Oncology Practice

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.

The US Food and Drug Administration (FDA) has granted accelerated approval to adagrasib (Krazati, Mirati Therapeutics) with cetuximab for certain patients with KRAS G12C–mutated colorectal cancer (CRC).

More specifically, the highly selective and potent small-molecule KRAS G12C inhibitor is now indicated for patients with locally advanced or metastatic KRAS G12C–mutated CRC — as determined by an FDA-approved test — who previously received fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy and, if eligible, a vascular endothelial growth factor inhibitor, according to an FDA press release.

The agent is the first KRAS inhibitor approved for CRC. Adagrasib was previously granted accelerated approval for KRAS G12C–mutated non–small cell lung cancer, based on findings from the KRYSTAL-12 trial.

The CRC approval was based on findings from the KRYSTAL-1 multicenter, single-arm expansion cohort trial, which reported an overall response rate of 34% among 94 enrolled patients. 

All responses were partial responses, and the median duration of response was 5.8 months, with 31% of responding patients experiencing a duration of response of at least 6 months.

Patients received 600 mg of adagrasib twice daily plus cetuximab administered in either a biweekly 500 mg/m² dose or an initial dose of 400 mg/m² followed by weekly doses of 250 mg/m². Those who discontinued adagrasib also had to discontinue cetuximab, but adagrasib could be continued if cetuximab was discontinued.

The recommended adagrasib dose is 600 mg given orally twice daily until disease progression or unacceptable toxicity, according to the prescribing information. 

Adverse reactions occurring in at least 20% of treated patients included rash, nausea, diarrhea, vomiting, fatigue, musculoskeletal pain, hepatotoxicity, headache, dry skin, abdominal pain, decreased appetite, edema, anemia, cough, dizziness, constipation, and peripheral neuropathy.

“Patients with KRAS G12C–mutated colorectal cancer have historically faced poor prognoses and remain in need of additional treatment options,” Scott Kopetz, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, stated earlier this year in a press release announcing the FDA’s decision to accept the drug application for priority review.

“Although KRAS had previously been considered ‘undruggable,’ these data from KRYSTAL-1 reinforce the potential benefit of adagrasib for these specific patients,” Dr. Kopetz said in the statement from Bristol Myers Squibb, which acquired Mirati Therapeutics in 2023.

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

The US Food and Drug Administration (FDA) has granted accelerated approval to adagrasib (Krazati, Mirati Therapeutics) with cetuximab for certain patients with KRAS G12C–mutated colorectal cancer (CRC).

More specifically, the highly selective and potent small-molecule KRAS G12C inhibitor is now indicated for patients with locally advanced or metastatic KRAS G12C–mutated CRC — as determined by an FDA-approved test — who previously received fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy and, if eligible, a vascular endothelial growth factor inhibitor, according to an FDA press release.

The agent is the first KRAS inhibitor approved for CRC. Adagrasib was previously granted accelerated approval for KRAS G12C–mutated non–small cell lung cancer, based on findings from the KRYSTAL-12 trial.

The CRC approval was based on findings from the KRYSTAL-1 multicenter, single-arm expansion cohort trial, which reported an overall response rate of 34% among 94 enrolled patients. 

All responses were partial responses, and the median duration of response was 5.8 months, with 31% of responding patients experiencing a duration of response of at least 6 months.

Patients received 600 mg of adagrasib twice daily plus cetuximab administered in either a biweekly 500 mg/m² dose or an initial dose of 400 mg/m² followed by weekly doses of 250 mg/m². Those who discontinued adagrasib also had to discontinue cetuximab, but adagrasib could be continued if cetuximab was discontinued.

The recommended adagrasib dose is 600 mg given orally twice daily until disease progression or unacceptable toxicity, according to the prescribing information. 

Adverse reactions occurring in at least 20% of treated patients included rash, nausea, diarrhea, vomiting, fatigue, musculoskeletal pain, hepatotoxicity, headache, dry skin, abdominal pain, decreased appetite, edema, anemia, cough, dizziness, constipation, and peripheral neuropathy.

“Patients with KRAS G12C–mutated colorectal cancer have historically faced poor prognoses and remain in need of additional treatment options,” Scott Kopetz, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, stated earlier this year in a press release announcing the FDA’s decision to accept the drug application for priority review.

“Although KRAS had previously been considered ‘undruggable,’ these data from KRYSTAL-1 reinforce the potential benefit of adagrasib for these specific patients,” Dr. Kopetz said in the statement from Bristol Myers Squibb, which acquired Mirati Therapeutics in 2023.

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

The US Food and Drug Administration (FDA) has granted accelerated approval to adagrasib (Krazati, Mirati Therapeutics) with cetuximab for certain patients with KRAS G12C–mutated colorectal cancer (CRC).

More specifically, the highly selective and potent small-molecule KRAS G12C inhibitor is now indicated for patients with locally advanced or metastatic KRAS G12C–mutated CRC — as determined by an FDA-approved test — who previously received fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy and, if eligible, a vascular endothelial growth factor inhibitor, according to an FDA press release.

The agent is the first KRAS inhibitor approved for CRC. Adagrasib was previously granted accelerated approval for KRAS G12C–mutated non–small cell lung cancer, based on findings from the KRYSTAL-12 trial.

The CRC approval was based on findings from the KRYSTAL-1 multicenter, single-arm expansion cohort trial, which reported an overall response rate of 34% among 94 enrolled patients. 

All responses were partial responses, and the median duration of response was 5.8 months, with 31% of responding patients experiencing a duration of response of at least 6 months.

Patients received 600 mg of adagrasib twice daily plus cetuximab administered in either a biweekly 500 mg/m² dose or an initial dose of 400 mg/m² followed by weekly doses of 250 mg/m². Those who discontinued adagrasib also had to discontinue cetuximab, but adagrasib could be continued if cetuximab was discontinued.

The recommended adagrasib dose is 600 mg given orally twice daily until disease progression or unacceptable toxicity, according to the prescribing information. 

Adverse reactions occurring in at least 20% of treated patients included rash, nausea, diarrhea, vomiting, fatigue, musculoskeletal pain, hepatotoxicity, headache, dry skin, abdominal pain, decreased appetite, edema, anemia, cough, dizziness, constipation, and peripheral neuropathy.

“Patients with KRAS G12C–mutated colorectal cancer have historically faced poor prognoses and remain in need of additional treatment options,” Scott Kopetz, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, stated earlier this year in a press release announcing the FDA’s decision to accept the drug application for priority review.

“Although KRAS had previously been considered ‘undruggable,’ these data from KRYSTAL-1 reinforce the potential benefit of adagrasib for these specific patients,” Dr. Kopetz said in the statement from Bristol Myers Squibb, which acquired Mirati Therapeutics in 2023.

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 Association 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 Association 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 Association 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.

prespuswibronostithehegepribrunuswamufrechibisloprohagerebouedrevulaclasliwrapijipenitripocowrasihiru

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.

[embed:render:related:node:269288]

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.

prespuswibronostithehegepribrunuswamufrechibisloprohagerebouedrevulaclasliwrapijipenitripocowrasihiru

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.

[embed:render:related:node:269288]

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.

prespuswibronostithehegepribrunuswamufrechibisloprohagerebouedrevulaclasliwrapijipenitripocowrasihiru

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.

[embed:render:related:node:269288]

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.

While Medicare Advantage (MA) plans are marketed as providing more generous benefits than traditional Medicare (TM), differences in the financial burden between beneficiaries switching to MA and staying with TM, are minimal, a longitudinal cohort analysis found.

In fact, according to a study by Sungchul Park, PhD, a health economist at Korea University in Seoul, and colleagues, the estimated annual out-of-pocket spending when switching to MA was $168 higher than staying in TM. That amounted to a 10.5% relative increase based on baseline out-of-pocket spending of $1597 annually among switchers, ranging widely, however, from a $133 decrease to a $469 increase. And for some, MA enrollment was associated with a higher likelihood of catastrophic financial burden.

“Our findings contrast with the notion that MA’s apparently more generous health insurance benefits lead to financial savings for enrollees,” Dr. Park and associates wrote in Annals of Internal Medicine.
 

The study

The analysis looked at costs for 7054 TM stayers and 1544 TM-to-MA switchers from the 2014-2020 Medical Expenditure Panel Survey, focusing on a cohort in which 18% of TM-covered individuals in year 1 switched to MA in year 2.

Comparative financial outcome measures included individual healthcare costs (out-of-pocket spending/cost sharing), financial burden (high/catastrophic), and subjective financial hardship (difficulty paying medical bills).

Although the overall out-of-pocket differences for MA were minimal and amounted to less than 1% of total healthcare expenses, MA was associated with a greater financial burden in vulnerable, especially in low-income populations. For every 100 beneficiaries with family incomes below 200% of the federal poverty level, one to six more switchers faced a catastrophic financial burden, with their out-of-pocket costs consuming more than 40% of household income in the year after switching.

The gap between the perception of lower costs and reality may be caused by a substantially heavier cost-sharing burden for certain services in MA plans, Dr. Park and associates pointed out. While MA enrollees generally paid less in some studies than the Part A hospital deductible for TM for inpatient stays of 3 days, they were more likely to face higher cost sharing for stays exceeding 7 days

Furthermore, whereas TM covers home health services without cost sharing, some MA plans have copayments. In addition, out-of-network health services can cost more. MA enrollees paid an average of $9 more for mental health services than for other in-network services and often encountered limited access to in-network providers. According to a 2021 study, only 18.2% of mental health professionals, 34.4% of cardiologists, 50.0% of psychiatrists, and 57.9% of primary care providers were included in MA networks,

An accompanying editorial noted that private MA plans will reap $83 billion in overpayments from U.S. taxpayers this year, according to Congress’s Medicare Payment Advisory Commission.

And as the data from Dr. Park and colleagues reveal, switchers don’t get much financial protection, according to primary care physician and healthcare researcher Steffi J. Woolhandler, MD, MPH, and internist David U. Himmelstein, MD, both of City University of New York at Hunter College in New York City.

“Medicare Advantage looks good when you’re healthy and don’t need much care. But when you need coverage, it often fails, leaving you with big bills and narrow choices for care,” Dr. Woolhandler said in an interview.

So how do these findings square with insurers’ hard-sell claims and enrollees’ perceptions that MA cuts out-of-pocket costs? “The likeliest explanation is that MA insurers have structured their benefits to advantage low-cost (that is, profitable) enrollees and disadvantage those requiring expensive care,” the editorial commentators wrote. For beneficiaries on inexpensive medications, MA plans would be a financial win. “But for patients requiring expensive chemotherapies, the 20% coinsurance that most MA plans charge could be financially ruinous.”

Commenting on the study but not involved in it, David A. Lipschutz, JD, LLB, associate director of the Center for Medicare Advocacy in Washington, DC, called the study an important one that provides more evidence that significant overpayments to MA plans don’t translate to better financial protections for plan enrollees, particularly lower-income individuals. “While there has been some recent movement to hold plans more accountable for providing necessary care, much more impactful action by policymakers is required to mitigate the harms of the growing privatization of the Medicare program,” he said. “MA overpayments could be redistributed to traditional Medicare in order to enrich all Medicare beneficiaries instead of just insurance companies.”

This study was supported by the National Research Foundation of Korea. Dr. Park disclosed no competing interests. One study coauthor reported support from government and not-for-profit research-funding bodies. Editorialists Dr. Woolhandler and Dr. Himmelstein had no competing interests to declare. Dr. Lipschutz disclosed Medicare advocacy work.

While Medicare Advantage (MA) plans are marketed as providing more generous benefits than traditional Medicare (TM), differences in the financial burden between beneficiaries switching to MA and staying with TM, are minimal, a longitudinal cohort analysis found.

In fact, according to a study by Sungchul Park, PhD, a health economist at Korea University in Seoul, and colleagues, the estimated annual out-of-pocket spending when switching to MA was $168 higher than staying in TM. That amounted to a 10.5% relative increase based on baseline out-of-pocket spending of $1597 annually among switchers, ranging widely, however, from a $133 decrease to a $469 increase. And for some, MA enrollment was associated with a higher likelihood of catastrophic financial burden.

“Our findings contrast with the notion that MA’s apparently more generous health insurance benefits lead to financial savings for enrollees,” Dr. Park and associates wrote in Annals of Internal Medicine.
 

The study

The analysis looked at costs for 7054 TM stayers and 1544 TM-to-MA switchers from the 2014-2020 Medical Expenditure Panel Survey, focusing on a cohort in which 18% of TM-covered individuals in year 1 switched to MA in year 2.

Comparative financial outcome measures included individual healthcare costs (out-of-pocket spending/cost sharing), financial burden (high/catastrophic), and subjective financial hardship (difficulty paying medical bills).

Although the overall out-of-pocket differences for MA were minimal and amounted to less than 1% of total healthcare expenses, MA was associated with a greater financial burden in vulnerable, especially in low-income populations. For every 100 beneficiaries with family incomes below 200% of the federal poverty level, one to six more switchers faced a catastrophic financial burden, with their out-of-pocket costs consuming more than 40% of household income in the year after switching.

The gap between the perception of lower costs and reality may be caused by a substantially heavier cost-sharing burden for certain services in MA plans, Dr. Park and associates pointed out. While MA enrollees generally paid less in some studies than the Part A hospital deductible for TM for inpatient stays of 3 days, they were more likely to face higher cost sharing for stays exceeding 7 days

Furthermore, whereas TM covers home health services without cost sharing, some MA plans have copayments. In addition, out-of-network health services can cost more. MA enrollees paid an average of $9 more for mental health services than for other in-network services and often encountered limited access to in-network providers. According to a 2021 study, only 18.2% of mental health professionals, 34.4% of cardiologists, 50.0% of psychiatrists, and 57.9% of primary care providers were included in MA networks,

An accompanying editorial noted that private MA plans will reap $83 billion in overpayments from U.S. taxpayers this year, according to Congress’s Medicare Payment Advisory Commission.

And as the data from Dr. Park and colleagues reveal, switchers don’t get much financial protection, according to primary care physician and healthcare researcher Steffi J. Woolhandler, MD, MPH, and internist David U. Himmelstein, MD, both of City University of New York at Hunter College in New York City.

“Medicare Advantage looks good when you’re healthy and don’t need much care. But when you need coverage, it often fails, leaving you with big bills and narrow choices for care,” Dr. Woolhandler said in an interview.

So how do these findings square with insurers’ hard-sell claims and enrollees’ perceptions that MA cuts out-of-pocket costs? “The likeliest explanation is that MA insurers have structured their benefits to advantage low-cost (that is, profitable) enrollees and disadvantage those requiring expensive care,” the editorial commentators wrote. For beneficiaries on inexpensive medications, MA plans would be a financial win. “But for patients requiring expensive chemotherapies, the 20% coinsurance that most MA plans charge could be financially ruinous.”

Commenting on the study but not involved in it, David A. Lipschutz, JD, LLB, associate director of the Center for Medicare Advocacy in Washington, DC, called the study an important one that provides more evidence that significant overpayments to MA plans don’t translate to better financial protections for plan enrollees, particularly lower-income individuals. “While there has been some recent movement to hold plans more accountable for providing necessary care, much more impactful action by policymakers is required to mitigate the harms of the growing privatization of the Medicare program,” he said. “MA overpayments could be redistributed to traditional Medicare in order to enrich all Medicare beneficiaries instead of just insurance companies.”

