User login
Gene test may offer insights into treatment response in advanced NSCLC
therapy despite their poor status, researchers reported.
Positive findings on the test, known as DetermaIO, were “associated with efficacy of response to ICI therapy in advanced NSCLC patients,” Matthew G. Varga, PhD, manager of scientific affairs at Oncocyte, said in an interview. “These data suggest that DetermaIO warrants further study in poor performance status patients as it has the potential to identify likely responders to ICI therapy.”
Oncocyte, which is developing the test, presented the findings in a poster at the annual meeting of the Society for Immunotherapy of Cancer.
According to Dr. Varga, “DetermaIO is an RT-qPCR test that can be applied to FFPE [formalin-fixed, paraffin-embedded] tissue specimens to quantify the relative gene expression of 27 genes and subsequently applies our proprietary algorithm to generate an IO score based on the gene expression profile. The DetermaIO score is a binary IO+ or IO– score, representing likely responder or nonresponder, respectively.”
The test was originally developed for triple negative breast cancer, Dr. Varga said, and it’s been validated in non–small cell lung cancer, metastatic urothelial carcinoma, and metastatic colorectal carcinoma.
For the study, the researchers retrospectively tracked associations between DetermaIO score and either progression-free survival (PFS) or overall survival (OS) in 147 patients in Canada with NSCLC who were treated with ICI monotherapy. All had programmed death-ligand 1 (PD-L1) ≥ 50%.
Overall, outcomes were poor: The median survival was 12.7 months, and median PFS was 7.0 months. These outcomes were even worse in those who underwent therapy as a second- line treatment: The median survival was 9.7 months, and median PFS was 4.4 months.
“DetermaIO was significantly associated with PFS at hazard ratio [HR] = 0.55, 95% [confidence interval] CI, 0.32-0.94, P = .028. In our analyses, a hazard ratio less than 1 suggests lower risk – i.e, that DetermaIO+ patients have lower risk of an event – death or progression – compared to a DetermaIO– patient,” Dr. Varga said. “The association for overall survival was not statistically significant, but it was suggestive of clinically meaningful benefit.”
He added that “we could identify likely responders from nonresponders, suggesting that the DetermaIO score adds both independent and incremental data to the existing gold standard biomarker. The objective response rate for all first-line patients – n = 78 – was 44.9%. Twenty-two DetermaIO– tumors had a 23% response rate (5 partial responses) whereas of the 56 DetermaIO+ patients, the response rate was 54% (2 complete response and 28 partial responses).”
A score on the test, he said, was not associated with OS or PFS in patients who received second-line or later treatment.
The study was not designed to evaluate the predictive power of the test. “For a biomarker to be defined as predictive requires a formal test of interaction between a treatment group (ICI monotherapy, for example) vs. a control group (chemo-only or other regimen),” Dr. Varga explained. “In our analysis, there was no group of patients who did not receive ICI monotherapy. Thus a test for interaction and a predictive claim cannot be made.”
The test is available for at no cost via an early access program, Dr. Varga said, and Oncocyte is getting ready to seek Medicare coverage. The ultimate cost of the test, he said, is unknown.
Oncocyte funded this study. Dr. Varga and several other study authors are Oncocyte employees, and another author is a paid consultant to the company.
therapy despite their poor status, researchers reported.
Positive findings on the test, known as DetermaIO, were “associated with efficacy of response to ICI therapy in advanced NSCLC patients,” Matthew G. Varga, PhD, manager of scientific affairs at Oncocyte, said in an interview. “These data suggest that DetermaIO warrants further study in poor performance status patients as it has the potential to identify likely responders to ICI therapy.”
Oncocyte, which is developing the test, presented the findings in a poster at the annual meeting of the Society for Immunotherapy of Cancer.
According to Dr. Varga, “DetermaIO is an RT-qPCR test that can be applied to FFPE [formalin-fixed, paraffin-embedded] tissue specimens to quantify the relative gene expression of 27 genes and subsequently applies our proprietary algorithm to generate an IO score based on the gene expression profile. The DetermaIO score is a binary IO+ or IO– score, representing likely responder or nonresponder, respectively.”
The test was originally developed for triple negative breast cancer, Dr. Varga said, and it’s been validated in non–small cell lung cancer, metastatic urothelial carcinoma, and metastatic colorectal carcinoma.
For the study, the researchers retrospectively tracked associations between DetermaIO score and either progression-free survival (PFS) or overall survival (OS) in 147 patients in Canada with NSCLC who were treated with ICI monotherapy. All had programmed death-ligand 1 (PD-L1) ≥ 50%.
Overall, outcomes were poor: The median survival was 12.7 months, and median PFS was 7.0 months. These outcomes were even worse in those who underwent therapy as a second- line treatment: The median survival was 9.7 months, and median PFS was 4.4 months.
“DetermaIO was significantly associated with PFS at hazard ratio [HR] = 0.55, 95% [confidence interval] CI, 0.32-0.94, P = .028. In our analyses, a hazard ratio less than 1 suggests lower risk – i.e, that DetermaIO+ patients have lower risk of an event – death or progression – compared to a DetermaIO– patient,” Dr. Varga said. “The association for overall survival was not statistically significant, but it was suggestive of clinically meaningful benefit.”
He added that “we could identify likely responders from nonresponders, suggesting that the DetermaIO score adds both independent and incremental data to the existing gold standard biomarker. The objective response rate for all first-line patients – n = 78 – was 44.9%. Twenty-two DetermaIO– tumors had a 23% response rate (5 partial responses) whereas of the 56 DetermaIO+ patients, the response rate was 54% (2 complete response and 28 partial responses).”
A score on the test, he said, was not associated with OS or PFS in patients who received second-line or later treatment.
The study was not designed to evaluate the predictive power of the test. “For a biomarker to be defined as predictive requires a formal test of interaction between a treatment group (ICI monotherapy, for example) vs. a control group (chemo-only or other regimen),” Dr. Varga explained. “In our analysis, there was no group of patients who did not receive ICI monotherapy. Thus a test for interaction and a predictive claim cannot be made.”
The test is available for at no cost via an early access program, Dr. Varga said, and Oncocyte is getting ready to seek Medicare coverage. The ultimate cost of the test, he said, is unknown.
Oncocyte funded this study. Dr. Varga and several other study authors are Oncocyte employees, and another author is a paid consultant to the company.
therapy despite their poor status, researchers reported.
Positive findings on the test, known as DetermaIO, were “associated with efficacy of response to ICI therapy in advanced NSCLC patients,” Matthew G. Varga, PhD, manager of scientific affairs at Oncocyte, said in an interview. “These data suggest that DetermaIO warrants further study in poor performance status patients as it has the potential to identify likely responders to ICI therapy.”
Oncocyte, which is developing the test, presented the findings in a poster at the annual meeting of the Society for Immunotherapy of Cancer.
According to Dr. Varga, “DetermaIO is an RT-qPCR test that can be applied to FFPE [formalin-fixed, paraffin-embedded] tissue specimens to quantify the relative gene expression of 27 genes and subsequently applies our proprietary algorithm to generate an IO score based on the gene expression profile. The DetermaIO score is a binary IO+ or IO– score, representing likely responder or nonresponder, respectively.”
The test was originally developed for triple negative breast cancer, Dr. Varga said, and it’s been validated in non–small cell lung cancer, metastatic urothelial carcinoma, and metastatic colorectal carcinoma.
For the study, the researchers retrospectively tracked associations between DetermaIO score and either progression-free survival (PFS) or overall survival (OS) in 147 patients in Canada with NSCLC who were treated with ICI monotherapy. All had programmed death-ligand 1 (PD-L1) ≥ 50%.
Overall, outcomes were poor: The median survival was 12.7 months, and median PFS was 7.0 months. These outcomes were even worse in those who underwent therapy as a second- line treatment: The median survival was 9.7 months, and median PFS was 4.4 months.
“DetermaIO was significantly associated with PFS at hazard ratio [HR] = 0.55, 95% [confidence interval] CI, 0.32-0.94, P = .028. In our analyses, a hazard ratio less than 1 suggests lower risk – i.e, that DetermaIO+ patients have lower risk of an event – death or progression – compared to a DetermaIO– patient,” Dr. Varga said. “The association for overall survival was not statistically significant, but it was suggestive of clinically meaningful benefit.”
He added that “we could identify likely responders from nonresponders, suggesting that the DetermaIO score adds both independent and incremental data to the existing gold standard biomarker. The objective response rate for all first-line patients – n = 78 – was 44.9%. Twenty-two DetermaIO– tumors had a 23% response rate (5 partial responses) whereas of the 56 DetermaIO+ patients, the response rate was 54% (2 complete response and 28 partial responses).”
A score on the test, he said, was not associated with OS or PFS in patients who received second-line or later treatment.
The study was not designed to evaluate the predictive power of the test. “For a biomarker to be defined as predictive requires a formal test of interaction between a treatment group (ICI monotherapy, for example) vs. a control group (chemo-only or other regimen),” Dr. Varga explained. “In our analysis, there was no group of patients who did not receive ICI monotherapy. Thus a test for interaction and a predictive claim cannot be made.”
The test is available for at no cost via an early access program, Dr. Varga said, and Oncocyte is getting ready to seek Medicare coverage. The ultimate cost of the test, he said, is unknown.
Oncocyte funded this study. Dr. Varga and several other study authors are Oncocyte employees, and another author is a paid consultant to the company.
FROM SITC 2022
Long-course radiation therapy better at organ-sparing in rectal cancer than short-term therapy
as part of a total neoadjuvant therapy (TNT) strategy, shows new research presented at the ASCO Gastrointestinal Cancers Symposium 2023.
“When we looked at the 2-year organ preservation rates, they were numerically higher in the long-course group versus the short-course group,” said study author J. Joshua Smith, MD, PhD,FACS, a colorectal surgeon with Memorial Sloan Kettering Cancer Center, New York. “Our study will be the first, to our knowledge, that examines a significant proportion of patients treated with the induction total neoadjuvant therapy approach – chemo first.”
An ideal outcome in rectal cancer is no need for surgery, Dr. Smith said. “If you can avoid surgery altogether and preserve the organ [the rectum], that’s a big win for the patient as they are usually able to avoid having a permanent or temporary ostomy.”
Long-course and short-course radiation have similar outcomes in terms of patients going on to need surgery, but it’s not clear which is superior in terms of organ sparing, toxicity, and side effects, said Paul Romesser, MD, a radiation oncologist with Memorial Sloan Kettering Cancer Center, New York, who served as first author of the study.
During the early months of the COVID-19 pandemic, the cancer center embraced short-course radiation in rectal cancer, Dr. Romesser said. “Once we emerged from the cloud of COVID, we said: ‘Well, what do we do now? Where do we go? Do we go back to what we did before? Or, do we go stick with the same? And what does that mean for organ preservation?’ ”
The researchers retrospectively identified 563 consecutive patients treated with TNT from 2018 to 2021. They focused on 332 who didn’t have metastatic disease, synchronous/metachronous malignancies, or nonadenocarcinoma histology (long course = 256, short course = 76). The groups had similar high-risk features, and about 82% were clinical stage III).
Patients most commonly received induction chemotherapy followed by consolidative radiation (78% long course, 70% short course).
The 2-year survival rates were similar, but organ preservation was higher in the long-course group versus the short-course group (40%; 95% confidence interval, 35%-47% vs. 29%; 95% CI, 20%-42%). And the 2-year local regrowth rate was also better in the long-course group versus the short-course group (20%; 95% CI, 12%-27% vs. 36%; 95% CI, 16%-52%).
Why might long-course therapy be better? “It’s probably just coming down to the biologically equivalent dose,” which is likely lower in short-course radiation, Dr. Romesser said.
Going forward, Dr. Romesser said he’ll tell patients about the findings of this study and a previous report published in 2022 that determined that “organ preservation is achievable in half of the patients with rectal cancer treated with total neoadjuvant therapy, without an apparent detriment in survival, compared with historical controls treated with chemoradiotherapy, TME [total mesorectal excision], and postoperative chemotherapy.” Dr. Smith is a coauthor of that study.
“Generally, I’ll steer patients toward long course, assuming all else is equal, and it’s not an undue burden on them financially and socially to come in for 5-6 weeks of chemoradiation,” Dr. Romesser said. He added that, “generally, the insurance companies recognize [short-course and long-course radiation] as both acceptable and standard treatment options for patients. We haven’t found that insurances will approve one, but not the other.”
The study was funded by the National Institutes of Health. Dr. Romesser disclosed consulting/advisory roles (EMD Serono, Faeth, Natera), research funding (XRad), and travel/accommodations/expenses (Elekta). Dr. Smith disclosed consulting/advisory roles (Foundation Medicine, Guardant Health). The other study authors reported no conflicts of interest.
The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
as part of a total neoadjuvant therapy (TNT) strategy, shows new research presented at the ASCO Gastrointestinal Cancers Symposium 2023.
“When we looked at the 2-year organ preservation rates, they were numerically higher in the long-course group versus the short-course group,” said study author J. Joshua Smith, MD, PhD,FACS, a colorectal surgeon with Memorial Sloan Kettering Cancer Center, New York. “Our study will be the first, to our knowledge, that examines a significant proportion of patients treated with the induction total neoadjuvant therapy approach – chemo first.”
