Federal Practitioner

Not too long ago, prostate-cancer genetics didn’t mean much to patient care. But in recent years, the landscape of therapy has transformed as researchers have discovered links between multiple genes and aggressive tumors. 

Now, as a hematologist-oncologist explained to attendees at an Association of VA Hematology/Oncology regional meeting in Detroit, genetic tests can guide treatment for some—but not all—men with prostate cancer.

For patients with mutations, appropriate supplemental medications “can improve overall outcomes and have a long-standing impact on patients” said Scott J. Dawsey, MD, of the John D. Dingell Veterans Affairs Medical Center in Detroit in an interview following the AVAHO meeting, which focused on the management of prostate cancer.

As Dawsey explained, about 10% of patients with prostate cancer appear to have genetic mutations, although the exact percentage is unclear. The mutations are especially common in metastatic forms of prostate cancer. They’re estimated to be present in 11.8%-16.2% of those cases.

While these proportions are relatively small, the number of overall prostate-cancer cases with mutations is large due to the high burden of the disease, Dawsey said. Prostate cancer is by far the most common cancer in men, and estimated 299,010 cases will be diagnosed in the United States this year.

According to Dawsey, genetic mutations seem to boost the risk of more aggressive disease—and the risk of other malignancies—by disrupting DNA repair. This process can lead to even more mutations that may “make the cancer behave and grow more aggressively.”

But not all prostate cancer patients need to undergo genetic testing. Dawsey urged colleagues to figure out which patients should be tested by consulting National Comprehensive Cancer Network (NCCN) guidelines and the newly updated US Department of Veterans Affairs (VA) prostate cancer clinical pathway.

The two sets of recommendations agree on germline testing in patients with cases that are metastatic, very high risk, and high risk. Lower-risk cases should only be tested if patients meet family history criteria. The sets of guidelines also recommend somatic testing in patients with metastatic cancer.

In addition to providing guidance about treatment, genetic test results can have implications regarding other potential malignancies that may affect patients, Dawsey said. The results may also have implications for cancer risk in family members.

Several drugs are now available for patients with genetic mutations, including checkpoint inhibitors and PARP inhibitors. The drugs, which have unique mechanisms of action, are given in addition to standard prostate cancer treatments, he said.

“If a patient doesn’t have one of these genetic changes,” he said, “these drugs aren’t an option.”

A long list of drugs or combinations of drugs are in clinical trials, including the poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors olaparib, abiraterone, and niraparib and the checkpoint inhibitors nivolumab and cemiplimab.

The drugs generally improve response rates and progression-free survival, Dawsey said, and patients are generally able to tolerate them. In regard to which drugs to choose, he suggested consulting the and NCCN guidelines and the VA oncology clinical pathway for prostate cancer.

Not too long ago, prostate-cancer genetics didn’t mean much to patient care. But in recent years, the landscape of therapy has transformed as researchers have discovered links between multiple genes and aggressive tumors. 

Now, as a hematologist-oncologist explained to attendees at an Association of VA Hematology/Oncology regional meeting in Detroit, genetic tests can guide treatment for some—but not all—men with prostate cancer.

For patients with mutations, appropriate supplemental medications “can improve overall outcomes and have a long-standing impact on patients” said Scott J. Dawsey, MD, of the John D. Dingell Veterans Affairs Medical Center in Detroit in an interview following the AVAHO meeting, which focused on the management of prostate cancer.

As Dawsey explained, about 10% of patients with prostate cancer appear to have genetic mutations, although the exact percentage is unclear. The mutations are especially common in metastatic forms of prostate cancer. They’re estimated to be present in 11.8%-16.2% of those cases.

While these proportions are relatively small, the number of overall prostate-cancer cases with mutations is large due to the high burden of the disease, Dawsey said. Prostate cancer is by far the most common cancer in men, and estimated 299,010 cases will be diagnosed in the United States this year.

According to Dawsey, genetic mutations seem to boost the risk of more aggressive disease—and the risk of other malignancies—by disrupting DNA repair. This process can lead to even more mutations that may “make the cancer behave and grow more aggressively.”

But not all prostate cancer patients need to undergo genetic testing. Dawsey urged colleagues to figure out which patients should be tested by consulting National Comprehensive Cancer Network (NCCN) guidelines and the newly updated US Department of Veterans Affairs (VA) prostate cancer clinical pathway.

The two sets of recommendations agree on germline testing in patients with cases that are metastatic, very high risk, and high risk. Lower-risk cases should only be tested if patients meet family history criteria. The sets of guidelines also recommend somatic testing in patients with metastatic cancer.

In addition to providing guidance about treatment, genetic test results can have implications regarding other potential malignancies that may affect patients, Dawsey said. The results may also have implications for cancer risk in family members.

Several drugs are now available for patients with genetic mutations, including checkpoint inhibitors and PARP inhibitors. The drugs, which have unique mechanisms of action, are given in addition to standard prostate cancer treatments, he said.

“If a patient doesn’t have one of these genetic changes,” he said, “these drugs aren’t an option.”

A long list of drugs or combinations of drugs are in clinical trials, including the poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors olaparib, abiraterone, and niraparib and the checkpoint inhibitors nivolumab and cemiplimab.

The drugs generally improve response rates and progression-free survival, Dawsey said, and patients are generally able to tolerate them. In regard to which drugs to choose, he suggested consulting the and NCCN guidelines and the VA oncology clinical pathway for prostate cancer.

Not too long ago, prostate-cancer genetics didn’t mean much to patient care. But in recent years, the landscape of therapy has transformed as researchers have discovered links between multiple genes and aggressive tumors. 

Now, as a hematologist-oncologist explained to attendees at an Association of VA Hematology/Oncology regional meeting in Detroit, genetic tests can guide treatment for some—but not all—men with prostate cancer.

For patients with mutations, appropriate supplemental medications “can improve overall outcomes and have a long-standing impact on patients” said Scott J. Dawsey, MD, of the John D. Dingell Veterans Affairs Medical Center in Detroit in an interview following the AVAHO meeting, which focused on the management of prostate cancer.

As Dawsey explained, about 10% of patients with prostate cancer appear to have genetic mutations, although the exact percentage is unclear. The mutations are especially common in metastatic forms of prostate cancer. They’re estimated to be present in 11.8%-16.2% of those cases.

While these proportions are relatively small, the number of overall prostate-cancer cases with mutations is large due to the high burden of the disease, Dawsey said. Prostate cancer is by far the most common cancer in men, and estimated 299,010 cases will be diagnosed in the United States this year.

According to Dawsey, genetic mutations seem to boost the risk of more aggressive disease—and the risk of other malignancies—by disrupting DNA repair. This process can lead to even more mutations that may “make the cancer behave and grow more aggressively.”

But not all prostate cancer patients need to undergo genetic testing. Dawsey urged colleagues to figure out which patients should be tested by consulting National Comprehensive Cancer Network (NCCN) guidelines and the newly updated US Department of Veterans Affairs (VA) prostate cancer clinical pathway.

The two sets of recommendations agree on germline testing in patients with cases that are metastatic, very high risk, and high risk. Lower-risk cases should only be tested if patients meet family history criteria. The sets of guidelines also recommend somatic testing in patients with metastatic cancer.

In addition to providing guidance about treatment, genetic test results can have implications regarding other potential malignancies that may affect patients, Dawsey said. The results may also have implications for cancer risk in family members.

Several drugs are now available for patients with genetic mutations, including checkpoint inhibitors and PARP inhibitors. The drugs, which have unique mechanisms of action, are given in addition to standard prostate cancer treatments, he said.

“If a patient doesn’t have one of these genetic changes,” he said, “these drugs aren’t an option.”

A long list of drugs or combinations of drugs are in clinical trials, including the poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors olaparib, abiraterone, and niraparib and the checkpoint inhibitors nivolumab and cemiplimab.

The drugs generally improve response rates and progression-free survival, Dawsey said, and patients are generally able to tolerate them. In regard to which drugs to choose, he suggested consulting the and NCCN guidelines and the VA oncology clinical pathway for prostate cancer.

Findings from the phase 3 ESOPEC trial demonstrate an overall survival advantage with a perioperative chemotherapy regimen known as FLOT, compared with a neoadjuvant chemoradiation approach, called CROSS, in patients with resectable, locally advanced esophageal adenocarcinoma.

The study results, presented as a late-breaking abstract at the annual meeting of the American Society of Clinical Oncology (ASCO), help settle a long-standing debate about whether chemotherapy with FLOT — 5-florouracil, leucovorin, oxaliplatin, and docetaxel — before and after surgery, or neoadjuvant radiation plus CROSS — carboplatin and paclitaxel — followed by surgery is the best approach.

There has been “considerable disagreement as to whether giving all adjuvant therapy upfront versus ‘sandwich’ adjuvant therapy before and after surgery is the better standard of care for locally advanced resectable esophageal cancer,” Jennifer Tseng, MD, of Boston Medical Center, Boston, said in an ASCO press release. This randomized clinical trial shows the sandwich approach “provides better outcomes.”

The practice-changing ESOPEC findings will have an important effect on the management of patients with resectable esophageal adenocarcinoma and gastroesophageal junction adenocarcinoma, but local and distant failures remain a challenge in this population, explained invited discussant Karyn A. Goodman, MD.

Advances since the initiation of ESOPEC — such as immunotherapy options and personalized strategies — suggest the esophageal adenocarcinoma story is still evolving, said Dr. Goodman, professor and vice chair of research and quality in the Department of Radiation Oncology at Icahn School of Medicine at Mount Sinai, New York. 
 

The ESOPEC trial

Both the FLOT and CROSS regimens are established standards of care in resectable esophageal adenocarcinoma, and the choice of treatment has largely varied based on geographical location.

The current randomized, prospective, open-label ESOPEC trial, however, demonstrated that FLOT can prolong overall survival, first author Jens Hoeppner, MD, from the University of Bielefeld in Detmold, Germany, reported.

Overall, 438 patients with locally advanced, resectable esophageal adenocarcinoma recruited between February 2016 and April 2020 from 25 sites in Germany and randomized to either FLOT (n = 221) or CROSS (n = 217). The median age was 63 years, and most (89.3%) were men. Patients were followed until November 2023, and median follow-up was 55 months.

Patients in the FLOT arm received four cycles — one every 2 weeks for 8 weeks — followed by surgery 4-6 weeks later. FLOT cycles were reinitiated 4-6 weeks after surgery and given every 2 weeks for 8 weeks.

Those in the CROSS arm received one cycle per week of radiation therapy for 5 weeks plus carboplatin and paclitaxel followed by surgery 4-6 weeks after the last cycle.

Overall, 86% received both neoadjuvant therapy and surgery in the FLOT arm versus 82.9% in the CROSS group. Among these patients, 16.8% in the FLOT group achieved a pathological complete remission versus 10.0% in the CROSS arm.

In the intention-to-treat population, median overall survival was almost twice as long in the FLOT group — 66 months versus 37 months. At 3 years, those who received FLOT had a 30% lower risk of dying (hazard ratio [HR], 0.70), with 57.4% of patients alive at that point, compared with 50.7% patients in the CROSS arm.

The 5-year overall survival was 50.6% in the FLOT group versus 38.7% in the CROSS group.

Patients receiving FLOT also demonstrated improved progression-free survival (PFS), with a median PFS of 38 months versus 16 months. The 3-year PFS was 51.6% with FLOT versus 35.0% with CROSS (HR, 0.66). The exploratory subgroup analyses for sex, age, ECOG status, and clinical T and N stages also favored FLOT.

The 30-day postoperative mortality was 1.0% in the FLOT group and 1.7% in the CROSS group, and the 90-day postoperative mortality rate was 3.2% and 5.6%, respectively.

Based on these findings, perioperative chemotherapy with FLOT should be preferred over neoadjuvant chemoradiation with CROSS, Dr. Hoeppner concluded.

Dr. Goodman agreed, noting that, in the wake of ESOPEC, FLOT will likely be adopted as a more standard approach in the United States for patients who are fit. And, for patients who are not candidates for FLOT, CROSS is a reasonable option, she said.

But, she asked, does it really have to be an either/or situation?

Multiple studies, including Dr. Goodman’s 2021 Alliance/CALGB 80803 study, have demonstrated promising outcomes with combined modalities and adapting therapy based on treatment response. Several trials, for instance, are evaluating combining FLOT and CROSS, with some showing the approach is feasible and comes with manageable toxicity.

It’s also important to look outside of FLOT and CROSS. During ESOPEC, new approaches entered the treatment landscape, including the use of adjuvant immunotherapy following neoadjuvant chemoradiation and surgery for noncomplete response.

Take the CheckMate 577 study, which found that adjuvant nivolumab immunotherapy after preoperative CROSS and surgery significantly reduced metastatic recurrence and doubled disease-free survival in patients who did not achieve a complete response. This approach is now a standard of care for those patients.

FLOT plus neoadjuvant nivolumab may also be a viable option, Dr. Goodman noted, but we haven’t yet seen “any benefit in survival with the combo of chemotherapy and immunotherapy for resectable esophago-gastric cancer.”

Further studies are needed to evaluate the synergy of immunotherapy and radiotherapy. The next chapter of the esophageal adenocarcinoma story may feature a “best-of-both-worlds” approach that combines induction chemotherapy, followed by personalized chemoradiation, surgery, and potentially adjuvant immunotherapy, Dr. Goodman explained.

While the ESOPEC findings are impressive, the 5-year overall survival of only 50% is still suboptimal, she noted. “Given the poor prognosis with this disease, we need to continue to develop clinical trials to identify better targets, novel treatment combinations, and select patients that will respond best to specific treatment.”

ESOPEC was funded by the Deutsche Forschungsgemeinschaft (German Research Foundation). Dr. Hoeppner reported receiving travel, accommodations, and expenses from Intuitive Surgical. Dr. Goodman reported a relationship with the National Cancer Institute and consulting or advisory roles for Novartis, Philips Healthcare, RenovoRX, and Roche/Genentech.

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

Findings from the phase 3 ESOPEC trial demonstrate an overall survival advantage with a perioperative chemotherapy regimen known as FLOT, compared with a neoadjuvant chemoradiation approach, called CROSS, in patients with resectable, locally advanced esophageal adenocarcinoma.

The study results, presented as a late-breaking abstract at the annual meeting of the American Society of Clinical Oncology (ASCO), help settle a long-standing debate about whether chemotherapy with FLOT — 5-florouracil, leucovorin, oxaliplatin, and docetaxel — before and after surgery, or neoadjuvant radiation plus CROSS — carboplatin and paclitaxel — followed by surgery is the best approach.

There has been “considerable disagreement as to whether giving all adjuvant therapy upfront versus ‘sandwich’ adjuvant therapy before and after surgery is the better standard of care for locally advanced resectable esophageal cancer,” Jennifer Tseng, MD, of Boston Medical Center, Boston, said in an ASCO press release. This randomized clinical trial shows the sandwich approach “provides better outcomes.”

The practice-changing ESOPEC findings will have an important effect on the management of patients with resectable esophageal adenocarcinoma and gastroesophageal junction adenocarcinoma, but local and distant failures remain a challenge in this population, explained invited discussant Karyn A. Goodman, MD.

Advances since the initiation of ESOPEC — such as immunotherapy options and personalized strategies — suggest the esophageal adenocarcinoma story is still evolving, said Dr. Goodman, professor and vice chair of research and quality in the Department of Radiation Oncology at Icahn School of Medicine at Mount Sinai, New York. 
 

The ESOPEC trial

Both the FLOT and CROSS regimens are established standards of care in resectable esophageal adenocarcinoma, and the choice of treatment has largely varied based on geographical location.

The current randomized, prospective, open-label ESOPEC trial, however, demonstrated that FLOT can prolong overall survival, first author Jens Hoeppner, MD, from the University of Bielefeld in Detmold, Germany, reported.

Overall, 438 patients with locally advanced, resectable esophageal adenocarcinoma recruited between February 2016 and April 2020 from 25 sites in Germany and randomized to either FLOT (n = 221) or CROSS (n = 217). The median age was 63 years, and most (89.3%) were men. Patients were followed until November 2023, and median follow-up was 55 months.

Patients in the FLOT arm received four cycles — one every 2 weeks for 8 weeks — followed by surgery 4-6 weeks later. FLOT cycles were reinitiated 4-6 weeks after surgery and given every 2 weeks for 8 weeks.

Those in the CROSS arm received one cycle per week of radiation therapy for 5 weeks plus carboplatin and paclitaxel followed by surgery 4-6 weeks after the last cycle.

Overall, 86% received both neoadjuvant therapy and surgery in the FLOT arm versus 82.9% in the CROSS group. Among these patients, 16.8% in the FLOT group achieved a pathological complete remission versus 10.0% in the CROSS arm.

In the intention-to-treat population, median overall survival was almost twice as long in the FLOT group — 66 months versus 37 months. At 3 years, those who received FLOT had a 30% lower risk of dying (hazard ratio [HR], 0.70), with 57.4% of patients alive at that point, compared with 50.7% patients in the CROSS arm.

The 5-year overall survival was 50.6% in the FLOT group versus 38.7% in the CROSS group.

Patients receiving FLOT also demonstrated improved progression-free survival (PFS), with a median PFS of 38 months versus 16 months. The 3-year PFS was 51.6% with FLOT versus 35.0% with CROSS (HR, 0.66). The exploratory subgroup analyses for sex, age, ECOG status, and clinical T and N stages also favored FLOT.

The 30-day postoperative mortality was 1.0% in the FLOT group and 1.7% in the CROSS group, and the 90-day postoperative mortality rate was 3.2% and 5.6%, respectively.

Based on these findings, perioperative chemotherapy with FLOT should be preferred over neoadjuvant chemoradiation with CROSS, Dr. Hoeppner concluded.

Dr. Goodman agreed, noting that, in the wake of ESOPEC, FLOT will likely be adopted as a more standard approach in the United States for patients who are fit. And, for patients who are not candidates for FLOT, CROSS is a reasonable option, she said.

But, she asked, does it really have to be an either/or situation?

