md., started recruiting for the trial’s 210 participants with one of a selection of solid cancers in February 2023. Response rate measured by objective tumor regression is the primary endpoint. OS and QoL will not be tracked. More details at clinicaltrials.gov.

All trial information is from the National Institutes of Health U.S. National Library of Medicine (online at clinicaltrials.gov).

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

Editor’s note: This article was changed on 24 February to remove an incorrect reference to osimertinib.

A number of new studies in lung cancer have started in recent months. Could one of your patients benefit from participating?

Untreated advanced non–small cell lung cancer (NSCLC). Adult patients with stage IIIB, IIIC, or IV disease without actionable genomic alterations can join a randomized, open-label, phase 3 study testing the survival advantage of datopotamab deruxtecan (Dato-DXd) (AstraZeneca/Daiichi Sankyo). Dato-DXd is one of a half dozen experimental antibody-drug conjugates that target TROP2, a transmembrane glycoprotein that is overexpressed in several solid tumors, including NSCLC. One group of participants will receive an intravenous (IV) infusion of Dato-DXd plus durvalumab (Imfinzi) for up to 4 years, and over the first 12 weeks, they will receive four rounds of IV carboplatin (Paraplatin). The other group will receive IV infusions of pembrolizumab (Keytruda) every 3 weeks plus a combination of standard IV chemotherapy appropriate for the patient’s histology (nonsquamous or squamous NSCLC). In the United States, centers in Arkansas, Nebraska, Ohio, and Texas started recruiting in December 2020; trial sites are planned in 16 other states and 23 other countries. The trialists plan to enroll 1,000 participants. Overall survival (OS) and progression-free survival (PFS) are the primary endpoints; quality of life (QoL) is not being tracked. More details at clinicaltrials.gov.

Untreated advanced or metastatic NSCLC. Adult patients in this clinical situation without actionable genomic alterations as well as those with a PD-L1 tumor proportion score (TPS) of < 50% are eligible to participate in a randomized, open-label, phase 3 trial of Dato-DXd in combination with pembrolizumab, with or without chemotherapy. One group of participants will receive IV Dato-DXd and pembrolizumab every 3 weeks. For the second group of patients, IV platinum chemotherapy will be added to the Dato-DXd and pembrolizumab for the first four rounds of treatment. The third group of individuals make up the comparator arm and will receive thrice-weekly IV pembrolizumab, pemetrexed (Alimta), plus platinum chemotherapy. All participants will be treated for approximately 2.5 years or until disease progression or death. The trial began recruiting 975 participants in Arizona, Florida, Maryland, and New Jersey, and in Japan in January 2023. The primary endpoints are OS and PFS; QoL will not be assessed. More details at clinicaltrials.gov.

Metastatic NSCLC. Individuals with this cancer who have a TPS of > 50% can also receive an antibody-drug conjugate targeting TROP2 in combination with pembrolizumab. This time, the product is sacituzumab govitecan (Trodelvy). The randomized, open-label phase 3 trial is testing whether the two drugs in combination improve survival and slow progression better than pembrolizumab alone. For approximately 2 years, one group of people in the trial will receive IV pembrolizumab every 3 weeks. The other group, in addition to the pembrolizumab, will receive IV sacituzumab govitecan weekly for 2 weeks then 1 week off until unacceptable toxicity, disease progression, withdrawal of consent, or death. Study sites in the states of Florida and Georgia, and in Australia, Taiwan, and Turkey, opened in February 2023 with the aim of recruiting 614 participants. Overall survival over 4 years and PFS are the primary outcomes. QoL is a secondary outcome. More details at clinicaltrials.gov.

Unresectable metastatic NSCLC. Individuals with this type of lung cancer are being recruited for a nonrandomized, phase 1/2 study to determine whether a combination of amivantamab (Rybrevant) and capmatinib (Tabrecta) is tolerable and more effective than either therapy alone. The two drugs inhibit different stages of mesenchymal-epithelial transition (MET), a step in cell development that is crucial for metastasis because it enhances cell mobility, invasion, and resistance to apoptosis. In the phase 1 study, participants will start with twice-daily tablets of capmatinib and IV amivantamab once weekly for 4 weeks then every 2 weeks. Doses will be adjusted on the basis of toxicities. In phase 2, a new group of participants will receive the refined doses for up to 2 years until progression or death. The study opened at the Oncology Institute of Hope and Innovation in Whittier, Calif., in December 2020 with the aim of recruiting 161 participants. Sites are gearing up in five more U.S. states and in Canada, Europe, and Asia. Objective response rate is the primary outcome of the phase 2 study, with OS and QoL as secondary endpoints. More details at clinicaltrials.gov.

Locally advanced or metastatic NSCLC with EGFR-exon-20 insertion mutations. Adults with this diagnosis who have not yet been treated and are not amenable to curative surgery or radiotherapy are sought for a randomized, open-label phase 3 trial testing whether investigational EGFR tyrosine-kinase inhibitor furmonertinib (from ArriVent) is more effective than chemotherapy for first-line treatment. Chemotherapy is currently standard of care in this indication with targeted therapies amivantamab-vmjw (Rybrevant) and mobocertinib succinate (Exkivity) as second-line options. Individuals in the trial will take daily tablets of furmonertinib or platinum-based IV chemotherapy for 32 months or until disease progression, whichever comes first. The study opened in December in sites across 15 U.S. states. Centers in a further nine states are gearing up, with the aim of enrolling a total of 375 people. The primary outcome is PFS. QoL and OS at 5 years are secondary outcomes. More details at clinicaltrials.gov.

NSCLC previously treated with at least one platinum chemotherapy and at least one targeted treatment. Adults aged 70 or younger with this type of lung cancer are eligible for a National Cancer Institute phase 2 investigation of autologous T-cell receptor (TCR) gene therapy. Unlike CAR T-cell therapy, which only reaches the 20% of cancer neoantigens that are expressed extracellularly, TCR technology can target the 80% of abnormal proteins that are expressed inside cancer cells. Participants will receive a single infusion of their own engineered T cells. They will attend follow-up visits every 3-6 months for 3 years, then join a long-term study in which they will be followed for 12 more years. The National Institutes of Health Clinical Center in Bethesda, Md., started recruiting for the trial’s 210 participants with one of a selection of solid cancers in February 2023. Response rate measured by objective tumor regression is the primary endpoint. OS and QoL will not be tracked. More details at clinicaltrials.gov.

All trial information is from the National Institutes of Health U.S. National Library of Medicine (online at clinicaltrials.gov).

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

Editor’s note: This article was changed on 24 February to remove an incorrect reference to osimertinib.