An ideal outcome in rectal cancer is no need for surgery, Dr. Smith said. “If you can avoid surgery altogether and preserve the organ [the rectum], that’s a big win for the patient as they are usually able to avoid having a permanent or temporary ostomy.”
Long-course and short-course radiation have similar outcomes in terms of patients going on to need surgery, but it’s not clear which is superior in terms of organ sparing, toxicity, and side effects, said Paul Romesser, MD, a radiation oncologist with Memorial Sloan Kettering Cancer Center, New York, who served as first author of the study.
During the early months of the COVID-19 pandemic, the cancer center embraced short-course radiation in rectal cancer, Dr. Romesser said. “Once we emerged from the cloud of COVID, we said: ‘Well, what do we do now? Where do we go? Do we go back to what we did before? Or, do we go stick with the same? And what does that mean for organ preservation?’ ”
The researchers retrospectively identified 563 consecutive patients treated with TNT from 2018 to 2021. They focused on 332 who didn’t have metastatic disease, synchronous/metachronous malignancies, or nonadenocarcinoma histology (long course = 256, short course = 76). The groups had similar high-risk features, and about 82% were clinical stage III).
Patients most commonly received induction chemotherapy followed by consolidative radiation (78% long course, 70% short course).
The 2-year survival rates were similar, but organ preservation was higher in the long-course group versus the short-course group (40%; 95% confidence interval, 35%-47% vs. 29%; 95% CI, 20%-42%). And the 2-year local regrowth rate was also better in the long-course group versus the short-course group (20%; 95% CI, 12%-27% vs. 36%; 95% CI, 16%-52%).
Why might long-course therapy be better? “It’s probably just coming down to the biologically equivalent dose,” which is likely lower in short-course radiation, Dr. Romesser said.
Going forward, Dr. Romesser said he’ll tell patients about the findings of this study and a previous report published in 2022 that determined that “organ preservation is achievable in half of the patients with rectal cancer treated with total neoadjuvant therapy, without an apparent detriment in survival, compared with historical controls treated with chemoradiotherapy, TME [total mesorectal excision], and postoperative chemotherapy.” Dr. Smith is a coauthor of that study.
“Generally, I’ll steer patients toward long course, assuming all else is equal, and it’s not an undue burden on them financially and socially to come in for 5-6 weeks of chemoradiation,” Dr. Romesser said. He added that, “generally, the insurance companies recognize [short-course and long-course radiation] as both acceptable and standard treatment options for patients. We haven’t found that insurances will approve one, but not the other.”
The study was funded by the National Institutes of Health. Dr. Romesser disclosed consulting/advisory roles (EMD Serono, Faeth, Natera), research funding (XRad), and travel/accommodations/expenses (Elekta). Dr. Smith disclosed consulting/advisory roles (Foundation Medicine, Guardant Health). The other study authors reported no conflicts of interest.
The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
as part of a total neoadjuvant therapy (TNT) strategy, shows new research presented at the ASCO Gastrointestinal Cancers Symposium 2023.
“When we looked at the 2-year organ preservation rates, they were numerically higher in the long-course group versus the short-course group,” said study author J. Joshua Smith, MD, PhD,FACS, a colorectal surgeon with Memorial Sloan Kettering Cancer Center, New York. “Our study will be the first, to our knowledge, that examines a significant proportion of patients treated with the induction total neoadjuvant therapy approach – chemo first.”
An ideal outcome in rectal cancer is no need for surgery, Dr. Smith said. “If you can avoid surgery altogether and preserve the organ [the rectum], that’s a big win for the patient as they are usually able to avoid having a permanent or temporary ostomy.”
Long-course and short-course radiation have similar outcomes in terms of patients going on to need surgery, but it’s not clear which is superior in terms of organ sparing, toxicity, and side effects, said Paul Romesser, MD, a radiation oncologist with Memorial Sloan Kettering Cancer Center, New York, who served as first author of the study.
During the early months of the COVID-19 pandemic, the cancer center embraced short-course radiation in rectal cancer, Dr. Romesser said. “Once we emerged from the cloud of COVID, we said: ‘Well, what do we do now? Where do we go? Do we go back to what we did before? Or, do we go stick with the same? And what does that mean for organ preservation?’ ”
The researchers retrospectively identified 563 consecutive patients treated with TNT from 2018 to 2021. They focused on 332 who didn’t have metastatic disease, synchronous/metachronous malignancies, or nonadenocarcinoma histology (long course = 256, short course = 76). The groups had similar high-risk features, and about 82% were clinical stage III).
Patients most commonly received induction chemotherapy followed by consolidative radiation (78% long course, 70% short course).
The 2-year survival rates were similar, but organ preservation was higher in the long-course group versus the short-course group (40%; 95% confidence interval, 35%-47% vs. 29%; 95% CI, 20%-42%). And the 2-year local regrowth rate was also better in the long-course group versus the short-course group (20%; 95% CI, 12%-27% vs. 36%; 95% CI, 16%-52%).
Why might long-course therapy be better? “It’s probably just coming down to the biologically equivalent dose,” which is likely lower in short-course radiation, Dr. Romesser said.
Going forward, Dr. Romesser said he’ll tell patients about the findings of this study and a previous report published in 2022 that determined that “organ preservation is achievable in half of the patients with rectal cancer treated with total neoadjuvant therapy, without an apparent detriment in survival, compared with historical controls treated with chemoradiotherapy, TME [total mesorectal excision], and postoperative chemotherapy.” Dr. Smith is a coauthor of that study.
“Generally, I’ll steer patients toward long course, assuming all else is equal, and it’s not an undue burden on them financially and socially to come in for 5-6 weeks of chemoradiation,” Dr. Romesser said. He added that, “generally, the insurance companies recognize [short-course and long-course radiation] as both acceptable and standard treatment options for patients. We haven’t found that insurances will approve one, but not the other.”
The study was funded by the National Institutes of Health. Dr. Romesser disclosed consulting/advisory roles (EMD Serono, Faeth, Natera), research funding (XRad), and travel/accommodations/expenses (Elekta). Dr. Smith disclosed consulting/advisory roles (Foundation Medicine, Guardant Health). The other study authors reported no conflicts of interest.
The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
FROM ASCO GI 2023
Immunotherapy with antibiotics doesn’t worsen biliary tract cancer outcomes
according to a new analysis of the landmark TOPAZ-1 clinical trial.
The findings, released at the ASCO Gastrointestinal Cancers Symposium 2023, suggest that “people with advanced biliary tract cancer can safely be treated with antibiotics while still benefiting from treatment with durvalumab plus chemotherapy,” said lead author Aiwu Ruth He, MD, PhD, a gastrointestinal oncologist with MedStar Georgetown University Hospital, Washington.
Antibiotic use during immune checkpoint inhibitor therapy has been associated with poorer outcomes. A review of 12 studies published in Frontiers in Oncology found that antibiotic use was associated with worse progression-free and overall survival.
“Patients with biliary tract cancer have the increased risk of biliary tract infection as the result of biliary tract obstruction, and they often receive antibiotics,” Dr. He said.
A 2020 report in eCancer suggested that antibiotics may disrupt gut bacteria and, as a result, interfere with the immune system’s responsiveness. “It has been a consensus that the use of broad-spectrum antibiotics should be avoided during the use of immunotherapy whenever possible,” the report authors wrote. “In addition, antibiotics should be prescribed only when properly indicated.”
However, cutting down on antibiotic use may be especially difficult in cancer patients since they frequently suffer from infections. “An antibiotic-resistant bacterial infection may cause serious issues for a cancer patient, who likely already has a suppressed immune system,” according to a 2017 information sheet posted by the Cancer Treatment Centers of America. “Chemotherapy may cause neutropenia, a reduction of white blood cells that help fight infections and viruses. Radiation therapy may damage the skin and cause irritation and wounds. Immunotherapy or targeted therapy drugs may trigger side effects that may lead to infections. Incisions from surgery or to insert ports or catheters may be vulnerable to infections.”
The new study
For the new subgroup analysis, researchers analyzed data from the phase 3 TOPAZ-1 clinical trial, which was a double-blinded analysis of durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer. The previously reported main findings from the study were positive with a median overall survival of 12.8 months in the durvalumab arm versus 11.5 months in the placebo arm (hazard ratio, 0.80; P = .021). These findings contributed to the Food and Drug Administration’s decision in 2022 to approve the treatment for use in locally advanced or metastatic biliary tract cancer.
Of 341 patients who received durvalumab treatment, 167 also took antibiotics. The median overall survival in the antibiotic and nonantibiotic groups were similar at 12.6 months (95% confidence interval, 9.7-14.8 months) and 13 months (95% CI, 10.8-14.7 months), respectively. Median progression-free survival was 7.3 months (95% CI, 6.5-7.7 months) and 7.2 months (95% CI, 5.9-7.4 months), respectively.
“The results support that advanced patients’ risk of death, and the risk that their cancer would grow, spread, or get worse, was not meaningfully different between patients who used antibiotics and those who did not use antibiotics at the same time as they were receiving durvalumab-based treatment,” Dr. He said. “The result is not surprising to me since it is not clear to me how and why antibiotics may affect the effectiveness of immunotherapy.”
Moving forward, she said, “additional studies are needed to further investigator the relationship between antibiotics use and effectiveness of immunotherapy. We need to understand why use of antibiotics during treatment with immunotherapy is correlated with poor outcomes in some circumstances but not in other circumstances.”
The study was funded by AstraZeneca. The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
according to a new analysis of the landmark TOPAZ-1 clinical trial.
The findings, released at the ASCO Gastrointestinal Cancers Symposium 2023, suggest that “people with advanced biliary tract cancer can safely be treated with antibiotics while still benefiting from treatment with durvalumab plus chemotherapy,” said lead author Aiwu Ruth He, MD, PhD, a gastrointestinal oncologist with MedStar Georgetown University Hospital, Washington.
Antibiotic use during immune checkpoint inhibitor therapy has been associated with poorer outcomes. A review of 12 studies published in Frontiers in Oncology found that antibiotic use was associated with worse progression-free and overall survival.
“Patients with biliary tract cancer have the increased risk of biliary tract infection as the result of biliary tract obstruction, and they often receive antibiotics,” Dr. He said.
A 2020 report in eCancer suggested that antibiotics may disrupt gut bacteria and, as a result, interfere with the immune system’s responsiveness. “It has been a consensus that the use of broad-spectrum antibiotics should be avoided during the use of immunotherapy whenever possible,” the report authors wrote. “In addition, antibiotics should be prescribed only when properly indicated.”
However, cutting down on antibiotic use may be especially difficult in cancer patients since they frequently suffer from infections. “An antibiotic-resistant bacterial infection may cause serious issues for a cancer patient, who likely already has a suppressed immune system,” according to a 2017 information sheet posted by the Cancer Treatment Centers of America. “Chemotherapy may cause neutropenia, a reduction of white blood cells that help fight infections and viruses. Radiation therapy may damage the skin and cause irritation and wounds. Immunotherapy or targeted therapy drugs may trigger side effects that may lead to infections. Incisions from surgery or to insert ports or catheters may be vulnerable to infections.”
The new study
For the new subgroup analysis, researchers analyzed data from the phase 3 TOPAZ-1 clinical trial, which was a double-blinded analysis of durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer. The previously reported main findings from the study were positive with a median overall survival of 12.8 months in the durvalumab arm versus 11.5 months in the placebo arm (hazard ratio, 0.80; P = .021). These findings contributed to the Food and Drug Administration’s decision in 2022 to approve the treatment for use in locally advanced or metastatic biliary tract cancer.
Of 341 patients who received durvalumab treatment, 167 also took antibiotics. The median overall survival in the antibiotic and nonantibiotic groups were similar at 12.6 months (95% confidence interval, 9.7-14.8 months) and 13 months (95% CI, 10.8-14.7 months), respectively. Median progression-free survival was 7.3 months (95% CI, 6.5-7.7 months) and 7.2 months (95% CI, 5.9-7.4 months), respectively.
“The results support that advanced patients’ risk of death, and the risk that their cancer would grow, spread, or get worse, was not meaningfully different between patients who used antibiotics and those who did not use antibiotics at the same time as they were receiving durvalumab-based treatment,” Dr. He said. “The result is not surprising to me since it is not clear to me how and why antibiotics may affect the effectiveness of immunotherapy.”
Moving forward, she said, “additional studies are needed to further investigator the relationship between antibiotics use and effectiveness of immunotherapy. We need to understand why use of antibiotics during treatment with immunotherapy is correlated with poor outcomes in some circumstances but not in other circumstances.”
The study was funded by AstraZeneca. The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
according to a new analysis of the landmark TOPAZ-1 clinical trial.
The findings, released at the ASCO Gastrointestinal Cancers Symposium 2023, suggest that “people with advanced biliary tract cancer can safely be treated with antibiotics while still benefiting from treatment with durvalumab plus chemotherapy,” said lead author Aiwu Ruth He, MD, PhD, a gastrointestinal oncologist with MedStar Georgetown University Hospital, Washington.