Multiple studies, including Dr. Goodman’s 2021 Alliance/CALGB 80803 study, have demonstrated promising outcomes with combined modalities and adapting therapy based on treatment response. Several trials, for instance, are evaluating combining FLOT and CROSS, with some showing the approach is feasible and comes with manageable toxicity.

It’s also important to look outside of FLOT and CROSS. During ESOPEC, new approaches entered the treatment landscape, including the use of adjuvant immunotherapy following neoadjuvant chemoradiation and surgery for noncomplete response.

Take the CheckMate 577 study, which found that adjuvant nivolumab immunotherapy after preoperative CROSS and surgery significantly reduced metastatic recurrence and doubled disease-free survival in patients who did not achieve a complete response. This approach is now a standard of care for those patients.

FLOT plus neoadjuvant nivolumab may also be a viable option, Dr. Goodman noted, but we haven’t yet seen “any benefit in survival with the combo of chemotherapy and immunotherapy for resectable esophago-gastric cancer.”

Further studies are needed to evaluate the synergy of immunotherapy and radiotherapy. The next chapter of the esophageal adenocarcinoma story may feature a “best-of-both-worlds” approach that combines induction chemotherapy, followed by personalized chemoradiation, surgery, and potentially adjuvant immunotherapy, Dr. Goodman explained.

While the ESOPEC findings are impressive, the 5-year overall survival of only 50% is still suboptimal, she noted. “Given the poor prognosis with this disease, we need to continue to develop clinical trials to identify better targets, novel treatment combinations, and select patients that will respond best to specific treatment.”

ESOPEC was funded by the Deutsche Forschungsgemeinschaft (German Research Foundation). Dr. Hoeppner reported receiving travel, accommodations, and expenses from Intuitive Surgical. Dr. Goodman reported a relationship with the National Cancer Institute and consulting or advisory roles for Novartis, Philips Healthcare, RenovoRX, and Roche/Genentech.

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

Findings from the phase 3 ESOPEC trial demonstrate an overall survival advantage with a perioperative chemotherapy regimen known as FLOT, compared with a neoadjuvant chemoradiation approach, called CROSS, in patients with resectable, locally advanced esophageal adenocarcinoma.

The study results, presented as a late-breaking abstract at the annual meeting of the American Society of Clinical Oncology (ASCO), help settle a long-standing debate about whether chemotherapy with FLOT — 5-florouracil, leucovorin, oxaliplatin, and docetaxel — before and after surgery, or neoadjuvant radiation plus CROSS — carboplatin and paclitaxel — followed by surgery is the best approach.

There has been “considerable disagreement as to whether giving all adjuvant therapy upfront versus ‘sandwich’ adjuvant therapy before and after surgery is the better standard of care for locally advanced resectable esophageal cancer,” Jennifer Tseng, MD, of Boston Medical Center, Boston, said in an ASCO press release. This randomized clinical trial shows the sandwich approach “provides better outcomes.”

The practice-changing ESOPEC findings will have an important effect on the management of patients with resectable esophageal adenocarcinoma and gastroesophageal junction adenocarcinoma, but local and distant failures remain a challenge in this population, explained invited discussant Karyn A. Goodman, MD.

Advances since the initiation of ESOPEC — such as immunotherapy options and personalized strategies — suggest the esophageal adenocarcinoma story is still evolving, said Dr. Goodman, professor and vice chair of research and quality in the Department of Radiation Oncology at Icahn School of Medicine at Mount Sinai, New York. 
 

The ESOPEC trial

Both the FLOT and CROSS regimens are established standards of care in resectable esophageal adenocarcinoma, and the choice of treatment has largely varied based on geographical location.

The current randomized, prospective, open-label ESOPEC trial, however, demonstrated that FLOT can prolong overall survival, first author Jens Hoeppner, MD, from the University of Bielefeld in Detmold, Germany, reported.

Overall, 438 patients with locally advanced, resectable esophageal adenocarcinoma recruited between February 2016 and April 2020 from 25 sites in Germany and randomized to either FLOT (n = 221) or CROSS (n = 217). The median age was 63 years, and most (89.3%) were men. Patients were followed until November 2023, and median follow-up was 55 months.

Patients in the FLOT arm received four cycles — one every 2 weeks for 8 weeks — followed by surgery 4-6 weeks later. FLOT cycles were reinitiated 4-6 weeks after surgery and given every 2 weeks for 8 weeks.

Those in the CROSS arm received one cycle per week of radiation therapy for 5 weeks plus carboplatin and paclitaxel followed by surgery 4-6 weeks after the last cycle.

Overall, 86% received both neoadjuvant therapy and surgery in the FLOT arm versus 82.9% in the CROSS group. Among these patients, 16.8% in the FLOT group achieved a pathological complete remission versus 10.0% in the CROSS arm.

In the intention-to-treat population, median overall survival was almost twice as long in the FLOT group — 66 months versus 37 months. At 3 years, those who received FLOT had a 30% lower risk of dying (hazard ratio [HR], 0.70), with 57.4% of patients alive at that point, compared with 50.7% patients in the CROSS arm.

The 5-year overall survival was 50.6% in the FLOT group versus 38.7% in the CROSS group.

Patients receiving FLOT also demonstrated improved progression-free survival (PFS), with a median PFS of 38 months versus 16 months. The 3-year PFS was 51.6% with FLOT versus 35.0% with CROSS (HR, 0.66). The exploratory subgroup analyses for sex, age, ECOG status, and clinical T and N stages also favored FLOT.

The 30-day postoperative mortality was 1.0% in the FLOT group and 1.7% in the CROSS group, and the 90-day postoperative mortality rate was 3.2% and 5.6%, respectively.

Based on these findings, perioperative chemotherapy with FLOT should be preferred over neoadjuvant chemoradiation with CROSS, Dr. Hoeppner concluded.

Dr. Goodman agreed, noting that, in the wake of ESOPEC, FLOT will likely be adopted as a more standard approach in the United States for patients who are fit. And, for patients who are not candidates for FLOT, CROSS is a reasonable option, she said.

But, she asked, does it really have to be an either/or situation?

Multiple studies, including Dr. Goodman’s 2021 Alliance/CALGB 80803 study, have demonstrated promising outcomes with combined modalities and adapting therapy based on treatment response. Several trials, for instance, are evaluating combining FLOT and CROSS, with some showing the approach is feasible and comes with manageable toxicity.

It’s also important to look outside of FLOT and CROSS. During ESOPEC, new approaches entered the treatment landscape, including the use of adjuvant immunotherapy following neoadjuvant chemoradiation and surgery for noncomplete response.

Take the CheckMate 577 study, which found that adjuvant nivolumab immunotherapy after preoperative CROSS and surgery significantly reduced metastatic recurrence and doubled disease-free survival in patients who did not achieve a complete response. This approach is now a standard of care for those patients.

FLOT plus neoadjuvant nivolumab may also be a viable option, Dr. Goodman noted, but we haven’t yet seen “any benefit in survival with the combo of chemotherapy and immunotherapy for resectable esophago-gastric cancer.”

Further studies are needed to evaluate the synergy of immunotherapy and radiotherapy. The next chapter of the esophageal adenocarcinoma story may feature a “best-of-both-worlds” approach that combines induction chemotherapy, followed by personalized chemoradiation, surgery, and potentially adjuvant immunotherapy, Dr. Goodman explained.

While the ESOPEC findings are impressive, the 5-year overall survival of only 50% is still suboptimal, she noted. “Given the poor prognosis with this disease, we need to continue to develop clinical trials to identify better targets, novel treatment combinations, and select patients that will respond best to specific treatment.”

ESOPEC was funded by the Deutsche Forschungsgemeinschaft (German Research Foundation). Dr. Hoeppner reported receiving travel, accommodations, and expenses from Intuitive Surgical. Dr. Goodman reported a relationship with the National Cancer Institute and consulting or advisory roles for Novartis, Philips Healthcare, RenovoRX, and Roche/Genentech.

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

Several new studies in lung cancer have opened their doors recently. Is one of your patients eligible to participate?

Resected stage II, IIIA, or IIIB with nodal involvement non–small cell lung cancer (NSCLC). Adult patients with this type of cancer can join a randomized, controlled, phase 3 study assessing whether an investigational drug called V940 added to pembrolizumab (Keytruda) delays cancer recurrence better than pembrolizumab alone.

V940 is an individualized neoantigen therapy designed to generate T-cell antitumor responses targeted to a patient’s specific mutation profile.

V940 plus pembrolizumab showed a trend toward longer recurrence-free survival vs pembrolizumab alone in a recent phase 2 study in melanoma (hazard ratio, 0.561; P = .053).

In the current trial, one group of participants will receive intramuscular injections of V940 every 3 weeks plus intravenous (IV) pembrolizumab every 6 weeks for up to approximately 1 year or until disease recurrence or unacceptable toxicity, whichever happens first. The other people in the trial will be on the same schedule, with a placebo replacing V940.

Centers in Florida, Georgia, Kentucky, Montana, New Jersey, New York, North Dakota, and six other countries started recruiting for the trial’s 868 participants in December 2023. Disease-free survival is the primary endpoint. Overall survival over approximately 12 years and quality of life (QoL) are secondary endpoints. More details at clinicaltrials.gov.

Metastatic NSCLC with a programmed cell death ligand 1 (PD-L1)–tumor proportion score of > 50%. Adults in this clinical situation are eligible for a randomized, open-label, phase 3 trial to determine whether an experimental antibody-drug conjugate called MK-2870 added to standard pembrolizumab prolongs survival.

MK-2870 delivers a cytotoxin to cancer cells by binding to trophoblast cell-surface antigen 2, known to promote tumor cell growth and metastasis. For up to 2 years, half of participants will receive MK-2870 by IV every 2 weeks plus IV pembrolizumab every 6 weeks. The other group will receive only pembrolizumab.

In December 2023, study sites in Georgia, Minnesota, Mississippi, Nevada, Oregon, Australia, Denmark, Taiwan, and Turkey started seeking the trial’s 614 participants. Overall survival over approximately 4 years is the primary endpoint; QoL is a secondary endpoint. More details at clinicaltrials.gov.

Untreated locally advanced or metastatic NSCLC with KRAS G12C mutations. Individuals with this type of lung cancer may be interested in a randomized, controlled, phase 3 study examining whether an experimental oral KRAS G12C inhibitor called LY3537982 boosts the effectiveness of standard treatment and patients can tolerate the combination. Currently approved KRAS G12C inhibitors sotorasib (Lumakras, Lumykras) and adagrasib (Krazati) are indicated for second-line treatment; this trial may lead to a first-line approval for newcomer LY3537982.

The trial has three parts: dose optimization, safety, and efficacy. During dose optimization, each participant will take one of two oral doses of LY3537982 and receive IV pembrolizumab every 3 weeks. In the safety phase, all participants will receive oral LY3537982 at the chosen dose plus standard therapy of 3-times-weekly IV pembrolizumab, pemetrexed, and a platinum therapy (cisplatin or carboplatin). In the experimental phase, for up to about 1 year, participants will receive one of these four options: Pembrolizumab plus LY3537982, pembrolizumab plus a placebo, standard therapy plus LY3537982, or standard therapy plus a placebo.

The study, which is planning to recruit 1016 participants, opened across 16 US states and 12 countries worldwide in December 2023. Sites in 11 more US states, the District of Columbia, Brazil, Canada, China, India, and 11 more European countries are gearing up. Adverse events and progression-free survival are the primary endpoints. Overall survival over approximately 3 years and QoL are secondary endpoints. More details at clinicaltrials.gov.

Unresectable, untreated locally advanced or metastatic non-squamous NSCLC with human epidermal growth factor receptor 2 (HER2) mutations. People with this diagnosis who have HER2 mutations instead of KRAS G12C mutations can participate in a phase 3 study comparing an investigational oral first-line treatment with standard IV therapy. The drug in this study, zongertinib, is a HER2 tyrosine kinase inhibitor.

For up to approximately 4 years, one group of participants will take oral zongertinib only, and the other individuals will receive IV pembrolizumab, pemetrexed, and a platinum agent (cisplatin or carboplatin). Study sites in California, Missouri, South Carolina, Australia, China, Japan, South Korea, and Singapore opened in January ready to welcome 270 participants. Progression-free survival is the primary outcome. Overall survival over 53 months and QoL are secondary endpoints. More details at clinicaltrials.gov.

Completely resected stage IIB, IIIA, or select IIIB, PD-L1–positive NSCLC. Adults with this type of lung cancer who have received adjuvant platinum-based chemotherapy may be eligible for a randomized, controlled, phase 3 study to assess whether two immune checkpoint inhibitors are better than one at delaying cancer recurrence. In this trial, tiragolumab will be added to the approved PD-L1 inhibitor atezolizumab (Tecentriq).

A recent study, however, found that tiragolumab did not confer an additional benefit when added to atezolizumab, carboplatin, and etoposide in untreated extensive-stage small cell lung cancer.

In the current trial, one group of participants will receive IV atezolizumab and tiragolumab, while the other people will receive a placebo instead of tiragolumab. Centers in California, Georgia, Illinois, New Mexico, Australia, China, South Korea, and Taiwan started recruiting for the trial’s 1150 participants in March 2024. Disease-free survival is the primary endpoint. Overall survival over approximately 15 years and QoL are secondary outcomes. More details at clinicaltrials.gov.

Previously treated metastatic or non-operable non-squamous NSCLC. Adults in this position who have received no more than one platinum-based chemotherapy and one anti–PD-L1 drug are sought for a randomized, open-label, phase 3 trial comparing second-line standard docetaxel with experimental antibody-drug conjugate sigvotatug vedotin. Patients who have tumors with certain treatable genomic alterations must have received at least one drug targeted to that alteration, as well as a platinum-based agent.

Approximately half the participants will receive sigvotatug vedotin by IV every 2 weeks, and the other half will receive IV docetaxel every 3 weeks. The study opened in March across 13 US states, France, Hungary, Poland, and Spain seeking 600 people eligible to participate. The primary outcomes are overall survival over approximately 5 years and objective response rate. QoL is a secondary outcome. More details at clinicaltrials.gov.All trial information is from the National Institutes of Health US National Library of Medicine (online at clinicaltrials.gov).

A version of this article appeared on Medscape.com .

Several new studies in lung cancer have opened their doors recently. Is one of your patients eligible to participate?

Resected stage II, IIIA, or IIIB with nodal involvement non–small cell lung cancer (NSCLC). Adult patients with this type of cancer can join a randomized, controlled, phase 3 study assessing whether an investigational drug called V940 added to pembrolizumab (Keytruda) delays cancer recurrence better than pembrolizumab alone.

V940 is an individualized neoantigen therapy designed to generate T-cell antitumor responses targeted to a patient’s specific mutation profile.

V940 plus pembrolizumab showed a trend toward longer recurrence-free survival vs pembrolizumab alone in a recent phase 2 study in melanoma (hazard ratio, 0.561; P = .053).

In the current trial, one group of participants will receive intramuscular injections of V940 every 3 weeks plus intravenous (IV) pembrolizumab every 6 weeks for up to approximately 1 year or until disease recurrence or unacceptable toxicity, whichever happens first. The other people in the trial will be on the same schedule, with a placebo replacing V940.

Centers in Florida, Georgia, Kentucky, Montana, New Jersey, New York, North Dakota, and six other countries started recruiting for the trial’s 868 participants in December 2023. Disease-free survival is the primary endpoint. Overall survival over approximately 12 years and quality of life (QoL) are secondary endpoints. More details at clinicaltrials.gov.

Metastatic NSCLC with a programmed cell death ligand 1 (PD-L1)–tumor proportion score of > 50%. Adults in this clinical situation are eligible for a randomized, open-label, phase 3 trial to determine whether an experimental antibody-drug conjugate called MK-2870 added to standard pembrolizumab prolongs survival.

MK-2870 delivers a cytotoxin to cancer cells by binding to trophoblast cell-surface antigen 2, known to promote tumor cell growth and metastasis. For up to 2 years, half of participants will receive MK-2870 by IV every 2 weeks plus IV pembrolizumab every 6 weeks. The other group will receive only pembrolizumab.

In December 2023, study sites in Georgia, Minnesota, Mississippi, Nevada, Oregon, Australia, Denmark, Taiwan, and Turkey started seeking the trial’s 614 participants. Overall survival over approximately 4 years is the primary endpoint; QoL is a secondary endpoint. More details at clinicaltrials.gov.

Untreated locally advanced or metastatic NSCLC with KRAS G12C mutations. Individuals with this type of lung cancer may be interested in a randomized, controlled, phase 3 study examining whether an experimental oral KRAS G12C inhibitor called LY3537982 boosts the effectiveness of standard treatment and patients can tolerate the combination. Currently approved KRAS G12C inhibitors sotorasib (Lumakras, Lumykras) and adagrasib (Krazati) are indicated for second-line treatment; this trial may lead to a first-line approval for newcomer LY3537982.

The trial has three parts: dose optimization, safety, and efficacy. During dose optimization, each participant will take one of two oral doses of LY3537982 and receive IV pembrolizumab every 3 weeks. In the safety phase, all participants will receive oral LY3537982 at the chosen dose plus standard therapy of 3-times-weekly IV pembrolizumab, pemetrexed, and a platinum therapy (cisplatin or carboplatin). In the experimental phase, for up to about 1 year, participants will receive one of these four options: Pembrolizumab plus LY3537982, pembrolizumab plus a placebo, standard therapy plus LY3537982, or standard therapy plus a placebo.

The study, which is planning to recruit 1016 participants, opened across 16 US states and 12 countries worldwide in December 2023. Sites in 11 more US states, the District of Columbia, Brazil, Canada, China, India, and 11 more European countries are gearing up. Adverse events and progression-free survival are the primary endpoints. Overall survival over approximately 3 years and QoL are secondary endpoints. More details at clinicaltrials.gov.

Unresectable, untreated locally advanced or metastatic non-squamous NSCLC with human epidermal growth factor receptor 2 (HER2) mutations. People with this diagnosis who have HER2 mutations instead of KRAS G12C mutations can participate in a phase 3 study comparing an investigational oral first-line treatment with standard IV therapy. The drug in this study, zongertinib, is a HER2 tyrosine kinase inhibitor.