This study was supported by the National Research Foundation of Korea. Dr. Park disclosed no competing interests. One study coauthor reported support from government and not-for-profit research-funding bodies. Editorialists Dr. Woolhandler and Dr. Himmelstein had no competing interests to declare. Dr. Lipschutz disclosed Medicare advocacy work.

While Medicare Advantage (MA) plans are marketed as providing more generous benefits than traditional Medicare (TM), differences in the financial burden between beneficiaries switching to MA and staying with TM, are minimal, a longitudinal cohort analysis found.

In fact, according to a study by Sungchul Park, PhD, a health economist at Korea University in Seoul, and colleagues, the estimated annual out-of-pocket spending when switching to MA was $168 higher than staying in TM. That amounted to a 10.5% relative increase based on baseline out-of-pocket spending of $1597 annually among switchers, ranging widely, however, from a $133 decrease to a $469 increase. And for some, MA enrollment was associated with a higher likelihood of catastrophic financial burden.

“Our findings contrast with the notion that MA’s apparently more generous health insurance benefits lead to financial savings for enrollees,” Dr. Park and associates wrote in Annals of Internal Medicine.
 

The study

The analysis looked at costs for 7054 TM stayers and 1544 TM-to-MA switchers from the 2014-2020 Medical Expenditure Panel Survey, focusing on a cohort in which 18% of TM-covered individuals in year 1 switched to MA in year 2.

Comparative financial outcome measures included individual healthcare costs (out-of-pocket spending/cost sharing), financial burden (high/catastrophic), and subjective financial hardship (difficulty paying medical bills).

Although the overall out-of-pocket differences for MA were minimal and amounted to less than 1% of total healthcare expenses, MA was associated with a greater financial burden in vulnerable, especially in low-income populations. For every 100 beneficiaries with family incomes below 200% of the federal poverty level, one to six more switchers faced a catastrophic financial burden, with their out-of-pocket costs consuming more than 40% of household income in the year after switching.

The gap between the perception of lower costs and reality may be caused by a substantially heavier cost-sharing burden for certain services in MA plans, Dr. Park and associates pointed out. While MA enrollees generally paid less in some studies than the Part A hospital deductible for TM for inpatient stays of 3 days, they were more likely to face higher cost sharing for stays exceeding 7 days

Furthermore, whereas TM covers home health services without cost sharing, some MA plans have copayments. In addition, out-of-network health services can cost more. MA enrollees paid an average of $9 more for mental health services than for other in-network services and often encountered limited access to in-network providers. According to a 2021 study, only 18.2% of mental health professionals, 34.4% of cardiologists, 50.0% of psychiatrists, and 57.9% of primary care providers were included in MA networks,

An accompanying editorial noted that private MA plans will reap $83 billion in overpayments from U.S. taxpayers this year, according to Congress’s Medicare Payment Advisory Commission.

And as the data from Dr. Park and colleagues reveal, switchers don’t get much financial protection, according to primary care physician and healthcare researcher Steffi J. Woolhandler, MD, MPH, and internist David U. Himmelstein, MD, both of City University of New York at Hunter College in New York City.

“Medicare Advantage looks good when you’re healthy and don’t need much care. But when you need coverage, it often fails, leaving you with big bills and narrow choices for care,” Dr. Woolhandler said in an interview.

So how do these findings square with insurers’ hard-sell claims and enrollees’ perceptions that MA cuts out-of-pocket costs? “The likeliest explanation is that MA insurers have structured their benefits to advantage low-cost (that is, profitable) enrollees and disadvantage those requiring expensive care,” the editorial commentators wrote. For beneficiaries on inexpensive medications, MA plans would be a financial win. “But for patients requiring expensive chemotherapies, the 20% coinsurance that most MA plans charge could be financially ruinous.”

Commenting on the study but not involved in it, David A. Lipschutz, JD, LLB, associate director of the Center for Medicare Advocacy in Washington, DC, called the study an important one that provides more evidence that significant overpayments to MA plans don’t translate to better financial protections for plan enrollees, particularly lower-income individuals. “While there has been some recent movement to hold plans more accountable for providing necessary care, much more impactful action by policymakers is required to mitigate the harms of the growing privatization of the Medicare program,” he said. “MA overpayments could be redistributed to traditional Medicare in order to enrich all Medicare beneficiaries instead of just insurance companies.”

This study was supported by the National Research Foundation of Korea. Dr. Park disclosed no competing interests. One study coauthor reported support from government and not-for-profit research-funding bodies. Editorialists Dr. Woolhandler and Dr. Himmelstein had no competing interests to declare. Dr. Lipschutz disclosed Medicare advocacy work.

Some 15%-20% of the world’s population are neurodivergent, with conditions such as autism, dyslexia, Tourette syndrome, attention-deficit/hyperactivity disorder (ADHD), and others. With different strengths and challenges around learning, engaging socially, or completing certain tasks, neurodivergent people can face barriers in the workforce.

Meanwhile, studies suggest that neurodivergent people may be overrepresented in STEM fields such as medicine. The medical field may self-select for traits associated with neurodivergent conditions, researchers say, including a hyperfocus on intense interests, pattern recognition, increased curiosity and empathy, and thinking quickly under pressure.

But neurodivergent physicians report difficult, even damaging, experiences in the healthcare field. They struggle with stigma, a culture of nondisclosure, and lack of accommodations, which can lead to burnout and poor mental health.

“The medical system and the mental health system are some of the spaces that are holding on tightly to some of the outdated understandings of things like autism and ADHD,” says Megan Anna Neff, PsyD, a psychologist with autism and ADHD based in Portland, Oregon.

Situations can get dire: A 2023 survey of more than 200 autistic doctors from several countries found that 77% had considered suicide and 24% had attempted it.

But here’s the crux of it: Many neurodivergent doctors believe their unique ways of thinking and outside-the-box creativity are skills and strengths that can benefit the field. And they say making medicine more inclusive — and better understanding how a neurodivergent physician’s brain works — would allow them to thrive.
 

Blending In and Breaking Down

The exact number of neurodivergent physicians in the workforce remains unknown. Existing studies are small and focus mainly on autism. But researchers believe the percentage could be higher than we think, because neurodiversity can be underidentified.

Although autism can sometimes be diagnosed as early as 18 months, it’s not uncommon to receive a diagnosis well into adulthood. “Like many late-identified autistic adults, I got my autism diagnosis in the context of autistic burnout,” says Melissa Houser, MD, a primary care physician who received a diagnosis in 2021. Dr. Houser, who uses the pronouns she/they, explains that her experience is common, “a consequence of chronically having your life’s demands exceed your capacity.”

Dr. Houser, who also has ADHD and dyslexia, among other neurodivergent conditions, says that before her diagnosis, she worked in a traditional practice setting. Eventually, she began to notice intense dysregulation and fatigue. “I began to have a lot more difficulties with communication and my motor planning and sequencing,” Dr. Houser says. “I was sleep-deprived, and my needs were not being met. I was in a situation where I had a complete lack of autonomy over my practice.”

Deep in burnout, Dr. Houser says she lost her ability to “mask,” a term used to describe how some neurodivergent people work to “blend in” with societal expectations. This led to further communication breakdowns with her supervisor. Finally, Dr. Houser saw a psychiatrist.

Shortly after her diagnosis, Dr. Houser quit her job and founded All Brains Belong, a nonprofit that provides neurodiversity-affirming medical care, education, and advocacy. Research has found that people with autism are at increased risk for physical health conditions, including immune conditions, gastrointestinal disorders, metabolic conditions, and increased mortality in hospital settings. Understanding these connections can “mean the difference between life and death” for neurodivergent patients, Dr. Houser says.

Yet, in a 2015 study that assessed providers’ ability to recognize autism, a high proportion were not aware that they had patients with autism spectrum disorder, and most reported lacking both the skills and the tools to care for them.
 

Different as a Doctor and a Patient

Bernadette Grosjean, MD, a retired associate professor of psychiatry at David Geffen School of Medicine at UCLA and a distinguished Fellow of the American Psychiatric Association, also found insight into lifelong experiences as both a doctor and a patient with her autism diagnosis, which came when she was 61.

“Looking back, I was a smart kid but kind of clumsy and different in other ways,” Dr. Grosjean says. According to a 2021 survey by Cambridge University, autistic individuals are significantly more likely to identify as LGBTQ+, and Dr. Grosjean, who is gay, says that not being fully accepted by family or friends played a role in her struggles with mental health issues.

Throughout her mental health treatment, Dr. Grosjean felt as though her providers “were expecting from me things that I didn’t know how to do or fix. I didn’t know how to be a ‘good’ patient,” she recalls.

As a psychiatrist, Dr. Grosjean started to notice that many of the women she treated for borderline personality disorder, which is categorized by unstable relationships and emotions, were autistic. “I then started asking lots of questions about myself — the fact that I’ve always been very sensitive or that I’ve been accused of being both hypersensitive and not having emotions, and I understood a lot.”

When Dr. Grosjean came across Autistic Doctors International, a group of over 800 autistic doctors worldwide, she says, “I found my tribe.” She now serves as the US lead for psychiatry for the group, which is focused on support, advocacy, research, and education around neurodiversity.

Psychiatric comorbidities can accompany neurodivergent conditions. But a growing body of research, including a 2022 study published in the European Archives of Psychiatry and Clinical Neuroscience, indicates that autism and ADHD are frequently misdiagnosed as depression or anxiety.

Dr. Neff was unaware of her conditions until one of her children was diagnosed with autism in 2021. She started to research it. “As I was learning about autism and girls, I was like, ‘Oh, my gosh, this is me,’ ” Dr. Neff recalls. Within a few weeks, she had her own diagnosis.

In hindsight, Dr. Neff has more clarity regarding her struggles in the traditional medical space. She had found it difficult to fit patients into short appointment windows and keep their notes concise. Although she loved hospital work, the environment had been overwhelming and led to burnout.
 

‘A Deficit-Based Lens’

Dr. Houser believes that too often, autism is viewed through a “deficit-based lens.” Stressors like sensory overload, changes in routine, or unexpected events can exacerbate behavioral challenges for neurodivergent people in the workplace. The DSM-5 criteria for autism, she points out, are largely based on autistic “stress behaviors.”

The result, Dr. Houser says, is that neurodivergent doctors are judged by their response to stressors that put them at a disadvantage rather than their capabilities under more positive circumstances. “The more dysregulated someone is,” she says, “the more likely they are to manifest those observable behaviors.”

Dr. Neff notes that medicine is a very “sensory overwhelming work environment.” Working in ob.gyn. and primary care clinics, she remembers often coming home with a headache and a low-grade fever. “I had no idea why, but I now realize it’s because I was so sensory sick.”

Fearing for her job, Dr. Neff intentionally waited until she was in private practice to disclose her neurodiversity. “I don’t think it would have been received well if I was in a hospital system,” she says. “There’s a lot of invalidation that can come when someone chooses to self-disclose, and their colleagues don’t have a framework in mind to understand.” In one instance, after revealing her diagnosis, she remembers a well-known researcher telling her she wasn’t autistic.
Dr. Grosjean has also had former colleagues invalidate her diagnosis, something she says “keeps people quiet.”
 

Understanding the Neurodivergent Brain

The general lack of education on how neurodivergent brains work, physicians with these conditions say, means they are not often recognized for how they can function with certain accommodations and how they could contribute in unique ways if their workplace challenges were reduced.

“What we know about autistic brains is that we are systems-thinking pattern matchers,” says Dr. Houser, who formed an interdisciplinary task force to explore medical conditions that are more common in autistic people. Through that comprehensive approach, she has worked to find best practices to treat the constellation of conditions that can arise among these patients. “My autistic brain allowed me to do that,” Dr. Houser says.

Catriona McVey, a medical student in the United Kingdom and creator of the blog Attention Deficit Doctor, points out that “ADHD brains are interest-driven; they can be very focused when you’re doing something enjoyable or new due to increased dopaminergic stimulation.” Ms. McVey speaks from personal experience. “I’ve hyperfocused before on an essay that interested me for over 10 hours,” she recalls, “so I imagine if I was interested in surgery, I could easily hyperfocus on a long operation.” 

Empathy is another key part of medical practice. Contrary to stereotypes of neurodivergent people lacking empathy, current research suggests this isn’t true. A concept known as the “double empathy problem,” a term coined by British researcher Damian Milton in 2012, challenges the misconception that autistic people do not have empathy, explains Dr. Grosjean.

Mr. Milton theorized that there are two types of empathy: emotional, when you feel someone else’s pain, and cognitive, which involves critical thinking to understand someone’s emotions or thoughts. “Autistic people have, in general, a lot of emotional empathy,” Dr. Grosjean says, “but the cognitive empathy they don’t have as well.”

Dr. Neff has experienced this in her practice. “I will often feel what my clients are feeling as they’re feeling it,” she says, adding that she has always had an innate ability to analyze and connect with clients. She’s good at observing the interplay of health conditions, incorporating biology, psychology, and social conceptualizations of issues, with nuance. She feels that recognizing behavioral patterns or psychological triggers in her patients helps her see them holistically and provide better care. “That was a skill even before I realized I was autistic, but I always thought it was just intuitive to everyone,” she says. 
 

Support Can Lead to Success

The Americans with Disabilities Act requires employers to provide reasonable accommodations to neurodivergent employees. However, getting those accommodations involves disclosure, which many physicians have reasons to avoid.

It also means more work. Requesting and putting adjustments in place can take a lot of time and energy to organize. Ms. McVey says they can be “long-winded, multistep tasks” that are not very compatible with ADHD. “Some doctors report that service pressures and funding are used as excuses to refuse adjustments,” she adds. 

Ms. McVey lists several workplace accommodations that could be helpful, including flexible working hours, a quiet space to complete paperwork, dictation software, and extra time for medical students to complete written exams.

Neurodivergent physicians have also called for increased diversity of senior leadership and utilizing “cognitive apprenticeship models,” where employees explain their thought processes and receive timely feedback.

But far too often, there is little intervention until a doctor reaches a crisis point. “I look forward to the day when we don’t have to wait until people are profoundly depleted to discover how their brains work,” says Dr. Houser.

Beyond logistical and structural changes in the medical field, Dr. Grosjean speaks of the simple need to listen to colleagues with an open mind and believe them when they express their feelings and experiences. “Everyone has a role to play in challenging stigma, misconceptions, and stereotypes,” Ms. McVey agrees. Ask yourself the old question, she suggests: “If not me, then who? If not now, then when?”

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

Some 15%-20% of the world’s population are neurodivergent, with conditions such as autism, dyslexia, Tourette syndrome, attention-deficit/hyperactivity disorder (ADHD), and others. With different strengths and challenges around learning, engaging socially, or completing certain tasks, neurodivergent people can face barriers in the workforce.

Meanwhile, studies suggest that neurodivergent people may be overrepresented in STEM fields such as medicine. The medical field may self-select for traits associated with neurodivergent conditions, researchers say, including a hyperfocus on intense interests, pattern recognition, increased curiosity and empathy, and thinking quickly under pressure.