Antibiotic use during immune checkpoint inhibitor therapy has been associated with poorer outcomes. A review of 12 studies published in Frontiers in Oncology found that antibiotic use was associated with worse progression-free and overall survival.
“Patients with biliary tract cancer have the increased risk of biliary tract infection as the result of biliary tract obstruction, and they often receive antibiotics,” Dr. He said.
A 2020 report in eCancer suggested that antibiotics may disrupt gut bacteria and, as a result, interfere with the immune system’s responsiveness. “It has been a consensus that the use of broad-spectrum antibiotics should be avoided during the use of immunotherapy whenever possible,” the report authors wrote. “In addition, antibiotics should be prescribed only when properly indicated.”
However, cutting down on antibiotic use may be especially difficult in cancer patients since they frequently suffer from infections. “An antibiotic-resistant bacterial infection may cause serious issues for a cancer patient, who likely already has a suppressed immune system,” according to a 2017 information sheet posted by the Cancer Treatment Centers of America. “Chemotherapy may cause neutropenia, a reduction of white blood cells that help fight infections and viruses. Radiation therapy may damage the skin and cause irritation and wounds. Immunotherapy or targeted therapy drugs may trigger side effects that may lead to infections. Incisions from surgery or to insert ports or catheters may be vulnerable to infections.”
The new study
For the new subgroup analysis, researchers analyzed data from the phase 3 TOPAZ-1 clinical trial, which was a double-blinded analysis of durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer. The previously reported main findings from the study were positive with a median overall survival of 12.8 months in the durvalumab arm versus 11.5 months in the placebo arm (hazard ratio, 0.80; P = .021). These findings contributed to the Food and Drug Administration’s decision in 2022 to approve the treatment for use in locally advanced or metastatic biliary tract cancer.
Of 341 patients who received durvalumab treatment, 167 also took antibiotics. The median overall survival in the antibiotic and nonantibiotic groups were similar at 12.6 months (95% confidence interval, 9.7-14.8 months) and 13 months (95% CI, 10.8-14.7 months), respectively. Median progression-free survival was 7.3 months (95% CI, 6.5-7.7 months) and 7.2 months (95% CI, 5.9-7.4 months), respectively.
“The results support that advanced patients’ risk of death, and the risk that their cancer would grow, spread, or get worse, was not meaningfully different between patients who used antibiotics and those who did not use antibiotics at the same time as they were receiving durvalumab-based treatment,” Dr. He said. “The result is not surprising to me since it is not clear to me how and why antibiotics may affect the effectiveness of immunotherapy.”
Moving forward, she said, “additional studies are needed to further investigator the relationship between antibiotics use and effectiveness of immunotherapy. We need to understand why use of antibiotics during treatment with immunotherapy is correlated with poor outcomes in some circumstances but not in other circumstances.”
The study was funded by AstraZeneca. The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
FROM ASCO GI 2023
Despite limits, COVID vaccines protect CLL patients
These findings don’t reveal whether the T-cell boost actually provides extra protection against COVID-19. Still, the study suggests that patients with CLL should be vaccinated no matter which medications they’re taking, coauthor and hematologist/oncologist Clemens-Martin Wendtner, MD, of the Munich (Germany) Clinic, said in an interview.
“Do not defer or pause treatment,” said Dr. Wendtner, whose study was published in Blood Advances.
Patients with CLL appear to have among the weakest responses to the COVID-19 vaccine among people with various types of blood cancer. A meta-analysis published in 2022 found that seropositivity rates following vaccination were just 51% in patients with CLL, compared with 80%-90% in those with acute leukemia and 76%-80% of those with myeloma.
“Usually, the response rate to vaccination among the nonimmunocompromised would be 95%,” Dr. Wendtner said.
Research has also suggested that patients treated with B-cell pathway inhibitors and anti-CD20 antibodies are especially likely to have poorer responses to COVID-19 vaccines, no surprise considering that their job is to dampen the immune system. But there’s an unanswered question, according to Dr. Wendtner: Does “just measuring B-cell response tell us everything about the immune response?”
The new prospective, single-institution study aims to answer that question in patients who each received two types of vaccines. Researchers compared peripheral blood mononuclear cell transcriptional response with antibody and T-cell response rates in 15 patients with CLL/small lymphocytic lymphoma following vaccination with both the Pfizer-BioNTech and AstraZeneca vaccines.
The average antibody response was limited. “Overall, 7/15 of patients failed to mount a humoral response even after three-dose vaccination,” the researchers reported. All of the patients were “heavily pretreated” with CLL medications such as venetoclax, an anti-CD20 monoclonal antibody.
By contrast, the T-cell response was much stronger: 80% of patients (12/15) had a robust response, a number that grew to 90% (14/15) after a booster. This response is “almost ideal” considering that the response in a nonimmunocompromised person would be about 99%, Dr. Wendtner said.
The study also revealed that vaccine responses were weaker in patients who took a combination of a Bruton tyrosine kinase inhibitor and venetoclax within a year.
Four patients developed COVID-19 infections with the Omicron variant about 6 months after vaccination. All had mild symptoms. A lone patient had a history of COVID-19 infection prior to vaccination.
The researchers noted that the study had several limitations, including its small size, its reliance on a single institution, and the differences in treatments and vaccination protocols among the patient population.
Broadly speaking, the study showed that “a vaccine is not in vain” in patients with CLL, “although the doctor might not detect an antibody response,” Dr. Wendtner said. He added that mixing vaccine types should provide more protection. Start with a viral vector vaccine followed by an mRNA vaccine or vice versa, he suggested.
In an interview, infectious disease physician Joshua A. Hill, MD, from Fred Hutchinson Cancer Center, Seattle, who wasn’t involved with the study, said it makes “important and interesting observations to reinforce other studies with similar findings.”
Specifically, Dr. Hill said, “despite the absence of a robust antibody response some of these patients who are on active treatment, patients can still generate robust cellular immune responses in the form of T-cell immunity. Our understanding is that having T cell immunity will provide important additional protection for developing severe disease, although is less easily tested.”
As for the best vaccination strategies, Dr. Hill said “patients should get vaccinated as soon as they are eligible, according to standard guidelines. If patients have not yet started therapy, they should get their indicated vaccines before starting treatment whenever possible.”
The German study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Bavarian State Ministry of Science and Art. Dr. Wendtner disclosed consultant fees from AstraZeneca and BioNTech, and another author disclosed consultant fees from AstraZeneca. The other authors reported no disclosures. Dr. Hill disclosed consultant fees from Moderna, Pfizer, and Gilead.
These findings don’t reveal whether the T-cell boost actually provides extra protection against COVID-19. Still, the study suggests that patients with CLL should be vaccinated no matter which medications they’re taking, coauthor and hematologist/oncologist Clemens-Martin Wendtner, MD, of the Munich (Germany) Clinic, said in an interview.
“Do not defer or pause treatment,” said Dr. Wendtner, whose study was published in Blood Advances.
Patients with CLL appear to have among the weakest responses to the COVID-19 vaccine among people with various types of blood cancer. A meta-analysis published in 2022 found that seropositivity rates following vaccination were just 51% in patients with CLL, compared with 80%-90% in those with acute leukemia and 76%-80% of those with myeloma.
“Usually, the response rate to vaccination among the nonimmunocompromised would be 95%,” Dr. Wendtner said.
Research has also suggested that patients treated with B-cell pathway inhibitors and anti-CD20 antibodies are especially likely to have poorer responses to COVID-19 vaccines, no surprise considering that their job is to dampen the immune system. But there’s an unanswered question, according to Dr. Wendtner: Does “just measuring B-cell response tell us everything about the immune response?”
The new prospective, single-institution study aims to answer that question in patients who each received two types of vaccines. Researchers compared peripheral blood mononuclear cell transcriptional response with antibody and T-cell response rates in 15 patients with CLL/small lymphocytic lymphoma following vaccination with both the Pfizer-BioNTech and AstraZeneca vaccines.
The average antibody response was limited. “Overall, 7/15 of patients failed to mount a humoral response even after three-dose vaccination,” the researchers reported. All of the patients were “heavily pretreated” with CLL medications such as venetoclax, an anti-CD20 monoclonal antibody.
By contrast, the T-cell response was much stronger: 80% of patients (12/15) had a robust response, a number that grew to 90% (14/15) after a booster. This response is “almost ideal” considering that the response in a nonimmunocompromised person would be about 99%, Dr. Wendtner said.
The study also revealed that vaccine responses were weaker in patients who took a combination of a Bruton tyrosine kinase inhibitor and venetoclax within a year.
Four patients developed COVID-19 infections with the Omicron variant about 6 months after vaccination. All had mild symptoms. A lone patient had a history of COVID-19 infection prior to vaccination.
The researchers noted that the study had several limitations, including its small size, its reliance on a single institution, and the differences in treatments and vaccination protocols among the patient population.
Broadly speaking, the study showed that “a vaccine is not in vain” in patients with CLL, “although the doctor might not detect an antibody response,” Dr. Wendtner said. He added that mixing vaccine types should provide more protection. Start with a viral vector vaccine followed by an mRNA vaccine or vice versa, he suggested.
In an interview, infectious disease physician Joshua A. Hill, MD, from Fred Hutchinson Cancer Center, Seattle, who wasn’t involved with the study, said it makes “important and interesting observations to reinforce other studies with similar findings.”
Specifically, Dr. Hill said, “despite the absence of a robust antibody response some of these patients who are on active treatment, patients can still generate robust cellular immune responses in the form of T-cell immunity. Our understanding is that having T cell immunity will provide important additional protection for developing severe disease, although is less easily tested.”
As for the best vaccination strategies, Dr. Hill said “patients should get vaccinated as soon as they are eligible, according to standard guidelines. If patients have not yet started therapy, they should get their indicated vaccines before starting treatment whenever possible.”
The German study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Bavarian State Ministry of Science and Art. Dr. Wendtner disclosed consultant fees from AstraZeneca and BioNTech, and another author disclosed consultant fees from AstraZeneca. The other authors reported no disclosures. Dr. Hill disclosed consultant fees from Moderna, Pfizer, and Gilead.
These findings don’t reveal whether the T-cell boost actually provides extra protection against COVID-19. Still, the study suggests that patients with CLL should be vaccinated no matter which medications they’re taking, coauthor and hematologist/oncologist Clemens-Martin Wendtner, MD, of the Munich (Germany) Clinic, said in an interview.
“Do not defer or pause treatment,” said Dr. Wendtner, whose study was published in Blood Advances.
Patients with CLL appear to have among the weakest responses to the COVID-19 vaccine among people with various types of blood cancer. A meta-analysis published in 2022 found that seropositivity rates following vaccination were just 51% in patients with CLL, compared with 80%-90% in those with acute leukemia and 76%-80% of those with myeloma.
“Usually, the response rate to vaccination among the nonimmunocompromised would be 95%,” Dr. Wendtner said.
Research has also suggested that patients treated with B-cell pathway inhibitors and anti-CD20 antibodies are especially likely to have poorer responses to COVID-19 vaccines, no surprise considering that their job is to dampen the immune system. But there’s an unanswered question, according to Dr. Wendtner: Does “just measuring B-cell response tell us everything about the immune response?”
The new prospective, single-institution study aims to answer that question in patients who each received two types of vaccines. Researchers compared peripheral blood mononuclear cell transcriptional response with antibody and T-cell response rates in 15 patients with CLL/small lymphocytic lymphoma following vaccination with both the Pfizer-BioNTech and AstraZeneca vaccines.
The average antibody response was limited. “Overall, 7/15 of patients failed to mount a humoral response even after three-dose vaccination,” the researchers reported. All of the patients were “heavily pretreated” with CLL medications such as venetoclax, an anti-CD20 monoclonal antibody.
By contrast, the T-cell response was much stronger: 80% of patients (12/15) had a robust response, a number that grew to 90% (14/15) after a booster. This response is “almost ideal” considering that the response in a nonimmunocompromised person would be about 99%, Dr. Wendtner said.
The study also revealed that vaccine responses were weaker in patients who took a combination of a Bruton tyrosine kinase inhibitor and venetoclax within a year.
Four patients developed COVID-19 infections with the Omicron variant about 6 months after vaccination. All had mild symptoms. A lone patient had a history of COVID-19 infection prior to vaccination.
The researchers noted that the study had several limitations, including its small size, its reliance on a single institution, and the differences in treatments and vaccination protocols among the patient population.
Broadly speaking, the study showed that “a vaccine is not in vain” in patients with CLL, “although the doctor might not detect an antibody response,” Dr. Wendtner said. He added that mixing vaccine types should provide more protection. Start with a viral vector vaccine followed by an mRNA vaccine or vice versa, he suggested.
In an interview, infectious disease physician Joshua A. Hill, MD, from Fred Hutchinson Cancer Center, Seattle, who wasn’t involved with the study, said it makes “important and interesting observations to reinforce other studies with similar findings.”
Specifically, Dr. Hill said, “despite the absence of a robust antibody response some of these patients who are on active treatment, patients can still generate robust cellular immune responses in the form of T-cell immunity. Our understanding is that having T cell immunity will provide important additional protection for developing severe disease, although is less easily tested.”