For up to approximately 4 years, one group of participants will take oral zongertinib only, and the other individuals will receive IV pembrolizumab, pemetrexed, and a platinum agent (cisplatin or carboplatin). Study sites in California, Missouri, South Carolina, Australia, China, Japan, South Korea, and Singapore opened in January ready to welcome 270 participants. Progression-free survival is the primary outcome. Overall survival over 53 months and QoL are secondary endpoints. More details at clinicaltrials.gov.

Completely resected stage IIB, IIIA, or select IIIB, PD-L1–positive NSCLC. Adults with this type of lung cancer who have received adjuvant platinum-based chemotherapy may be eligible for a randomized, controlled, phase 3 study to assess whether two immune checkpoint inhibitors are better than one at delaying cancer recurrence. In this trial, tiragolumab will be added to the approved PD-L1 inhibitor atezolizumab (Tecentriq).

A recent study, however, found that tiragolumab did not confer an additional benefit when added to atezolizumab, carboplatin, and etoposide in untreated extensive-stage small cell lung cancer.

In the current trial, one group of participants will receive IV atezolizumab and tiragolumab, while the other people will receive a placebo instead of tiragolumab. Centers in California, Georgia, Illinois, New Mexico, Australia, China, South Korea, and Taiwan started recruiting for the trial’s 1150 participants in March 2024. Disease-free survival is the primary endpoint. Overall survival over approximately 15 years and QoL are secondary outcomes. More details at clinicaltrials.gov.

Previously treated metastatic or non-operable non-squamous NSCLC. Adults in this position who have received no more than one platinum-based chemotherapy and one anti–PD-L1 drug are sought for a randomized, open-label, phase 3 trial comparing second-line standard docetaxel with experimental antibody-drug conjugate sigvotatug vedotin. Patients who have tumors with certain treatable genomic alterations must have received at least one drug targeted to that alteration, as well as a platinum-based agent.

Approximately half the participants will receive sigvotatug vedotin by IV every 2 weeks, and the other half will receive IV docetaxel every 3 weeks. The study opened in March across 13 US states, France, Hungary, Poland, and Spain seeking 600 people eligible to participate. The primary outcomes are overall survival over approximately 5 years and objective response rate. QoL is a secondary outcome. More details at clinicaltrials.gov.All trial information is from the National Institutes of Health US National Library of Medicine (online at clinicaltrials.gov).

A version of this article appeared on Medscape.com .

Several new studies in lung cancer have opened their doors recently. Is one of your patients eligible to participate?

Resected stage II, IIIA, or IIIB with nodal involvement non–small cell lung cancer (NSCLC). Adult patients with this type of cancer can join a randomized, controlled, phase 3 study assessing whether an investigational drug called V940 added to pembrolizumab (Keytruda) delays cancer recurrence better than pembrolizumab alone.

V940 is an individualized neoantigen therapy designed to generate T-cell antitumor responses targeted to a patient’s specific mutation profile.

V940 plus pembrolizumab showed a trend toward longer recurrence-free survival vs pembrolizumab alone in a recent phase 2 study in melanoma (hazard ratio, 0.561; P = .053).

In the current trial, one group of participants will receive intramuscular injections of V940 every 3 weeks plus intravenous (IV) pembrolizumab every 6 weeks for up to approximately 1 year or until disease recurrence or unacceptable toxicity, whichever happens first. The other people in the trial will be on the same schedule, with a placebo replacing V940.

Centers in Florida, Georgia, Kentucky, Montana, New Jersey, New York, North Dakota, and six other countries started recruiting for the trial’s 868 participants in December 2023. Disease-free survival is the primary endpoint. Overall survival over approximately 12 years and quality of life (QoL) are secondary endpoints. More details at clinicaltrials.gov.

Metastatic NSCLC with a programmed cell death ligand 1 (PD-L1)–tumor proportion score of > 50%. Adults in this clinical situation are eligible for a randomized, open-label, phase 3 trial to determine whether an experimental antibody-drug conjugate called MK-2870 added to standard pembrolizumab prolongs survival.

MK-2870 delivers a cytotoxin to cancer cells by binding to trophoblast cell-surface antigen 2, known to promote tumor cell growth and metastasis. For up to 2 years, half of participants will receive MK-2870 by IV every 2 weeks plus IV pembrolizumab every 6 weeks. The other group will receive only pembrolizumab.

In December 2023, study sites in Georgia, Minnesota, Mississippi, Nevada, Oregon, Australia, Denmark, Taiwan, and Turkey started seeking the trial’s 614 participants. Overall survival over approximately 4 years is the primary endpoint; QoL is a secondary endpoint. More details at clinicaltrials.gov.

Untreated locally advanced or metastatic NSCLC with KRAS G12C mutations. Individuals with this type of lung cancer may be interested in a randomized, controlled, phase 3 study examining whether an experimental oral KRAS G12C inhibitor called LY3537982 boosts the effectiveness of standard treatment and patients can tolerate the combination. Currently approved KRAS G12C inhibitors sotorasib (Lumakras, Lumykras) and adagrasib (Krazati) are indicated for second-line treatment; this trial may lead to a first-line approval for newcomer LY3537982.

The trial has three parts: dose optimization, safety, and efficacy. During dose optimization, each participant will take one of two oral doses of LY3537982 and receive IV pembrolizumab every 3 weeks. In the safety phase, all participants will receive oral LY3537982 at the chosen dose plus standard therapy of 3-times-weekly IV pembrolizumab, pemetrexed, and a platinum therapy (cisplatin or carboplatin). In the experimental phase, for up to about 1 year, participants will receive one of these four options: Pembrolizumab plus LY3537982, pembrolizumab plus a placebo, standard therapy plus LY3537982, or standard therapy plus a placebo.

The study, which is planning to recruit 1016 participants, opened across 16 US states and 12 countries worldwide in December 2023. Sites in 11 more US states, the District of Columbia, Brazil, Canada, China, India, and 11 more European countries are gearing up. Adverse events and progression-free survival are the primary endpoints. Overall survival over approximately 3 years and QoL are secondary endpoints. More details at clinicaltrials.gov.

Unresectable, untreated locally advanced or metastatic non-squamous NSCLC with human epidermal growth factor receptor 2 (HER2) mutations. People with this diagnosis who have HER2 mutations instead of KRAS G12C mutations can participate in a phase 3 study comparing an investigational oral first-line treatment with standard IV therapy. The drug in this study, zongertinib, is a HER2 tyrosine kinase inhibitor.

For up to approximately 4 years, one group of participants will take oral zongertinib only, and the other individuals will receive IV pembrolizumab, pemetrexed, and a platinum agent (cisplatin or carboplatin). Study sites in California, Missouri, South Carolina, Australia, China, Japan, South Korea, and Singapore opened in January ready to welcome 270 participants. Progression-free survival is the primary outcome. Overall survival over 53 months and QoL are secondary endpoints. More details at clinicaltrials.gov.

Completely resected stage IIB, IIIA, or select IIIB, PD-L1–positive NSCLC. Adults with this type of lung cancer who have received adjuvant platinum-based chemotherapy may be eligible for a randomized, controlled, phase 3 study to assess whether two immune checkpoint inhibitors are better than one at delaying cancer recurrence. In this trial, tiragolumab will be added to the approved PD-L1 inhibitor atezolizumab (Tecentriq).

A recent study, however, found that tiragolumab did not confer an additional benefit when added to atezolizumab, carboplatin, and etoposide in untreated extensive-stage small cell lung cancer.

In the current trial, one group of participants will receive IV atezolizumab and tiragolumab, while the other people will receive a placebo instead of tiragolumab. Centers in California, Georgia, Illinois, New Mexico, Australia, China, South Korea, and Taiwan started recruiting for the trial’s 1150 participants in March 2024. Disease-free survival is the primary endpoint. Overall survival over approximately 15 years and QoL are secondary outcomes. More details at clinicaltrials.gov.

Previously treated metastatic or non-operable non-squamous NSCLC. Adults in this position who have received no more than one platinum-based chemotherapy and one anti–PD-L1 drug are sought for a randomized, open-label, phase 3 trial comparing second-line standard docetaxel with experimental antibody-drug conjugate sigvotatug vedotin. Patients who have tumors with certain treatable genomic alterations must have received at least one drug targeted to that alteration, as well as a platinum-based agent.

Approximately half the participants will receive sigvotatug vedotin by IV every 2 weeks, and the other half will receive IV docetaxel every 3 weeks. The study opened in March across 13 US states, France, Hungary, Poland, and Spain seeking 600 people eligible to participate. The primary outcomes are overall survival over approximately 5 years and objective response rate. QoL is a secondary outcome. More details at clinicaltrials.gov.All trial information is from the National Institutes of Health US National Library of Medicine (online at clinicaltrials.gov).

A version of this article appeared on Medscape.com .

This transcript has been edited for clarity. 

Andrew N. Wilner, MD: My guest today is Dr. Jose Merino, editor in chief of the Neurology family of journals and professor of neurology and co-vice chair of education at Georgetown University in Washington, DC.

Our program today is a follow-up of Dr. Merino’s presentation at the recent American Academy of Neurology meeting in Denver, Colorado. Along with two other panelists, Dr. Merino discussed the role of open-access publication and the dangers of predatory journals. 

Jose G. Merino, MD, MPhil: Thank you for having me here. It’s a pleasure.
 

Open Access Defined

Dr. Wilner: I remember when publication in neurology was pretty straightforward. It was either the green journal or the blue journal, but things have certainly changed. I think one topic that is not clear to everyone is this concept of open access. Could you define that for us? 

Dr. Merino: Sure. Open access is a mode of publication that fosters more open or accessible science. The idea of open access is that it combines two main elements. One is that the papers that are published become immediately available to anybody with an internet connection anywhere in the world without any restrictions. 

The second important element from open access, which makes it different from other models we can talk about, is the fact that the authors retain the copyright of their work, but they give the journal and readers a license to use, reproduce, and modify the content.

This is different, for example, from instances where we have funder mandates. For example, NIH papers have to become available 6 months after publication, so they’re available to everybody but not immediately. 

Then copyright is retained, in the case of NIH employees, for example, by the government or by the journals themselves. The two elements of open access, I think, are immediate access to the material and the fact that it’s published with a Creative Commons license. 

Dr. Wilner: I remember that when a journal article was published, say, in Neurology, if you didn’t have a subscription to Neurology, you went to the library that hopefully had a subscription.

If they didn’t have it, you would write to the author and say, “Hey, I heard you have this great paper because the abstract was out there. Could you send me a reprint?” Has that whole universe evaporated? 

Dr. Merino: It depends on how the paper is published. For example, in Neurology, some of the research we publish is open access. Basically, if you have an internet connection, you can access the paper.

That’s the case for papers published in our wholly open-access journals in the Neurology family like Neurology Neuroimmunology & Neuroinflammation, Neurology Genetics, or Neurology Education. 

For other papers that are published in Neurology, not under open access, there is a paywall. For some of them, the paywall comes down after a few months based on funder mandates and so on. As I was mentioning, the NIH-funded papers are available 6 months later. 

In the first 6 months, you may have to go to your library, and if your library has a subscription, you can download it directly. [This is also true for] those that always stay behind the paywall, where you have to have a subscription or your library has to have a subscription.
 

Is Pay to Publish a Red Flag?

Dr. Wilner: I’m a professional writer. With any luck, when I write something, I get paid to write it. There’s been a long tradition in academic medicine that when you submit an article to, say, Neurology, you don’t get paid as an author for the publication. Your reward is the honor of it being published. 

Neurology supports itself in various ways, including advertising and so on. That’s been the contract: free publication for work that merits it, and the journal survives on its own. 

With open access, one of the things that’s happened is that — and I’ve published open access myself — is that I get a notification that I need to pay to have my article that I’ve slaved over published. Explain that, please. 

Dr. Merino: This is the issue with open access. As I mentioned, the paper gets published. You’re giving the journal a license to publish it. You’re retaining the copyright of your work. That means that the journal cannot make money or support itself by just publishing open access because they belong to you. 

Typically, open-access journals are not in print and don’t have much in terms of advertising. The contract is you’re giving me a license to publish it, but it’s your journal, so you’re paying a fee for the journal expenses to basically produce your paper. That’s what’s happening with open access. 

That’s been recognized with many funders, for example, with NIH funding or many of the European funders, they’re including open-access fees as part of their funding for research. Now, of course, this doesn’t help if you’re not a funded researcher or if you’re a fellow who’s doing work and so on. 

Typically, most journals will have waived fees or lower fees for these situations. The reason for the open-access fee is the fact that you’re retaining the copyright. You’re not giving it to the journal who can then use it to generate its revenue for supporting itself, the editorial staff, and so on. 

Dr. Wilner: This idea of charging for publication has created a satellite business of what are called predatory journals. How does one know if the open-access journal that I’m submitting to is really just in the business of wanting my $300 or my $900 to get published? How do I know if that’s a reasonable place to publish? 
 

Predatory Journals

Dr. Merino: That’s a big challenge that has come with this whole idea of open access and the fact that now, many journals are online only, so you’re no longer seeing a physical copy. That has given rise to the predatory journals. 

The predatory journal, by definition, is a journal that claims to be open access. They’ll take your paper and publish it, but they don’t provide all the other services that you would typically expect from the fact that you’re paying an open-access fee. This includes getting appropriate peer review, production of the manuscript, and long-term curation and storage of the manuscript. 

Many predatory journals will take your open-access fee, accept any paper that you submit, regardless of the quality, because they’re charging the fees for that. They don’t send it to real peer review, and then in a few months, the journal disappears so there’s no way for anybody to actually find your paper anymore. 

There are certain checklists. Dr. David Moher at the University of Toronto has produced some work trying to help us identify predatory journals. 

One thing I typically suggest to people who ask me this question is: Have you ever heard of this journal before? Does the journal have a track record? How far back does the story of the journal go? Is it supported by a publisher that you know? Do you know anybody who has published there? Is it something you can easily access?

If in doubt, always ask your friendly medical librarian. There used to be lists that were kept in terms of predatory journals that were being constantly updated, but those had to be shut down. As far as I understand, there were legal issues in terms of how things got on that list. 

I think that overall, if you’ve heard of it, if it’s relevant, if it’s known in your field, and if your librarian knows it, it’s probably a good legitimate open-access journal. There are many very good legitimate open-access journals. 

I mentioned the two that we have in our family, but all the other major journals have their own open-access journal within their family. There are some, like BMC or PLOS, that are completely open-access and legitimate journals. 
 

Impact Factor

Dr. Wilner: What about impact factor? Many journals boast about their impact factor. I’m not sure how to interpret that number. 

Dr. Merino: Impact factor is very interesting. The impact factor was developed by medical librarians to try to identify the journals they should be subscribing to. It’s a measure of the average citations to an average paper in the journal. 

It doesn’t tell you about specific papers. It tells you, on average, how many of the papers in this journal get cited so many times. It’s calculated by the number of articles that were cited divided by the number of articles that were published. Journals that publish many papers, like Neurology, have a hard time bringing up their impact factor beyond a certain level. 

Similarly, very small journals with one or two very highly cited papers have a very high impact factor. It’s being used as a measure, perhaps inappropriately, of how good or how reputable a journal is. We all say we don’t care about journal impact factors, but we all know our journal impact factor and we used to know it to three decimals. Now, they changed the system, and there’s only one decimal point, which makes more sense. 

This is more important, for example, for authors when deciding where to submit papers. I know that in some countries, particularly in Europe, the impact factor of the journal where you publish has an impact on your promotion decisions. 

I would say what’s even more important than the impact factor, is to say, “Well, is this the journal that fits the scope of my paper? Is this the journal that reaches the audience that I want to reach when I write my paper?” 

There are some papers, for example, that are very influential. The impact factor just captures citations. There are some papers that are very influential that may not get cited very often. There may be papers that change clinical practice. 

If you read a paper that tells you that you should be changing how you treat your patients with myasthenia based on this paper, that may not get cited. It’s a very clinically focused paper, but it’s probably more impactful than one that gets cited very much in some respect, or they make it to public policy decisions, and so on. 

I think it’s important to look more at the audience and the journal scope when you submit your papers. 

Dr. Wilner: One other technical question. The journals also say they’re indexed in PubMed or Google Scholar. If I want to publish my paper and I want it indexed where the right people are going to find it, where does it need to be indexed? 

Dr. Merino: I grew up using Index Medicus, MedlinePlus, and the Library of Science. I still do. If I need to find something, I go to PubMed. Ideally, papers are listed in MedlinePlus or can be found in PubMed. They’re not the same thing, but you can find them through them. 

That would be an important thing. Nowadays, a lot more people are using Google Scholar or Google just to identify papers. It may be a little bit less relevant, but it’s still a measure of the quality of the journal before they get indexed in some of these. For example, if you get listed in MedlinePlus, it has gone through certain quality checks by the index itself to see whether they would accept the journal or not. That’s something you want to check.

Typically, most of the large journals or the journals you and I know about are listed in more than one place, right? They’re listed in Scopus and Web of Science. They’re listed in MedlinePlus and so on. Again, if you’re submitting your paper, go somewhere where you know the journal and you’ve heard about it. 

Dr. Wilner: I’m not going to ask you about artificial intelligence. We can do that another time. I want to ask something closer to me, which is this question of publish or perish. 

There seems to be, in academics, more emphasis on the number of papers that one has published rather than their quality. How does a younger academician or one who really needs to publish cope with that? 

Dr. Merino: Many people are writing up research that may not be relevant or that may not be high quality just because you need to have a long list of papers to get promoted, for example, if you’re an academician. 

Doug Altman, who was a very influential person in the field quality of not only medical statistics but also medical publishing, had the idea that we need less research, but we need better research. 

We often receive papers where you say, well, what’s the rationale behind the question in this paper? It’s like they had a large amount of data and were trying to squeeze as much as they could out of that. I think, as a young academician, the important thing to think about is whether it is an important question that matters to you and to the field, from whatever perspective, whether it’s going to advance research, advance clinical care, or have public policy implications. 