But neurodivergent physicians report difficult, even damaging, experiences in the healthcare field. They struggle with stigma, a culture of nondisclosure, and lack of accommodations, which can lead to burnout and poor mental health.

“The medical system and the mental health system are some of the spaces that are holding on tightly to some of the outdated understandings of things like autism and ADHD,” says Megan Anna Neff, PsyD, a psychologist with autism and ADHD based in Portland, Oregon.

Situations can get dire: A 2023 survey of more than 200 autistic doctors from several countries found that 77% had considered suicide and 24% had attempted it.

But here’s the crux of it: Many neurodivergent doctors believe their unique ways of thinking and outside-the-box creativity are skills and strengths that can benefit the field. And they say making medicine more inclusive — and better understanding how a neurodivergent physician’s brain works — would allow them to thrive.
 

Blending In and Breaking Down

The exact number of neurodivergent physicians in the workforce remains unknown. Existing studies are small and focus mainly on autism. But researchers believe the percentage could be higher than we think, because neurodiversity can be underidentified.

Although autism can sometimes be diagnosed as early as 18 months, it’s not uncommon to receive a diagnosis well into adulthood. “Like many late-identified autistic adults, I got my autism diagnosis in the context of autistic burnout,” says Melissa Houser, MD, a primary care physician who received a diagnosis in 2021. Dr. Houser, who uses the pronouns she/they, explains that her experience is common, “a consequence of chronically having your life’s demands exceed your capacity.”

Dr. Houser, who also has ADHD and dyslexia, among other neurodivergent conditions, says that before her diagnosis, she worked in a traditional practice setting. Eventually, she began to notice intense dysregulation and fatigue. “I began to have a lot more difficulties with communication and my motor planning and sequencing,” Dr. Houser says. “I was sleep-deprived, and my needs were not being met. I was in a situation where I had a complete lack of autonomy over my practice.”

Deep in burnout, Dr. Houser says she lost her ability to “mask,” a term used to describe how some neurodivergent people work to “blend in” with societal expectations. This led to further communication breakdowns with her supervisor. Finally, Dr. Houser saw a psychiatrist.

Shortly after her diagnosis, Dr. Houser quit her job and founded All Brains Belong, a nonprofit that provides neurodiversity-affirming medical care, education, and advocacy. Research has found that people with autism are at increased risk for physical health conditions, including immune conditions, gastrointestinal disorders, metabolic conditions, and increased mortality in hospital settings. Understanding these connections can “mean the difference between life and death” for neurodivergent patients, Dr. Houser says.

Yet, in a 2015 study that assessed providers’ ability to recognize autism, a high proportion were not aware that they had patients with autism spectrum disorder, and most reported lacking both the skills and the tools to care for them.
 

Different as a Doctor and a Patient

Bernadette Grosjean, MD, a retired associate professor of psychiatry at David Geffen School of Medicine at UCLA and a distinguished Fellow of the American Psychiatric Association, also found insight into lifelong experiences as both a doctor and a patient with her autism diagnosis, which came when she was 61.

“Looking back, I was a smart kid but kind of clumsy and different in other ways,” Dr. Grosjean says. According to a 2021 survey by Cambridge University, autistic individuals are significantly more likely to identify as LGBTQ+, and Dr. Grosjean, who is gay, says that not being fully accepted by family or friends played a role in her struggles with mental health issues.

Throughout her mental health treatment, Dr. Grosjean felt as though her providers “were expecting from me things that I didn’t know how to do or fix. I didn’t know how to be a ‘good’ patient,” she recalls.

As a psychiatrist, Dr. Grosjean started to notice that many of the women she treated for borderline personality disorder, which is categorized by unstable relationships and emotions, were autistic. “I then started asking lots of questions about myself — the fact that I’ve always been very sensitive or that I’ve been accused of being both hypersensitive and not having emotions, and I understood a lot.”

When Dr. Grosjean came across Autistic Doctors International, a group of over 800 autistic doctors worldwide, she says, “I found my tribe.” She now serves as the US lead for psychiatry for the group, which is focused on support, advocacy, research, and education around neurodiversity.

Psychiatric comorbidities can accompany neurodivergent conditions. But a growing body of research, including a 2022 study published in the European Archives of Psychiatry and Clinical Neuroscience, indicates that autism and ADHD are frequently misdiagnosed as depression or anxiety.

Dr. Neff was unaware of her conditions until one of her children was diagnosed with autism in 2021. She started to research it. “As I was learning about autism and girls, I was like, ‘Oh, my gosh, this is me,’ ” Dr. Neff recalls. Within a few weeks, she had her own diagnosis.

In hindsight, Dr. Neff has more clarity regarding her struggles in the traditional medical space. She had found it difficult to fit patients into short appointment windows and keep their notes concise. Although she loved hospital work, the environment had been overwhelming and led to burnout.
 

‘A Deficit-Based Lens’

Dr. Houser believes that too often, autism is viewed through a “deficit-based lens.” Stressors like sensory overload, changes in routine, or unexpected events can exacerbate behavioral challenges for neurodivergent people in the workplace. The DSM-5 criteria for autism, she points out, are largely based on autistic “stress behaviors.”

The result, Dr. Houser says, is that neurodivergent doctors are judged by their response to stressors that put them at a disadvantage rather than their capabilities under more positive circumstances. “The more dysregulated someone is,” she says, “the more likely they are to manifest those observable behaviors.”

Dr. Neff notes that medicine is a very “sensory overwhelming work environment.” Working in ob.gyn. and primary care clinics, she remembers often coming home with a headache and a low-grade fever. “I had no idea why, but I now realize it’s because I was so sensory sick.”

Fearing for her job, Dr. Neff intentionally waited until she was in private practice to disclose her neurodiversity. “I don’t think it would have been received well if I was in a hospital system,” she says. “There’s a lot of invalidation that can come when someone chooses to self-disclose, and their colleagues don’t have a framework in mind to understand.” In one instance, after revealing her diagnosis, she remembers a well-known researcher telling her she wasn’t autistic.
Dr. Grosjean has also had former colleagues invalidate her diagnosis, something she says “keeps people quiet.”
 

Understanding the Neurodivergent Brain

The general lack of education on how neurodivergent brains work, physicians with these conditions say, means they are not often recognized for how they can function with certain accommodations and how they could contribute in unique ways if their workplace challenges were reduced.

“What we know about autistic brains is that we are systems-thinking pattern matchers,” says Dr. Houser, who formed an interdisciplinary task force to explore medical conditions that are more common in autistic people. Through that comprehensive approach, she has worked to find best practices to treat the constellation of conditions that can arise among these patients. “My autistic brain allowed me to do that,” Dr. Houser says.

Catriona McVey, a medical student in the United Kingdom and creator of the blog Attention Deficit Doctor, points out that “ADHD brains are interest-driven; they can be very focused when you’re doing something enjoyable or new due to increased dopaminergic stimulation.” Ms. McVey speaks from personal experience. “I’ve hyperfocused before on an essay that interested me for over 10 hours,” she recalls, “so I imagine if I was interested in surgery, I could easily hyperfocus on a long operation.” 

Empathy is another key part of medical practice. Contrary to stereotypes of neurodivergent people lacking empathy, current research suggests this isn’t true. A concept known as the “double empathy problem,” a term coined by British researcher Damian Milton in 2012, challenges the misconception that autistic people do not have empathy, explains Dr. Grosjean.

Mr. Milton theorized that there are two types of empathy: emotional, when you feel someone else’s pain, and cognitive, which involves critical thinking to understand someone’s emotions or thoughts. “Autistic people have, in general, a lot of emotional empathy,” Dr. Grosjean says, “but the cognitive empathy they don’t have as well.”

Dr. Neff has experienced this in her practice. “I will often feel what my clients are feeling as they’re feeling it,” she says, adding that she has always had an innate ability to analyze and connect with clients. She’s good at observing the interplay of health conditions, incorporating biology, psychology, and social conceptualizations of issues, with nuance. She feels that recognizing behavioral patterns or psychological triggers in her patients helps her see them holistically and provide better care. “That was a skill even before I realized I was autistic, but I always thought it was just intuitive to everyone,” she says. 
 

Support Can Lead to Success

The Americans with Disabilities Act requires employers to provide reasonable accommodations to neurodivergent employees. However, getting those accommodations involves disclosure, which many physicians have reasons to avoid.

It also means more work. Requesting and putting adjustments in place can take a lot of time and energy to organize. Ms. McVey says they can be “long-winded, multistep tasks” that are not very compatible with ADHD. “Some doctors report that service pressures and funding are used as excuses to refuse adjustments,” she adds. 

Ms. McVey lists several workplace accommodations that could be helpful, including flexible working hours, a quiet space to complete paperwork, dictation software, and extra time for medical students to complete written exams.

Neurodivergent physicians have also called for increased diversity of senior leadership and utilizing “cognitive apprenticeship models,” where employees explain their thought processes and receive timely feedback.

But far too often, there is little intervention until a doctor reaches a crisis point. “I look forward to the day when we don’t have to wait until people are profoundly depleted to discover how their brains work,” says Dr. Houser.

Beyond logistical and structural changes in the medical field, Dr. Grosjean speaks of the simple need to listen to colleagues with an open mind and believe them when they express their feelings and experiences. “Everyone has a role to play in challenging stigma, misconceptions, and stereotypes,” Ms. McVey agrees. Ask yourself the old question, she suggests: “If not me, then who? If not now, then when?”

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

Some 15%-20% of the world’s population are neurodivergent, with conditions such as autism, dyslexia, Tourette syndrome, attention-deficit/hyperactivity disorder (ADHD), and others. With different strengths and challenges around learning, engaging socially, or completing certain tasks, neurodivergent people can face barriers in the workforce.

Meanwhile, studies suggest that neurodivergent people may be overrepresented in STEM fields such as medicine. The medical field may self-select for traits associated with neurodivergent conditions, researchers say, including a hyperfocus on intense interests, pattern recognition, increased curiosity and empathy, and thinking quickly under pressure.

But neurodivergent physicians report difficult, even damaging, experiences in the healthcare field. They struggle with stigma, a culture of nondisclosure, and lack of accommodations, which can lead to burnout and poor mental health.

“The medical system and the mental health system are some of the spaces that are holding on tightly to some of the outdated understandings of things like autism and ADHD,” says Megan Anna Neff, PsyD, a psychologist with autism and ADHD based in Portland, Oregon.

Situations can get dire: A 2023 survey of more than 200 autistic doctors from several countries found that 77% had considered suicide and 24% had attempted it.

But here’s the crux of it: Many neurodivergent doctors believe their unique ways of thinking and outside-the-box creativity are skills and strengths that can benefit the field. And they say making medicine more inclusive — and better understanding how a neurodivergent physician’s brain works — would allow them to thrive.
 

Blending In and Breaking Down

The exact number of neurodivergent physicians in the workforce remains unknown. Existing studies are small and focus mainly on autism. But researchers believe the percentage could be higher than we think, because neurodiversity can be underidentified.

Although autism can sometimes be diagnosed as early as 18 months, it’s not uncommon to receive a diagnosis well into adulthood. “Like many late-identified autistic adults, I got my autism diagnosis in the context of autistic burnout,” says Melissa Houser, MD, a primary care physician who received a diagnosis in 2021. Dr. Houser, who uses the pronouns she/they, explains that her experience is common, “a consequence of chronically having your life’s demands exceed your capacity.”

Dr. Houser, who also has ADHD and dyslexia, among other neurodivergent conditions, says that before her diagnosis, she worked in a traditional practice setting. Eventually, she began to notice intense dysregulation and fatigue. “I began to have a lot more difficulties with communication and my motor planning and sequencing,” Dr. Houser says. “I was sleep-deprived, and my needs were not being met. I was in a situation where I had a complete lack of autonomy over my practice.”

Deep in burnout, Dr. Houser says she lost her ability to “mask,” a term used to describe how some neurodivergent people work to “blend in” with societal expectations. This led to further communication breakdowns with her supervisor. Finally, Dr. Houser saw a psychiatrist.

Shortly after her diagnosis, Dr. Houser quit her job and founded All Brains Belong, a nonprofit that provides neurodiversity-affirming medical care, education, and advocacy. Research has found that people with autism are at increased risk for physical health conditions, including immune conditions, gastrointestinal disorders, metabolic conditions, and increased mortality in hospital settings. Understanding these connections can “mean the difference between life and death” for neurodivergent patients, Dr. Houser says.

Yet, in a 2015 study that assessed providers’ ability to recognize autism, a high proportion were not aware that they had patients with autism spectrum disorder, and most reported lacking both the skills and the tools to care for them.
 

Different as a Doctor and a Patient

Bernadette Grosjean, MD, a retired associate professor of psychiatry at David Geffen School of Medicine at UCLA and a distinguished Fellow of the American Psychiatric Association, also found insight into lifelong experiences as both a doctor and a patient with her autism diagnosis, which came when she was 61.

“Looking back, I was a smart kid but kind of clumsy and different in other ways,” Dr. Grosjean says. According to a 2021 survey by Cambridge University, autistic individuals are significantly more likely to identify as LGBTQ+, and Dr. Grosjean, who is gay, says that not being fully accepted by family or friends played a role in her struggles with mental health issues.

Throughout her mental health treatment, Dr. Grosjean felt as though her providers “were expecting from me things that I didn’t know how to do or fix. I didn’t know how to be a ‘good’ patient,” she recalls.

As a psychiatrist, Dr. Grosjean started to notice that many of the women she treated for borderline personality disorder, which is categorized by unstable relationships and emotions, were autistic. “I then started asking lots of questions about myself — the fact that I’ve always been very sensitive or that I’ve been accused of being both hypersensitive and not having emotions, and I understood a lot.”

When Dr. Grosjean came across Autistic Doctors International, a group of over 800 autistic doctors worldwide, she says, “I found my tribe.” She now serves as the US lead for psychiatry for the group, which is focused on support, advocacy, research, and education around neurodiversity.

Psychiatric comorbidities can accompany neurodivergent conditions. But a growing body of research, including a 2022 study published in the European Archives of Psychiatry and Clinical Neuroscience, indicates that autism and ADHD are frequently misdiagnosed as depression or anxiety.

Dr. Neff was unaware of her conditions until one of her children was diagnosed with autism in 2021. She started to research it. “As I was learning about autism and girls, I was like, ‘Oh, my gosh, this is me,’ ” Dr. Neff recalls. Within a few weeks, she had her own diagnosis.

In hindsight, Dr. Neff has more clarity regarding her struggles in the traditional medical space. She had found it difficult to fit patients into short appointment windows and keep their notes concise. Although she loved hospital work, the environment had been overwhelming and led to burnout.
 

‘A Deficit-Based Lens’

Dr. Houser believes that too often, autism is viewed through a “deficit-based lens.” Stressors like sensory overload, changes in routine, or unexpected events can exacerbate behavioral challenges for neurodivergent people in the workplace. The DSM-5 criteria for autism, she points out, are largely based on autistic “stress behaviors.”

The result, Dr. Houser says, is that neurodivergent doctors are judged by their response to stressors that put them at a disadvantage rather than their capabilities under more positive circumstances. “The more dysregulated someone is,” she says, “the more likely they are to manifest those observable behaviors.”