As for the best vaccination strategies, Dr. Hill said “patients should get vaccinated as soon as they are eligible, according to standard guidelines. If patients have not yet started therapy, they should get their indicated vaccines before starting treatment whenever possible.”
The German study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Bavarian State Ministry of Science and Art. Dr. Wendtner disclosed consultant fees from AstraZeneca and BioNTech, and another author disclosed consultant fees from AstraZeneca. The other authors reported no disclosures. Dr. Hill disclosed consultant fees from Moderna, Pfizer, and Gilead.
FROM BLOOD ADVANCES
Palliative radiotherapy successfully reduces end-stage liver cancer pain
Most patients with end-stage hepatocellular carcinoma experience pain, but when it’s severe, how best to control the pain is debatable. A number of studies, including one recently presented at the ASCO Gastrointestinal Cancers Symposium 2023, shows that low-dose radiotherapy can improve pain, and in this case, even improve survival.
The study, conducted by Laura Dawson, MD, a radiation oncologist with the Princess Margaret Cancer Center, Toronto, was conducted in 66 patients with painful hepatocellular carcinoma or liver metastases. They were randomized to receive either palliative radiotherapy (single fraction 8 gray) or standard pain control. Sixty-three percent of patients treated with radiotherapy reported significant improvements in mild pain compared with 28% of patients who received standard pain control (P = .03).
Currently, palliative radiotherapy to control pain in late stage cancer may be an option for some patients with other types of advanced cancer, but in liver cancer, there is little data to support its routine use in patients with terminal hepatocellular carcinoma. “Several prior studies have shown radiation therapy may be delivered safely and that it may help patients with hepatic cancer pain,” Dr. Dawson said. But the previous studies have mostly been single-arm, she said, and many lacked patient-reported outcomes.
In liver cancer, existing therapies are largely inadequate for pain relief, especially for moderate to severe pain. Systemic therapy isn’t effective for rapid pain relief. And, for a subset of patients with end-stage liver cancer, standard pain control with acetaminophen, steroids, and narcotics either is not effective or cannot be tolerated because of underlying cirrhosis or poor liver function due to the cancer.
Although not clinically significant, palliative radiotherapy improved 3-month survival (51%) compared with patients who received best supportive care (33%, P = .07). “Interestingly, there was a trend for improved survival in those patients who received radiation with a 3-month survival of 51% versus 33% of those who received best supportive care. Clearly, the study was not powered for this, but it is very intriguing and hopefully sets the stage for future clinical trials.”
In this study, “simple radiotherapy was used and could consist of two beams, opposed or oblique parallel pair, or simple intensity modulated radiation. This is available with any medical linear accelerator or any cancer center,” Dr. Dawson said. “.”
New data reported at ASCO GI
The Dawson et al. study included 66 patients with liver cancer who had pain scores of at least 4. They had pain that was specific to the liver and they were unsuitable for or refractory to other therapies with no other planned therapies, such as immunotherapy. Their pain was refractory to standard treatments. Of the patients, 43 had liver metastasis from cancers that originated in the colon (12), breast (5), pancreas (4), lung (3), hepatocellular carcinoma (23), or other sites (19).
At 59%, more than half of patients had ECOG performance status of 2 or 3, suggesting the cancer had progressed to the extent that they were confined to a bed or chair for more than half of their waking hours (level 3) or they were capable of self-care but unable to work (level 2). Of the 66 patients, 42 patients completed 1-month assessments and of these, 67% of 24 patients receiving palliative radiotherapy (21% had no increase in opioids) and 22% of 18 patients receiving best supportive care (with no increase in opioids) reported improvements in their worst pain levels.
The primary endpoint – the proportion of patients with a clinically important improvement in pain 1 month after therapy – was met. “There was a significant improvement in all pain endpoints from baseline to one month, with more patients who received radiotherapy reporting clinically important reduction of pain (a reduction by 2 or more on the 0 to 10 scale). The primary endpoint was pain – worst pain, and 67% of those patients who had radiation reported an improvement in their pain at worst in the past 24 hours versus 22% treated with best supportive care, with a P value .004,” Dr. Dawson said.
Adverse events of at least grade 2 or higher occurred 30 days after radiotherapy, affecting 58% of patients compared with 33% of patients who did not receive the treatment. Adverse events at grade 3 or higher were uncommon.
Dr. Dawson reports institutional research funding from Merck.
The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Most patients with end-stage hepatocellular carcinoma experience pain, but when it’s severe, how best to control the pain is debatable. A number of studies, including one recently presented at the ASCO Gastrointestinal Cancers Symposium 2023, shows that low-dose radiotherapy can improve pain, and in this case, even improve survival.
The study, conducted by Laura Dawson, MD, a radiation oncologist with the Princess Margaret Cancer Center, Toronto, was conducted in 66 patients with painful hepatocellular carcinoma or liver metastases. They were randomized to receive either palliative radiotherapy (single fraction 8 gray) or standard pain control. Sixty-three percent of patients treated with radiotherapy reported significant improvements in mild pain compared with 28% of patients who received standard pain control (P = .03).
Currently, palliative radiotherapy to control pain in late stage cancer may be an option for some patients with other types of advanced cancer, but in liver cancer, there is little data to support its routine use in patients with terminal hepatocellular carcinoma. “Several prior studies have shown radiation therapy may be delivered safely and that it may help patients with hepatic cancer pain,” Dr. Dawson said. But the previous studies have mostly been single-arm, she said, and many lacked patient-reported outcomes.
In liver cancer, existing therapies are largely inadequate for pain relief, especially for moderate to severe pain. Systemic therapy isn’t effective for rapid pain relief. And, for a subset of patients with end-stage liver cancer, standard pain control with acetaminophen, steroids, and narcotics either is not effective or cannot be tolerated because of underlying cirrhosis or poor liver function due to the cancer.
Although not clinically significant, palliative radiotherapy improved 3-month survival (51%) compared with patients who received best supportive care (33%, P = .07). “Interestingly, there was a trend for improved survival in those patients who received radiation with a 3-month survival of 51% versus 33% of those who received best supportive care. Clearly, the study was not powered for this, but it is very intriguing and hopefully sets the stage for future clinical trials.”
In this study, “simple radiotherapy was used and could consist of two beams, opposed or oblique parallel pair, or simple intensity modulated radiation. This is available with any medical linear accelerator or any cancer center,” Dr. Dawson said. “.”
New data reported at ASCO GI
The Dawson et al. study included 66 patients with liver cancer who had pain scores of at least 4. They had pain that was specific to the liver and they were unsuitable for or refractory to other therapies with no other planned therapies, such as immunotherapy. Their pain was refractory to standard treatments. Of the patients, 43 had liver metastasis from cancers that originated in the colon (12), breast (5), pancreas (4), lung (3), hepatocellular carcinoma (23), or other sites (19).
At 59%, more than half of patients had ECOG performance status of 2 or 3, suggesting the cancer had progressed to the extent that they were confined to a bed or chair for more than half of their waking hours (level 3) or they were capable of self-care but unable to work (level 2). Of the 66 patients, 42 patients completed 1-month assessments and of these, 67% of 24 patients receiving palliative radiotherapy (21% had no increase in opioids) and 22% of 18 patients receiving best supportive care (with no increase in opioids) reported improvements in their worst pain levels.
The primary endpoint – the proportion of patients with a clinically important improvement in pain 1 month after therapy – was met. “There was a significant improvement in all pain endpoints from baseline to one month, with more patients who received radiotherapy reporting clinically important reduction of pain (a reduction by 2 or more on the 0 to 10 scale). The primary endpoint was pain – worst pain, and 67% of those patients who had radiation reported an improvement in their pain at worst in the past 24 hours versus 22% treated with best supportive care, with a P value .004,” Dr. Dawson said.
Adverse events of at least grade 2 or higher occurred 30 days after radiotherapy, affecting 58% of patients compared with 33% of patients who did not receive the treatment. Adverse events at grade 3 or higher were uncommon.
Dr. Dawson reports institutional research funding from Merck.
The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Most patients with end-stage hepatocellular carcinoma experience pain, but when it’s severe, how best to control the pain is debatable. A number of studies, including one recently presented at the ASCO Gastrointestinal Cancers Symposium 2023, shows that low-dose radiotherapy can improve pain, and in this case, even improve survival.
The study, conducted by Laura Dawson, MD, a radiation oncologist with the Princess Margaret Cancer Center, Toronto, was conducted in 66 patients with painful hepatocellular carcinoma or liver metastases. They were randomized to receive either palliative radiotherapy (single fraction 8 gray) or standard pain control. Sixty-three percent of patients treated with radiotherapy reported significant improvements in mild pain compared with 28% of patients who received standard pain control (P = .03).
Currently, palliative radiotherapy to control pain in late stage cancer may be an option for some patients with other types of advanced cancer, but in liver cancer, there is little data to support its routine use in patients with terminal hepatocellular carcinoma. “Several prior studies have shown radiation therapy may be delivered safely and that it may help patients with hepatic cancer pain,” Dr. Dawson said. But the previous studies have mostly been single-arm, she said, and many lacked patient-reported outcomes.
In liver cancer, existing therapies are largely inadequate for pain relief, especially for moderate to severe pain. Systemic therapy isn’t effective for rapid pain relief. And, for a subset of patients with end-stage liver cancer, standard pain control with acetaminophen, steroids, and narcotics either is not effective or cannot be tolerated because of underlying cirrhosis or poor liver function due to the cancer.
Although not clinically significant, palliative radiotherapy improved 3-month survival (51%) compared with patients who received best supportive care (33%, P = .07). “Interestingly, there was a trend for improved survival in those patients who received radiation with a 3-month survival of 51% versus 33% of those who received best supportive care. Clearly, the study was not powered for this, but it is very intriguing and hopefully sets the stage for future clinical trials.”
In this study, “simple radiotherapy was used and could consist of two beams, opposed or oblique parallel pair, or simple intensity modulated radiation. This is available with any medical linear accelerator or any cancer center,” Dr. Dawson said. “.”
New data reported at ASCO GI
The Dawson et al. study included 66 patients with liver cancer who had pain scores of at least 4. They had pain that was specific to the liver and they were unsuitable for or refractory to other therapies with no other planned therapies, such as immunotherapy. Their pain was refractory to standard treatments. Of the patients, 43 had liver metastasis from cancers that originated in the colon (12), breast (5), pancreas (4), lung (3), hepatocellular carcinoma (23), or other sites (19).
At 59%, more than half of patients had ECOG performance status of 2 or 3, suggesting the cancer had progressed to the extent that they were confined to a bed or chair for more than half of their waking hours (level 3) or they were capable of self-care but unable to work (level 2). Of the 66 patients, 42 patients completed 1-month assessments and of these, 67% of 24 patients receiving palliative radiotherapy (21% had no increase in opioids) and 22% of 18 patients receiving best supportive care (with no increase in opioids) reported improvements in their worst pain levels.
The primary endpoint – the proportion of patients with a clinically important improvement in pain 1 month after therapy – was met. “There was a significant improvement in all pain endpoints from baseline to one month, with more patients who received radiotherapy reporting clinically important reduction of pain (a reduction by 2 or more on the 0 to 10 scale). The primary endpoint was pain – worst pain, and 67% of those patients who had radiation reported an improvement in their pain at worst in the past 24 hours versus 22% treated with best supportive care, with a P value .004,” Dr. Dawson said.
Adverse events of at least grade 2 or higher occurred 30 days after radiotherapy, affecting 58% of patients compared with 33% of patients who did not receive the treatment. Adverse events at grade 3 or higher were uncommon.
Dr. Dawson reports institutional research funding from Merck.
The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
FROM ASCO GI 2023
Topical CBD oil study suggests benefits for pain, healing in systemic sclerosis digital ulcers
Topical cannabidiol (CBD) oil appeared to lower pain scores and reduce painkiller use vs. standard treatment in patients with digital ulcers due to systemic sclerosis, a small new study finds. Patients who received the treatment also showed signs of more healing.
The study, published in Advances in Skin & Wound Care, is far from definitive since it’s retrospective and tracked only 45 patients. But the findings add to other research suggesting dermatologic benefits from the topical use of CBD, an ingredient in cannabis that’s widely available and doesn’t cause people to become high or become addicted.
“This is a good first step in trying to address scleroderma digital ulcer pain and healing,” University of Colorado rheumatologist Melissa Griffith, MD, said in an interview. “Digital ulcers cause great impact on quality of life, daily activities of living, and pain, so we are always looking for new, effective tools.”
According to Dr. Griffith, digital ulcers occur in scleroderma due to Raynaud’s phenomenon with reversible vasospasm. “Unlike patients with primary Raynaud’s phenomenon, patients will develop ischemia of digits, leading to digital ulcers due to the vasculopathy or vascular remodeling that occurs in scleroderma,” she said.
Current treatments include removal of causative drugs/toxins and warmth, rest, and pain control, although “no trials exist to compare the scleroderma digital ulcer or digital ischemia treatments to each other,” Dr. Griffith said.