Is this one where the answer will be important no matter what the answer is? If you’re thinking of that, your work will be well recognized, people will know you, and you’ll get invited to collaborate. I think that’s the most important thing rather than just churning out a large number of papers. 

The productivity will come from the fact that you start by saying, let me ask something that’s really meaningful to me and to the field, with a good question and using strong research methodology. 

Dr. Wilner: Thanks for that, Dr. Merino. I think that’s very valuable for all of us. This has been a great discussion. Do you have any final comments before we wrap up? 

Dr. Merino: I want to encourage people to continue reading medical journals all the time and submitting to us, again, good research and important questions with robust methodology. That’s what we’re looking for in Neurology and most serious medical journals.
 

Dr. Wilner is an associate professor of neurology at the University of Tennessee Health Science Center, Memphis. Dr. Merino is a professor in the department of neurology at Georgetown University Medical Center, Washington, DC. Dr. Wilner reported conflicts of interest with Accordant Health Services and Lulu Publishing. Dr. Merino reported no relevant conflicts of interest.

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

This transcript has been edited for clarity. 

Andrew N. Wilner, MD: My guest today is Dr. Jose Merino, editor in chief of the Neurology family of journals and professor of neurology and co-vice chair of education at Georgetown University in Washington, DC.

Our program today is a follow-up of Dr. Merino’s presentation at the recent American Academy of Neurology meeting in Denver, Colorado. Along with two other panelists, Dr. Merino discussed the role of open-access publication and the dangers of predatory journals. 

Jose G. Merino, MD, MPhil: Thank you for having me here. It’s a pleasure.
 

Open Access Defined

Dr. Wilner: I remember when publication in neurology was pretty straightforward. It was either the green journal or the blue journal, but things have certainly changed. I think one topic that is not clear to everyone is this concept of open access. Could you define that for us? 

Dr. Merino: Sure. Open access is a mode of publication that fosters more open or accessible science. The idea of open access is that it combines two main elements. One is that the papers that are published become immediately available to anybody with an internet connection anywhere in the world without any restrictions. 

The second important element from open access, which makes it different from other models we can talk about, is the fact that the authors retain the copyright of their work, but they give the journal and readers a license to use, reproduce, and modify the content.

This is different, for example, from instances where we have funder mandates. For example, NIH papers have to become available 6 months after publication, so they’re available to everybody but not immediately. 

Then copyright is retained, in the case of NIH employees, for example, by the government or by the journals themselves. The two elements of open access, I think, are immediate access to the material and the fact that it’s published with a Creative Commons license. 

Dr. Wilner: I remember that when a journal article was published, say, in Neurology, if you didn’t have a subscription to Neurology, you went to the library that hopefully had a subscription.

If they didn’t have it, you would write to the author and say, “Hey, I heard you have this great paper because the abstract was out there. Could you send me a reprint?” Has that whole universe evaporated? 

Dr. Merino: It depends on how the paper is published. For example, in Neurology, some of the research we publish is open access. Basically, if you have an internet connection, you can access the paper.

That’s the case for papers published in our wholly open-access journals in the Neurology family like Neurology Neuroimmunology & Neuroinflammation, Neurology Genetics, or Neurology Education. 

For other papers that are published in Neurology, not under open access, there is a paywall. For some of them, the paywall comes down after a few months based on funder mandates and so on. As I was mentioning, the NIH-funded papers are available 6 months later. 

In the first 6 months, you may have to go to your library, and if your library has a subscription, you can download it directly. [This is also true for] those that always stay behind the paywall, where you have to have a subscription or your library has to have a subscription.
 

Is Pay to Publish a Red Flag?

Dr. Wilner: I’m a professional writer. With any luck, when I write something, I get paid to write it. There’s been a long tradition in academic medicine that when you submit an article to, say, Neurology, you don’t get paid as an author for the publication. Your reward is the honor of it being published. 

Neurology supports itself in various ways, including advertising and so on. That’s been the contract: free publication for work that merits it, and the journal survives on its own. 

With open access, one of the things that’s happened is that — and I’ve published open access myself — is that I get a notification that I need to pay to have my article that I’ve slaved over published. Explain that, please. 

Dr. Merino: This is the issue with open access. As I mentioned, the paper gets published. You’re giving the journal a license to publish it. You’re retaining the copyright of your work. That means that the journal cannot make money or support itself by just publishing open access because they belong to you. 

Typically, open-access journals are not in print and don’t have much in terms of advertising. The contract is you’re giving me a license to publish it, but it’s your journal, so you’re paying a fee for the journal expenses to basically produce your paper. That’s what’s happening with open access. 

That’s been recognized with many funders, for example, with NIH funding or many of the European funders, they’re including open-access fees as part of their funding for research. Now, of course, this doesn’t help if you’re not a funded researcher or if you’re a fellow who’s doing work and so on. 

Typically, most journals will have waived fees or lower fees for these situations. The reason for the open-access fee is the fact that you’re retaining the copyright. You’re not giving it to the journal who can then use it to generate its revenue for supporting itself, the editorial staff, and so on. 

Dr. Wilner: This idea of charging for publication has created a satellite business of what are called predatory journals. How does one know if the open-access journal that I’m submitting to is really just in the business of wanting my $300 or my $900 to get published? How do I know if that’s a reasonable place to publish? 
 

Predatory Journals

Dr. Merino: That’s a big challenge that has come with this whole idea of open access and the fact that now, many journals are online only, so you’re no longer seeing a physical copy. That has given rise to the predatory journals. 

The predatory journal, by definition, is a journal that claims to be open access. They’ll take your paper and publish it, but they don’t provide all the other services that you would typically expect from the fact that you’re paying an open-access fee. This includes getting appropriate peer review, production of the manuscript, and long-term curation and storage of the manuscript. 

Many predatory journals will take your open-access fee, accept any paper that you submit, regardless of the quality, because they’re charging the fees for that. They don’t send it to real peer review, and then in a few months, the journal disappears so there’s no way for anybody to actually find your paper anymore. 

There are certain checklists. Dr. David Moher at the University of Toronto has produced some work trying to help us identify predatory journals. 

One thing I typically suggest to people who ask me this question is: Have you ever heard of this journal before? Does the journal have a track record? How far back does the story of the journal go? Is it supported by a publisher that you know? Do you know anybody who has published there? Is it something you can easily access?

If in doubt, always ask your friendly medical librarian. There used to be lists that were kept in terms of predatory journals that were being constantly updated, but those had to be shut down. As far as I understand, there were legal issues in terms of how things got on that list. 

I think that overall, if you’ve heard of it, if it’s relevant, if it’s known in your field, and if your librarian knows it, it’s probably a good legitimate open-access journal. There are many very good legitimate open-access journals. 

I mentioned the two that we have in our family, but all the other major journals have their own open-access journal within their family. There are some, like BMC or PLOS, that are completely open-access and legitimate journals. 
 

Impact Factor

Dr. Wilner: What about impact factor? Many journals boast about their impact factor. I’m not sure how to interpret that number. 

Dr. Merino: Impact factor is very interesting. The impact factor was developed by medical librarians to try to identify the journals they should be subscribing to. It’s a measure of the average citations to an average paper in the journal. 

It doesn’t tell you about specific papers. It tells you, on average, how many of the papers in this journal get cited so many times. It’s calculated by the number of articles that were cited divided by the number of articles that were published. Journals that publish many papers, like Neurology, have a hard time bringing up their impact factor beyond a certain level. 

Similarly, very small journals with one or two very highly cited papers have a very high impact factor. It’s being used as a measure, perhaps inappropriately, of how good or how reputable a journal is. We all say we don’t care about journal impact factors, but we all know our journal impact factor and we used to know it to three decimals. Now, they changed the system, and there’s only one decimal point, which makes more sense. 

This is more important, for example, for authors when deciding where to submit papers. I know that in some countries, particularly in Europe, the impact factor of the journal where you publish has an impact on your promotion decisions. 

I would say what’s even more important than the impact factor, is to say, “Well, is this the journal that fits the scope of my paper? Is this the journal that reaches the audience that I want to reach when I write my paper?” 

There are some papers, for example, that are very influential. The impact factor just captures citations. There are some papers that are very influential that may not get cited very often. There may be papers that change clinical practice. 

If you read a paper that tells you that you should be changing how you treat your patients with myasthenia based on this paper, that may not get cited. It’s a very clinically focused paper, but it’s probably more impactful than one that gets cited very much in some respect, or they make it to public policy decisions, and so on. 

I think it’s important to look more at the audience and the journal scope when you submit your papers. 

Dr. Wilner: One other technical question. The journals also say they’re indexed in PubMed or Google Scholar. If I want to publish my paper and I want it indexed where the right people are going to find it, where does it need to be indexed? 

Dr. Merino: I grew up using Index Medicus, MedlinePlus, and the Library of Science. I still do. If I need to find something, I go to PubMed. Ideally, papers are listed in MedlinePlus or can be found in PubMed. They’re not the same thing, but you can find them through them. 

That would be an important thing. Nowadays, a lot more people are using Google Scholar or Google just to identify papers. It may be a little bit less relevant, but it’s still a measure of the quality of the journal before they get indexed in some of these. For example, if you get listed in MedlinePlus, it has gone through certain quality checks by the index itself to see whether they would accept the journal or not. That’s something you want to check.

Typically, most of the large journals or the journals you and I know about are listed in more than one place, right? They’re listed in Scopus and Web of Science. They’re listed in MedlinePlus and so on. Again, if you’re submitting your paper, go somewhere where you know the journal and you’ve heard about it. 

Dr. Wilner: I’m not going to ask you about artificial intelligence. We can do that another time. I want to ask something closer to me, which is this question of publish or perish. 

There seems to be, in academics, more emphasis on the number of papers that one has published rather than their quality. How does a younger academician or one who really needs to publish cope with that? 

Dr. Merino: Many people are writing up research that may not be relevant or that may not be high quality just because you need to have a long list of papers to get promoted, for example, if you’re an academician. 

Doug Altman, who was a very influential person in the field quality of not only medical statistics but also medical publishing, had the idea that we need less research, but we need better research. 

We often receive papers where you say, well, what’s the rationale behind the question in this paper? It’s like they had a large amount of data and were trying to squeeze as much as they could out of that. I think, as a young academician, the important thing to think about is whether it is an important question that matters to you and to the field, from whatever perspective, whether it’s going to advance research, advance clinical care, or have public policy implications. 

Is this one where the answer will be important no matter what the answer is? If you’re thinking of that, your work will be well recognized, people will know you, and you’ll get invited to collaborate. I think that’s the most important thing rather than just churning out a large number of papers. 

The productivity will come from the fact that you start by saying, let me ask something that’s really meaningful to me and to the field, with a good question and using strong research methodology. 

Dr. Wilner: Thanks for that, Dr. Merino. I think that’s very valuable for all of us. This has been a great discussion. Do you have any final comments before we wrap up? 

Dr. Merino: I want to encourage people to continue reading medical journals all the time and submitting to us, again, good research and important questions with robust methodology. That’s what we’re looking for in Neurology and most serious medical journals.
 

Dr. Wilner is an associate professor of neurology at the University of Tennessee Health Science Center, Memphis. Dr. Merino is a professor in the department of neurology at Georgetown University Medical Center, Washington, DC. Dr. Wilner reported conflicts of interest with Accordant Health Services and Lulu Publishing. Dr. Merino reported no relevant conflicts of interest.

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

This transcript has been edited for clarity. 

Andrew N. Wilner, MD: My guest today is Dr. Jose Merino, editor in chief of the Neurology family of journals and professor of neurology and co-vice chair of education at Georgetown University in Washington, DC.

Our program today is a follow-up of Dr. Merino’s presentation at the recent American Academy of Neurology meeting in Denver, Colorado. Along with two other panelists, Dr. Merino discussed the role of open-access publication and the dangers of predatory journals. 

Jose G. Merino, MD, MPhil: Thank you for having me here. It’s a pleasure.
 

Open Access Defined

Dr. Wilner: I remember when publication in neurology was pretty straightforward. It was either the green journal or the blue journal, but things have certainly changed. I think one topic that is not clear to everyone is this concept of open access. Could you define that for us? 

Dr. Merino: Sure. Open access is a mode of publication that fosters more open or accessible science. The idea of open access is that it combines two main elements. One is that the papers that are published become immediately available to anybody with an internet connection anywhere in the world without any restrictions. 

The second important element from open access, which makes it different from other models we can talk about, is the fact that the authors retain the copyright of their work, but they give the journal and readers a license to use, reproduce, and modify the content.

This is different, for example, from instances where we have funder mandates. For example, NIH papers have to become available 6 months after publication, so they’re available to everybody but not immediately. 

Then copyright is retained, in the case of NIH employees, for example, by the government or by the journals themselves. The two elements of open access, I think, are immediate access to the material and the fact that it’s published with a Creative Commons license. 

Dr. Wilner: I remember that when a journal article was published, say, in Neurology, if you didn’t have a subscription to Neurology, you went to the library that hopefully had a subscription.

If they didn’t have it, you would write to the author and say, “Hey, I heard you have this great paper because the abstract was out there. Could you send me a reprint?” Has that whole universe evaporated? 

Dr. Merino: It depends on how the paper is published. For example, in Neurology, some of the research we publish is open access. Basically, if you have an internet connection, you can access the paper.

That’s the case for papers published in our wholly open-access journals in the Neurology family like Neurology Neuroimmunology & Neuroinflammation, Neurology Genetics, or Neurology Education. 

For other papers that are published in Neurology, not under open access, there is a paywall. For some of them, the paywall comes down after a few months based on funder mandates and so on. As I was mentioning, the NIH-funded papers are available 6 months later. 

In the first 6 months, you may have to go to your library, and if your library has a subscription, you can download it directly. [This is also true for] those that always stay behind the paywall, where you have to have a subscription or your library has to have a subscription.
 

Is Pay to Publish a Red Flag?

Dr. Wilner: I’m a professional writer. With any luck, when I write something, I get paid to write it. There’s been a long tradition in academic medicine that when you submit an article to, say, Neurology, you don’t get paid as an author for the publication. Your reward is the honor of it being published. 

Neurology supports itself in various ways, including advertising and so on. That’s been the contract: free publication for work that merits it, and the journal survives on its own. 

With open access, one of the things that’s happened is that — and I’ve published open access myself — is that I get a notification that I need to pay to have my article that I’ve slaved over published. Explain that, please. 

Dr. Merino: This is the issue with open access. As I mentioned, the paper gets published. You’re giving the journal a license to publish it. You’re retaining the copyright of your work. That means that the journal cannot make money or support itself by just publishing open access because they belong to you. 

Typically, open-access journals are not in print and don’t have much in terms of advertising. The contract is you’re giving me a license to publish it, but it’s your journal, so you’re paying a fee for the journal expenses to basically produce your paper. That’s what’s happening with open access. 

That’s been recognized with many funders, for example, with NIH funding or many of the European funders, they’re including open-access fees as part of their funding for research. Now, of course, this doesn’t help if you’re not a funded researcher or if you’re a fellow who’s doing work and so on. 

Typically, most journals will have waived fees or lower fees for these situations. The reason for the open-access fee is the fact that you’re retaining the copyright. You’re not giving it to the journal who can then use it to generate its revenue for supporting itself, the editorial staff, and so on. 

Dr. Wilner: This idea of charging for publication has created a satellite business of what are called predatory journals. How does one know if the open-access journal that I’m submitting to is really just in the business of wanting my $300 or my $900 to get published? How do I know if that’s a reasonable place to publish? 
 

Predatory Journals

Dr. Merino: That’s a big challenge that has come with this whole idea of open access and the fact that now, many journals are online only, so you’re no longer seeing a physical copy. That has given rise to the predatory journals. 

The predatory journal, by definition, is a journal that claims to be open access. They’ll take your paper and publish it, but they don’t provide all the other services that you would typically expect from the fact that you’re paying an open-access fee. This includes getting appropriate peer review, production of the manuscript, and long-term curation and storage of the manuscript. 

Many predatory journals will take your open-access fee, accept any paper that you submit, regardless of the quality, because they’re charging the fees for that. They don’t send it to real peer review, and then in a few months, the journal disappears so there’s no way for anybody to actually find your paper anymore. 

There are certain checklists. Dr. David Moher at the University of Toronto has produced some work trying to help us identify predatory journals. 

One thing I typically suggest to people who ask me this question is: Have you ever heard of this journal before? Does the journal have a track record? How far back does the story of the journal go? Is it supported by a publisher that you know? Do you know anybody who has published there? Is it something you can easily access?

If in doubt, always ask your friendly medical librarian. There used to be lists that were kept in terms of predatory journals that were being constantly updated, but those had to be shut down. As far as I understand, there were legal issues in terms of how things got on that list. 

I think that overall, if you’ve heard of it, if it’s relevant, if it’s known in your field, and if your librarian knows it, it’s probably a good legitimate open-access journal. There are many very good legitimate open-access journals. 

I mentioned the two that we have in our family, but all the other major journals have their own open-access journal within their family. There are some, like BMC or PLOS, that are completely open-access and legitimate journals. 
 

Impact Factor

Dr. Wilner: What about impact factor? Many journals boast about their impact factor. I’m not sure how to interpret that number. 

Dr. Merino: Impact factor is very interesting. The impact factor was developed by medical librarians to try to identify the journals they should be subscribing to. It’s a measure of the average citations to an average paper in the journal. 

It doesn’t tell you about specific papers. It tells you, on average, how many of the papers in this journal get cited so many times. It’s calculated by the number of articles that were cited divided by the number of articles that were published. Journals that publish many papers, like Neurology, have a hard time bringing up their impact factor beyond a certain level. 

Similarly, very small journals with one or two very highly cited papers have a very high impact factor. It’s being used as a measure, perhaps inappropriately, of how good or how reputable a journal is. We all say we don’t care about journal impact factors, but we all know our journal impact factor and we used to know it to three decimals. Now, they changed the system, and there’s only one decimal point, which makes more sense. 