Dr. Neff notes that medicine is a very “sensory overwhelming work environment.” Working in ob.gyn. and primary care clinics, she remembers often coming home with a headache and a low-grade fever. “I had no idea why, but I now realize it’s because I was so sensory sick.”

Fearing for her job, Dr. Neff intentionally waited until she was in private practice to disclose her neurodiversity. “I don’t think it would have been received well if I was in a hospital system,” she says. “There’s a lot of invalidation that can come when someone chooses to self-disclose, and their colleagues don’t have a framework in mind to understand.” In one instance, after revealing her diagnosis, she remembers a well-known researcher telling her she wasn’t autistic.
Dr. Grosjean has also had former colleagues invalidate her diagnosis, something she says “keeps people quiet.”
 

Understanding the Neurodivergent Brain

The general lack of education on how neurodivergent brains work, physicians with these conditions say, means they are not often recognized for how they can function with certain accommodations and how they could contribute in unique ways if their workplace challenges were reduced.

“What we know about autistic brains is that we are systems-thinking pattern matchers,” says Dr. Houser, who formed an interdisciplinary task force to explore medical conditions that are more common in autistic people. Through that comprehensive approach, she has worked to find best practices to treat the constellation of conditions that can arise among these patients. “My autistic brain allowed me to do that,” Dr. Houser says.

Catriona McVey, a medical student in the United Kingdom and creator of the blog Attention Deficit Doctor, points out that “ADHD brains are interest-driven; they can be very focused when you’re doing something enjoyable or new due to increased dopaminergic stimulation.” Ms. McVey speaks from personal experience. “I’ve hyperfocused before on an essay that interested me for over 10 hours,” she recalls, “so I imagine if I was interested in surgery, I could easily hyperfocus on a long operation.” 

Empathy is another key part of medical practice. Contrary to stereotypes of neurodivergent people lacking empathy, current research suggests this isn’t true. A concept known as the “double empathy problem,” a term coined by British researcher Damian Milton in 2012, challenges the misconception that autistic people do not have empathy, explains Dr. Grosjean.

Mr. Milton theorized that there are two types of empathy: emotional, when you feel someone else’s pain, and cognitive, which involves critical thinking to understand someone’s emotions or thoughts. “Autistic people have, in general, a lot of emotional empathy,” Dr. Grosjean says, “but the cognitive empathy they don’t have as well.”

Dr. Neff has experienced this in her practice. “I will often feel what my clients are feeling as they’re feeling it,” she says, adding that she has always had an innate ability to analyze and connect with clients. She’s good at observing the interplay of health conditions, incorporating biology, psychology, and social conceptualizations of issues, with nuance. She feels that recognizing behavioral patterns or psychological triggers in her patients helps her see them holistically and provide better care. “That was a skill even before I realized I was autistic, but I always thought it was just intuitive to everyone,” she says. 
 

Support Can Lead to Success

The Americans with Disabilities Act requires employers to provide reasonable accommodations to neurodivergent employees. However, getting those accommodations involves disclosure, which many physicians have reasons to avoid.

It also means more work. Requesting and putting adjustments in place can take a lot of time and energy to organize. Ms. McVey says they can be “long-winded, multistep tasks” that are not very compatible with ADHD. “Some doctors report that service pressures and funding are used as excuses to refuse adjustments,” she adds. 

Ms. McVey lists several workplace accommodations that could be helpful, including flexible working hours, a quiet space to complete paperwork, dictation software, and extra time for medical students to complete written exams.

Neurodivergent physicians have also called for increased diversity of senior leadership and utilizing “cognitive apprenticeship models,” where employees explain their thought processes and receive timely feedback.

But far too often, there is little intervention until a doctor reaches a crisis point. “I look forward to the day when we don’t have to wait until people are profoundly depleted to discover how their brains work,” says Dr. Houser.

Beyond logistical and structural changes in the medical field, Dr. Grosjean speaks of the simple need to listen to colleagues with an open mind and believe them when they express their feelings and experiences. “Everyone has a role to play in challenging stigma, misconceptions, and stereotypes,” Ms. McVey agrees. Ask yourself the old question, she suggests: “If not me, then who? If not now, then when?”

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

TOPLINE:

Lung cancer screening was associated with earlier-stage diagnoses and improved survival in a retrospective analysis of a large cohort with low screening uptake. 

METHODOLOGY:

• Randomized trials have shown a mortality benefit with low-dose CT screening to detect lung cancer, but the benefits in clinical practice remain unclear, and lung cancer screening uptake has been slow.
• In this study, researchers assessed the impact of lung cancer screening among Veteran Health Administration patients diagnosed with lung cancer between 2011 and 2018.
• The team evaluated lung cancer stage at diagnosis, lung cancer–specific survival, and overall survival in patients with lung cancer who did vs did not receive screening before their diagnosis.
• Statistical analyses included Cox regression modeling and inverse propensity weighting with lead-time bias adjustment.

TAKEAWAY:

• Among 57,919 individuals diagnosed with lung cancer during the study period, 2167 (3.9%) underwent screening with at least one low-dose CT before receiving their diagnosis. There were no significant differences in age, gender, or race among patients who had prior screening and those who did not.
• Screened patients had double the rate of stage I diagnoses compared with unscreened patients (52% vs 27%) and about one third the rate of stage IV diagnoses (11% vs 32%).
• Patients who received screening before their cancer diagnosis had better overall survival rates compared with unscreened patients. The overall survival rates were 81.2% vs 56.6% at 1 year, 69.9% vs 41.1% at 2 years, and 44.9% vs 22.3% at 5 years, respectively. Lung cancer–specific survival was also better: The survival rates were 82.5% vs 58.7% at 1 year, 74.3% vs 44.4% at 2 years, and 59.0% vs 29.7% at 5 years, respectively.
• A subset analysis of screening-eligible patients (defined as those between the ages of 50-88 who were smokers with a pack-year history of ≥ 20 years or former smokers who quit within 15 years) showed that among those who underwent National Comprehensive Cancer Network guideline-concordant treatment within 12 months of diagnosis, screening resulted in “substantial” reductions in all-cause mortality (adjusted hazard ratio [aHR], 0.79) and lung cancer–specific mortality (aHR, 0.61).

IN PRACTICE:

“These findings provide corroboration of the results of randomized [lung cancer screening] trials in clinical practice,” the authors wrote. “We hope that the striking association between [lung cancer screening], earlier stage diagnosis of lung cancer, and improved mortality spurs a more robust uptake of this life-saving intervention into clinical practice.”

SOURCE:

The study, led by Donna M. Edwards MD, PhD, of the University of Michigan School of Medicine, Ann Arbor, Michigan, was published online in Cancer.

LIMITATIONS:

The study was limited by its retrospective and correlative design, and the authors also were unable to assess whether lung cancer screening contributed to more subsequence procedures in screened vs unscreened patients.

DISCLOSURES:

The study was funded by the LUNGevity Foundation, US Department of Veterans Affairs, National Cancer Institute, and Lung Precision Oncology Program. One author declared being a consultant for industry. The other authors declared no conflicts of interest.

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

TOPLINE:

Lung cancer screening was associated with earlier-stage diagnoses and improved survival in a retrospective analysis of a large cohort with low screening uptake. 

METHODOLOGY:

• Randomized trials have shown a mortality benefit with low-dose CT screening to detect lung cancer, but the benefits in clinical practice remain unclear, and lung cancer screening uptake has been slow.
• In this study, researchers assessed the impact of lung cancer screening among Veteran Health Administration patients diagnosed with lung cancer between 2011 and 2018.
• The team evaluated lung cancer stage at diagnosis, lung cancer–specific survival, and overall survival in patients with lung cancer who did vs did not receive screening before their diagnosis.
• Statistical analyses included Cox regression modeling and inverse propensity weighting with lead-time bias adjustment.

TAKEAWAY:

• Among 57,919 individuals diagnosed with lung cancer during the study period, 2167 (3.9%) underwent screening with at least one low-dose CT before receiving their diagnosis. There were no significant differences in age, gender, or race among patients who had prior screening and those who did not.
• Screened patients had double the rate of stage I diagnoses compared with unscreened patients (52% vs 27%) and about one third the rate of stage IV diagnoses (11% vs 32%).
• Patients who received screening before their cancer diagnosis had better overall survival rates compared with unscreened patients. The overall survival rates were 81.2% vs 56.6% at 1 year, 69.9% vs 41.1% at 2 years, and 44.9% vs 22.3% at 5 years, respectively. Lung cancer–specific survival was also better: The survival rates were 82.5% vs 58.7% at 1 year, 74.3% vs 44.4% at 2 years, and 59.0% vs 29.7% at 5 years, respectively.
• A subset analysis of screening-eligible patients (defined as those between the ages of 50-88 who were smokers with a pack-year history of ≥ 20 years or former smokers who quit within 15 years) showed that among those who underwent National Comprehensive Cancer Network guideline-concordant treatment within 12 months of diagnosis, screening resulted in “substantial” reductions in all-cause mortality (adjusted hazard ratio [aHR], 0.79) and lung cancer–specific mortality (aHR, 0.61).

IN PRACTICE:

“These findings provide corroboration of the results of randomized [lung cancer screening] trials in clinical practice,” the authors wrote. “We hope that the striking association between [lung cancer screening], earlier stage diagnosis of lung cancer, and improved mortality spurs a more robust uptake of this life-saving intervention into clinical practice.”

SOURCE:

The study, led by Donna M. Edwards MD, PhD, of the University of Michigan School of Medicine, Ann Arbor, Michigan, was published online in Cancer.

LIMITATIONS:

The study was limited by its retrospective and correlative design, and the authors also were unable to assess whether lung cancer screening contributed to more subsequence procedures in screened vs unscreened patients.

DISCLOSURES:

The study was funded by the LUNGevity Foundation, US Department of Veterans Affairs, National Cancer Institute, and Lung Precision Oncology Program. One author declared being a consultant for industry. The other authors declared no conflicts of interest.

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

TOPLINE:

Lung cancer screening was associated with earlier-stage diagnoses and improved survival in a retrospective analysis of a large cohort with low screening uptake. 

METHODOLOGY:

• Randomized trials have shown a mortality benefit with low-dose CT screening to detect lung cancer, but the benefits in clinical practice remain unclear, and lung cancer screening uptake has been slow.
• In this study, researchers assessed the impact of lung cancer screening among Veteran Health Administration patients diagnosed with lung cancer between 2011 and 2018.
• The team evaluated lung cancer stage at diagnosis, lung cancer–specific survival, and overall survival in patients with lung cancer who did vs did not receive screening before their diagnosis.
• Statistical analyses included Cox regression modeling and inverse propensity weighting with lead-time bias adjustment.

TAKEAWAY:

• Among 57,919 individuals diagnosed with lung cancer during the study period, 2167 (3.9%) underwent screening with at least one low-dose CT before receiving their diagnosis. There were no significant differences in age, gender, or race among patients who had prior screening and those who did not.
• Screened patients had double the rate of stage I diagnoses compared with unscreened patients (52% vs 27%) and about one third the rate of stage IV diagnoses (11% vs 32%).
• Patients who received screening before their cancer diagnosis had better overall survival rates compared with unscreened patients. The overall survival rates were 81.2% vs 56.6% at 1 year, 69.9% vs 41.1% at 2 years, and 44.9% vs 22.3% at 5 years, respectively. Lung cancer–specific survival was also better: The survival rates were 82.5% vs 58.7% at 1 year, 74.3% vs 44.4% at 2 years, and 59.0% vs 29.7% at 5 years, respectively.
• A subset analysis of screening-eligible patients (defined as those between the ages of 50-88 who were smokers with a pack-year history of ≥ 20 years or former smokers who quit within 15 years) showed that among those who underwent National Comprehensive Cancer Network guideline-concordant treatment within 12 months of diagnosis, screening resulted in “substantial” reductions in all-cause mortality (adjusted hazard ratio [aHR], 0.79) and lung cancer–specific mortality (aHR, 0.61).

IN PRACTICE:

“These findings provide corroboration of the results of randomized [lung cancer screening] trials in clinical practice,” the authors wrote. “We hope that the striking association between [lung cancer screening], earlier stage diagnosis of lung cancer, and improved mortality spurs a more robust uptake of this life-saving intervention into clinical practice.”

SOURCE:

The study, led by Donna M. Edwards MD, PhD, of the University of Michigan School of Medicine, Ann Arbor, Michigan, was published online in Cancer.

LIMITATIONS:

The study was limited by its retrospective and correlative design, and the authors also were unable to assess whether lung cancer screening contributed to more subsequence procedures in screened vs unscreened patients.

DISCLOSURES:

The study was funded by the LUNGevity Foundation, US Department of Veterans Affairs, National Cancer Institute, and Lung Precision Oncology Program. One author declared being a consultant for industry. The other authors declared no conflicts of interest.

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

In the wake of a debilitating cyberattack against one of the nation’s largest health care systems, Marvin Ruckle, a nurse at an Ascension hospital in Wichita, Kansas, said he had a frightening experience: He nearly gave a baby “the wrong dose of narcotic” because of confusing paperwork.

Ruckle, who has worked in the neonatal intensive care unit at Ascension Via Christi St. Joseph for two decades, said it was “hard to decipher which was the correct dose” on the medication record. He’d “never seen that happen,” he said, “when we were on the computer system” before the cyberattack.

A May 8 ransomware attack against Ascension, a Catholic health system with 140 hospitals in at least 10 states, locked providers out of systems that track and coordinate nearly every aspect of patient care. They include its systems for electronic health records, some phones, and ones “utilized to order certain tests, procedures and medications,” the company said in a May 9 statement.

More than a dozen doctors and nurses who work for the sprawling health system told Michigan Public and KFF Health News that patient care at its hospitals across the nation was compromised in the fallout of the cyberattack over the past several weeks. Clinicians working for hospitals in three states described harrowing lapses, including delayed or lost lab results, medication errors, and an absence of routine safety checks via technology to prevent potentially fatal mistakes.

Despite a precipitous rise in cyberattacks against the health sector in recent years, a weeks-long disruption of this magnitude is beyond what most health systems are prepared for, said John S. Clark, an associate chief pharmacy officer at the University of Michigan health system.

“I don’t believe that anyone is fully prepared,” he said. Most emergency management plans “are designed around long-term downtimes that are into one, two, or three days.”

Ascension in a public statement May 9 said its care teams were “trained for these kinds of disruptions,” but did not respond to questions in early June about whether it had prepared for longer periods of downtime. Ascension said June 14 it had restored access to electronic health records across its network, but that patient “medical records and other information collected between May 8” and when the service was restored “may be temporarily inaccessible as we work to update the portal with information collected during the system downtime.”

Ruckle said he “had no training” for the cyberattack.
 

Back to Paper

Lisa Watson, an intensive care unit nurse at Ascension Via Christi St. Francis hospital in Wichita, described her own close call. She said she nearly administered the wrong medication to a critically ill patient because she couldn’t scan it as she normally would. “My patient probably would have passed away had I not caught it,” she said.

Watson is no stranger to using paper for patients’ medical charts, saying she did so “for probably half of my career,” before electronic health records became ubiquitous in hospitals. What happened after the cyberattack was “by no means the same.”

“When we paper-charted, we had systems in place to get those orders to other departments in a timely manner,” she said, “and those have all gone away.”