Therapy for vasospasm begins with calcium channel blockers such as amlodipine and nifedipine, she said, followed by phosphodiesterase type 5 inhibitors such as sildenafil or endothelin receptor antagonist medications such as bosentan. “If these fail, we use an IV option – epoprostenol. Other options are sympathectomy surgery, Botox, digital nerve blocks, biofeedback, and SSRIs,” she said. “These treatments work fairly well in most patients, but there are patients who break through these therapies and have ongoing digital ischemia, leading to digital ulcers, pain, infections, acro-osteolysis, and auto-amputation. There is definitely room to improve on our current treatment paradigm.”
For the new study, researchers in Italy led by Amelia Spinella, MD, PhD, of University Hospital of Modena, retrospectively tracked 45 patients with systemic sclerosis and at least one digital ulcer (40 women; average age, 53 years) who were treated in 2019. All patients’ ulcers were resistant to opioid therapy at the maximum tolerated dose, and all had undergone periodic iloprost infusion every 30-40 days. Based on each patient’s clinical situation, they had received calcium-channel blockers, phosphodiesterase type 5 inhibitors (sildenafil), and/or endothelin receptor antagonists (bosentan or macitentan). The researchers noted that all patients underwent surgical debridement regularly following wound bed preparation procedures and received advanced dressings (alginate, hydrocolloid, hydrofiber, hydrogel, and polyurethane foam or film). Of the 45 patients, 25 treated their wounds daily over the course of a month by administering four drops of a preparation of 10% CBD oil in acidic form and 90% hemp oil over the wound bed and perilesional skin and then covering it with a nonadhesive cloth.
“Basal wound-related pain NRS [numeric rating scale] scores decreased from 8.4 (standard deviation [SD], 0.8) at the baseline (T0) to 6.0 (SD, 0.82) after 1 month of CBD treatment (T1; P < .0001),” the researchers reported. “Across the same time period, volitional incident pain NRS scores decreased from 9.32 (SD, 0.75; T0) to 6.8 (SD, 1.12; T1; P < .0001). In addition, mean total hours of sleep per night increased from 2.56 (SD, 1.28) to 5.67 (SD, 0.85) hours (P < .0001).” Twelve of the 25 needed additional painkiller therapy.
Complete digital ulcer healing occurred by the end of the study in 18 of 25 (72%) CBD-treated patients, compared with 6 of 20 (30%) control patients.
In contrast, the control group didn’t see any significant improvement in wound-related pain, volitional incident pain, or sleep. All needed additional painkiller therapy. Six developed ulcer infections and received antibiotics.
No significant adverse effects were reported, although 28% of those in the CBD oil group said they had mild effects such as itch and perilesional erythema.
The authors of the new study called for larger, randomized controlled, multicenter trials to confirm the benefit of CBD topical treatment.
In recent years, researchers have devoted more attention to topical CBD as a treatment for skin conditions. While limited, the evidence suggests they “may be effective for the treatment of various inflammatory skin disorders,” researchers wrote in a 2022 report. “Although promising, additional research is necessary to evaluate efficacy and to determine dosing, safety, and long-term treatment guidelines.”
Dr. Griffith, who did not take part in the new study but is familiar with its findings, said she was especially surprised by the hint that topical CBD improves healing in addition to relieving symptoms. “I thought only pain would be affected. This is a great outcome if it can be replicated.”
As for future research, she said “there are difficulties with reproducing this at a big scale in the U.S. given CBD commercial variability. The big issue is the standardization of CBD extraction and production. It is really hard for us as physicians to know what patients are getting. Some online CBD orders contain THC [the major psychoactive ingredient of cannabis] > 0.3% or no CBD at all.”
Still, she said, “physicians and patients may consider this when standard therapies are not working or causing too many adverse effects,” especially since “the downsides here seem fairly minimal – at worst itchiness and redness that did not prevent patients from continuing in the study.”
No details about study funding were provided. The authors and Dr. Griffith report no disclosures.
Topical cannabidiol (CBD) oil appeared to lower pain scores and reduce painkiller use vs. standard treatment in patients with digital ulcers due to systemic sclerosis, a small new study finds. Patients who received the treatment also showed signs of more healing.
The study, published in Advances in Skin & Wound Care, is far from definitive since it’s retrospective and tracked only 45 patients. But the findings add to other research suggesting dermatologic benefits from the topical use of CBD, an ingredient in cannabis that’s widely available and doesn’t cause people to become high or become addicted.
“This is a good first step in trying to address scleroderma digital ulcer pain and healing,” University of Colorado rheumatologist Melissa Griffith, MD, said in an interview. “Digital ulcers cause great impact on quality of life, daily activities of living, and pain, so we are always looking for new, effective tools.”
According to Dr. Griffith, digital ulcers occur in scleroderma due to Raynaud’s phenomenon with reversible vasospasm. “Unlike patients with primary Raynaud’s phenomenon, patients will develop ischemia of digits, leading to digital ulcers due to the vasculopathy or vascular remodeling that occurs in scleroderma,” she said.
Current treatments include removal of causative drugs/toxins and warmth, rest, and pain control, although “no trials exist to compare the scleroderma digital ulcer or digital ischemia treatments to each other,” Dr. Griffith said.
Therapy for vasospasm begins with calcium channel blockers such as amlodipine and nifedipine, she said, followed by phosphodiesterase type 5 inhibitors such as sildenafil or endothelin receptor antagonist medications such as bosentan. “If these fail, we use an IV option – epoprostenol. Other options are sympathectomy surgery, Botox, digital nerve blocks, biofeedback, and SSRIs,” she said. “These treatments work fairly well in most patients, but there are patients who break through these therapies and have ongoing digital ischemia, leading to digital ulcers, pain, infections, acro-osteolysis, and auto-amputation. There is definitely room to improve on our current treatment paradigm.”
For the new study, researchers in Italy led by Amelia Spinella, MD, PhD, of University Hospital of Modena, retrospectively tracked 45 patients with systemic sclerosis and at least one digital ulcer (40 women; average age, 53 years) who were treated in 2019. All patients’ ulcers were resistant to opioid therapy at the maximum tolerated dose, and all had undergone periodic iloprost infusion every 30-40 days. Based on each patient’s clinical situation, they had received calcium-channel blockers, phosphodiesterase type 5 inhibitors (sildenafil), and/or endothelin receptor antagonists (bosentan or macitentan). The researchers noted that all patients underwent surgical debridement regularly following wound bed preparation procedures and received advanced dressings (alginate, hydrocolloid, hydrofiber, hydrogel, and polyurethane foam or film). Of the 45 patients, 25 treated their wounds daily over the course of a month by administering four drops of a preparation of 10% CBD oil in acidic form and 90% hemp oil over the wound bed and perilesional skin and then covering it with a nonadhesive cloth.
“Basal wound-related pain NRS [numeric rating scale] scores decreased from 8.4 (standard deviation [SD], 0.8) at the baseline (T0) to 6.0 (SD, 0.82) after 1 month of CBD treatment (T1; P < .0001),” the researchers reported. “Across the same time period, volitional incident pain NRS scores decreased from 9.32 (SD, 0.75; T0) to 6.8 (SD, 1.12; T1; P < .0001). In addition, mean total hours of sleep per night increased from 2.56 (SD, 1.28) to 5.67 (SD, 0.85) hours (P < .0001).” Twelve of the 25 needed additional painkiller therapy.
Complete digital ulcer healing occurred by the end of the study in 18 of 25 (72%) CBD-treated patients, compared with 6 of 20 (30%) control patients.
In contrast, the control group didn’t see any significant improvement in wound-related pain, volitional incident pain, or sleep. All needed additional painkiller therapy. Six developed ulcer infections and received antibiotics.
No significant adverse effects were reported, although 28% of those in the CBD oil group said they had mild effects such as itch and perilesional erythema.
The authors of the new study called for larger, randomized controlled, multicenter trials to confirm the benefit of CBD topical treatment.
In recent years, researchers have devoted more attention to topical CBD as a treatment for skin conditions. While limited, the evidence suggests they “may be effective for the treatment of various inflammatory skin disorders,” researchers wrote in a 2022 report. “Although promising, additional research is necessary to evaluate efficacy and to determine dosing, safety, and long-term treatment guidelines.”
Dr. Griffith, who did not take part in the new study but is familiar with its findings, said she was especially surprised by the hint that topical CBD improves healing in addition to relieving symptoms. “I thought only pain would be affected. This is a great outcome if it can be replicated.”
As for future research, she said “there are difficulties with reproducing this at a big scale in the U.S. given CBD commercial variability. The big issue is the standardization of CBD extraction and production. It is really hard for us as physicians to know what patients are getting. Some online CBD orders contain THC [the major psychoactive ingredient of cannabis] > 0.3% or no CBD at all.”
Still, she said, “physicians and patients may consider this when standard therapies are not working or causing too many adverse effects,” especially since “the downsides here seem fairly minimal – at worst itchiness and redness that did not prevent patients from continuing in the study.”
No details about study funding were provided. The authors and Dr. Griffith report no disclosures.
Topical cannabidiol (CBD) oil appeared to lower pain scores and reduce painkiller use vs. standard treatment in patients with digital ulcers due to systemic sclerosis, a small new study finds. Patients who received the treatment also showed signs of more healing.
The study, published in Advances in Skin & Wound Care, is far from definitive since it’s retrospective and tracked only 45 patients. But the findings add to other research suggesting dermatologic benefits from the topical use of CBD, an ingredient in cannabis that’s widely available and doesn’t cause people to become high or become addicted.
“This is a good first step in trying to address scleroderma digital ulcer pain and healing,” University of Colorado rheumatologist Melissa Griffith, MD, said in an interview. “Digital ulcers cause great impact on quality of life, daily activities of living, and pain, so we are always looking for new, effective tools.”
According to Dr. Griffith, digital ulcers occur in scleroderma due to Raynaud’s phenomenon with reversible vasospasm. “Unlike patients with primary Raynaud’s phenomenon, patients will develop ischemia of digits, leading to digital ulcers due to the vasculopathy or vascular remodeling that occurs in scleroderma,” she said.
Current treatments include removal of causative drugs/toxins and warmth, rest, and pain control, although “no trials exist to compare the scleroderma digital ulcer or digital ischemia treatments to each other,” Dr. Griffith said.
Therapy for vasospasm begins with calcium channel blockers such as amlodipine and nifedipine, she said, followed by phosphodiesterase type 5 inhibitors such as sildenafil or endothelin receptor antagonist medications such as bosentan. “If these fail, we use an IV option – epoprostenol. Other options are sympathectomy surgery, Botox, digital nerve blocks, biofeedback, and SSRIs,” she said. “These treatments work fairly well in most patients, but there are patients who break through these therapies and have ongoing digital ischemia, leading to digital ulcers, pain, infections, acro-osteolysis, and auto-amputation. There is definitely room to improve on our current treatment paradigm.”
For the new study, researchers in Italy led by Amelia Spinella, MD, PhD, of University Hospital of Modena, retrospectively tracked 45 patients with systemic sclerosis and at least one digital ulcer (40 women; average age, 53 years) who were treated in 2019. All patients’ ulcers were resistant to opioid therapy at the maximum tolerated dose, and all had undergone periodic iloprost infusion every 30-40 days. Based on each patient’s clinical situation, they had received calcium-channel blockers, phosphodiesterase type 5 inhibitors (sildenafil), and/or endothelin receptor antagonists (bosentan or macitentan). The researchers noted that all patients underwent surgical debridement regularly following wound bed preparation procedures and received advanced dressings (alginate, hydrocolloid, hydrofiber, hydrogel, and polyurethane foam or film). Of the 45 patients, 25 treated their wounds daily over the course of a month by administering four drops of a preparation of 10% CBD oil in acidic form and 90% hemp oil over the wound bed and perilesional skin and then covering it with a nonadhesive cloth.
“Basal wound-related pain NRS [numeric rating scale] scores decreased from 8.4 (standard deviation [SD], 0.8) at the baseline (T0) to 6.0 (SD, 0.82) after 1 month of CBD treatment (T1; P < .0001),” the researchers reported. “Across the same time period, volitional incident pain NRS scores decreased from 9.32 (SD, 0.75; T0) to 6.8 (SD, 1.12; T1; P < .0001). In addition, mean total hours of sleep per night increased from 2.56 (SD, 1.28) to 5.67 (SD, 0.85) hours (P < .0001).” Twelve of the 25 needed additional painkiller therapy.
Complete digital ulcer healing occurred by the end of the study in 18 of 25 (72%) CBD-treated patients, compared with 6 of 20 (30%) control patients.
In contrast, the control group didn’t see any significant improvement in wound-related pain, volitional incident pain, or sleep. All needed additional painkiller therapy. Six developed ulcer infections and received antibiotics.
No significant adverse effects were reported, although 28% of those in the CBD oil group said they had mild effects such as itch and perilesional erythema.
The authors of the new study called for larger, randomized controlled, multicenter trials to confirm the benefit of CBD topical treatment.
In recent years, researchers have devoted more attention to topical CBD as a treatment for skin conditions. While limited, the evidence suggests they “may be effective for the treatment of various inflammatory skin disorders,” researchers wrote in a 2022 report. “Although promising, additional research is necessary to evaluate efficacy and to determine dosing, safety, and long-term treatment guidelines.”