This is more important, for example, for authors when deciding where to submit papers. I know that in some countries, particularly in Europe, the impact factor of the journal where you publish has an impact on your promotion decisions. 

I would say what’s even more important than the impact factor, is to say, “Well, is this the journal that fits the scope of my paper? Is this the journal that reaches the audience that I want to reach when I write my paper?” 

There are some papers, for example, that are very influential. The impact factor just captures citations. There are some papers that are very influential that may not get cited very often. There may be papers that change clinical practice. 

If you read a paper that tells you that you should be changing how you treat your patients with myasthenia based on this paper, that may not get cited. It’s a very clinically focused paper, but it’s probably more impactful than one that gets cited very much in some respect, or they make it to public policy decisions, and so on. 

I think it’s important to look more at the audience and the journal scope when you submit your papers. 

Dr. Wilner: One other technical question. The journals also say they’re indexed in PubMed or Google Scholar. If I want to publish my paper and I want it indexed where the right people are going to find it, where does it need to be indexed? 

Dr. Merino: I grew up using Index Medicus, MedlinePlus, and the Library of Science. I still do. If I need to find something, I go to PubMed. Ideally, papers are listed in MedlinePlus or can be found in PubMed. They’re not the same thing, but you can find them through them. 

That would be an important thing. Nowadays, a lot more people are using Google Scholar or Google just to identify papers. It may be a little bit less relevant, but it’s still a measure of the quality of the journal before they get indexed in some of these. For example, if you get listed in MedlinePlus, it has gone through certain quality checks by the index itself to see whether they would accept the journal or not. That’s something you want to check.

Typically, most of the large journals or the journals you and I know about are listed in more than one place, right? They’re listed in Scopus and Web of Science. They’re listed in MedlinePlus and so on. Again, if you’re submitting your paper, go somewhere where you know the journal and you’ve heard about it. 

Dr. Wilner: I’m not going to ask you about artificial intelligence. We can do that another time. I want to ask something closer to me, which is this question of publish or perish. 

There seems to be, in academics, more emphasis on the number of papers that one has published rather than their quality. How does a younger academician or one who really needs to publish cope with that? 

Dr. Merino: Many people are writing up research that may not be relevant or that may not be high quality just because you need to have a long list of papers to get promoted, for example, if you’re an academician. 

Doug Altman, who was a very influential person in the field quality of not only medical statistics but also medical publishing, had the idea that we need less research, but we need better research. 

We often receive papers where you say, well, what’s the rationale behind the question in this paper? It’s like they had a large amount of data and were trying to squeeze as much as they could out of that. I think, as a young academician, the important thing to think about is whether it is an important question that matters to you and to the field, from whatever perspective, whether it’s going to advance research, advance clinical care, or have public policy implications. 

Is this one where the answer will be important no matter what the answer is? If you’re thinking of that, your work will be well recognized, people will know you, and you’ll get invited to collaborate. I think that’s the most important thing rather than just churning out a large number of papers. 

The productivity will come from the fact that you start by saying, let me ask something that’s really meaningful to me and to the field, with a good question and using strong research methodology. 

Dr. Wilner: Thanks for that, Dr. Merino. I think that’s very valuable for all of us. This has been a great discussion. Do you have any final comments before we wrap up? 

Dr. Merino: I want to encourage people to continue reading medical journals all the time and submitting to us, again, good research and important questions with robust methodology. That’s what we’re looking for in Neurology and most serious medical journals.
 

Dr. Wilner is an associate professor of neurology at the University of Tennessee Health Science Center, Memphis. Dr. Merino is a professor in the department of neurology at Georgetown University Medical Center, Washington, DC. Dr. Wilner reported conflicts of interest with Accordant Health Services and Lulu Publishing. Dr. Merino reported no relevant conflicts of interest.

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

CHICAGO — Adding carboplatin to standard anthracycline/taxane treatment for early-stage triple-negative breast cancer (TNBC) improves event-free and overall survival in the neoadjuvant and adjuvant setting, according to a phase 3 trial presented at the annual meeting of the American Society of Clinical Oncology (ASCO).

The outcomes of the South Korean study, dubbed PEARLY, provide strong evidence for incorporating carboplatin into both the neoadjuvant and adjuvant settings in patients with early-stage TNBC, said lead investigator and presenter Joohyuk Sohn, MD, PhD, a medical oncologist at Yonsei University, Seoul, South Korea.

In early-stage TNBC, carboplatin is already being incorporated into the neoadjuvant setting on the basis of trial results from KEYNOTE-522 that demonstrated improved pathologic complete response rates and event-free survival with the platinum alongside pembrolizumab.

However, the overall survival benefit of carboplatin in this setting remains unclear, as does the benefit of platinum add-on in the adjuvant setting, Dr. Sohn explained.

Dr. Sohn and colleagues randomized 868 patients evenly to either standard treatment — doxorubicin, anthracycline, and cyclophosphamide followed by a taxane — or an experimental arm that added carboplatin to the taxane phase of treatment.

About 30% of women were treated in the adjuvant setting, the rest in the neoadjuvant setting. The two arms of the study were generally well balanced — about 80% of patients had stage II disease, half were node negative, and 11% had deleterious germline mutations.

The primary endpoint, event-free survival, was broadly defined. Events included disease progression, local or distant recurrence, occurrence of a second primary cancer, inoperable status after neoadjuvant therapy, or death from any cause.

Adding carboplatin increased 5-year event-free survival rates from 75.1% to 82.3% (hazard ratio [HR], 0.67; P = .012) with the benefit holding across various subgroup analyses and particularly strong for adjuvant carboplatin (HR, 0.26).

Five-year overall survival was also better in the carboplatin arm — 90.7% vs 87% in the control arm (HR, 0.65; 95% CI, 0.42-1.02) — but that benefit did not reach statistical significance (P = .057)

Invasive disease-free survival (HR, 0.73) and distant recurrence-free survival (HR, 0.77) favored carboplatin, but the results also weren’t statistically significant.

Overall, 46% of patients had a pathologic complete response with carboplatin vs nearly 40% in the control arm. The pathologic complete response benefit from carboplatin add-on was consistent with past reports.

As expected, adding carboplatin to treatment increased hematologic toxicity and other adverse events, with three-quarters of patients experiencing grade 3 or worse adverse events vs 56.7% of control participants. There was one death in the carboplatin arm from pneumonia and two in the control arm — one from septic shock and the other from suicide.

Dr. Sohn and colleagues, however, did not observe a quality of life difference between the two groups.

“The PEARLY trial provides compelling evidence for including carboplatin in the treatment of early-stage TNBC,” Dr. Sohn concluded, adding that the results underscore the benefit in the neoadjuvant setting and suggest “potential applicability in the adjuvant setting post surgery.”

Study discussant Javier Cortes, MD, PhD, believes that the PEARLY provides a strong signal for adding carboplatin in the adjuvant setting.

“That’s something I would do in my clinical practice,” said Dr. Cortes, head of the International Breast Cancer Center in Barcelona, Spain. “After ASCO this year, I would offer taxanes plus carboplatin following anthracyclines.”

An audience member, William Sikov, MD, a breast cancer specialist at Brown University in Providence, Rhode Island, said he hopes “we’ve reached the end of a road that started many years ago in terms of incorporating carboplatin as part of neoadjuvant and adjuvant therapy for triple-negative breast cancer, where we finally [reach] consensus that this is necessary in our triple-negative patients.”

The work was funded by the government of South Korea and others. Dr. Sohn reported stock in Daiichi Sankyo and research funding from Daiichi and other companies. Dr. Cortes disclosed numerous industry ties, including honoraria, research funding, and/or travel expenses from AstraZeneca, Daiichi, and others.

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

CHICAGO — Adding carboplatin to standard anthracycline/taxane treatment for early-stage triple-negative breast cancer (TNBC) improves event-free and overall survival in the neoadjuvant and adjuvant setting, according to a phase 3 trial presented at the annual meeting of the American Society of Clinical Oncology (ASCO).

The outcomes of the South Korean study, dubbed PEARLY, provide strong evidence for incorporating carboplatin into both the neoadjuvant and adjuvant settings in patients with early-stage TNBC, said lead investigator and presenter Joohyuk Sohn, MD, PhD, a medical oncologist at Yonsei University, Seoul, South Korea.

In early-stage TNBC, carboplatin is already being incorporated into the neoadjuvant setting on the basis of trial results from KEYNOTE-522 that demonstrated improved pathologic complete response rates and event-free survival with the platinum alongside pembrolizumab.

However, the overall survival benefit of carboplatin in this setting remains unclear, as does the benefit of platinum add-on in the adjuvant setting, Dr. Sohn explained.

Dr. Sohn and colleagues randomized 868 patients evenly to either standard treatment — doxorubicin, anthracycline, and cyclophosphamide followed by a taxane — or an experimental arm that added carboplatin to the taxane phase of treatment.

About 30% of women were treated in the adjuvant setting, the rest in the neoadjuvant setting. The two arms of the study were generally well balanced — about 80% of patients had stage II disease, half were node negative, and 11% had deleterious germline mutations.

The primary endpoint, event-free survival, was broadly defined. Events included disease progression, local or distant recurrence, occurrence of a second primary cancer, inoperable status after neoadjuvant therapy, or death from any cause.

Adding carboplatin increased 5-year event-free survival rates from 75.1% to 82.3% (hazard ratio [HR], 0.67; P = .012) with the benefit holding across various subgroup analyses and particularly strong for adjuvant carboplatin (HR, 0.26).

Five-year overall survival was also better in the carboplatin arm — 90.7% vs 87% in the control arm (HR, 0.65; 95% CI, 0.42-1.02) — but that benefit did not reach statistical significance (P = .057)

Invasive disease-free survival (HR, 0.73) and distant recurrence-free survival (HR, 0.77) favored carboplatin, but the results also weren’t statistically significant.

Overall, 46% of patients had a pathologic complete response with carboplatin vs nearly 40% in the control arm. The pathologic complete response benefit from carboplatin add-on was consistent with past reports.

As expected, adding carboplatin to treatment increased hematologic toxicity and other adverse events, with three-quarters of patients experiencing grade 3 or worse adverse events vs 56.7% of control participants. There was one death in the carboplatin arm from pneumonia and two in the control arm — one from septic shock and the other from suicide.

Dr. Sohn and colleagues, however, did not observe a quality of life difference between the two groups.

“The PEARLY trial provides compelling evidence for including carboplatin in the treatment of early-stage TNBC,” Dr. Sohn concluded, adding that the results underscore the benefit in the neoadjuvant setting and suggest “potential applicability in the adjuvant setting post surgery.”

Study discussant Javier Cortes, MD, PhD, believes that the PEARLY provides a strong signal for adding carboplatin in the adjuvant setting.

“That’s something I would do in my clinical practice,” said Dr. Cortes, head of the International Breast Cancer Center in Barcelona, Spain. “After ASCO this year, I would offer taxanes plus carboplatin following anthracyclines.”

An audience member, William Sikov, MD, a breast cancer specialist at Brown University in Providence, Rhode Island, said he hopes “we’ve reached the end of a road that started many years ago in terms of incorporating carboplatin as part of neoadjuvant and adjuvant therapy for triple-negative breast cancer, where we finally [reach] consensus that this is necessary in our triple-negative patients.”

The work was funded by the government of South Korea and others. Dr. Sohn reported stock in Daiichi Sankyo and research funding from Daiichi and other companies. Dr. Cortes disclosed numerous industry ties, including honoraria, research funding, and/or travel expenses from AstraZeneca, Daiichi, and others.

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

CHICAGO — Adding carboplatin to standard anthracycline/taxane treatment for early-stage triple-negative breast cancer (TNBC) improves event-free and overall survival in the neoadjuvant and adjuvant setting, according to a phase 3 trial presented at the annual meeting of the American Society of Clinical Oncology (ASCO).

The outcomes of the South Korean study, dubbed PEARLY, provide strong evidence for incorporating carboplatin into both the neoadjuvant and adjuvant settings in patients with early-stage TNBC, said lead investigator and presenter Joohyuk Sohn, MD, PhD, a medical oncologist at Yonsei University, Seoul, South Korea.

In early-stage TNBC, carboplatin is already being incorporated into the neoadjuvant setting on the basis of trial results from KEYNOTE-522 that demonstrated improved pathologic complete response rates and event-free survival with the platinum alongside pembrolizumab.

However, the overall survival benefit of carboplatin in this setting remains unclear, as does the benefit of platinum add-on in the adjuvant setting, Dr. Sohn explained.

Dr. Sohn and colleagues randomized 868 patients evenly to either standard treatment — doxorubicin, anthracycline, and cyclophosphamide followed by a taxane — or an experimental arm that added carboplatin to the taxane phase of treatment.

About 30% of women were treated in the adjuvant setting, the rest in the neoadjuvant setting. The two arms of the study were generally well balanced — about 80% of patients had stage II disease, half were node negative, and 11% had deleterious germline mutations.

The primary endpoint, event-free survival, was broadly defined. Events included disease progression, local or distant recurrence, occurrence of a second primary cancer, inoperable status after neoadjuvant therapy, or death from any cause.

Adding carboplatin increased 5-year event-free survival rates from 75.1% to 82.3% (hazard ratio [HR], 0.67; P = .012) with the benefit holding across various subgroup analyses and particularly strong for adjuvant carboplatin (HR, 0.26).

Five-year overall survival was also better in the carboplatin arm — 90.7% vs 87% in the control arm (HR, 0.65; 95% CI, 0.42-1.02) — but that benefit did not reach statistical significance (P = .057)

Invasive disease-free survival (HR, 0.73) and distant recurrence-free survival (HR, 0.77) favored carboplatin, but the results also weren’t statistically significant.

Overall, 46% of patients had a pathologic complete response with carboplatin vs nearly 40% in the control arm. The pathologic complete response benefit from carboplatin add-on was consistent with past reports.

As expected, adding carboplatin to treatment increased hematologic toxicity and other adverse events, with three-quarters of patients experiencing grade 3 or worse adverse events vs 56.7% of control participants. There was one death in the carboplatin arm from pneumonia and two in the control arm — one from septic shock and the other from suicide.

Dr. Sohn and colleagues, however, did not observe a quality of life difference between the two groups.

“The PEARLY trial provides compelling evidence for including carboplatin in the treatment of early-stage TNBC,” Dr. Sohn concluded, adding that the results underscore the benefit in the neoadjuvant setting and suggest “potential applicability in the adjuvant setting post surgery.”

Study discussant Javier Cortes, MD, PhD, believes that the PEARLY provides a strong signal for adding carboplatin in the adjuvant setting.

“That’s something I would do in my clinical practice,” said Dr. Cortes, head of the International Breast Cancer Center in Barcelona, Spain. “After ASCO this year, I would offer taxanes plus carboplatin following anthracyclines.”

An audience member, William Sikov, MD, a breast cancer specialist at Brown University in Providence, Rhode Island, said he hopes “we’ve reached the end of a road that started many years ago in terms of incorporating carboplatin as part of neoadjuvant and adjuvant therapy for triple-negative breast cancer, where we finally [reach] consensus that this is necessary in our triple-negative patients.”

The work was funded by the government of South Korea and others. Dr. Sohn reported stock in Daiichi Sankyo and research funding from Daiichi and other companies. Dr. Cortes disclosed numerous industry ties, including honoraria, research funding, and/or travel expenses from AstraZeneca, Daiichi, and others.

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

CHICAGO – Circulating tumor DNA (ctDNA), or DNA shed from tumors that is detected in the bloodstream, has shown increasing promise as a prognostic tool in gastrointestinal cancers, allowing investigators to make real-time assessments of treatment response and the likelihood of recurrence.

Depending on the type of assay and analysis used, ctDNA can provide a wealth of information about cancer genetic variants. ctDNA assays can be used for primary screening, to track tumor burden, or to detect minimal residual disease (MRD) after cancer surgery.

However, ctDNA’s role in guiding clinical decisions is still being defined. Australian investigators presented research showing that a negative ctDNA finding can be used to avoid unnecessary chemotherapy in postoperative stage II colon cancer patients without affecting survival outcomes, at the annual meeting of the American Society of Clinical Oncology (ASCO), in Chicago.

The same group also presented exploratory findings showing that positive ctDNA is a significant predictor of recurrence in people with early-stage pancreatic cancer following surgery. However, the investigators concluded, ctDNA status should not be used to inform treatment decisions concerning duration of adjuvant chemotherapy in these patients.
 

DYNAMIC Trial Results

Jeanne Tie, MD, of the Peter MacCallum Cancer Centre in Melbourne, presented 5-year survival results at ASCO from the DYNAMIC randomized controlled trial, whose 2-year findings had already shown ctDNA to be helpful in stratifying stage II colon cancer patients for adjuvant chemotherapy or no treatment.

Because surgery is curative in 80% of these patients, it is important to identify the minority that will need chemotherapy, Dr. Tie said.

At 5 years’ follow-up, Dr. Tie reported, patients randomized to a ctDNA-guided approach (negative ctDNA post surgery resulted in no treatment, and positive ctDNA led to adjuvant chemotherapy) did not see differences in overall survival compared with conventionally managed patients, who received chemotherapy at the clinician’s discretion.

Among ctDNA-guided patients in the study (n = 302), 5-year overall survival was 93.8%. For conventionally managed patients (n = 153), overall survival was 93.3% at 5 years (hazard ratio [HR], 1.05; 95% CI, 0.47-2.37; P = .887).

Further, the researchers found that a high ctDNA clearance rate was achieved with adjuvant chemotherapy in postoperative patients who were ctDNA positive. And 5-year recurrence rates were markedly lower in patients who achieved ctDNA clearance, compared with those who did not: 85.2% vs 20% (HR, 15.4; 95% CI, 3.91-61.0; P < .001).

“This approach of only treating patients with a positive ctDNA achieved excellent survival outcomes, including in patients with T4 disease. A high ctDNA clearance rate can be achieved with adjuvant chemotherapy, and this in turn was associated with favorable outcomes,” Dr. Tie said during the meeting. “And finally, the precision of the ctDNA approach may be further refined by increasing [the number of genetic variants] tracked and by incorporating ctDNA molecular burden. However, these findings will require further validation.”
 