Melissa LaRue, an ICU nurse at Ascension Saint Agnes Hospital in Baltimore, described a close call with “administering the wrong dosage” of a patient’s blood pressure medication. “Luckily,” she said, it was “triple-checked and remedied before that could happen. But I think the potential for harm is there when you have so much information and paperwork that you have to go through.”

Clinicians say their hospitals have relied on slapdash workarounds, using handwritten notes, faxes, sticky notes, and basic computer spreadsheets — many devised on the fly by doctors and nurses — to care for patients.

More than a dozen other nurses and doctors, some of them without union protections, at Ascension hospitals in Michigan recounted situations in which they say patient care was compromised. Those clinicians spoke on the condition that they not be named for fear of retaliation by their employer.

An Ascension hospital emergency room doctor in Detroit said a man on the city’s east side was given a dangerous narcotic intended for another patient because of a paperwork mix-up. As a result, the patient’s breathing slowed to the point that he had to be put on a ventilator. “We intubated him and we sent him to the ICU because he got the wrong medication.”

A nurse in a Michigan Ascension hospital ER said a woman with low blood sugar and “altered mental status” went into cardiac arrest and died after staff said they waited four hours for lab results they needed to determine how to treat her, but never received. “If I started having crushing chest pain in the middle of work and thought I was having a big one, I would grab someone to drive me down the street to another hospital,” the same ER nurse said.

Similar concerns reportedly led a travel nurse at an Ascension hospital in Indiana to quit. “I just want to warn those patients that are coming to any of the Ascension facilities that there will be delays in care. There is potential for error and for harm,” Justin Neisser told CBS4 in Indianapolis in May.

Several nurses and doctors at Ascension hospitals said they feared the errors they’ve witnessed since the cyberattack began could threaten their professional licenses. “This is how a RaDonda Vaught happens,” one nurse said, referring to the Tennessee nurse who was convicted of criminally negligent homicide in 2022 for a fatal drug error.

Reporters were not able to review records to verify clinicians’ claims because of privacy laws surrounding patients’ medical information that apply to health care professionals.

Ascension declined to answer questions about claims that care has been affected by the ransomware attack. “As we have made clear throughout this cyber attack which has impacted our system and our dedicated clinical providers, caring for our patients is our highest priority,” Sean Fitzpatrick, Ascension’s vice president of external communications, said via email on June 3. “We are confident that our care providers in our hospitals and facilities continue to provide quality medical care.”

The federal government requires hospitals to protect patients’ sensitive health data, according to cybersecurity experts. However, there are no federal requirements for hospitals to prevent or prepare for cyberattacks that could compromise their electronic systems.
 

Hospitals: ‘The No.1 Target of Ransomware’

“We’ve started to think about these as public health issues and disasters on the scale of earthquakes or hurricanes,” said Jeff Tully, a co-director of the Center for Healthcare Cybersecurity at the University of California-San Diego. “These types of cybersecurity incidents should be thought of as a matter of when, and not if.”

Josh Corman, a cybersecurity expert and advocate, said ransom crews regard hospitals as the perfect prey: “They have terrible security and they’ll pay. So almost immediately, hospitals went to the No. 1 target of ransomware.”

In 2023, the health sector experienced the largest share of ransomware attacks of 16 infrastructure sectors considered vital to national security or safety, according to an FBI report on internet crimes. In March, the federal Department of Health and Human Services said reported large breaches involving ransomware had jumped by 264% over the past five years.

A cyberattack this year on Change Healthcare, a unit of UnitedHealth Group’s Optum division that processes billions of health care transactions every year, crippled the business of providers, pharmacies, and hospitals.

In May, UnitedHealth Group CEO Andrew Witty told lawmakers the company paid a $22 million ransom as a result of the Change Healthcare attack — which occurred after hackers accessed a company portal that didn’t have multifactor authentication, a basic cybersecurity tool.

The Biden administration in recent months has pushed to bolster health care cybersecurity standards, but it’s not clear which new measures will be required.

In January, HHS nudged companies to improve email security, add multifactor authentication, and institute cybersecurity training and testing, among other voluntary measures. The Centers for Medicare & Medicaid Services is expected to release new requirements for hospitals, but the scope and timing are unclear. The same is true of an update HHS is expected to make to patient privacy regulations.

HHS said the voluntary measures “will inform the creation of new enforceable cybersecurity standards,” department spokesperson Jeff Nesbit said in a statement.

“The recent cyberattack at Ascension only underscores the need for everyone in the health care ecosystem to do their part to secure their systems and protect patients,” Nesbit said.

Meanwhile, lobbyists for the hospital industry contend cybersecurity mandates or penalties are misplaced and would curtail hospitals’ resources to fend off attacks.

“Hospitals and health systems are not the primary source of cyber risk exposure facing the health care sector,” the American Hospital Association, the largest lobbying group for U.S. hospitals, said in an April statement prepared for U.S. House lawmakers. Most large data breaches that hit hospitals in 2023 originated with third-party “business associates” or other health entities, including CMS itself, the AHA statement said.

Hospitals consolidating into large multistate health systems face increased risk of data breaches and ransomware attacks, according to one study. Ascension in 2022 was the third-largest hospital chain in the U.S. by number of beds, according to the most recent data from the federal Agency for Healthcare Research and Quality.

And while cybersecurity regulations can quickly become outdated, they can at least make it clear that if health systems fail to implement basic protections there “should be consequences for that,” Jim Bagian, a former director of the National Center for Patient Safety at the Veterans Health Administration, told Michigan Public’s Stateside.

Patients can pay the price when lapses occur. Those in hospital care face a greater likelihood of death during a cyberattack, according to researchers at the University of Minnesota School of Public Health.

Workers concerned about patient safety at Ascension hospitals in Michigan have called for the company to make changes.

“We implore Ascension to recognize the internal problems that continue to plague its hospitals, both publicly and transparently,” said Dina Carlisle, a nurse and the president of the OPEIU Local 40 union, which represents nurses at Ascension Providence Rochester. At least 125 staff members at that Ascension hospital have signed a petition asking administrators to temporarily reduce elective surgeries and nonemergency patient admissions, like under the protocols many hospitals adopted early in the covid-19 pandemic.

Watson, the Kansas ICU nurse, said in late May that nurses had urged management to bring in more nurses to help manage the workflow. “Everything that we say has fallen on deaf ears,” she said.

“It is very hard to be a nurse at Ascension right now,” Watson said in late May. “It is very hard to be a patient at Ascension right now.”

If you’re a patient or worker at an Ascension hospital and would like to tell KFF Health News about your experiences, click here to share your story with us.
 

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

In the wake of a debilitating cyberattack against one of the nation’s largest health care systems, Marvin Ruckle, a nurse at an Ascension hospital in Wichita, Kansas, said he had a frightening experience: He nearly gave a baby “the wrong dose of narcotic” because of confusing paperwork.

Ruckle, who has worked in the neonatal intensive care unit at Ascension Via Christi St. Joseph for two decades, said it was “hard to decipher which was the correct dose” on the medication record. He’d “never seen that happen,” he said, “when we were on the computer system” before the cyberattack.

A May 8 ransomware attack against Ascension, a Catholic health system with 140 hospitals in at least 10 states, locked providers out of systems that track and coordinate nearly every aspect of patient care. They include its systems for electronic health records, some phones, and ones “utilized to order certain tests, procedures and medications,” the company said in a May 9 statement.

More than a dozen doctors and nurses who work for the sprawling health system told Michigan Public and KFF Health News that patient care at its hospitals across the nation was compromised in the fallout of the cyberattack over the past several weeks. Clinicians working for hospitals in three states described harrowing lapses, including delayed or lost lab results, medication errors, and an absence of routine safety checks via technology to prevent potentially fatal mistakes.

Despite a precipitous rise in cyberattacks against the health sector in recent years, a weeks-long disruption of this magnitude is beyond what most health systems are prepared for, said John S. Clark, an associate chief pharmacy officer at the University of Michigan health system.

“I don’t believe that anyone is fully prepared,” he said. Most emergency management plans “are designed around long-term downtimes that are into one, two, or three days.”

Ascension in a public statement May 9 said its care teams were “trained for these kinds of disruptions,” but did not respond to questions in early June about whether it had prepared for longer periods of downtime. Ascension said June 14 it had restored access to electronic health records across its network, but that patient “medical records and other information collected between May 8” and when the service was restored “may be temporarily inaccessible as we work to update the portal with information collected during the system downtime.”

Ruckle said he “had no training” for the cyberattack.
 

Back to Paper

Lisa Watson, an intensive care unit nurse at Ascension Via Christi St. Francis hospital in Wichita, described her own close call. She said she nearly administered the wrong medication to a critically ill patient because she couldn’t scan it as she normally would. “My patient probably would have passed away had I not caught it,” she said.

Watson is no stranger to using paper for patients’ medical charts, saying she did so “for probably half of my career,” before electronic health records became ubiquitous in hospitals. What happened after the cyberattack was “by no means the same.”

“When we paper-charted, we had systems in place to get those orders to other departments in a timely manner,” she said, “and those have all gone away.”

Melissa LaRue, an ICU nurse at Ascension Saint Agnes Hospital in Baltimore, described a close call with “administering the wrong dosage” of a patient’s blood pressure medication. “Luckily,” she said, it was “triple-checked and remedied before that could happen. But I think the potential for harm is there when you have so much information and paperwork that you have to go through.”

Clinicians say their hospitals have relied on slapdash workarounds, using handwritten notes, faxes, sticky notes, and basic computer spreadsheets — many devised on the fly by doctors and nurses — to care for patients.

More than a dozen other nurses and doctors, some of them without union protections, at Ascension hospitals in Michigan recounted situations in which they say patient care was compromised. Those clinicians spoke on the condition that they not be named for fear of retaliation by their employer.

An Ascension hospital emergency room doctor in Detroit said a man on the city’s east side was given a dangerous narcotic intended for another patient because of a paperwork mix-up. As a result, the patient’s breathing slowed to the point that he had to be put on a ventilator. “We intubated him and we sent him to the ICU because he got the wrong medication.”

A nurse in a Michigan Ascension hospital ER said a woman with low blood sugar and “altered mental status” went into cardiac arrest and died after staff said they waited four hours for lab results they needed to determine how to treat her, but never received. “If I started having crushing chest pain in the middle of work and thought I was having a big one, I would grab someone to drive me down the street to another hospital,” the same ER nurse said.

Similar concerns reportedly led a travel nurse at an Ascension hospital in Indiana to quit. “I just want to warn those patients that are coming to any of the Ascension facilities that there will be delays in care. There is potential for error and for harm,” Justin Neisser told CBS4 in Indianapolis in May.

Several nurses and doctors at Ascension hospitals said they feared the errors they’ve witnessed since the cyberattack began could threaten their professional licenses. “This is how a RaDonda Vaught happens,” one nurse said, referring to the Tennessee nurse who was convicted of criminally negligent homicide in 2022 for a fatal drug error.

Reporters were not able to review records to verify clinicians’ claims because of privacy laws surrounding patients’ medical information that apply to health care professionals.

Ascension declined to answer questions about claims that care has been affected by the ransomware attack. “As we have made clear throughout this cyber attack which has impacted our system and our dedicated clinical providers, caring for our patients is our highest priority,” Sean Fitzpatrick, Ascension’s vice president of external communications, said via email on June 3. “We are confident that our care providers in our hospitals and facilities continue to provide quality medical care.”

The federal government requires hospitals to protect patients’ sensitive health data, according to cybersecurity experts. However, there are no federal requirements for hospitals to prevent or prepare for cyberattacks that could compromise their electronic systems.
 

Hospitals: ‘The No.1 Target of Ransomware’

“We’ve started to think about these as public health issues and disasters on the scale of earthquakes or hurricanes,” said Jeff Tully, a co-director of the Center for Healthcare Cybersecurity at the University of California-San Diego. “These types of cybersecurity incidents should be thought of as a matter of when, and not if.”

Josh Corman, a cybersecurity expert and advocate, said ransom crews regard hospitals as the perfect prey: “They have terrible security and they’ll pay. So almost immediately, hospitals went to the No. 1 target of ransomware.”

In 2023, the health sector experienced the largest share of ransomware attacks of 16 infrastructure sectors considered vital to national security or safety, according to an FBI report on internet crimes. In March, the federal Department of Health and Human Services said reported large breaches involving ransomware had jumped by 264% over the past five years.

A cyberattack this year on Change Healthcare, a unit of UnitedHealth Group’s Optum division that processes billions of health care transactions every year, crippled the business of providers, pharmacies, and hospitals.

In May, UnitedHealth Group CEO Andrew Witty told lawmakers the company paid a $22 million ransom as a result of the Change Healthcare attack — which occurred after hackers accessed a company portal that didn’t have multifactor authentication, a basic cybersecurity tool.

The Biden administration in recent months has pushed to bolster health care cybersecurity standards, but it’s not clear which new measures will be required.

In January, HHS nudged companies to improve email security, add multifactor authentication, and institute cybersecurity training and testing, among other voluntary measures. The Centers for Medicare & Medicaid Services is expected to release new requirements for hospitals, but the scope and timing are unclear. The same is true of an update HHS is expected to make to patient privacy regulations.

HHS said the voluntary measures “will inform the creation of new enforceable cybersecurity standards,” department spokesperson Jeff Nesbit said in a statement.

“The recent cyberattack at Ascension only underscores the need for everyone in the health care ecosystem to do their part to secure their systems and protect patients,” Nesbit said.

Meanwhile, lobbyists for the hospital industry contend cybersecurity mandates or penalties are misplaced and would curtail hospitals’ resources to fend off attacks.

“Hospitals and health systems are not the primary source of cyber risk exposure facing the health care sector,” the American Hospital Association, the largest lobbying group for U.S. hospitals, said in an April statement prepared for U.S. House lawmakers. Most large data breaches that hit hospitals in 2023 originated with third-party “business associates” or other health entities, including CMS itself, the AHA statement said.

Hospitals consolidating into large multistate health systems face increased risk of data breaches and ransomware attacks, according to one study. Ascension in 2022 was the third-largest hospital chain in the U.S. by number of beds, according to the most recent data from the federal Agency for Healthcare Research and Quality.

And while cybersecurity regulations can quickly become outdated, they can at least make it clear that if health systems fail to implement basic protections there “should be consequences for that,” Jim Bagian, a former director of the National Center for Patient Safety at the Veterans Health Administration, told Michigan Public’s Stateside.

Patients can pay the price when lapses occur. Those in hospital care face a greater likelihood of death during a cyberattack, according to researchers at the University of Minnesota School of Public Health.

Workers concerned about patient safety at Ascension hospitals in Michigan have called for the company to make changes.

“We implore Ascension to recognize the internal problems that continue to plague its hospitals, both publicly and transparently,” said Dina Carlisle, a nurse and the president of the OPEIU Local 40 union, which represents nurses at Ascension Providence Rochester. At least 125 staff members at that Ascension hospital have signed a petition asking administrators to temporarily reduce elective surgeries and nonemergency patient admissions, like under the protocols many hospitals adopted early in the covid-19 pandemic.

Watson, the Kansas ICU nurse, said in late May that nurses had urged management to bring in more nurses to help manage the workflow. “Everything that we say has fallen on deaf ears,” she said.