Dr. Griffith, who did not take part in the new study but is familiar with its findings, said she was especially surprised by the hint that topical CBD improves healing in addition to relieving symptoms. “I thought only pain would be affected. This is a great outcome if it can be replicated.”
As for future research, she said “there are difficulties with reproducing this at a big scale in the U.S. given CBD commercial variability. The big issue is the standardization of CBD extraction and production. It is really hard for us as physicians to know what patients are getting. Some online CBD orders contain THC [the major psychoactive ingredient of cannabis] > 0.3% or no CBD at all.”
Still, she said, “physicians and patients may consider this when standard therapies are not working or causing too many adverse effects,” especially since “the downsides here seem fairly minimal – at worst itchiness and redness that did not prevent patients from continuing in the study.”
No details about study funding were provided. The authors and Dr. Griffith report no disclosures.
FROM ADVANCED IN SKIN & WOUND CARE
VEXAS syndrome: More common, variable, and severe than expected
A recently discovered inflammatory disease known as VEXAS syndrome is more common, variable, and dangerous than previously understood, according to results of a retrospective observational study of a large health care system database. The findings, published in JAMA, found that it struck 1 in 4,269 men over the age of 50 in a largely White population and caused a wide variety of symptoms.
“The disease is quite severe,” study lead author David Beck, MD, PhD, of the department of medicine at NYU Langone Health, said in an interview. Patients with the condition “have a variety of clinical symptoms affecting different parts of the body and are being managed by different medical specialties.”
Dr. Beck and colleagues first described VEXAS (vacuoles, E1-ubiquitin-activating enzyme, X-linked, autoinflammatory, somatic) syndrome in 2020. They linked it to mutations in the UBA1 (ubiquitin-like modifier activating enzyme 1) gene. The enzyme initiates a process that identifies misfolded proteins as targets for degradation.
“VEXAS syndrome is characterized by anemia and inflammation in the skin, lungs, cartilage, and joints,” Dr. Beck said. “These symptoms are frequently mistaken for other rheumatic or hematologic diseases. However, this syndrome has a different cause, is treated differently, requires additional monitoring, and can be far more severe.”
According to him, hundreds of people have been diagnosed with the disease in the short time since it was defined. The disease is believed to be fatal in some cases. A previous report found that the median survival was 9 years among patients with a certain variant; that was significantly less than patients with two other variants.
For the new study, researchers searched for UBA1 variants in genetic data from 163,096 subjects (mean age, 52.8 years; 94% White, 61% women) who took part in the Geisinger MyCode Community Health Initiative. The 1996-2022 data comes from patients at 10 Pennsylvania hospitals.
Eleven people (9 males, 2 females) had likely UBA1 variants, and all had anemia. The cases accounted for 1 in 13,591 unrelated people (95% confidence interval, 1:7,775-1:23,758), 1 in 4,269 men older than 50 years (95% CI, 1:2,319-1:7,859), and 1 in 26,238 women older than 50 years (95% CI, 1:7,196-1:147,669).
Other common findings included macrocytosis (91%), skin problems (73%), and pulmonary disease (91%). Ten patients (91%) required transfusions.
Five of the 11 subjects didn’t meet the previously defined criteria for VEXAS syndrome. None had been diagnosed with the condition, which is not surprising considering that it hadn’t been discovered and described until recently.
Just over half of the patients – 55% – had a clinical diagnosis that was previously linked to VEXAS syndrome. “This means that slightly less than half of the patients with VEXAS syndrome had no clear associated clinical diagnosis,” Dr. Beck said. “The lack of associated clinical diagnoses may be due to the variety of nonspecific clinical characteristics that span different subspecialities in VEXAS syndrome. VEXAS syndrome represents an example of a multisystem disease where patients and their symptoms may get lost in the shuffle.”
In the future, “professionals should look out for patients with unexplained inflammation – and some combination of hematologic, rheumatologic, pulmonary, and dermatologic clinical manifestations – that either don’t carry a clinical diagnosis or don’t respond to first-line therapies,” Dr. Beck said. “These patients will also frequently be anemic, have low platelet counts, elevated markers of inflammation in the blood, and be dependent on corticosteroids.”
Diagnosis can be made via genetic testing, but the study authors note that it “is not routinely offered on standard workup for myeloid neoplasms or immune dysregulation diagnostic panels.”
As for treatment, Dr. Beck said the disease “can be partially controlled by multiple different anticytokine therapies or biologics. However, in most cases, patients still need additional steroids and/or disease-modifying antirheumatic agents [DMARDs]. In addition, bone marrow transplantation has shown signs of being a highly effective therapy.”
The study authors say more research is needed to understand the disease’s prevalence in more diverse populations.
In an interview, Matthew J. Koster, MD, a rheumatologist at Mayo Clinic in Rochester, Minn., who’s studied the disease but didn’t take part in this research project, said the findings are valid and “highly important.
“The findings of this study highlight what many academic and quaternary referral centers were wondering: Is VEXAS really more common than we think, with patients hiding in plain sight? The answer is yes,” he said. “Currently, there are less than 400 cases reported in the literature of VEXAS, but large centers are diagnosing this condition with some frequency. For example, at Mayo Clinic in Rochester, we diagnose on average one new patient with VEXAS every 7-14 days and have diagnosed 60 in the past 18 months. A national collaborative group in France has diagnosed approximately 250 patients over that same time frame when pooling patients nationwide.”
The prevalence is high enough, he said, that “clinicians should consider that some of the patients with diseases that are not responding to treatment may in fact have VEXAS rather than ‘refractory’ relapsing polychondritis or ‘recalcitrant’ rheumatoid arthritis, etc.”
The National Institute of Health funded the study. Dr. Beck, the other authors, and Dr. Koster report no disclosures.
A recently discovered inflammatory disease known as VEXAS syndrome is more common, variable, and dangerous than previously understood, according to results of a retrospective observational study of a large health care system database. The findings, published in JAMA, found that it struck 1 in 4,269 men over the age of 50 in a largely White population and caused a wide variety of symptoms.
“The disease is quite severe,” study lead author David Beck, MD, PhD, of the department of medicine at NYU Langone Health, said in an interview. Patients with the condition “have a variety of clinical symptoms affecting different parts of the body and are being managed by different medical specialties.”
Dr. Beck and colleagues first described VEXAS (vacuoles, E1-ubiquitin-activating enzyme, X-linked, autoinflammatory, somatic) syndrome in 2020. They linked it to mutations in the UBA1 (ubiquitin-like modifier activating enzyme 1) gene. The enzyme initiates a process that identifies misfolded proteins as targets for degradation.
“VEXAS syndrome is characterized by anemia and inflammation in the skin, lungs, cartilage, and joints,” Dr. Beck said. “These symptoms are frequently mistaken for other rheumatic or hematologic diseases. However, this syndrome has a different cause, is treated differently, requires additional monitoring, and can be far more severe.”
According to him, hundreds of people have been diagnosed with the disease in the short time since it was defined. The disease is believed to be fatal in some cases. A previous report found that the median survival was 9 years among patients with a certain variant; that was significantly less than patients with two other variants.
For the new study, researchers searched for UBA1 variants in genetic data from 163,096 subjects (mean age, 52.8 years; 94% White, 61% women) who took part in the Geisinger MyCode Community Health Initiative. The 1996-2022 data comes from patients at 10 Pennsylvania hospitals.
Eleven people (9 males, 2 females) had likely UBA1 variants, and all had anemia. The cases accounted for 1 in 13,591 unrelated people (95% confidence interval, 1:7,775-1:23,758), 1 in 4,269 men older than 50 years (95% CI, 1:2,319-1:7,859), and 1 in 26,238 women older than 50 years (95% CI, 1:7,196-1:147,669).
Other common findings included macrocytosis (91%), skin problems (73%), and pulmonary disease (91%). Ten patients (91%) required transfusions.
Five of the 11 subjects didn’t meet the previously defined criteria for VEXAS syndrome. None had been diagnosed with the condition, which is not surprising considering that it hadn’t been discovered and described until recently.
Just over half of the patients – 55% – had a clinical diagnosis that was previously linked to VEXAS syndrome. “This means that slightly less than half of the patients with VEXAS syndrome had no clear associated clinical diagnosis,” Dr. Beck said. “The lack of associated clinical diagnoses may be due to the variety of nonspecific clinical characteristics that span different subspecialities in VEXAS syndrome. VEXAS syndrome represents an example of a multisystem disease where patients and their symptoms may get lost in the shuffle.”
In the future, “professionals should look out for patients with unexplained inflammation – and some combination of hematologic, rheumatologic, pulmonary, and dermatologic clinical manifestations – that either don’t carry a clinical diagnosis or don’t respond to first-line therapies,” Dr. Beck said. “These patients will also frequently be anemic, have low platelet counts, elevated markers of inflammation in the blood, and be dependent on corticosteroids.”
Diagnosis can be made via genetic testing, but the study authors note that it “is not routinely offered on standard workup for myeloid neoplasms or immune dysregulation diagnostic panels.”
As for treatment, Dr. Beck said the disease “can be partially controlled by multiple different anticytokine therapies or biologics. However, in most cases, patients still need additional steroids and/or disease-modifying antirheumatic agents [DMARDs]. In addition, bone marrow transplantation has shown signs of being a highly effective therapy.”
The study authors say more research is needed to understand the disease’s prevalence in more diverse populations.
In an interview, Matthew J. Koster, MD, a rheumatologist at Mayo Clinic in Rochester, Minn., who’s studied the disease but didn’t take part in this research project, said the findings are valid and “highly important.
“The findings of this study highlight what many academic and quaternary referral centers were wondering: Is VEXAS really more common than we think, with patients hiding in plain sight? The answer is yes,” he said. “Currently, there are less than 400 cases reported in the literature of VEXAS, but large centers are diagnosing this condition with some frequency. For example, at Mayo Clinic in Rochester, we diagnose on average one new patient with VEXAS every 7-14 days and have diagnosed 60 in the past 18 months. A national collaborative group in France has diagnosed approximately 250 patients over that same time frame when pooling patients nationwide.”
The prevalence is high enough, he said, that “clinicians should consider that some of the patients with diseases that are not responding to treatment may in fact have VEXAS rather than ‘refractory’ relapsing polychondritis or ‘recalcitrant’ rheumatoid arthritis, etc.”
The National Institute of Health funded the study. Dr. Beck, the other authors, and Dr. Koster report no disclosures.
A recently discovered inflammatory disease known as VEXAS syndrome is more common, variable, and dangerous than previously understood, according to results of a retrospective observational study of a large health care system database. The findings, published in JAMA, found that it struck 1 in 4,269 men over the age of 50 in a largely White population and caused a wide variety of symptoms.
“The disease is quite severe,” study lead author David Beck, MD, PhD, of the department of medicine at NYU Langone Health, said in an interview. Patients with the condition “have a variety of clinical symptoms affecting different parts of the body and are being managed by different medical specialties.”
Dr. Beck and colleagues first described VEXAS (vacuoles, E1-ubiquitin-activating enzyme, X-linked, autoinflammatory, somatic) syndrome in 2020. They linked it to mutations in the UBA1 (ubiquitin-like modifier activating enzyme 1) gene. The enzyme initiates a process that identifies misfolded proteins as targets for degradation.
“VEXAS syndrome is characterized by anemia and inflammation in the skin, lungs, cartilage, and joints,” Dr. Beck said. “These symptoms are frequently mistaken for other rheumatic or hematologic diseases. However, this syndrome has a different cause, is treated differently, requires additional monitoring, and can be far more severe.”
According to him, hundreds of people have been diagnosed with the disease in the short time since it was defined. The disease is believed to be fatal in some cases. A previous report found that the median survival was 9 years among patients with a certain variant; that was significantly less than patients with two other variants.
For the new study, researchers searched for UBA1 variants in genetic data from 163,096 subjects (mean age, 52.8 years; 94% White, 61% women) who took part in the Geisinger MyCode Community Health Initiative. The 1996-2022 data comes from patients at 10 Pennsylvania hospitals.
Eleven people (9 males, 2 females) had likely UBA1 variants, and all had anemia. The cases accounted for 1 in 13,591 unrelated people (95% confidence interval, 1:7,775-1:23,758), 1 in 4,269 men older than 50 years (95% CI, 1:2,319-1:7,859), and 1 in 26,238 women older than 50 years (95% CI, 1:7,196-1:147,669).
Other common findings included macrocytosis (91%), skin problems (73%), and pulmonary disease (91%). Ten patients (91%) required transfusions.
Five of the 11 subjects didn’t meet the previously defined criteria for VEXAS syndrome. None had been diagnosed with the condition, which is not surprising considering that it hadn’t been discovered and described until recently.
Just over half of the patients – 55% – had a clinical diagnosis that was previously linked to VEXAS syndrome. “This means that slightly less than half of the patients with VEXAS syndrome had no clear associated clinical diagnosis,” Dr. Beck said. “The lack of associated clinical diagnoses may be due to the variety of nonspecific clinical characteristics that span different subspecialities in VEXAS syndrome. VEXAS syndrome represents an example of a multisystem disease where patients and their symptoms may get lost in the shuffle.”