DYNAMIC-Pancreas Study Results

In a separate presentation during the same session, Belinda Lee, MD, also of the Peter MacCallum Cancer Centre, showed results from the DYNAMIC-Pancreas study, which looked at ctDNA testing a median 5 weeks after surgery in 102 people with early-stage (Eastern Cooperative Oncology Group 0-1) pancreatic cancer. Patients who were ctDNA positive received 6 months of adjuvant chemotherapy of the physician’s choice (FOLFIRINOX or gemcitabine/capecitabine) while those who were ctDNA negative after surgery had the option to de-escalate to 3 months of chemotherapy treatment at the physician’s discretion.

At a median 3 years’ follow-up, Dr. Lee and colleagues found that the median recurrence-free survival was 13 months for patients who were ctDNA positive after surgery and 22 months for those who were ctDNA negative (HR, 0.52; P = .003), showing that positive ctDNA is prognostic of earlier recurrence independent of other factors.

Dr. Lee said that, given the high recurrence risk also seen in ctDNA-negative patients, reducing duration of chemotherapy was not recommended based on ctDNA-negative status.

In an interview, Stacey Cohen, MD, of Fred Hutch Cancer Center in Seattle, Washington, the discussant on the two presentations at ASCO, said that, until these results are further validated in stage II colon cancer patients,t it is unlikely that they will change clinical practice guidelines.

“They did an amazing job,” Dr. Cohen said of the researchers. “They’re at the forefront of the field of actually doing prospective analysis. And yet there are still some gaps that are missing in our understanding.”

The assays used in both studies, Dr. Cohen noted, are used only in research and are not available commercially in the United States. That, plus the fact that physicians were allowed to choose between chemotherapy regimens, made it harder to parse the results.

“Provider choice increases bias,” Dr. Cohen said. “And I think that’s the problem of having two chemo regimens to choose from, or in the case of the colon cancer trial, not selecting whether patients got a single chemotherapy agent or a doublet. These are pretty big differences.”

But the field is moving quickly, “and it is an exciting time to improve patient selection for chemotherapy treatment,” she continued.

Allowing physicians to choose chemotherapy regimens reflected real-world clinical practice, “especially given that this study is designed to test a strategy rather than a specific treatment, said Dr. Tie in an interview. “More work will need to be done to specifically address the question of which chemotherapy regimen is more effective to treat ctDNA-positive disease.”

Dr. Cohen noted that, while evidence is mounting to support the value of ctDNA in colon cancer, there is far less evidence for pancreatic cancer.

Dr. Lee and colleagues’ study “adds to the literature, and I think what it teaches us is that ctDNA remains a prognostic risk factor,” she said. “But we saw that even patients who are negative have a high recurrence risk. So we’re not ready to act on it yet. As with the colon cancer study, different chemotherapy regimens were used, and for different time lengths.”

Whether in colon cancer or pancreatic cancer, ctDNA results, “are highly tied to which assay you’re using and which scenario you’re testing them in,” Dr. Cohen said.

Dr. Tie and colleagues’ study was sponsored by her institution, with additional funding received from the Australian government, the National Institutes of Health, and other foundations. She disclosed speaking and/or consulting fees from Haystack Oncology, Amgen, Novartis, Bristol-Myers Squibb, Merck, AstraZeneca, and others. Dr. Lee’s study was sponsored by the Marcus Foundation. She disclosed receiving honoraria from Roche. Dr. Cohen reported no conflicts of interest.

CHICAGO – Circulating tumor DNA (ctDNA), or DNA shed from tumors that is detected in the bloodstream, has shown increasing promise as a prognostic tool in gastrointestinal cancers, allowing investigators to make real-time assessments of treatment response and the likelihood of recurrence.

Depending on the type of assay and analysis used, ctDNA can provide a wealth of information about cancer genetic variants. ctDNA assays can be used for primary screening, to track tumor burden, or to detect minimal residual disease (MRD) after cancer surgery.

However, ctDNA’s role in guiding clinical decisions is still being defined. Australian investigators presented research showing that a negative ctDNA finding can be used to avoid unnecessary chemotherapy in postoperative stage II colon cancer patients without affecting survival outcomes, at the annual meeting of the American Society of Clinical Oncology (ASCO), in Chicago.

The same group also presented exploratory findings showing that positive ctDNA is a significant predictor of recurrence in people with early-stage pancreatic cancer following surgery. However, the investigators concluded, ctDNA status should not be used to inform treatment decisions concerning duration of adjuvant chemotherapy in these patients.
 

DYNAMIC Trial Results

Jeanne Tie, MD, of the Peter MacCallum Cancer Centre in Melbourne, presented 5-year survival results at ASCO from the DYNAMIC randomized controlled trial, whose 2-year findings had already shown ctDNA to be helpful in stratifying stage II colon cancer patients for adjuvant chemotherapy or no treatment.

Because surgery is curative in 80% of these patients, it is important to identify the minority that will need chemotherapy, Dr. Tie said.

At 5 years’ follow-up, Dr. Tie reported, patients randomized to a ctDNA-guided approach (negative ctDNA post surgery resulted in no treatment, and positive ctDNA led to adjuvant chemotherapy) did not see differences in overall survival compared with conventionally managed patients, who received chemotherapy at the clinician’s discretion.

Among ctDNA-guided patients in the study (n = 302), 5-year overall survival was 93.8%. For conventionally managed patients (n = 153), overall survival was 93.3% at 5 years (hazard ratio [HR], 1.05; 95% CI, 0.47-2.37; P = .887).

Further, the researchers found that a high ctDNA clearance rate was achieved with adjuvant chemotherapy in postoperative patients who were ctDNA positive. And 5-year recurrence rates were markedly lower in patients who achieved ctDNA clearance, compared with those who did not: 85.2% vs 20% (HR, 15.4; 95% CI, 3.91-61.0; P < .001).

“This approach of only treating patients with a positive ctDNA achieved excellent survival outcomes, including in patients with T4 disease. A high ctDNA clearance rate can be achieved with adjuvant chemotherapy, and this in turn was associated with favorable outcomes,” Dr. Tie said during the meeting. “And finally, the precision of the ctDNA approach may be further refined by increasing [the number of genetic variants] tracked and by incorporating ctDNA molecular burden. However, these findings will require further validation.”
 

DYNAMIC-Pancreas Study Results

In a separate presentation during the same session, Belinda Lee, MD, also of the Peter MacCallum Cancer Centre, showed results from the DYNAMIC-Pancreas study, which looked at ctDNA testing a median 5 weeks after surgery in 102 people with early-stage (Eastern Cooperative Oncology Group 0-1) pancreatic cancer. Patients who were ctDNA positive received 6 months of adjuvant chemotherapy of the physician’s choice (FOLFIRINOX or gemcitabine/capecitabine) while those who were ctDNA negative after surgery had the option to de-escalate to 3 months of chemotherapy treatment at the physician’s discretion.

At a median 3 years’ follow-up, Dr. Lee and colleagues found that the median recurrence-free survival was 13 months for patients who were ctDNA positive after surgery and 22 months for those who were ctDNA negative (HR, 0.52; P = .003), showing that positive ctDNA is prognostic of earlier recurrence independent of other factors.

Dr. Lee said that, given the high recurrence risk also seen in ctDNA-negative patients, reducing duration of chemotherapy was not recommended based on ctDNA-negative status.

In an interview, Stacey Cohen, MD, of Fred Hutch Cancer Center in Seattle, Washington, the discussant on the two presentations at ASCO, said that, until these results are further validated in stage II colon cancer patients,t it is unlikely that they will change clinical practice guidelines.

“They did an amazing job,” Dr. Cohen said of the researchers. “They’re at the forefront of the field of actually doing prospective analysis. And yet there are still some gaps that are missing in our understanding.”

The assays used in both studies, Dr. Cohen noted, are used only in research and are not available commercially in the United States. That, plus the fact that physicians were allowed to choose between chemotherapy regimens, made it harder to parse the results.

“Provider choice increases bias,” Dr. Cohen said. “And I think that’s the problem of having two chemo regimens to choose from, or in the case of the colon cancer trial, not selecting whether patients got a single chemotherapy agent or a doublet. These are pretty big differences.”

But the field is moving quickly, “and it is an exciting time to improve patient selection for chemotherapy treatment,” she continued.

Allowing physicians to choose chemotherapy regimens reflected real-world clinical practice, “especially given that this study is designed to test a strategy rather than a specific treatment, said Dr. Tie in an interview. “More work will need to be done to specifically address the question of which chemotherapy regimen is more effective to treat ctDNA-positive disease.”

Dr. Cohen noted that, while evidence is mounting to support the value of ctDNA in colon cancer, there is far less evidence for pancreatic cancer.

Dr. Lee and colleagues’ study “adds to the literature, and I think what it teaches us is that ctDNA remains a prognostic risk factor,” she said. “But we saw that even patients who are negative have a high recurrence risk. So we’re not ready to act on it yet. As with the colon cancer study, different chemotherapy regimens were used, and for different time lengths.”

Whether in colon cancer or pancreatic cancer, ctDNA results, “are highly tied to which assay you’re using and which scenario you’re testing them in,” Dr. Cohen said.

Dr. Tie and colleagues’ study was sponsored by her institution, with additional funding received from the Australian government, the National Institutes of Health, and other foundations. She disclosed speaking and/or consulting fees from Haystack Oncology, Amgen, Novartis, Bristol-Myers Squibb, Merck, AstraZeneca, and others. Dr. Lee’s study was sponsored by the Marcus Foundation. She disclosed receiving honoraria from Roche. Dr. Cohen reported no conflicts of interest.

CHICAGO – Circulating tumor DNA (ctDNA), or DNA shed from tumors that is detected in the bloodstream, has shown increasing promise as a prognostic tool in gastrointestinal cancers, allowing investigators to make real-time assessments of treatment response and the likelihood of recurrence.

Depending on the type of assay and analysis used, ctDNA can provide a wealth of information about cancer genetic variants. ctDNA assays can be used for primary screening, to track tumor burden, or to detect minimal residual disease (MRD) after cancer surgery.

However, ctDNA’s role in guiding clinical decisions is still being defined. Australian investigators presented research showing that a negative ctDNA finding can be used to avoid unnecessary chemotherapy in postoperative stage II colon cancer patients without affecting survival outcomes, at the annual meeting of the American Society of Clinical Oncology (ASCO), in Chicago.

The same group also presented exploratory findings showing that positive ctDNA is a significant predictor of recurrence in people with early-stage pancreatic cancer following surgery. However, the investigators concluded, ctDNA status should not be used to inform treatment decisions concerning duration of adjuvant chemotherapy in these patients.
 

DYNAMIC Trial Results

Jeanne Tie, MD, of the Peter MacCallum Cancer Centre in Melbourne, presented 5-year survival results at ASCO from the DYNAMIC randomized controlled trial, whose 2-year findings had already shown ctDNA to be helpful in stratifying stage II colon cancer patients for adjuvant chemotherapy or no treatment.

Because surgery is curative in 80% of these patients, it is important to identify the minority that will need chemotherapy, Dr. Tie said.

At 5 years’ follow-up, Dr. Tie reported, patients randomized to a ctDNA-guided approach (negative ctDNA post surgery resulted in no treatment, and positive ctDNA led to adjuvant chemotherapy) did not see differences in overall survival compared with conventionally managed patients, who received chemotherapy at the clinician’s discretion.

Among ctDNA-guided patients in the study (n = 302), 5-year overall survival was 93.8%. For conventionally managed patients (n = 153), overall survival was 93.3% at 5 years (hazard ratio [HR], 1.05; 95% CI, 0.47-2.37; P = .887).

Further, the researchers found that a high ctDNA clearance rate was achieved with adjuvant chemotherapy in postoperative patients who were ctDNA positive. And 5-year recurrence rates were markedly lower in patients who achieved ctDNA clearance, compared with those who did not: 85.2% vs 20% (HR, 15.4; 95% CI, 3.91-61.0; P < .001).

“This approach of only treating patients with a positive ctDNA achieved excellent survival outcomes, including in patients with T4 disease. A high ctDNA clearance rate can be achieved with adjuvant chemotherapy, and this in turn was associated with favorable outcomes,” Dr. Tie said during the meeting. “And finally, the precision of the ctDNA approach may be further refined by increasing [the number of genetic variants] tracked and by incorporating ctDNA molecular burden. However, these findings will require further validation.”
 

DYNAMIC-Pancreas Study Results

In a separate presentation during the same session, Belinda Lee, MD, also of the Peter MacCallum Cancer Centre, showed results from the DYNAMIC-Pancreas study, which looked at ctDNA testing a median 5 weeks after surgery in 102 people with early-stage (Eastern Cooperative Oncology Group 0-1) pancreatic cancer. Patients who were ctDNA positive received 6 months of adjuvant chemotherapy of the physician’s choice (FOLFIRINOX or gemcitabine/capecitabine) while those who were ctDNA negative after surgery had the option to de-escalate to 3 months of chemotherapy treatment at the physician’s discretion.

At a median 3 years’ follow-up, Dr. Lee and colleagues found that the median recurrence-free survival was 13 months for patients who were ctDNA positive after surgery and 22 months for those who were ctDNA negative (HR, 0.52; P = .003), showing that positive ctDNA is prognostic of earlier recurrence independent of other factors.

Dr. Lee said that, given the high recurrence risk also seen in ctDNA-negative patients, reducing duration of chemotherapy was not recommended based on ctDNA-negative status.

In an interview, Stacey Cohen, MD, of Fred Hutch Cancer Center in Seattle, Washington, the discussant on the two presentations at ASCO, said that, until these results are further validated in stage II colon cancer patients,t it is unlikely that they will change clinical practice guidelines.

“They did an amazing job,” Dr. Cohen said of the researchers. “They’re at the forefront of the field of actually doing prospective analysis. And yet there are still some gaps that are missing in our understanding.”

The assays used in both studies, Dr. Cohen noted, are used only in research and are not available commercially in the United States. That, plus the fact that physicians were allowed to choose between chemotherapy regimens, made it harder to parse the results.

“Provider choice increases bias,” Dr. Cohen said. “And I think that’s the problem of having two chemo regimens to choose from, or in the case of the colon cancer trial, not selecting whether patients got a single chemotherapy agent or a doublet. These are pretty big differences.”

But the field is moving quickly, “and it is an exciting time to improve patient selection for chemotherapy treatment,” she continued.

Allowing physicians to choose chemotherapy regimens reflected real-world clinical practice, “especially given that this study is designed to test a strategy rather than a specific treatment, said Dr. Tie in an interview. “More work will need to be done to specifically address the question of which chemotherapy regimen is more effective to treat ctDNA-positive disease.”

Dr. Cohen noted that, while evidence is mounting to support the value of ctDNA in colon cancer, there is far less evidence for pancreatic cancer.

Dr. Lee and colleagues’ study “adds to the literature, and I think what it teaches us is that ctDNA remains a prognostic risk factor,” she said. “But we saw that even patients who are negative have a high recurrence risk. So we’re not ready to act on it yet. As with the colon cancer study, different chemotherapy regimens were used, and for different time lengths.”

Whether in colon cancer or pancreatic cancer, ctDNA results, “are highly tied to which assay you’re using and which scenario you’re testing them in,” Dr. Cohen said.

Dr. Tie and colleagues’ study was sponsored by her institution, with additional funding received from the Australian government, the National Institutes of Health, and other foundations. She disclosed speaking and/or consulting fees from Haystack Oncology, Amgen, Novartis, Bristol-Myers Squibb, Merck, AstraZeneca, and others. Dr. Lee’s study was sponsored by the Marcus Foundation. She disclosed receiving honoraria from Roche. Dr. Cohen reported no conflicts of interest.

WASHINGTON — In 2013, Vishal A. Patel, MD, was completing a fellowship in Mohs surgery and cutaneous oncology at Columbia University Irving Medical Center, New York City, when a study was published showing that most nonmelanoma skin cancers (NMSCs) were treated with surgery, regardless of the patient’s life expectancy. Life expectancy “should enter into treatment decisions,” the authors concluded.

“The article got a lot of pushback from the Mohs surgeons,” and the value of surgery in older adults and particularly those with limited life expectancy “became a hot topic,” Dr. Patel recalled at the ElderDerm conference hosted by the Department of Dermatology at George Washington University, Washington, DC, and described as a first-of-its-kind meeting dedicated to improving dermatologic care for older adults.

Christine Kilgore

Today, however, more than a decade later, guidelines still promote surgical therapy as the gold standard across the board, and questions raised by the study are still unaddressed, Dr. Patel, associate professor of dermatology and medicine/oncology at George Washington University, said at the meeting. These questions are becoming increasingly urgent as the incidence of skin cancer, especially NMSC, rises in the older adult population, especially in patients older than 85 years. “It’s a function of our training and our treatment guidelines that we reach for the most definitive treatment, which happens to be the most aggressive, in these patients,” added Dr. Patel, who is also director of the cutaneous oncology program at the GW Cancer Center.

“Sometimes we lose track of what ... we need to do” to provide care that reflects the best interests of the older patient, he continued. “Surgery may be the gold standard for treating the majority of NMSCs ... but is it the [best option] for what our older patients and patients with limited life expectancy need?”

Learning about what truly matters to the patient is a key element of the “age-friendly, whole-person care” that dermatologists must embrace as older adults become an increasingly large subset of their patient population, Christina Prather, MD, director and associate professor of geriatrics and palliative medicine at George Washington University, said at the meeting.

By 2040, projections are that the number of adults aged 85 years and older in the United States will be nearly quadruple the number in 2000, according to one estimate.

“We know that there are less than 6000 practicing geriatricians in the country ... [so the healthcare system] needs more of you who know how to bring an age-friendly approach to care,” Dr. Prather said. Dermatology is among the specialties that need to be “geriatricized.”
 