“It is very hard to be a nurse at Ascension right now,” Watson said in late May. “It is very hard to be a patient at Ascension right now.”

If you’re a patient or worker at an Ascension hospital and would like to tell KFF Health News about your experiences, click here to share your story with us.
 

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

In the wake of a debilitating cyberattack against one of the nation’s largest health care systems, Marvin Ruckle, a nurse at an Ascension hospital in Wichita, Kansas, said he had a frightening experience: He nearly gave a baby “the wrong dose of narcotic” because of confusing paperwork.

Ruckle, who has worked in the neonatal intensive care unit at Ascension Via Christi St. Joseph for two decades, said it was “hard to decipher which was the correct dose” on the medication record. He’d “never seen that happen,” he said, “when we were on the computer system” before the cyberattack.

A May 8 ransomware attack against Ascension, a Catholic health system with 140 hospitals in at least 10 states, locked providers out of systems that track and coordinate nearly every aspect of patient care. They include its systems for electronic health records, some phones, and ones “utilized to order certain tests, procedures and medications,” the company said in a May 9 statement.

More than a dozen doctors and nurses who work for the sprawling health system told Michigan Public and KFF Health News that patient care at its hospitals across the nation was compromised in the fallout of the cyberattack over the past several weeks. Clinicians working for hospitals in three states described harrowing lapses, including delayed or lost lab results, medication errors, and an absence of routine safety checks via technology to prevent potentially fatal mistakes.

Despite a precipitous rise in cyberattacks against the health sector in recent years, a weeks-long disruption of this magnitude is beyond what most health systems are prepared for, said John S. Clark, an associate chief pharmacy officer at the University of Michigan health system.

“I don’t believe that anyone is fully prepared,” he said. Most emergency management plans “are designed around long-term downtimes that are into one, two, or three days.”

Ascension in a public statement May 9 said its care teams were “trained for these kinds of disruptions,” but did not respond to questions in early June about whether it had prepared for longer periods of downtime. Ascension said June 14 it had restored access to electronic health records across its network, but that patient “medical records and other information collected between May 8” and when the service was restored “may be temporarily inaccessible as we work to update the portal with information collected during the system downtime.”

Ruckle said he “had no training” for the cyberattack.
 

Back to Paper

Lisa Watson, an intensive care unit nurse at Ascension Via Christi St. Francis hospital in Wichita, described her own close call. She said she nearly administered the wrong medication to a critically ill patient because she couldn’t scan it as she normally would. “My patient probably would have passed away had I not caught it,” she said.

Watson is no stranger to using paper for patients’ medical charts, saying she did so “for probably half of my career,” before electronic health records became ubiquitous in hospitals. What happened after the cyberattack was “by no means the same.”

“When we paper-charted, we had systems in place to get those orders to other departments in a timely manner,” she said, “and those have all gone away.”

Melissa LaRue, an ICU nurse at Ascension Saint Agnes Hospital in Baltimore, described a close call with “administering the wrong dosage” of a patient’s blood pressure medication. “Luckily,” she said, it was “triple-checked and remedied before that could happen. But I think the potential for harm is there when you have so much information and paperwork that you have to go through.”

Clinicians say their hospitals have relied on slapdash workarounds, using handwritten notes, faxes, sticky notes, and basic computer spreadsheets — many devised on the fly by doctors and nurses — to care for patients.

More than a dozen other nurses and doctors, some of them without union protections, at Ascension hospitals in Michigan recounted situations in which they say patient care was compromised. Those clinicians spoke on the condition that they not be named for fear of retaliation by their employer.

An Ascension hospital emergency room doctor in Detroit said a man on the city’s east side was given a dangerous narcotic intended for another patient because of a paperwork mix-up. As a result, the patient’s breathing slowed to the point that he had to be put on a ventilator. “We intubated him and we sent him to the ICU because he got the wrong medication.”

A nurse in a Michigan Ascension hospital ER said a woman with low blood sugar and “altered mental status” went into cardiac arrest and died after staff said they waited four hours for lab results they needed to determine how to treat her, but never received. “If I started having crushing chest pain in the middle of work and thought I was having a big one, I would grab someone to drive me down the street to another hospital,” the same ER nurse said.

Similar concerns reportedly led a travel nurse at an Ascension hospital in Indiana to quit. “I just want to warn those patients that are coming to any of the Ascension facilities that there will be delays in care. There is potential for error and for harm,” Justin Neisser told CBS4 in Indianapolis in May.

Several nurses and doctors at Ascension hospitals said they feared the errors they’ve witnessed since the cyberattack began could threaten their professional licenses. “This is how a RaDonda Vaught happens,” one nurse said, referring to the Tennessee nurse who was convicted of criminally negligent homicide in 2022 for a fatal drug error.

Reporters were not able to review records to verify clinicians’ claims because of privacy laws surrounding patients’ medical information that apply to health care professionals.

Ascension declined to answer questions about claims that care has been affected by the ransomware attack. “As we have made clear throughout this cyber attack which has impacted our system and our dedicated clinical providers, caring for our patients is our highest priority,” Sean Fitzpatrick, Ascension’s vice president of external communications, said via email on June 3. “We are confident that our care providers in our hospitals and facilities continue to provide quality medical care.”

The federal government requires hospitals to protect patients’ sensitive health data, according to cybersecurity experts. However, there are no federal requirements for hospitals to prevent or prepare for cyberattacks that could compromise their electronic systems.
 

Hospitals: ‘The No.1 Target of Ransomware’

“We’ve started to think about these as public health issues and disasters on the scale of earthquakes or hurricanes,” said Jeff Tully, a co-director of the Center for Healthcare Cybersecurity at the University of California-San Diego. “These types of cybersecurity incidents should be thought of as a matter of when, and not if.”

Josh Corman, a cybersecurity expert and advocate, said ransom crews regard hospitals as the perfect prey: “They have terrible security and they’ll pay. So almost immediately, hospitals went to the No. 1 target of ransomware.”

In 2023, the health sector experienced the largest share of ransomware attacks of 16 infrastructure sectors considered vital to national security or safety, according to an FBI report on internet crimes. In March, the federal Department of Health and Human Services said reported large breaches involving ransomware had jumped by 264% over the past five years.

A cyberattack this year on Change Healthcare, a unit of UnitedHealth Group’s Optum division that processes billions of health care transactions every year, crippled the business of providers, pharmacies, and hospitals.

In May, UnitedHealth Group CEO Andrew Witty told lawmakers the company paid a $22 million ransom as a result of the Change Healthcare attack — which occurred after hackers accessed a company portal that didn’t have multifactor authentication, a basic cybersecurity tool.

The Biden administration in recent months has pushed to bolster health care cybersecurity standards, but it’s not clear which new measures will be required.

In January, HHS nudged companies to improve email security, add multifactor authentication, and institute cybersecurity training and testing, among other voluntary measures. The Centers for Medicare & Medicaid Services is expected to release new requirements for hospitals, but the scope and timing are unclear. The same is true of an update HHS is expected to make to patient privacy regulations.

HHS said the voluntary measures “will inform the creation of new enforceable cybersecurity standards,” department spokesperson Jeff Nesbit said in a statement.

“The recent cyberattack at Ascension only underscores the need for everyone in the health care ecosystem to do their part to secure their systems and protect patients,” Nesbit said.

Meanwhile, lobbyists for the hospital industry contend cybersecurity mandates or penalties are misplaced and would curtail hospitals’ resources to fend off attacks.

“Hospitals and health systems are not the primary source of cyber risk exposure facing the health care sector,” the American Hospital Association, the largest lobbying group for U.S. hospitals, said in an April statement prepared for U.S. House lawmakers. Most large data breaches that hit hospitals in 2023 originated with third-party “business associates” or other health entities, including CMS itself, the AHA statement said.

Hospitals consolidating into large multistate health systems face increased risk of data breaches and ransomware attacks, according to one study. Ascension in 2022 was the third-largest hospital chain in the U.S. by number of beds, according to the most recent data from the federal Agency for Healthcare Research and Quality.

And while cybersecurity regulations can quickly become outdated, they can at least make it clear that if health systems fail to implement basic protections there “should be consequences for that,” Jim Bagian, a former director of the National Center for Patient Safety at the Veterans Health Administration, told Michigan Public’s Stateside.

Patients can pay the price when lapses occur. Those in hospital care face a greater likelihood of death during a cyberattack, according to researchers at the University of Minnesota School of Public Health.

Workers concerned about patient safety at Ascension hospitals in Michigan have called for the company to make changes.

“We implore Ascension to recognize the internal problems that continue to plague its hospitals, both publicly and transparently,” said Dina Carlisle, a nurse and the president of the OPEIU Local 40 union, which represents nurses at Ascension Providence Rochester. At least 125 staff members at that Ascension hospital have signed a petition asking administrators to temporarily reduce elective surgeries and nonemergency patient admissions, like under the protocols many hospitals adopted early in the covid-19 pandemic.

Watson, the Kansas ICU nurse, said in late May that nurses had urged management to bring in more nurses to help manage the workflow. “Everything that we say has fallen on deaf ears,” she said.

“It is very hard to be a nurse at Ascension right now,” Watson said in late May. “It is very hard to be a patient at Ascension right now.”

If you’re a patient or worker at an Ascension hospital and would like to tell KFF Health News about your experiences, click here to share your story with us.
 

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

CHICAGO — Prominent Chinese oncologist Tony Shu-Kam Mok, MD, who presented as first author of a phase 3 non–small cell lung cancer study at ASCO 2024, made a dramatic swerve in his career path at age 36.

After 20 years in Canada — 7 spent practicing community oncology near Toronto — Dr. Mok was visiting family in his native Hong Kong back in 1996 when a job offer there enabled him to revive his early dream of doing academic research. Dr. Mok and his family moved back home just before the former British colony was returned to China in 1997.

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That leap of faith helped Dr. Mok play a role in the global paradigm shift on treating lung cancer. He chairs the department of clinical oncology at the Chinese University of Hong Kong. A leader in ushering in targeted therapies and personalized medicine in China and globally, he has helped advance the goal of transforming lung cancer from a death sentence to a chronic disease.

Among Dr. Mok’s other accomplishments, he has published eight books and more than 200 journal articles. Since 2006, he has been writing a twice-weekly column in the Hong Kong Economic Times. At the annual meeting of the American Society of Clinical Oncology (ASCO), Dr. Mok sat down with this news organization to discuss his latest findings, his career path, and China’s ever-growing presence in multinational clinical trials, pharmaceuticals, and cancer research in general.
 

Question: At ASCO 2024 in Chicago, you presented as first author of the KRYSTAL-12 study. Can you give a short “elevator speech” summarizing those findings?

Dr. Mok: KRYSTAL-12 is a randomized phase 3 study comparing adagrasib with docetaxel in patients with previously treated advanced/metastatic non–small cell lung cancer harboring a KRAS G12C-mutation. And the findings are positive, with a median progression free survival of 5.5 months vs 3.8 months, with a significant hazard ratio [of 0.58]. And then there are also differences in their response rates of 32% versus 9%, and that gives you an [odds] ratio of 4.86. So yes, it’s significant.

Question: Now that you’ve given this presentation and perhaps taken some good, meaningful questions about it, are there any further points you’d like to make — anything you’d like to add?

Dr. Mok: You have to understand that whatever I said has been scrutinized by the pharmaceutical company, but now I can say whatever I like. I think the key point is that we actually have made the first so-called achievement in the KRAS G12C space. But this is only the beginning.

I want to note that the median progression-free survival is different, but not the best. The median 5.5 months result is good, but not good enough. So, we still have to work hard to answer the question: How can we best deliver care to patients with KRAS G12C?
 

Question: Speaking more generally about the challenges of targeting KRAS, what issues arise in terms of biomarker testing for KRAS mutations in the clinic? Dr. Mok: In colorectal cancer, there has been testing for KRAS [mutations] for a long, long time. So, most of the laboratories, as long as they are well equipped, will be able to test for KRAS. Usually, the cheaper way is to buy PCR [polymerase chain reaction]. However, these days it’s getting trendier to use NGS [next-generation sequencing]. So, one way or another, specificity is very high. I don’t think we have too much of a problem. The only difference between colorectal cancer and lung cancer is that the tissue sample may not be as good for lung cancer with a small biopsy, but otherwise testing is not an issue.

Question: What clinical trials should oncologist be watching to come into this space?Dr. Mok: There are a lot. Right now, there is the so-called first-line study that’s coming up. So, I can cite you some examples for the KRYSTAL-7 trial, which is the combination of pembrolizumab together with adagrasib in the PD-L1 Tumor Proportion Score ≥ 50%.

That’s one example. And then there is the CodeBreaK 202 trial, which is actually the combination of chemotherapy with sotorasib versus chemotherapy and I-O [immune-oncology]. That is also an ongoing study.
 

Question: I also want to ask you some background questions about yourself. Back in the day, you lived in Canada and were a community oncologist. Then you made a very big change in your life and moved back home to Hong Kong in 1996, on the eve of its return to China the following year.

Dr. Mok: Well, I was born and raised in Hong Kong, but I left for Canada for education when I was 16 and kind of stayed there and got medical school oncology training and then started my practice. At that time, I never imagined myself going back. But 1996 was a big year. Incidentally, I went back to Hong Kong then to visit my friends and was offered a job at the Chinese University of Hong Kong. Then 1997 was coming. I found it very exciting that we could work with China. So that’s why I decided to return. And this was probably one of my best decisions I ever made in my life.

Question: And you went from being a community oncologist to academic research?

Dr. Mok: Here’s a personal thing that I can share with you: When I finished my oncology training at Princess Margaret Hospital in Toronto, I thought of going into research and becoming an academic. However, my son was born. Household costs went up, and I didn’t want to be a low-income, poor PhD student, so I decided that I may as well go into private practice. Returning to Hong Kong [in 1996] gave me a second chance. I went from being a community oncologist for seven years in Canada to a totally new environment in Hong Kong, where I started my academic work at age 36. It has been a good journey.

Question: Why do you say that was the best decision you ever made?Dr. Mok: At that time, it took me about 2 weeks to make this important decision. Basically: I had to give up my big house and my big car in Canada and move back to a small apartment in Hong Kong. That was a tough decision to make. However, it was a matter of certainty versus uncertainty.

In Canada, I actually had a very stable situation. I had a big practice in the Scarborough area [of Toronto], with a lot of Chinese patients, so I had a better, more comfortable life. It was predictable. But then I asked myself what I would be like in 10 years if I stayed in Canada versus Hong Kong. My answer is that I had no idea what would happen to me 10 years later in Hong Kong. In certain parts of life, you have to decide between certainty and uncertainty. And this time, uncertainty brought me great adventure. I definitely would not have done the things I’ve done if I’d stayed in Canada.



Question: At this ASCO, you’ve spoken primarily about your latest research on non–small cell lung cancer with KRAS G12C mutation.Dr. Mok: Actually, my research has been mostly on targeted therapy. My first break was on the EGFR [epidermal growth factor receptor] mutation. I was one of the first to help define personalized medicine according to the EGFR mutation in the IPASS study [2009]. That’s how I started my academic career.