In the future, “professionals should look out for patients with unexplained inflammation – and some combination of hematologic, rheumatologic, pulmonary, and dermatologic clinical manifestations – that either don’t carry a clinical diagnosis or don’t respond to first-line therapies,” Dr. Beck said. “These patients will also frequently be anemic, have low platelet counts, elevated markers of inflammation in the blood, and be dependent on corticosteroids.”
Diagnosis can be made via genetic testing, but the study authors note that it “is not routinely offered on standard workup for myeloid neoplasms or immune dysregulation diagnostic panels.”
As for treatment, Dr. Beck said the disease “can be partially controlled by multiple different anticytokine therapies or biologics. However, in most cases, patients still need additional steroids and/or disease-modifying antirheumatic agents [DMARDs]. In addition, bone marrow transplantation has shown signs of being a highly effective therapy.”
The study authors say more research is needed to understand the disease’s prevalence in more diverse populations.
In an interview, Matthew J. Koster, MD, a rheumatologist at Mayo Clinic in Rochester, Minn., who’s studied the disease but didn’t take part in this research project, said the findings are valid and “highly important.
“The findings of this study highlight what many academic and quaternary referral centers were wondering: Is VEXAS really more common than we think, with patients hiding in plain sight? The answer is yes,” he said. “Currently, there are less than 400 cases reported in the literature of VEXAS, but large centers are diagnosing this condition with some frequency. For example, at Mayo Clinic in Rochester, we diagnose on average one new patient with VEXAS every 7-14 days and have diagnosed 60 in the past 18 months. A national collaborative group in France has diagnosed approximately 250 patients over that same time frame when pooling patients nationwide.”
The prevalence is high enough, he said, that “clinicians should consider that some of the patients with diseases that are not responding to treatment may in fact have VEXAS rather than ‘refractory’ relapsing polychondritis or ‘recalcitrant’ rheumatoid arthritis, etc.”
The National Institute of Health funded the study. Dr. Beck, the other authors, and Dr. Koster report no disclosures.
FROM JAMA
Mpox: Dermatology registry data pinpoints unique signs
that frequently appeared before systemic illness and a much lower overall numbers of lesions.
“Just these two findings alone show how important it is to remain clinically vigilant as dermatologists,” Esther Freeman, MD, PhD, director of global health dermatology at Massachusetts General Hospital, Boston, said in an interview. She is the corresponding author of the study, which analyzed 101 mpox cases from 13 countries and was published online on in the Journal of the American Academy of Dermatology.
“Mpox appeared to manifest differently than in previous outbreaks with morphologic and clinical evolutions much different than previously reported in endemic and prior outbreaks,” added Dr. Freeman. “Dermatologists should continue to keep mpox on the differential as it continues to circulate at low levels in the population and is a mimicker of many other common skin diseases.”
According to the Centers for Disease Control and Prevention, as of Jan. 20, 2023, there have been 30,061 cases of mpox in the United States during the outbreak that began in 2022; 23 people died. Worldwide, the number of cases neared 85,000.
Most of the affected cases were among gay, bisexual, and other men who have sex with men. A vaccination effort began last summer, and the number of cases soon plummeted. The national daily case count in January has been in the single digits.
For the new report, dermatologists tracked cases via the American Academy of Dermatology/International League of Dermatologic Societies (AAD/ILDS) Dermatology COVID-19, Monkeypox (mpox), and Emerging Infections Registry. The new report includes data about cases entered from Aug. 4 to Nov. 13. Of these cases, 97% were male, median age was 35 years, 62% were White, 20% were Hispanic, and 11% were Black.
Just over half (54%) of patients reported skin lesions as the first sign of disease, while others had signs such as fever (16%) and malaise (9%). “This is a sharp contrast to endemic or prior outbreaks in which a ‘flu-like’ prodrome preceded lesions,” Dr. Freeman said. “Dermatologists should be aware that patients may come in with mpox skin lesions as their only initial symptoms.”
In contrast to past outbreaks where patients may have had dozens or hundreds of lesions, 20% had only 1 lesion, while 52% had 2-5 lesions, and 20% had 6-20 lesions. “There may be only a few lesions, so index of suspicion needs to be high,” Dr. Freeman said.
According to the study, “the most common skin lesion morphologies and secondary characteristics reported included papules, vesicles/blisters, pustules, erosions/ulcers and crust/scabs.” Dr. Freeman cautioned that “lesions may not go through the ‘typical’ progression from papule to pustule. The initial lesion could even be an ulceration or a crust. For dermatologists, this means you need to have a high index of suspicion, especially if you see a new onset lesion in the groin or perianal area, though they can also start elsewhere.”
She added that “the lesion you see on exam could be a classic pustule/pseudopustule, but it might not be – it could be a small perianal erosion or ulceration. If you have any concern it could be mpox, it’s a good idea to test by PCR.”
Morbilliform rash, scarring reported
The study also highlighted 10 cases of morbilliform rash. “A morbilliform exanthem is pretty nonspecific, and usually cases of mpox have more specific features,” dermatologist and study coauthor Misha Rosenbach, MD, of the University of Pennsylvania, Philadelphia, said in an interview.
“Given the current low rates of mpox, I do not think most dermatologists need to worry about mpox when evaluating morbilliform exanthems. However, in high-risk patients or patients with other morphologies, it is worth noting that there’s a chance that this may be related.”
Emory University dermatologist Howa Yeung, MD, MSc, who wasn’t involved with the study, said in an interview that morbilliform rashes in the mouth/tongue area, mostly on days 1-5, should be considered a possible sign of mpox. “While I didn’t typically think of monkeypox virus as a cause of viral exanthems, I will now add it to my differential diagnoses.”
In the report, 13% of patients had scarring, “an outcome underemphasized in the current literature” that could have long-term emotional and mental effects, the authors noted. “Some patients, particularly immunosuppressed patients, have had very large and/or ulceronecrotic lesions,” Dr. Rosenbach said. “Their scarring can be quite significant. There is, to date, very little guidance for clinicians or patients on how to mitigate this risk and, if scarring is developing, how best to manage it.”
As for lessons from the findings, Dr. Yeung said, “dermatologists need to be aware that patients with mpox can have multiple morphologies at the same time and lesions can skip stages.” And, he pointed out, it’s clear that wound care is important to prevent scarring.
The AAD has a resource page on skin care in patients with mpox that includes information about preventing scarring. Examples of mpox rashes are available on the CDC website.
The study was supported by a grant from the International League of Dermatologic Societies and in-kind support from the American Academy of Dermatology. Dr. Freeman is a coauthor for UpToDate. Dr. Freeman and Dr. Rosenbach are members of the AAD Ad Hoc Task Force to Create Monkeypox Content. Study authors reported no other disclosures, and Dr. Yeung has no disclosures.
that frequently appeared before systemic illness and a much lower overall numbers of lesions.
“Just these two findings alone show how important it is to remain clinically vigilant as dermatologists,” Esther Freeman, MD, PhD, director of global health dermatology at Massachusetts General Hospital, Boston, said in an interview. She is the corresponding author of the study, which analyzed 101 mpox cases from 13 countries and was published online on in the Journal of the American Academy of Dermatology.
“Mpox appeared to manifest differently than in previous outbreaks with morphologic and clinical evolutions much different than previously reported in endemic and prior outbreaks,” added Dr. Freeman. “Dermatologists should continue to keep mpox on the differential as it continues to circulate at low levels in the population and is a mimicker of many other common skin diseases.”
According to the Centers for Disease Control and Prevention, as of Jan. 20, 2023, there have been 30,061 cases of mpox in the United States during the outbreak that began in 2022; 23 people died. Worldwide, the number of cases neared 85,000.
Most of the affected cases were among gay, bisexual, and other men who have sex with men. A vaccination effort began last summer, and the number of cases soon plummeted. The national daily case count in January has been in the single digits.
For the new report, dermatologists tracked cases via the American Academy of Dermatology/International League of Dermatologic Societies (AAD/ILDS) Dermatology COVID-19, Monkeypox (mpox), and Emerging Infections Registry. The new report includes data about cases entered from Aug. 4 to Nov. 13. Of these cases, 97% were male, median age was 35 years, 62% were White, 20% were Hispanic, and 11% were Black.
Just over half (54%) of patients reported skin lesions as the first sign of disease, while others had signs such as fever (16%) and malaise (9%). “This is a sharp contrast to endemic or prior outbreaks in which a ‘flu-like’ prodrome preceded lesions,” Dr. Freeman said. “Dermatologists should be aware that patients may come in with mpox skin lesions as their only initial symptoms.”
In contrast to past outbreaks where patients may have had dozens or hundreds of lesions, 20% had only 1 lesion, while 52% had 2-5 lesions, and 20% had 6-20 lesions. “There may be only a few lesions, so index of suspicion needs to be high,” Dr. Freeman said.
According to the study, “the most common skin lesion morphologies and secondary characteristics reported included papules, vesicles/blisters, pustules, erosions/ulcers and crust/scabs.” Dr. Freeman cautioned that “lesions may not go through the ‘typical’ progression from papule to pustule. The initial lesion could even be an ulceration or a crust. For dermatologists, this means you need to have a high index of suspicion, especially if you see a new onset lesion in the groin or perianal area, though they can also start elsewhere.”
She added that “the lesion you see on exam could be a classic pustule/pseudopustule, but it might not be – it could be a small perianal erosion or ulceration. If you have any concern it could be mpox, it’s a good idea to test by PCR.”
Morbilliform rash, scarring reported
The study also highlighted 10 cases of morbilliform rash. “A morbilliform exanthem is pretty nonspecific, and usually cases of mpox have more specific features,” dermatologist and study coauthor Misha Rosenbach, MD, of the University of Pennsylvania, Philadelphia, said in an interview.
“Given the current low rates of mpox, I do not think most dermatologists need to worry about mpox when evaluating morbilliform exanthems. However, in high-risk patients or patients with other morphologies, it is worth noting that there’s a chance that this may be related.”
Emory University dermatologist Howa Yeung, MD, MSc, who wasn’t involved with the study, said in an interview that morbilliform rashes in the mouth/tongue area, mostly on days 1-5, should be considered a possible sign of mpox. “While I didn’t typically think of monkeypox virus as a cause of viral exanthems, I will now add it to my differential diagnoses.”
In the report, 13% of patients had scarring, “an outcome underemphasized in the current literature” that could have long-term emotional and mental effects, the authors noted. “Some patients, particularly immunosuppressed patients, have had very large and/or ulceronecrotic lesions,” Dr. Rosenbach said. “Their scarring can be quite significant. There is, to date, very little guidance for clinicians or patients on how to mitigate this risk and, if scarring is developing, how best to manage it.”
As for lessons from the findings, Dr. Yeung said, “dermatologists need to be aware that patients with mpox can have multiple morphologies at the same time and lesions can skip stages.” And, he pointed out, it’s clear that wound care is important to prevent scarring.
The AAD has a resource page on skin care in patients with mpox that includes information about preventing scarring. Examples of mpox rashes are available on the CDC website.
The study was supported by a grant from the International League of Dermatologic Societies and in-kind support from the American Academy of Dermatology. Dr. Freeman is a coauthor for UpToDate. Dr. Freeman and Dr. Rosenbach are members of the AAD Ad Hoc Task Force to Create Monkeypox Content. Study authors reported no other disclosures, and Dr. Yeung has no disclosures.
that frequently appeared before systemic illness and a much lower overall numbers of lesions.
“Just these two findings alone show how important it is to remain clinically vigilant as dermatologists,” Esther Freeman, MD, PhD, director of global health dermatology at Massachusetts General Hospital, Boston, said in an interview. She is the corresponding author of the study, which analyzed 101 mpox cases from 13 countries and was published online on in the Journal of the American Academy of Dermatology.
“Mpox appeared to manifest differently than in previous outbreaks with morphologic and clinical evolutions much different than previously reported in endemic and prior outbreaks,” added Dr. Freeman. “Dermatologists should continue to keep mpox on the differential as it continues to circulate at low levels in the population and is a mimicker of many other common skin diseases.”
According to the Centers for Disease Control and Prevention, as of Jan. 20, 2023, there have been 30,061 cases of mpox in the United States during the outbreak that began in 2022; 23 people died. Worldwide, the number of cases neared 85,000.
Most of the affected cases were among gay, bisexual, and other men who have sex with men. A vaccination effort began last summer, and the number of cases soon plummeted. The national daily case count in January has been in the single digits.
For the new report, dermatologists tracked cases via the American Academy of Dermatology/International League of Dermatologic Societies (AAD/ILDS) Dermatology COVID-19, Monkeypox (mpox), and Emerging Infections Registry. The new report includes data about cases entered from Aug. 4 to Nov. 13. Of these cases, 97% were male, median age was 35 years, 62% were White, 20% were Hispanic, and 11% were Black.
Just over half (54%) of patients reported skin lesions as the first sign of disease, while others had signs such as fever (16%) and malaise (9%). “This is a sharp contrast to endemic or prior outbreaks in which a ‘flu-like’ prodrome preceded lesions,” Dr. Freeman said. “Dermatologists should be aware that patients may come in with mpox skin lesions as their only initial symptoms.”