NMSC Increasing in the Older Population

The incidence of skin cancer is rising faster than that of any other cancer, Dr. Patel said. One window into the epidemiology, he said, comes from recently published data showing that an average of 6.1 million adults were treated each year for skin cancer during 2016-2018 (5.2 million of them for NMSC) — an increase from an average of 5.8 million annually in the 2012-2015 period. The data come from the Medical Expenditure Panel Survey (MEPS), which is conducted by the US Public Health Service through the Agency for Healthcare Research and Quality and the Centers for Disease Control and Prevention.

As a frame of reference, the average number of adults treated each year for nonskin cancers during these periods rose from 10.8 to 11.9 million, according to the 2023 MEPS data. “Skin cancer is about one-third of all cancers combined,” Dr. Patel said.

Not only is the incidence of NMSC significantly higher than that of melanoma but it also shows a more prominent aging trend. This was documented recently in a long-term observational study from Japan, in which researchers looked at the change in the median age of patients with NMSC and melanoma, compared with cancers of other organs, from 1991 to 2020 and found that NMSC had by far the greatest rise in median age, to a median age of 80 years in 2021.

Even more notable, Dr. Patel said, was a particularly marked increase in the number of patients with skin cancer aged 90 years and older. In 2021, this group of older adults accounted for 17% of patients receiving treatment for skin cancer at the Japanese hospital where the data were collected.

The 2013 study that stirred Dr. Patel as a fellow was of 1536 consecutive patients diagnosed with NMSC at two dermatology clinics (a University of California San Francisco–based private clinic and a Veterans Affairs Medical Center clinic) and followed for 6 years. “What’s interesting and worth thinking about is that, regardless of patients’ life expectancy, NMSCs were treated aggressively and surgically, and the choice of surgery was not influenced by the patient’s poor prognosis in a multivariate model” adjusted for tumor and patient characteristics, he said at the meeting.

The researchers defined limited life expectancy as either 85 years or older or having a Charleston Comorbidity Index ≥ 3. Approximately half of the patients with limited life expectancy died within 5 years, none of NMSC. Most patients with limited life expectancy were not often bothered by their tumors, and approximately one in five reported a treatment complication within 2 years. The 5-year tumor recurrence rate was 3.7%.

A more recent study looked at 1181 patients older than 85 years with NMSC referred for Mohs surgery. Almost all patients in the multicenter, prospective cohort study (91.3%) were treated with Mohs.

Treated patients were more likely to have facial tumors and higher functional status than those not treated with Mohs surgery, and the most common reasons provided by surgeons for proceeding with the surgery were a patient desire for a high cure rate (66%), higher functional status for age (57%), and high-risk tumor type (40%). Almost 42% of the referred patients were 89 years or older.

“Granted, [the reasons] are justified indications for surgery,” Dr. Patel said. Yet the study brings up the question of “whether we need to do Mohs surgery this frequently in elderly patients?” In an email after the meeting, he added, “it’s a question we may need to reconsider as the elderly population continues to increase and median age of NMSC rises.”
 

Underutilized Management Options for NMSC

In his practice, discussions of treatment options are preceded by a thorough discussion of the disease itself. Many lesions are low risk, and helping patients understand risks, as well as understanding what is important to the patient — especially those with limited life expectancy — will guide shared decision-making to choose the best treatment, Dr. Patel said at the meeting.

The dermatologist’s risk assessment — both staging and stratifying risk as it relates to specific outcomes such as recurrence, metastases, or death — takes on added importance in the older patient, he emphasized. “I think we underutilize the risk assessment.”

Also underutilized is the option of shave removal for low-risk squamous cell carcinomas and basal cell carcinomas, Dr. Patel said, noting that, in the National Comprehensive Cancer Network guidelines, “there’s an option for shave removal and nothing more if you have clear margins.”

Alternatively, disc excision with the initial biopsy can often be considered. “Having that intent to treat at the time of biopsy may be all that needs to be done” in older patients with obvious or highly suspicious lesions, he said.

Systemic immunotherapy has joined the treatment armamentarium for advanced basal cell carcinoma and advanced cutaneous squamous cell carcinoma, and if early, ongoing research of intralesional programmed cell death protein 1 inhibitor treatment advances, this could be another option for older adults in the future, Dr. Patel said. Targeting drug delivery directly to the tumor would lower the total dose, decrease systemic exposure, and could be used to avoid surgery for some groups of patients, such as those with limited life expectancy.

A Personal Story, a Word on Melanoma

Dr. Prather recalled when her 97-year-old grandfather had a skin lesion on his forehead removed, and a conversation he had with her mother about whether he really needed to have the procedure because he had cognitive impairment and was on oral anticoagulants.

The clinician “said it absolutely had to go. ... I can’t tell you how much his doctors’ visits and wound care consumed my family’s life for the next few years — for this thing that never quite healed,” she said.

“Was it necessary? The more I’ve learned over time is that it wasn’t,” Dr. Prather added. “We have to take time [with our older patients] and think critically. What is feasible? What makes the most sense? What is the most important thing I need to know about the patient?”

Also important, Dr. Patel noted, is the big-picture consideration of skin cancer treatment costs. The MEPS survey data showing the rising prevalence of skin cancer treatment also documented the economic burden: A nearly 30% increase in the average annual cost of treating NMSC from $5 billion in 2012-2015 to $6.5 billion in 2016-2018. (The average annual costs of treating melanoma decreased slightly.) “Skin cancer is a big drain on our limited resources,” he said.

With melanoma as well, dermatologists must think critically and holistically about the individual patient — and not have “a single view lens of the disease and how we treat the disease,” said Dr. Patel, urging the audience to read a “Sounding Board” article published in The New England Journal of Medicine in 2021. The article argued that there is overdiagnosis of cutaneous melanoma stemming from increased screening, falling clinical thresholds for biopsy, and falling pathological thresholds for labeling morphologic changes as cancer.

“There’s a diagnostic disconnect and a problem of overdiagnosis ... because we’re afraid to miss or make a mistake,” he said. “It leads to the question, do all lesions denoted as skin cancers need aggressive treatment? What does it mean for the patient in front of you?”

Dr. Patel reported receiving honoraria from Regeneron, Almirall, Biofrontera, Sun Pharma, and SkylineDx and serving on the speaker bureau of Regeneron and Almirall. He is chief medical officer for Lazarus AI and is cofounder of the Skin Cancer Outcomes consortium. Dr. Prather disclosed relationships with the National Institutes of Health, AHRQ, The Washington Home Foundation, and the Alzheimer’s Association.

A version of this article appeared on Medscape.com.

WASHINGTON — In 2013, Vishal A. Patel, MD, was completing a fellowship in Mohs surgery and cutaneous oncology at Columbia University Irving Medical Center, New York City, when a study was published showing that most nonmelanoma skin cancers (NMSCs) were treated with surgery, regardless of the patient’s life expectancy. Life expectancy “should enter into treatment decisions,” the authors concluded.

“The article got a lot of pushback from the Mohs surgeons,” and the value of surgery in older adults and particularly those with limited life expectancy “became a hot topic,” Dr. Patel recalled at the ElderDerm conference hosted by the Department of Dermatology at George Washington University, Washington, DC, and described as a first-of-its-kind meeting dedicated to improving dermatologic care for older adults.

Christine Kilgore

Today, however, more than a decade later, guidelines still promote surgical therapy as the gold standard across the board, and questions raised by the study are still unaddressed, Dr. Patel, associate professor of dermatology and medicine/oncology at George Washington University, said at the meeting. These questions are becoming increasingly urgent as the incidence of skin cancer, especially NMSC, rises in the older adult population, especially in patients older than 85 years. “It’s a function of our training and our treatment guidelines that we reach for the most definitive treatment, which happens to be the most aggressive, in these patients,” added Dr. Patel, who is also director of the cutaneous oncology program at the GW Cancer Center.

“Sometimes we lose track of what ... we need to do” to provide care that reflects the best interests of the older patient, he continued. “Surgery may be the gold standard for treating the majority of NMSCs ... but is it the [best option] for what our older patients and patients with limited life expectancy need?”

Learning about what truly matters to the patient is a key element of the “age-friendly, whole-person care” that dermatologists must embrace as older adults become an increasingly large subset of their patient population, Christina Prather, MD, director and associate professor of geriatrics and palliative medicine at George Washington University, said at the meeting.

By 2040, projections are that the number of adults aged 85 years and older in the United States will be nearly quadruple the number in 2000, according to one estimate.

“We know that there are less than 6000 practicing geriatricians in the country ... [so the healthcare system] needs more of you who know how to bring an age-friendly approach to care,” Dr. Prather said. Dermatology is among the specialties that need to be “geriatricized.”
 

NMSC Increasing in the Older Population

The incidence of skin cancer is rising faster than that of any other cancer, Dr. Patel said. One window into the epidemiology, he said, comes from recently published data showing that an average of 6.1 million adults were treated each year for skin cancer during 2016-2018 (5.2 million of them for NMSC) — an increase from an average of 5.8 million annually in the 2012-2015 period. The data come from the Medical Expenditure Panel Survey (MEPS), which is conducted by the US Public Health Service through the Agency for Healthcare Research and Quality and the Centers for Disease Control and Prevention.

As a frame of reference, the average number of adults treated each year for nonskin cancers during these periods rose from 10.8 to 11.9 million, according to the 2023 MEPS data. “Skin cancer is about one-third of all cancers combined,” Dr. Patel said.

Not only is the incidence of NMSC significantly higher than that of melanoma but it also shows a more prominent aging trend. This was documented recently in a long-term observational study from Japan, in which researchers looked at the change in the median age of patients with NMSC and melanoma, compared with cancers of other organs, from 1991 to 2020 and found that NMSC had by far the greatest rise in median age, to a median age of 80 years in 2021.

Even more notable, Dr. Patel said, was a particularly marked increase in the number of patients with skin cancer aged 90 years and older. In 2021, this group of older adults accounted for 17% of patients receiving treatment for skin cancer at the Japanese hospital where the data were collected.

The 2013 study that stirred Dr. Patel as a fellow was of 1536 consecutive patients diagnosed with NMSC at two dermatology clinics (a University of California San Francisco–based private clinic and a Veterans Affairs Medical Center clinic) and followed for 6 years. “What’s interesting and worth thinking about is that, regardless of patients’ life expectancy, NMSCs were treated aggressively and surgically, and the choice of surgery was not influenced by the patient’s poor prognosis in a multivariate model” adjusted for tumor and patient characteristics, he said at the meeting.

The researchers defined limited life expectancy as either 85 years or older or having a Charleston Comorbidity Index ≥ 3. Approximately half of the patients with limited life expectancy died within 5 years, none of NMSC. Most patients with limited life expectancy were not often bothered by their tumors, and approximately one in five reported a treatment complication within 2 years. The 5-year tumor recurrence rate was 3.7%.

A more recent study looked at 1181 patients older than 85 years with NMSC referred for Mohs surgery. Almost all patients in the multicenter, prospective cohort study (91.3%) were treated with Mohs.

Treated patients were more likely to have facial tumors and higher functional status than those not treated with Mohs surgery, and the most common reasons provided by surgeons for proceeding with the surgery were a patient desire for a high cure rate (66%), higher functional status for age (57%), and high-risk tumor type (40%). Almost 42% of the referred patients were 89 years or older.

“Granted, [the reasons] are justified indications for surgery,” Dr. Patel said. Yet the study brings up the question of “whether we need to do Mohs surgery this frequently in elderly patients?” In an email after the meeting, he added, “it’s a question we may need to reconsider as the elderly population continues to increase and median age of NMSC rises.”
 

Underutilized Management Options for NMSC

In his practice, discussions of treatment options are preceded by a thorough discussion of the disease itself. Many lesions are low risk, and helping patients understand risks, as well as understanding what is important to the patient — especially those with limited life expectancy — will guide shared decision-making to choose the best treatment, Dr. Patel said at the meeting.

The dermatologist’s risk assessment — both staging and stratifying risk as it relates to specific outcomes such as recurrence, metastases, or death — takes on added importance in the older patient, he emphasized. “I think we underutilize the risk assessment.”

Also underutilized is the option of shave removal for low-risk squamous cell carcinomas and basal cell carcinomas, Dr. Patel said, noting that, in the National Comprehensive Cancer Network guidelines, “there’s an option for shave removal and nothing more if you have clear margins.”

Alternatively, disc excision with the initial biopsy can often be considered. “Having that intent to treat at the time of biopsy may be all that needs to be done” in older patients with obvious or highly suspicious lesions, he said.

Systemic immunotherapy has joined the treatment armamentarium for advanced basal cell carcinoma and advanced cutaneous squamous cell carcinoma, and if early, ongoing research of intralesional programmed cell death protein 1 inhibitor treatment advances, this could be another option for older adults in the future, Dr. Patel said. Targeting drug delivery directly to the tumor would lower the total dose, decrease systemic exposure, and could be used to avoid surgery for some groups of patients, such as those with limited life expectancy.

A Personal Story, a Word on Melanoma

Dr. Prather recalled when her 97-year-old grandfather had a skin lesion on his forehead removed, and a conversation he had with her mother about whether he really needed to have the procedure because he had cognitive impairment and was on oral anticoagulants.

The clinician “said it absolutely had to go. ... I can’t tell you how much his doctors’ visits and wound care consumed my family’s life for the next few years — for this thing that never quite healed,” she said.

“Was it necessary? The more I’ve learned over time is that it wasn’t,” Dr. Prather added. “We have to take time [with our older patients] and think critically. What is feasible? What makes the most sense? What is the most important thing I need to know about the patient?”

Also important, Dr. Patel noted, is the big-picture consideration of skin cancer treatment costs. The MEPS survey data showing the rising prevalence of skin cancer treatment also documented the economic burden: A nearly 30% increase in the average annual cost of treating NMSC from $5 billion in 2012-2015 to $6.5 billion in 2016-2018. (The average annual costs of treating melanoma decreased slightly.) “Skin cancer is a big drain on our limited resources,” he said.

With melanoma as well, dermatologists must think critically and holistically about the individual patient — and not have “a single view lens of the disease and how we treat the disease,” said Dr. Patel, urging the audience to read a “Sounding Board” article published in The New England Journal of Medicine in 2021. The article argued that there is overdiagnosis of cutaneous melanoma stemming from increased screening, falling clinical thresholds for biopsy, and falling pathological thresholds for labeling morphologic changes as cancer.

“There’s a diagnostic disconnect and a problem of overdiagnosis ... because we’re afraid to miss or make a mistake,” he said. “It leads to the question, do all lesions denoted as skin cancers need aggressive treatment? What does it mean for the patient in front of you?”

Dr. Patel reported receiving honoraria from Regeneron, Almirall, Biofrontera, Sun Pharma, and SkylineDx and serving on the speaker bureau of Regeneron and Almirall. He is chief medical officer for Lazarus AI and is cofounder of the Skin Cancer Outcomes consortium. Dr. Prather disclosed relationships with the National Institutes of Health, AHRQ, The Washington Home Foundation, and the Alzheimer’s Association.

A version of this article appeared on Medscape.com.

WASHINGTON — In 2013, Vishal A. Patel, MD, was completing a fellowship in Mohs surgery and cutaneous oncology at Columbia University Irving Medical Center, New York City, when a study was published showing that most nonmelanoma skin cancers (NMSCs) were treated with surgery, regardless of the patient’s life expectancy. Life expectancy “should enter into treatment decisions,” the authors concluded.

“The article got a lot of pushback from the Mohs surgeons,” and the value of surgery in older adults and particularly those with limited life expectancy “became a hot topic,” Dr. Patel recalled at the ElderDerm conference hosted by the Department of Dermatology at George Washington University, Washington, DC, and described as a first-of-its-kind meeting dedicated to improving dermatologic care for older adults.

Christine Kilgore

Today, however, more than a decade later, guidelines still promote surgical therapy as the gold standard across the board, and questions raised by the study are still unaddressed, Dr. Patel, associate professor of dermatology and medicine/oncology at George Washington University, said at the meeting. These questions are becoming increasingly urgent as the incidence of skin cancer, especially NMSC, rises in the older adult population, especially in patients older than 85 years. “It’s a function of our training and our treatment guidelines that we reach for the most definitive treatment, which happens to be the most aggressive, in these patients,” added Dr. Patel, who is also director of the cutaneous oncology program at the GW Cancer Center.

“Sometimes we lose track of what ... we need to do” to provide care that reflects the best interests of the older patient, he continued. “Surgery may be the gold standard for treating the majority of NMSCs ... but is it the [best option] for what our older patients and patients with limited life expectancy need?”

Learning about what truly matters to the patient is a key element of the “age-friendly, whole-person care” that dermatologists must embrace as older adults become an increasingly large subset of their patient population, Christina Prather, MD, director and associate professor of geriatrics and palliative medicine at George Washington University, said at the meeting.

By 2040, projections are that the number of adults aged 85 years and older in the United States will be nearly quadruple the number in 2000, according to one estimate.

“We know that there are less than 6000 practicing geriatricians in the country ... [so the healthcare system] needs more of you who know how to bring an age-friendly approach to care,” Dr. Prather said. Dermatology is among the specialties that need to be “geriatricized.”
 

NMSC Increasing in the Older Population

The incidence of skin cancer is rising faster than that of any other cancer, Dr. Patel said. One window into the epidemiology, he said, comes from recently published data showing that an average of 6.1 million adults were treated each year for skin cancer during 2016-2018 (5.2 million of them for NMSC) — an increase from an average of 5.8 million annually in the 2012-2015 period. The data come from the Medical Expenditure Panel Survey (MEPS), which is conducted by the US Public Health Service through the Agency for Healthcare Research and Quality and the Centers for Disease Control and Prevention.

As a frame of reference, the average number of adults treated each year for nonskin cancers during these periods rose from 10.8 to 11.9 million, according to the 2023 MEPS data. “Skin cancer is about one-third of all cancers combined,” Dr. Patel said.

Not only is the incidence of NMSC significantly higher than that of melanoma but it also shows a more prominent aging trend. This was documented recently in a long-term observational study from Japan, in which researchers looked at the change in the median age of patients with NMSC and melanoma, compared with cancers of other organs, from 1991 to 2020 and found that NMSC had by far the greatest rise in median age, to a median age of 80 years in 2021.