Question: I read some quotes from your writing some years back about “living with imperfection,” and where you wrote about the whole continuum of cancer research. Years ago, you noted that lung cancer was moving from being a death sentence to becoming a chronic condition.

Dr. Mok: The objective is this: A lot of cancer patients, especially lung cancer patients, had a very short survival, but now we are able to identify a subgroup of patients with a driver oncogene.

And with that, we can use a tyrosine kinase inhibitor — which although it has toxicity, it’s manageable toxicity — such that you can take one pill a day and continue to live a normal life. So that would be not so different from diabetes or hypertension: You live with the disease. So that’s what we like to see: the conversion of a fatal disease into a chronic disease.
 

Question: So many countries now, including the United States and many others, are facing the challenges of cancer care in rural versus urban areas. Is this a topic you’d be willing to address? Dr. Mok: Well, in Hong Kong we don’t have rural areas! But in China, this is a major problem. There most of the cancer care is focused on the so-called three major cities [Shanghai, Beijing, Guangzhou]. And after that, there are second-tier cities that also have reasonably good care. But when you filter down to the third and fourth layer, the oncology care actually deteriorates. So that’s why we end up with a lot of people from the more rural areas moving and going to the city looking for care and consultation. So yes, the disparity is significant.

But China is a growing country. It takes time to change. Right now, we can see at ASCO this year, there are a lot of investigators from China sharing their new findings, which is a major development, compared to 10 years ago. Therefore, I think that when you have this type of proliferative development, eventually the good care, the high-quality care will filter down to more rural areas. So, at this moment, I think there is still a lot of work to do.
 

Question: You’ve talked about how oncologists from China are coming up in the field, and this year they have an even greater presence at ASCO, as well as oncologists from elsewhere in Asia, including South Korea, Japan, and Vietnam. You’ve been coming to ASCO for many years. Can you talk about the factors behind China’s increasing presence? Dr. Mok: I think it’s a combination of factors. First of all, I had the honor of working with lung cancer researchers from China from way back, 25 years ago. At that time, we all had nothing. Then with the development of multitargeted therapies, they managed to build up a very good infrastructure for clinical trials. And then, based on that good infrastructure, they were able to do international collaborative studies and provide a supply of patient resources and high-quality data. So, they’ve learned the trick, done a good job, but they cannot have so-called independence until there is a development of pharmaceuticals in China.

And then over the past 10 years, there’s been a proliferation — actually an explosion I would even say — of high-quality pharmaceutical companies in China. First, they’ve got the resources to build the companies. Second, they’ve got the talent resources returning from the United States. So, putting all that together, these were able to go from start-ups to full-fledged functional companies in a very short time.

And with that, they actually sponsored a lot of trials within China. And you can see that putting all the components together: you’ve got high-quality researchers, you’ve got the infrastructure, and now you’ve got your drugs and the money to do the trials. As a result, you’ve got a lot of good data coming from China.
 

Question: There’s also a population with these mutations.Dr. Mok: That for one, but most have multitargeted therapies, but they also have immunotherapies that have nothing to do with the high incidence. But I think in a sense, in the beginning, they were doing `me-too’ compounds, but now I think they are starting to do ‘me-better’ compounds.

Question: Is there anything you want to say about some of the other presentations that have your name on them at ASCO this year?Dr. Mok: I think the most important one I was engaged in is the CROWN study. The CROWN study is actually a phase 3 study that compares lorlatinib versus crizotinib in patients with advanced, ALK-positive non–small cell lung cancer.

This is a 5-year follow-up, and we were actually able to report an outrageously encouraging 5-year progression-free rate at 60%, meaning that the patient is walking in the door 5 years later when they are on the drug, and 60% of them actually do not have progression, not death, just not progression, just staying on the same pill—which is quite outrageously good for lung cancer.

CHICAGO — Prominent Chinese oncologist Tony Shu-Kam Mok, MD, who presented as first author of a phase 3 non–small cell lung cancer study at ASCO 2024, made a dramatic swerve in his career path at age 36.

After 20 years in Canada — 7 spent practicing community oncology near Toronto — Dr. Mok was visiting family in his native Hong Kong back in 1996 when a job offer there enabled him to revive his early dream of doing academic research. Dr. Mok and his family moved back home just before the former British colony was returned to China in 1997.

rophosabrehotruslemulotritevevagugaclohafrucrocabrihatriclagepepracrucechecrithethushicladruuamedrepopusovotritrimamatriletreshechemechosidrispujechap

That leap of faith helped Dr. Mok play a role in the global paradigm shift on treating lung cancer. He chairs the department of clinical oncology at the Chinese University of Hong Kong. A leader in ushering in targeted therapies and personalized medicine in China and globally, he has helped advance the goal of transforming lung cancer from a death sentence to a chronic disease.

Among Dr. Mok’s other accomplishments, he has published eight books and more than 200 journal articles. Since 2006, he has been writing a twice-weekly column in the Hong Kong Economic Times. At the annual meeting of the American Society of Clinical Oncology (ASCO), Dr. Mok sat down with this news organization to discuss his latest findings, his career path, and China’s ever-growing presence in multinational clinical trials, pharmaceuticals, and cancer research in general.
 

Question: At ASCO 2024 in Chicago, you presented as first author of the KRYSTAL-12 study. Can you give a short “elevator speech” summarizing those findings?

Dr. Mok: KRYSTAL-12 is a randomized phase 3 study comparing adagrasib with docetaxel in patients with previously treated advanced/metastatic non–small cell lung cancer harboring a KRAS G12C-mutation. And the findings are positive, with a median progression free survival of 5.5 months vs 3.8 months, with a significant hazard ratio [of 0.58]. And then there are also differences in their response rates of 32% versus 9%, and that gives you an [odds] ratio of 4.86. So yes, it’s significant.

Question: Now that you’ve given this presentation and perhaps taken some good, meaningful questions about it, are there any further points you’d like to make — anything you’d like to add?

Dr. Mok: You have to understand that whatever I said has been scrutinized by the pharmaceutical company, but now I can say whatever I like. I think the key point is that we actually have made the first so-called achievement in the KRAS G12C space. But this is only the beginning.

I want to note that the median progression-free survival is different, but not the best. The median 5.5 months result is good, but not good enough. So, we still have to work hard to answer the question: How can we best deliver care to patients with KRAS G12C?
 

Question: Speaking more generally about the challenges of targeting KRAS, what issues arise in terms of biomarker testing for KRAS mutations in the clinic? Dr. Mok: In colorectal cancer, there has been testing for KRAS [mutations] for a long, long time. So, most of the laboratories, as long as they are well equipped, will be able to test for KRAS. Usually, the cheaper way is to buy PCR [polymerase chain reaction]. However, these days it’s getting trendier to use NGS [next-generation sequencing]. So, one way or another, specificity is very high. I don’t think we have too much of a problem. The only difference between colorectal cancer and lung cancer is that the tissue sample may not be as good for lung cancer with a small biopsy, but otherwise testing is not an issue.

Question: What clinical trials should oncologist be watching to come into this space?Dr. Mok: There are a lot. Right now, there is the so-called first-line study that’s coming up. So, I can cite you some examples for the KRYSTAL-7 trial, which is the combination of pembrolizumab together with adagrasib in the PD-L1 Tumor Proportion Score ≥ 50%.

That’s one example. And then there is the CodeBreaK 202 trial, which is actually the combination of chemotherapy with sotorasib versus chemotherapy and I-O [immune-oncology]. That is also an ongoing study.
 

Question: I also want to ask you some background questions about yourself. Back in the day, you lived in Canada and were a community oncologist. Then you made a very big change in your life and moved back home to Hong Kong in 1996, on the eve of its return to China the following year.

Dr. Mok: Well, I was born and raised in Hong Kong, but I left for Canada for education when I was 16 and kind of stayed there and got medical school oncology training and then started my practice. At that time, I never imagined myself going back. But 1996 was a big year. Incidentally, I went back to Hong Kong then to visit my friends and was offered a job at the Chinese University of Hong Kong. Then 1997 was coming. I found it very exciting that we could work with China. So that’s why I decided to return. And this was probably one of my best decisions I ever made in my life.

Question: And you went from being a community oncologist to academic research?

Dr. Mok: Here’s a personal thing that I can share with you: When I finished my oncology training at Princess Margaret Hospital in Toronto, I thought of going into research and becoming an academic. However, my son was born. Household costs went up, and I didn’t want to be a low-income, poor PhD student, so I decided that I may as well go into private practice. Returning to Hong Kong [in 1996] gave me a second chance. I went from being a community oncologist for seven years in Canada to a totally new environment in Hong Kong, where I started my academic work at age 36. It has been a good journey.

Question: Why do you say that was the best decision you ever made?Dr. Mok: At that time, it took me about 2 weeks to make this important decision. Basically: I had to give up my big house and my big car in Canada and move back to a small apartment in Hong Kong. That was a tough decision to make. However, it was a matter of certainty versus uncertainty.

In Canada, I actually had a very stable situation. I had a big practice in the Scarborough area [of Toronto], with a lot of Chinese patients, so I had a better, more comfortable life. It was predictable. But then I asked myself what I would be like in 10 years if I stayed in Canada versus Hong Kong. My answer is that I had no idea what would happen to me 10 years later in Hong Kong. In certain parts of life, you have to decide between certainty and uncertainty. And this time, uncertainty brought me great adventure. I definitely would not have done the things I’ve done if I’d stayed in Canada.



Question: At this ASCO, you’ve spoken primarily about your latest research on non–small cell lung cancer with KRAS G12C mutation.Dr. Mok: Actually, my research has been mostly on targeted therapy. My first break was on the EGFR [epidermal growth factor receptor] mutation. I was one of the first to help define personalized medicine according to the EGFR mutation in the IPASS study [2009]. That’s how I started my academic career.



Question: I read some quotes from your writing some years back about “living with imperfection,” and where you wrote about the whole continuum of cancer research. Years ago, you noted that lung cancer was moving from being a death sentence to becoming a chronic condition.

Dr. Mok: The objective is this: A lot of cancer patients, especially lung cancer patients, had a very short survival, but now we are able to identify a subgroup of patients with a driver oncogene.

And with that, we can use a tyrosine kinase inhibitor — which although it has toxicity, it’s manageable toxicity — such that you can take one pill a day and continue to live a normal life. So that would be not so different from diabetes or hypertension: You live with the disease. So that’s what we like to see: the conversion of a fatal disease into a chronic disease.
 

Question: So many countries now, including the United States and many others, are facing the challenges of cancer care in rural versus urban areas. Is this a topic you’d be willing to address? Dr. Mok: Well, in Hong Kong we don’t have rural areas! But in China, this is a major problem. There most of the cancer care is focused on the so-called three major cities [Shanghai, Beijing, Guangzhou]. And after that, there are second-tier cities that also have reasonably good care. But when you filter down to the third and fourth layer, the oncology care actually deteriorates. So that’s why we end up with a lot of people from the more rural areas moving and going to the city looking for care and consultation. So yes, the disparity is significant.

But China is a growing country. It takes time to change. Right now, we can see at ASCO this year, there are a lot of investigators from China sharing their new findings, which is a major development, compared to 10 years ago. Therefore, I think that when you have this type of proliferative development, eventually the good care, the high-quality care will filter down to more rural areas. So, at this moment, I think there is still a lot of work to do.
 

Question: You’ve talked about how oncologists from China are coming up in the field, and this year they have an even greater presence at ASCO, as well as oncologists from elsewhere in Asia, including South Korea, Japan, and Vietnam. You’ve been coming to ASCO for many years. Can you talk about the factors behind China’s increasing presence? Dr. Mok: I think it’s a combination of factors. First of all, I had the honor of working with lung cancer researchers from China from way back, 25 years ago. At that time, we all had nothing. Then with the development of multitargeted therapies, they managed to build up a very good infrastructure for clinical trials. And then, based on that good infrastructure, they were able to do international collaborative studies and provide a supply of patient resources and high-quality data. So, they’ve learned the trick, done a good job, but they cannot have so-called independence until there is a development of pharmaceuticals in China.

And then over the past 10 years, there’s been a proliferation — actually an explosion I would even say — of high-quality pharmaceutical companies in China. First, they’ve got the resources to build the companies. Second, they’ve got the talent resources returning from the United States. So, putting all that together, these were able to go from start-ups to full-fledged functional companies in a very short time.

And with that, they actually sponsored a lot of trials within China. And you can see that putting all the components together: you’ve got high-quality researchers, you’ve got the infrastructure, and now you’ve got your drugs and the money to do the trials. As a result, you’ve got a lot of good data coming from China.
 

Question: There’s also a population with these mutations.Dr. Mok: That for one, but most have multitargeted therapies, but they also have immunotherapies that have nothing to do with the high incidence. But I think in a sense, in the beginning, they were doing `me-too’ compounds, but now I think they are starting to do ‘me-better’ compounds.

Question: Is there anything you want to say about some of the other presentations that have your name on them at ASCO this year?Dr. Mok: I think the most important one I was engaged in is the CROWN study. The CROWN study is actually a phase 3 study that compares lorlatinib versus crizotinib in patients with advanced, ALK-positive non–small cell lung cancer.

This is a 5-year follow-up, and we were actually able to report an outrageously encouraging 5-year progression-free rate at 60%, meaning that the patient is walking in the door 5 years later when they are on the drug, and 60% of them actually do not have progression, not death, just not progression, just staying on the same pill—which is quite outrageously good for lung cancer.

CHICAGO — Prominent Chinese oncologist Tony Shu-Kam Mok, MD, who presented as first author of a phase 3 non–small cell lung cancer study at ASCO 2024, made a dramatic swerve in his career path at age 36.

After 20 years in Canada — 7 spent practicing community oncology near Toronto — Dr. Mok was visiting family in his native Hong Kong back in 1996 when a job offer there enabled him to revive his early dream of doing academic research. Dr. Mok and his family moved back home just before the former British colony was returned to China in 1997.

rophosabrehotruslemulotritevevagugaclohafrucrocabrihatriclagepepracrucechecrithethushicladruuamedrepopusovotritrimamatriletreshechemechosidrispujechap

That leap of faith helped Dr. Mok play a role in the global paradigm shift on treating lung cancer. He chairs the department of clinical oncology at the Chinese University of Hong Kong. A leader in ushering in targeted therapies and personalized medicine in China and globally, he has helped advance the goal of transforming lung cancer from a death sentence to a chronic disease.

Among Dr. Mok’s other accomplishments, he has published eight books and more than 200 journal articles. Since 2006, he has been writing a twice-weekly column in the Hong Kong Economic Times. At the annual meeting of the American Society of Clinical Oncology (ASCO), Dr. Mok sat down with this news organization to discuss his latest findings, his career path, and China’s ever-growing presence in multinational clinical trials, pharmaceuticals, and cancer research in general.
 

Question: At ASCO 2024 in Chicago, you presented as first author of the KRYSTAL-12 study. Can you give a short “elevator speech” summarizing those findings?

Dr. Mok: KRYSTAL-12 is a randomized phase 3 study comparing adagrasib with docetaxel in patients with previously treated advanced/metastatic non–small cell lung cancer harboring a KRAS G12C-mutation. And the findings are positive, with a median progression free survival of 5.5 months vs 3.8 months, with a significant hazard ratio [of 0.58]. And then there are also differences in their response rates of 32% versus 9%, and that gives you an [odds] ratio of 4.86. So yes, it’s significant.

Question: Now that you’ve given this presentation and perhaps taken some good, meaningful questions about it, are there any further points you’d like to make — anything you’d like to add?

Dr. Mok: You have to understand that whatever I said has been scrutinized by the pharmaceutical company, but now I can say whatever I like. I think the key point is that we actually have made the first so-called achievement in the KRAS G12C space. But this is only the beginning.

I want to note that the median progression-free survival is different, but not the best. The median 5.5 months result is good, but not good enough. So, we still have to work hard to answer the question: How can we best deliver care to patients with KRAS G12C?
 

Question: Speaking more generally about the challenges of targeting KRAS, what issues arise in terms of biomarker testing for KRAS mutations in the clinic? Dr. Mok: In colorectal cancer, there has been testing for KRAS [mutations] for a long, long time. So, most of the laboratories, as long as they are well equipped, will be able to test for KRAS. Usually, the cheaper way is to buy PCR [polymerase chain reaction]. However, these days it’s getting trendier to use NGS [next-generation sequencing]. So, one way or another, specificity is very high. I don’t think we have too much of a problem. The only difference between colorectal cancer and lung cancer is that the tissue sample may not be as good for lung cancer with a small biopsy, but otherwise testing is not an issue.

Question: What clinical trials should oncologist be watching to come into this space?Dr. Mok: There are a lot. Right now, there is the so-called first-line study that’s coming up. So, I can cite you some examples for the KRYSTAL-7 trial, which is the combination of pembrolizumab together with adagrasib in the PD-L1 Tumor Proportion Score ≥ 50%.

That’s one example. And then there is the CodeBreaK 202 trial, which is actually the combination of chemotherapy with sotorasib versus chemotherapy and I-O [immune-oncology]. That is also an ongoing study.
 

Question: I also want to ask you some background questions about yourself. Back in the day, you lived in Canada and were a community oncologist. Then you made a very big change in your life and moved back home to Hong Kong in 1996, on the eve of its return to China the following year.

Dr. Mok: Well, I was born and raised in Hong Kong, but I left for Canada for education when I was 16 and kind of stayed there and got medical school oncology training and then started my practice. At that time, I never imagined myself going back. But 1996 was a big year. Incidentally, I went back to Hong Kong then to visit my friends and was offered a job at the Chinese University of Hong Kong. Then 1997 was coming. I found it very exciting that we could work with China. So that’s why I decided to return. And this was probably one of my best decisions I ever made in my life.

Question: And you went from being a community oncologist to academic research?

Dr. Mok: Here’s a personal thing that I can share with you: When I finished my oncology training at Princess Margaret Hospital in Toronto, I thought of going into research and becoming an academic. However, my son was born. Household costs went up, and I didn’t want to be a low-income, poor PhD student, so I decided that I may as well go into private practice. Returning to Hong Kong [in 1996] gave me a second chance. I went from being a community oncologist for seven years in Canada to a totally new environment in Hong Kong, where I started my academic work at age 36. It has been a good journey.

Question: Why do you say that was the best decision you ever made?Dr. Mok: At that time, it took me about 2 weeks to make this important decision. Basically: I had to give up my big house and my big car in Canada and move back to a small apartment in Hong Kong. That was a tough decision to make. However, it was a matter of certainty versus uncertainty.

In Canada, I actually had a very stable situation. I had a big practice in the Scarborough area [of Toronto], with a lot of Chinese patients, so I had a better, more comfortable life. It was predictable. But then I asked myself what I would be like in 10 years if I stayed in Canada versus Hong Kong. My answer is that I had no idea what would happen to me 10 years later in Hong Kong. In certain parts of life, you have to decide between certainty and uncertainty. And this time, uncertainty brought me great adventure. I definitely would not have done the things I’ve done if I’d stayed in Canada.



Question: At this ASCO, you’ve spoken primarily about your latest research on non–small cell lung cancer with KRAS G12C mutation.Dr. Mok: Actually, my research has been mostly on targeted therapy. My first break was on the EGFR [epidermal growth factor receptor] mutation. I was one of the first to help define personalized medicine according to the EGFR mutation in the IPASS study [2009]. That’s how I started my academic career.



Question: I read some quotes from your writing some years back about “living with imperfection,” and where you wrote about the whole continuum of cancer research. Years ago, you noted that lung cancer was moving from being a death sentence to becoming a chronic condition.

Dr. Mok: The objective is this: A lot of cancer patients, especially lung cancer patients, had a very short survival, but now we are able to identify a subgroup of patients with a driver oncogene.

And with that, we can use a tyrosine kinase inhibitor — which although it has toxicity, it’s manageable toxicity — such that you can take one pill a day and continue to live a normal life. So that would be not so different from diabetes or hypertension: You live with the disease. So that’s what we like to see: the conversion of a fatal disease into a chronic disease.
 

Question: So many countries now, including the United States and many others, are facing the challenges of cancer care in rural versus urban areas. Is this a topic you’d be willing to address? Dr. Mok: Well, in Hong Kong we don’t have rural areas! But in China, this is a major problem. There most of the cancer care is focused on the so-called three major cities [Shanghai, Beijing, Guangzhou]. And after that, there are second-tier cities that also have reasonably good care. But when you filter down to the third and fourth layer, the oncology care actually deteriorates. So that’s why we end up with a lot of people from the more rural areas moving and going to the city looking for care and consultation. So yes, the disparity is significant.

But China is a growing country. It takes time to change. Right now, we can see at ASCO this year, there are a lot of investigators from China sharing their new findings, which is a major development, compared to 10 years ago. Therefore, I think that when you have this type of proliferative development, eventually the good care, the high-quality care will filter down to more rural areas. So, at this moment, I think there is still a lot of work to do.
 

Question: You’ve talked about how oncologists from China are coming up in the field, and this year they have an even greater presence at ASCO, as well as oncologists from elsewhere in Asia, including South Korea, Japan, and Vietnam. You’ve been coming to ASCO for many years. Can you talk about the factors behind China’s increasing presence? Dr. Mok: I think it’s a combination of factors. First of all, I had the honor of working with lung cancer researchers from China from way back, 25 years ago. At that time, we all had nothing. Then with the development of multitargeted therapies, they managed to build up a very good infrastructure for clinical trials. And then, based on that good infrastructure, they were able to do international collaborative studies and provide a supply of patient resources and high-quality data. So, they’ve learned the trick, done a good job, but they cannot have so-called independence until there is a development of pharmaceuticals in China.

And then over the past 10 years, there’s been a proliferation — actually an explosion I would even say — of high-quality pharmaceutical companies in China. First, they’ve got the resources to build the companies. Second, they’ve got the talent resources returning from the United States. So, putting all that together, these were able to go from start-ups to full-fledged functional companies in a very short time.

And with that, they actually sponsored a lot of trials within China. And you can see that putting all the components together: you’ve got high-quality researchers, you’ve got the infrastructure, and now you’ve got your drugs and the money to do the trials. As a result, you’ve got a lot of good data coming from China.
 

Question: There’s also a population with these mutations.Dr. Mok: That for one, but most have multitargeted therapies, but they also have immunotherapies that have nothing to do with the high incidence. But I think in a sense, in the beginning, they were doing `me-too’ compounds, but now I think they are starting to do ‘me-better’ compounds.

Question: Is there anything you want to say about some of the other presentations that have your name on them at ASCO this year?Dr. Mok: I think the most important one I was engaged in is the CROWN study. The CROWN study is actually a phase 3 study that compares lorlatinib versus crizotinib in patients with advanced, ALK-positive non–small cell lung cancer.

This is a 5-year follow-up, and we were actually able to report an outrageously encouraging 5-year progression-free rate at 60%, meaning that the patient is walking in the door 5 years later when they are on the drug, and 60% of them actually do not have progression, not death, just not progression, just staying on the same pill—which is quite outrageously good for lung cancer.

Pembrolizumab (Keytruda) is a programmed cell death protein 1 (PD-1) blocking antibody used to treat different malignancies including melanoma, non–small cell lung cancer, and other advanced solid tumors and hematologic malignancies. Various dermatological side effects have been associated with pembrolizumab, including pruritus, bullous pemphigoid, vitiligo, lichenoid skin reactions, psoriasis, and rarely, life-threatening conditions like Steven-Johnson syndrome and drug rash with eosinophilia and systemic symptoms (DRESS).

Lichen planus-like adverse drug reactions, as seen in this patient, are also referred to as lichenoid drug eruption or drug-induced lichen planus. This cutaneous reaction is one of the more rare side effects of pembrolizumab. It should be noted that in lichenoid reactions, keratinocytes expressing PD-L1 are particularly affected, leading to a dense CD4/CD8 positive lymphocytic infiltration in the basal layer, necrosis of keratinocytes, acanthosis, and hypergranulosis. Subsequently, the cutaneous adverse reaction is a target effect of the PD-1/PD-L1 pathway and not a general hypersensitivity reaction. Clinically, both lichen planus and lichenoid drug eruptions exhibit erythematous papules and plaques. Lichenoid drug eruptions, however, can be scaly, pruritic, and heal with more hyperpigmentation.

A skin biopsy revealed irregular epidermal hyperplasia with jagged rete ridges. Within the dermis, there was a lichenoid inflammatory cell infiltrate obscuring the dermal-epidermal junction. The inflammatory cell infiltrate contained lymphocytes, histiocytes, and eosinophils. A diagnosis of a lichen planus-like adverse drug reaction to pembrolizumab was favored.

If the reaction is mild, topical corticosteroids and oral antihistamines can help with the drug-induced lichen planus. For more severe cases, systemic steroids can be given to help ease the reaction. Physicians should be aware of potential adverse drug effects that can mimic other medical conditions.

BiluMartin_Donna_FLORIDA_web.jpg

The case and photo were submitted by Ms. Towe, Nova Southeastern University College of Osteopathic Medicine, Davie, Florida, and Dr. Berke, Three Rivers Dermatology, Coraopolis, Pennsylvania. The column was edited by Donna Bilu Martin, MD.
 

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.

References

Bansal A et al. Indian Dermatol Online J. 2023 Apr 4;14(3):391-4. doi: 10.4103/idoj.idoj_377_22.

Sethi A, Raj M. Cureus. 2021 Mar 8;13(3):e13768. doi: 10.7759/cureus.13768.

Pembrolizumab (Keytruda) is a programmed cell death protein 1 (PD-1) blocking antibody used to treat different malignancies including melanoma, non–small cell lung cancer, and other advanced solid tumors and hematologic malignancies. Various dermatological side effects have been associated with pembrolizumab, including pruritus, bullous pemphigoid, vitiligo, lichenoid skin reactions, psoriasis, and rarely, life-threatening conditions like Steven-Johnson syndrome and drug rash with eosinophilia and systemic symptoms (DRESS).

Lichen planus-like adverse drug reactions, as seen in this patient, are also referred to as lichenoid drug eruption or drug-induced lichen planus. This cutaneous reaction is one of the more rare side effects of pembrolizumab. It should be noted that in lichenoid reactions, keratinocytes expressing PD-L1 are particularly affected, leading to a dense CD4/CD8 positive lymphocytic infiltration in the basal layer, necrosis of keratinocytes, acanthosis, and hypergranulosis. Subsequently, the cutaneous adverse reaction is a target effect of the PD-1/PD-L1 pathway and not a general hypersensitivity reaction. Clinically, both lichen planus and lichenoid drug eruptions exhibit erythematous papules and plaques. Lichenoid drug eruptions, however, can be scaly, pruritic, and heal with more hyperpigmentation.

A skin biopsy revealed irregular epidermal hyperplasia with jagged rete ridges. Within the dermis, there was a lichenoid inflammatory cell infiltrate obscuring the dermal-epidermal junction. The inflammatory cell infiltrate contained lymphocytes, histiocytes, and eosinophils. A diagnosis of a lichen planus-like adverse drug reaction to pembrolizumab was favored.

If the reaction is mild, topical corticosteroids and oral antihistamines can help with the drug-induced lichen planus. For more severe cases, systemic steroids can be given to help ease the reaction. Physicians should be aware of potential adverse drug effects that can mimic other medical conditions.

BiluMartin_Donna_FLORIDA_web.jpg

The case and photo were submitted by Ms. Towe, Nova Southeastern University College of Osteopathic Medicine, Davie, Florida, and Dr. Berke, Three Rivers Dermatology, Coraopolis, Pennsylvania. The column was edited by Donna Bilu Martin, MD.
 

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.

References

Bansal A et al. Indian Dermatol Online J. 2023 Apr 4;14(3):391-4. doi: 10.4103/idoj.idoj_377_22.

Sethi A, Raj M. Cureus. 2021 Mar 8;13(3):e13768. doi: 10.7759/cureus.13768.

Pembrolizumab (Keytruda) is a programmed cell death protein 1 (PD-1) blocking antibody used to treat different malignancies including melanoma, non–small cell lung cancer, and other advanced solid tumors and hematologic malignancies. Various dermatological side effects have been associated with pembrolizumab, including pruritus, bullous pemphigoid, vitiligo, lichenoid skin reactions, psoriasis, and rarely, life-threatening conditions like Steven-Johnson syndrome and drug rash with eosinophilia and systemic symptoms (DRESS).

Lichen planus-like adverse drug reactions, as seen in this patient, are also referred to as lichenoid drug eruption or drug-induced lichen planus. This cutaneous reaction is one of the more rare side effects of pembrolizumab. It should be noted that in lichenoid reactions, keratinocytes expressing PD-L1 are particularly affected, leading to a dense CD4/CD8 positive lymphocytic infiltration in the basal layer, necrosis of keratinocytes, acanthosis, and hypergranulosis. Subsequently, the cutaneous adverse reaction is a target effect of the PD-1/PD-L1 pathway and not a general hypersensitivity reaction. Clinically, both lichen planus and lichenoid drug eruptions exhibit erythematous papules and plaques. Lichenoid drug eruptions, however, can be scaly, pruritic, and heal with more hyperpigmentation.

A skin biopsy revealed irregular epidermal hyperplasia with jagged rete ridges. Within the dermis, there was a lichenoid inflammatory cell infiltrate obscuring the dermal-epidermal junction. The inflammatory cell infiltrate contained lymphocytes, histiocytes, and eosinophils. A diagnosis of a lichen planus-like adverse drug reaction to pembrolizumab was favored.

If the reaction is mild, topical corticosteroids and oral antihistamines can help with the drug-induced lichen planus. For more severe cases, systemic steroids can be given to help ease the reaction. Physicians should be aware of potential adverse drug effects that can mimic other medical conditions.

BiluMartin_Donna_FLORIDA_web.jpg

The case and photo were submitted by Ms. Towe, Nova Southeastern University College of Osteopathic Medicine, Davie, Florida, and Dr. Berke, Three Rivers Dermatology, Coraopolis, Pennsylvania. The column was edited by Donna Bilu Martin, MD.
 

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.

References

Bansal A et al. Indian Dermatol Online J. 2023 Apr 4;14(3):391-4. doi: 10.4103/idoj.idoj_377_22.

Sethi A, Raj M. Cureus. 2021 Mar 8;13(3):e13768. doi: 10.7759/cureus.13768.