Even more notable, Dr. Patel said, was a particularly marked increase in the number of patients with skin cancer aged 90 years and older. In 2021, this group of older adults accounted for 17% of patients receiving treatment for skin cancer at the Japanese hospital where the data were collected.

The 2013 study that stirred Dr. Patel as a fellow was of 1536 consecutive patients diagnosed with NMSC at two dermatology clinics (a University of California San Francisco–based private clinic and a Veterans Affairs Medical Center clinic) and followed for 6 years. “What’s interesting and worth thinking about is that, regardless of patients’ life expectancy, NMSCs were treated aggressively and surgically, and the choice of surgery was not influenced by the patient’s poor prognosis in a multivariate model” adjusted for tumor and patient characteristics, he said at the meeting.

The researchers defined limited life expectancy as either 85 years or older or having a Charleston Comorbidity Index ≥ 3. Approximately half of the patients with limited life expectancy died within 5 years, none of NMSC. Most patients with limited life expectancy were not often bothered by their tumors, and approximately one in five reported a treatment complication within 2 years. The 5-year tumor recurrence rate was 3.7%.

A more recent study looked at 1181 patients older than 85 years with NMSC referred for Mohs surgery. Almost all patients in the multicenter, prospective cohort study (91.3%) were treated with Mohs.

Treated patients were more likely to have facial tumors and higher functional status than those not treated with Mohs surgery, and the most common reasons provided by surgeons for proceeding with the surgery were a patient desire for a high cure rate (66%), higher functional status for age (57%), and high-risk tumor type (40%). Almost 42% of the referred patients were 89 years or older.

“Granted, [the reasons] are justified indications for surgery,” Dr. Patel said. Yet the study brings up the question of “whether we need to do Mohs surgery this frequently in elderly patients?” In an email after the meeting, he added, “it’s a question we may need to reconsider as the elderly population continues to increase and median age of NMSC rises.”
 

Underutilized Management Options for NMSC

In his practice, discussions of treatment options are preceded by a thorough discussion of the disease itself. Many lesions are low risk, and helping patients understand risks, as well as understanding what is important to the patient — especially those with limited life expectancy — will guide shared decision-making to choose the best treatment, Dr. Patel said at the meeting.

The dermatologist’s risk assessment — both staging and stratifying risk as it relates to specific outcomes such as recurrence, metastases, or death — takes on added importance in the older patient, he emphasized. “I think we underutilize the risk assessment.”

Also underutilized is the option of shave removal for low-risk squamous cell carcinomas and basal cell carcinomas, Dr. Patel said, noting that, in the National Comprehensive Cancer Network guidelines, “there’s an option for shave removal and nothing more if you have clear margins.”

Alternatively, disc excision with the initial biopsy can often be considered. “Having that intent to treat at the time of biopsy may be all that needs to be done” in older patients with obvious or highly suspicious lesions, he said.

Systemic immunotherapy has joined the treatment armamentarium for advanced basal cell carcinoma and advanced cutaneous squamous cell carcinoma, and if early, ongoing research of intralesional programmed cell death protein 1 inhibitor treatment advances, this could be another option for older adults in the future, Dr. Patel said. Targeting drug delivery directly to the tumor would lower the total dose, decrease systemic exposure, and could be used to avoid surgery for some groups of patients, such as those with limited life expectancy.

A Personal Story, a Word on Melanoma

Dr. Prather recalled when her 97-year-old grandfather had a skin lesion on his forehead removed, and a conversation he had with her mother about whether he really needed to have the procedure because he had cognitive impairment and was on oral anticoagulants.

The clinician “said it absolutely had to go. ... I can’t tell you how much his doctors’ visits and wound care consumed my family’s life for the next few years — for this thing that never quite healed,” she said.

“Was it necessary? The more I’ve learned over time is that it wasn’t,” Dr. Prather added. “We have to take time [with our older patients] and think critically. What is feasible? What makes the most sense? What is the most important thing I need to know about the patient?”

Also important, Dr. Patel noted, is the big-picture consideration of skin cancer treatment costs. The MEPS survey data showing the rising prevalence of skin cancer treatment also documented the economic burden: A nearly 30% increase in the average annual cost of treating NMSC from $5 billion in 2012-2015 to $6.5 billion in 2016-2018. (The average annual costs of treating melanoma decreased slightly.) “Skin cancer is a big drain on our limited resources,” he said.

With melanoma as well, dermatologists must think critically and holistically about the individual patient — and not have “a single view lens of the disease and how we treat the disease,” said Dr. Patel, urging the audience to read a “Sounding Board” article published in The New England Journal of Medicine in 2021. The article argued that there is overdiagnosis of cutaneous melanoma stemming from increased screening, falling clinical thresholds for biopsy, and falling pathological thresholds for labeling morphologic changes as cancer.

“There’s a diagnostic disconnect and a problem of overdiagnosis ... because we’re afraid to miss or make a mistake,” he said. “It leads to the question, do all lesions denoted as skin cancers need aggressive treatment? What does it mean for the patient in front of you?”

Dr. Patel reported receiving honoraria from Regeneron, Almirall, Biofrontera, Sun Pharma, and SkylineDx and serving on the speaker bureau of Regeneron and Almirall. He is chief medical officer for Lazarus AI and is cofounder of the Skin Cancer Outcomes consortium. Dr. Prather disclosed relationships with the National Institutes of Health, AHRQ, The Washington Home Foundation, and the Alzheimer’s Association.

A version of this article appeared on Medscape.com.

In October 2023, Robert Card — a grenade instructor in the Army Reserve — shot and killed 18 people in Maine, before turning the gun on himself. As reported by The New York Times, his family said that he had become increasingly erratic and violent during the months before the rampage.

A postmortem conducted by the Chronic Traumatic Encephalopathy (CTE) Center at Boston University found “significant evidence of traumatic brain injuries” [TBIs] and “significant degeneration, axonal and myelin loss, inflammation, and small blood vessel injury” in the white matter, the center’s director, Ann McKee, MD, said in a press release. “These findings align with our previous studies on the effects of blast injury in humans and experimental models.”

Members of the military, such as Mr. Card, are exposed to blasts from repeated firing of heavy weapons not only during combat but also during training.

New data suggest that repeated blast exposure may impair the brain’s waste clearance system, leading to biomarker changes indicative of preclinical Alzheimer’s disease 20 years earlier than typical. A higher index of suspicion for dementia or Alzheimer’s disease may be warranted in patients with a history of blast exposure or subconcussive brain injury who present with cognitive issues, according to experts interviewed.

In 2022, the US Department of Defense (DOD) launched its Warfighter Brain Health Initiative with the aim of “optimizing service member brain health and countering traumatic brain injuries.”

In April 2024, the Blast Overpressure Safety Act was introduced in the Senate to require the DOD to enact better blast screening, tracking, prevention, and treatment. The DOD initiated 26 blast overpressure studies.

Heather Snyder, PhD, Alzheimer’s Association vice president of Medical and Scientific Relations, said that an important component of that research involves “the need to study the difference between TBI-caused dementia and dementia caused independently” and “the need to study biomarkers to better understand the long-term consequences of TBI.”
 

What Is the Underlying Biology?

Dr. Snyder was the lead author of a white paper produced by the Alzheimer’s Association in 2018 on military-related risk factors for Alzheimer’s disease and related dementias. “There is a lot of work trying to understand the effect of pure blast waves on the brain, as opposed to the actual impact of the injury,” she said.

The white paper speculated that blast exposure may be analogous to subconcussive brain injury in athletes where there are no obvious immediate clinical symptoms or neurological dysfunction but which can cause cumulative injury and functional impairment over time.

“We are also trying to understand the underlying biology around brain changes, such as accumulation of tau and amyloid and other specific markers related to brain changes in Alzheimer’s disease,” said Dr. Snyder, chair of the Peer Reviewed Alzheimer’s Research Program Programmatic Panel for Alzheimer’s Disease/Alzheimer’s Disease and Related Dementias and TBI.
 

Common Biomarker Signatures

A recent study in Neurology comparing 51 veterans with mild TBI (mTBI) with 85 veterans and civilians with no lifetime history of TBI is among the first to explore these biomarker changes in human beings.

“Our findings suggest that chronic neuropathologic processes associated with blast mTBI share properties in common with pathogenic processes that are precursors to Alzheimer’s disease onset,” said coauthor Elaine R. Peskind, MD, professor of psychiatry and behavioral sciences, University of Washington, Seattle.

The largely male participants were a mean age of 34 years and underwent standardized clinical and neuropsychological testing as well as lumbar puncture to collect cerebrospinal fluid (CSF). The mTBI group had experienced at least one war zone blast or combined blast/impact that met criteria for mTBI, but 91% had more than one blast mTBI, and the study took place over 13 years.

The researchers found that the mTBI group “had biomarker signatures in common with the earliest stages of Alzheimer’s disease,” said Dr. Peskind.

For example, at age 50, they had lower mean levels of CSF amyloid beta 42 (Abeta42), the earliest marker of brain parenchymal Abeta deposition, compared with the control group (154 pg/mL and 1864 pg/mL lower, respectively).

High CSF phosphorylated tau181 (p-tau181) and total tau are established biomarkers for Alzheimer’s disease. However, levels of these biomarkers remained “relatively constant with age” in participants with mTBI but were higher in older ages for the non-TBI group.

The mTBI group also showed worse cognitive performance at older ages (P < .08). Poorer verbal memory and verbal fluency performance were associated with lower CSF Abeta42 in older participants (P ≤ .05).

In Alzheimer’s disease, a reduction in CSF Abeta42 may occur up to 20 years before the onset of clinical symptoms, according to Dr. Peskind. “But what we don’t know from this study is what this means, as total tau protein and p-tau181 in the CSF were also low, which isn’t entirely typical in the picture of preclinical Alzheimer’s disease,” she said. However, changes in total tau and p-tau181 lag behind changes in Abeta42.
 

Is Impaired Clearance the Culprit?

Coauthor Jeffrey Iliff, PhD, professor, University of Washington Department of Psychiatry and Behavioral Sciences and University of Washington Department of Neurology, Seattle, elaborated.

“In the setting of Alzheimer’s disease, a signature of the disease is reduced CSF Abeta42, which is thought to reflect that much of the amyloid gets ‘stuck’ in the brain in the form of amyloid plaques,” he said. “There are usually higher levels of phosphorylated tau and total tau, which are thought to reflect the presence of tau tangles and degeneration of neurons in the brain. But in this study, all of those were lowered, which is not exactly an Alzheimer’s disease profile.”

Dr. Iliff, associate director for research, VA Northwest Mental Illness Research, Education, and Clinical Center at VA Puget Sound Health Care System, Seattle, suggested that the culprit may be impairment in the brain’s glymphatic system. “Recently described biological research supports [the concept of] clearance of waste out of the brain during sleep via the glymphatic system, with amyloid and tau being cleared from the brain interstitium during sleep.”

A recent hypothesis is that blast TBI impairs that process. “This is why we see less of those proteins in the CSF. They’re not being cleared, which might contribute downstream to the clumping up of protein in the brain,” he suggested.

The evidence base corroborating that hypothesis is in its infancy; however, new research conducted by Dr. Iliff and his colleagues sheds light on this potential mechanism.

In blast TBI, energy from the explosion and resulting overpressure wave are “transmitted through the brain, which causes tissues of different densities — such as gray and white matter — to accelerate at different rates,” according to Dr. Iliff. This results in the shearing and stretching of brain tissue, leading to a “diffuse pattern of tissue damage.”

It is known that blast TBI has clinical overlap and associations with posttraumatic stress disorder (PTSD), depression, and persistent neurobehavioral symptoms; that veterans with a history of TBI are more than twice as likely to die by suicide than veterans with no TBI history; and that TBI may increase the risk for Alzheimer’s disease and related dementing disorders, as well as CTE.

The missing link may be the glymphatic system — a “brain-wide network of perivascular pathways, along which CSF and interstitial fluid (ISF) exchange, supporting the clearance of interstitial solutes, including amyloid-beta.”

Dr. Iliff and his group previously found that glymphatic function is “markedly and chronically impaired” following impact TBI in mice and that this impairment is associated with the mislocalization of astroglial aquaporin 4 (AQP4), a water channel that lines perivascular spaces and plays a role in healthy glymphatic exchange.

In their new study, the researchers examined both the expression and the localization of AQP4 in the human postmortem frontal cortex and found “distinct laminar differences” in AQP4 expression following blast exposure. They observed similar changes as well as impairment of glymphatic function, which emerged 28 days following blast injury in a mouse model of repetitive blast mTBI.

And in a cohort of veterans with blast mTBI, blast exposure was found to be associated with an increased burden of frontal cortical MRI-visible perivascular spaces — a “putative neuroimaging marker” of glymphatic perivascular dysfunction.

The earlier Neurology study “showed impairment of biomarkers in the CSF, but the new study showed ‘why’ or ‘how’ these biomarkers are impaired, which is via impairment of the glymphatic clearance process,” Dr. Iliff explained.
 

Veterans Especially Vulnerable

Dr. Peskind, co-director of the VA Northwest Mental Illness Research, Education and Clinical Center, VA Puget Sound Health Care System, noted that while the veterans in the earlier study had at least one TBI, the average number was 20, and it was more common to have more than 50 mTBIs than to have a single one.

“These were highly exposed combat vets,” she said. “And that number doesn’t even account for subconcussive exposure to blasts, which now appear to cause detectable brain damage, even in the absence of a diagnosable TBI.”

The Maine shooter, Mr. Card, had not seen combat and was not assessed for TBI during a psychiatric hospitalization, according to The New York Times.

Dr. Peskind added that this type of blast damage is likely specific to individuals in the military. “It isn’t the sound that causes the damage,” she explained. “It’s the blast wave, the pressure wave, and there aren’t a lot of other occupations that have those types of occupational exposures.”

Dr. Snyder added that the majority of blast TBIs have been studied in military personnel, and she is not aware of studies that have looked at blast injuries in other industries, such as demolition or mining, to see if they have the same type of biologic consequences.

Dr. Snyder hopes that the researchers will follow the participants in the Neurology study and continue looking at specific markers related to Alzheimer’s disease brain changes. What the research so far shows “is that, at an earlier age, we’re starting to see those markers changing, suggesting that the underlying biology in people with mild blast TBI is similar to the underlying biology in Alzheimer’s disease as well.”

Michael Alosco, PhD, associate professor and vice chair of research, department of neurology, Boston University Chobanian & Avedisian School of Medicine, called the issue of blast exposure and TBI “a very complex and nuanced topic,” especially because TBI is “considered a risk factor of Alzheimer’s disease” and “different types of TBIs could trigger distinct pathophysiologic processes; however, the long-term impact of repetitive blast TBIs on neurodegenerative disease changes remains unknown.”

He coauthored an editorial on the earlier Neurology study that noted its limitations, such as a small sample size and lack of consideration of lifestyle and health factors but acknowledged that the “findings provide preliminary evidence that repetitive blast exposures might influence beta-amyloid accumulation.”
 

Clinical Implications

For Dr. Peskind, the “inflection point” was seeing lower CSF Abeta42, about 20 years earlier than ages 60 and 70, which is more typical in cognitively normal community volunteers.

But she described herself as “loath to say that veterans or service members have a 20-year acceleration of risk of Alzheimer’s disease,” adding, “I don’t want to scare the heck out of our service members of veterans.” Although “this is what we fear, we’re not ready to say it for sure yet because we need to do more work. Nevertheless, it does increase the index of suspicion.”

The clinical take-home messages are not unique to service members or veterans or people with a history of head injuries or a genetic predisposition to Alzheimer’s disease, she emphasized. “If anyone of any age or occupation comes in with cognitive issues, such as [impaired] memory or executive function, they deserve a workup for dementing disorders.” Frontotemporal dementia, for example, can present earlier than Alzheimer’s disease typically does.

Common comorbidities with TBI are PTSD and obstructive sleep apnea (OSA), which can also cause cognitive issues and are also risk factors for dementia.

Dr. Iliff agreed. “If you see a veteran with a history of PTSD, a history of blast TBI, and a history of OSA or some combination of those three, I recommend having a higher index of suspicion [for potential dementia] than for an average person without any of these, even at a younger age than one would ordinarily expect.”

Of all of these factors, the only truly directly modifiable one is sleep disruption, including that caused by OSA or sleep disorders related to PTSD, he added. “Epidemiologic data suggest a connection particularly between midlife sleep disruption and the risk of dementia and Alzheimer’s disease, and so it’s worth thinking about sleep as a modifiable risk factor even as early as the 40s and 50s, whether the patient is or isn’t a veteran.”

Dr. Peskind recommended asking patients, “Do they snore? Do they thrash about during sleep? Do they have trauma nightmares? This will inform the type of intervention required.”

Dr. Alosco added that there is no known “safe” threshold of exposure to blasts, and that thresholds are “unclear, particularly at the individual level.” In American football, there is a dose-response relationship between years of play and risk for later-life neurological disorder. “The best way to mitigate risk is to limit cumulative exposure,” he said.

The study by Li and colleagues was funded by grant funding from the Department of Veterans Affairs Rehabilitation Research and Development Service and the University of Washington Friends of Alzheimer’s Research. Other sources of funding to individual researchers are listed in the original paper. The study by Braun and colleagues was supported by the National Heart, Lung and Blood Institute; the Department of Veterans Affairs Rehabilitation Research and Development Service; and the National Institute on Aging. The white paper included studies that received funding from numerous sources, including the National Institutes of Health and the DOD. Dr. Iliff serves as the chair of the Scientific Advisory Board for Applied Cognition Inc., from which he receives compensation and in which he holds an equity stake. In the last year, he served as a paid consultant to Gryphon Biosciences. Dr. Peskind has served as a paid consultant to the companies Genentech, Roche, and Alpha Cognition. Dr. Alosco was supported by grant funding from the NIH; he received research support from Rainwater Charitable Foundation Inc., and Life Molecular Imaging Inc.; he has received a single honorarium from the Michael J. Fox Foundation for services unrelated to this editorial; and he received royalties from Oxford University Press Inc. The other authors’ disclosures are listed in the original papers.