In contrast to past outbreaks where patients may have had dozens or hundreds of lesions, 20% had only 1 lesion, while 52% had 2-5 lesions, and 20% had 6-20 lesions. “There may be only a few lesions, so index of suspicion needs to be high,” Dr. Freeman said.
According to the study, “the most common skin lesion morphologies and secondary characteristics reported included papules, vesicles/blisters, pustules, erosions/ulcers and crust/scabs.” Dr. Freeman cautioned that “lesions may not go through the ‘typical’ progression from papule to pustule. The initial lesion could even be an ulceration or a crust. For dermatologists, this means you need to have a high index of suspicion, especially if you see a new onset lesion in the groin or perianal area, though they can also start elsewhere.”
She added that “the lesion you see on exam could be a classic pustule/pseudopustule, but it might not be – it could be a small perianal erosion or ulceration. If you have any concern it could be mpox, it’s a good idea to test by PCR.”
Morbilliform rash, scarring reported
The study also highlighted 10 cases of morbilliform rash. “A morbilliform exanthem is pretty nonspecific, and usually cases of mpox have more specific features,” dermatologist and study coauthor Misha Rosenbach, MD, of the University of Pennsylvania, Philadelphia, said in an interview.
“Given the current low rates of mpox, I do not think most dermatologists need to worry about mpox when evaluating morbilliform exanthems. However, in high-risk patients or patients with other morphologies, it is worth noting that there’s a chance that this may be related.”
Emory University dermatologist Howa Yeung, MD, MSc, who wasn’t involved with the study, said in an interview that morbilliform rashes in the mouth/tongue area, mostly on days 1-5, should be considered a possible sign of mpox. “While I didn’t typically think of monkeypox virus as a cause of viral exanthems, I will now add it to my differential diagnoses.”
In the report, 13% of patients had scarring, “an outcome underemphasized in the current literature” that could have long-term emotional and mental effects, the authors noted. “Some patients, particularly immunosuppressed patients, have had very large and/or ulceronecrotic lesions,” Dr. Rosenbach said. “Their scarring can be quite significant. There is, to date, very little guidance for clinicians or patients on how to mitigate this risk and, if scarring is developing, how best to manage it.”
As for lessons from the findings, Dr. Yeung said, “dermatologists need to be aware that patients with mpox can have multiple morphologies at the same time and lesions can skip stages.” And, he pointed out, it’s clear that wound care is important to prevent scarring.
The AAD has a resource page on skin care in patients with mpox that includes information about preventing scarring. Examples of mpox rashes are available on the CDC website.
The study was supported by a grant from the International League of Dermatologic Societies and in-kind support from the American Academy of Dermatology. Dr. Freeman is a coauthor for UpToDate. Dr. Freeman and Dr. Rosenbach are members of the AAD Ad Hoc Task Force to Create Monkeypox Content. Study authors reported no other disclosures, and Dr. Yeung has no disclosures.
FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
Off their pricey CML meds, many thrive
When imatinib (Gleevec) appeared on the market just over 2 decades ago, it revolutionized the treatment of chronic myelogenous leukemia (CML) and transformed it from a grim diagnosis into a largely treatable form of blood cancer. New generations of tyrosine kinase inhibitors (TKIs) have continued to expand options for patients, and many can look forward to normal lifespans.
But these medications cause side effects and can be expensive. Long-term data doesn’t exist for the newer therapies, so no one knows whether they can harm patients over time. None of this is particularly unusual for medications to treat chronic illness, but now there’s a twist:
“Our focus has changed because the results of treatment are so good,” hematologist-oncologist Ehab L. Atallah, MD, of the Medical College of Wisconsin, Milwaukee, said in an interview. “We’re trying to get people off their medication.”
Still, research estimates that only 20% of patients with CML will be eligible for treatment discontinuation and benefit from it in the long term. As a result, the wide majority of patients will need to be on drugs indefinitely.
Gleevec: A new age dawns
In the early 1990s, before the era of TKIs, the 5-year relative survival rate from CML was just 27%, and the 10-year rate was only 9.5%, according to a 2008 report. “If someone showed up with CML, their only option was to go to a bone marrow transplant. About half survived the transplant, and half of those had significant complications from it,” Dr. Atallah said. According to him, just about everyone who didn’t get transplantation would go on to die.
Then came Gleevec, which received Food and Drug Administration approval in 2001. It ushered in the era of “targeted” cancer treatment by specifically killing CML cells, instead of relying on traditional chemotherapy’s carpet-bombing approach.
“Gleevec and other TKIs have revolutionized how CML is treated, and patients are now living normal lives,” hematologist-oncologist Catherine Lai, MD, MPH, of the University of Pennsylvania, Philadelphia, said in an interview.
Alan Fahnestock, a 68-year-old retired telecommunications specialist in north-central Washington state, is one of the fortunate patients.
He was diagnosed with CML in 2004 after he underwent a thoracic CT scan in light of his tobacco use. “My GP found something odd in my lungs and referred me to a pulmonologist, who couldn’t figure it out either. He transmitted blood samples to my eventual hematologist/oncologist,” Mr. Fahnestock said in an interview. “It’s not clear to me that anybody ever figured out what the ‘oddity’ was. It has since apparently gone away. But the oncologist ran all the tests and came up with CML.”
Mr. Fahnestock hadn’t noticed any symptoms, although “this is, perhaps, because I tend not to pay a lot of attention to such things, having abused my body fairly severely over the years and having been borderline anemic since I was a kid. I don’t really expect to feel great and am a bit of a fatalist: I just get on with things until I no longer can.”
His physician prescribed Gleevec. “I had no particularly notable side effects, and carried on with my life pretty much as if nothing had happened,” Mr. Fahnestock said. He stayed on the drug for almost 20 years.
CML rooted in chromosome swap
It’s not clear exactly what causes CML, although the Mayo Clinic says most cases are linked to an abnormal, extra-short “Philadelphia chromosome,” created when two chromosomes swap material. This happens after birth.
Mr. Fahnestock thinks he happened to develop a random mutation. He also wonders if his work stints in the former Soviet Union in Vladivostok, “where the Soviet nuclear submarine fleet was decomposing,” and in Kiev, Ukraine, “which is not all that far from Chernobyl,” may be responsible.
Most patients, like Mr. Fahnestock, are men. Males will account for about 5,190 of the cases diagnosed in 2023, according to the American Cancer Society, compared to 3,740 in females.
Mr. Fahnestock’s CML diagnosis came at a fairly young age, when he was in his 40s. The average patient is diagnosed at 64. But it’s not unusual that he experienced no apparent symptoms when the cancer was found. In fact, that’s the norm.
Most patients with the disease – which is diagnosed in about 8,900 patients in the United States each year – are asymptomatic or have mild symptoms, Dr. Lai said. Their disease is discovered when “an elevated white count is found on routine blood work,” she said.
“The other group of patients typically present with very elevated white blood cell counts and splenomegaly with symptoms of fatigue and other constitutional symptoms. When the WBC count is very high, it is important to rule out transformation to accelerated or blast phase and also rule out an acute leukemia.”
Polymerase chain reaction is an especially important test during diagnosis, Dr. Atallah said, since it provides baseline data about the cancer that can be tracked.
TKIs: Mainstay of treatment
Four drugs are FDA approved for initial treatment of CML: imatinib (Gleevec), the second-generation TKIs dasatinib (Sprycel) and the third-generation TKI nilotinib (Tasigna). The third-generation TKIs bosutinib (Bosulif) and ponatinib (Iclusig) are approved for use as first-line treatments for patients who cannot tolerate the other drugs or are resistant to them.
The first-in-class drug asciminib (Scemblix), approved by the FDA in 2021, is a third-line drug for patients who failed treatment with two other TKIs and certain patients with the T315I mutation.
Dr. Lai said that it’s crucial to avoid side effects as much as possible “since the goal is for patients to be compliant and take the pill every day and not miss doses.” In younger patients, “I typically choose a second-generation TKI as my first choice, since there is a higher likelihood of getting into a deep molecular remission more quickly. If treatment-free remission is something a patient is interested in, a second-generation TKI is more likely to make this happen.”
According to Dr. Atallah, about half of patients end up using more than one drug because their initial choices either don’t work or cause intolerable side effects. Nevertheless, Dr. Lai noted: “Overall, patients do extremely well if compliant with their medication.”
Exceptions include the noncompliant and patients with more aggressive disease, like an accelerated or a blast phase, she said. For the latter patients, “allogenic bone marrow transplant should be considered once the patient is in remission.”
In remission, consider drug omission
How should patients be monitored if they are doing well?
“In general, I tend to follow patients monthly for the first six months after starting therapy, to make sure they are tolerating it well and to help manage side effects,” Dr. Lai said. “After that, I follow once every three months, and then often space out visits depending on whether they hit their molecular milestones and how long they’re in remission.”
In certain cases, patients may be taken off medication. The most recent National Comprehensive Cancer Network guidelines for treatment of CML, published in 2021, say that “discontinuation of TKI therapy (with close monitoring) is feasible in carefully selected, consenting patients” with early stage CML who’ve reached remission, defined as deep molecular response (DMR) of at least MR 4.0 for at least 2 years.
The guidelines caution that disease recurrence appears in “approximately 40%-60% of patients who discontinue TKI therapy after achieving DMR experience recurrence within 12 months of treatment cessation, in some cases as early as one month after discontinuation of TKI therapy.”
Still, the guidelines add that “resumption of TKI therapy immediately after recurrence results in the achievement of DMR in almost all patients.”
Dr. Atallah said stopping medication can be especially helpful for patients who grapple with side effects such as fatigue, diarrhea, and muscle aches. Some patients who take the drugs fear losing their health insurance and facing sky-high drug expenses. In 2018, average daily TKI costs for patients with CML were over $350, a 2020 report found.
Many patients were prescribed hugely expensive second-line treatments rather than inexpensive generic imatinib, the report said, despite “no evidence that later-generation TKIs provide superior progression free or overall survival.”
Many patients, however, refuse to consider stopping their medication, Dr. Atallah said. More data about treatment-free remission is needed, and the 21 U.S. academic medical centers in the H. Jean Khoury Cure CML Consortium are gathering information about patient outcomes.
Mr. Fahnestock is a fan of treatment-free remission. He stopped taking Gleevec about 2 years ago on the advice of his physician after he reached undetectable levels of disease.
“It was sort of a nonevent, really, with no discernible physical effects beyond exacerbation of the osteoarthritis in my hands,” he said. According to him, it’s not clear if this effect is linked to his eliminating the medication.
“I also vaguely hoped I’d feel better, even though I’d never been able to nail down any deleterious side effects,” he said. “No such luck, as it happens.”
Blood work has indicated no resurgence of the disease, and Mr. Fahnestock continues to volunteer as a rural firefighter.
“In general, I’m apparently reasonably healthy for my age, despite my folly [in younger years], and firefighting requires me to stay in reasonable shape,” he said. “I’ve recently been made aware of minor kidney issues and prediabetes. But, hell, I’m genetically scheduled to croak within 5 years or so, so why worry?”
National survival statistics in CML vary by factors such as gender and age, as a 2021 study revealed, and men have worse outcomes. Still, there’s a good chance Mr. Fahnestock won’t need to worry about CML ever again.
Dr. Atallah disclosed research support from Novartis and Takeda and has served both of those firms and Bristol-Myers Squibb as a consultant advisor. Dr. Lai discloses tied with Bristol-Myers Squibb, Jazz, Genentech, Novartis, Abbvie, Daiichi Sankyo, Astellas, MacroGenics, Servier, and Taiho. Mr. Fahnestock has no disclosures.
When imatinib (Gleevec) appeared on the market just over 2 decades ago, it revolutionized the treatment of chronic myelogenous leukemia (CML) and transformed it from a grim diagnosis into a largely treatable form of blood cancer. New generations of tyrosine kinase inhibitors (TKIs) have continued to expand options for patients, and many can look forward to normal lifespans.
But these medications cause side effects and can be expensive. Long-term data doesn’t exist for the newer therapies, so no one knows whether they can harm patients over time. None of this is particularly unusual for medications to treat chronic illness, but now there’s a twist:
“Our focus has changed because the results of treatment are so good,” hematologist-oncologist Ehab L. Atallah, MD, of the Medical College of Wisconsin, Milwaukee, said in an interview. “We’re trying to get people off their medication.”
Still, research estimates that only 20% of patients with CML will be eligible for treatment discontinuation and benefit from it in the long term. As a result, the wide majority of patients will need to be on drugs indefinitely.
Gleevec: A new age dawns
In the early 1990s, before the era of TKIs, the 5-year relative survival rate from CML was just 27%, and the 10-year rate was only 9.5%, according to a 2008 report. “If someone showed up with CML, their only option was to go to a bone marrow transplant. About half survived the transplant, and half of those had significant complications from it,” Dr. Atallah said. According to him, just about everyone who didn’t get transplantation would go on to die.
Then came Gleevec, which received Food and Drug Administration approval in 2001. It ushered in the era of “targeted” cancer treatment by specifically killing CML cells, instead of relying on traditional chemotherapy’s carpet-bombing approach.
“Gleevec and other TKIs have revolutionized how CML is treated, and patients are now living normal lives,” hematologist-oncologist Catherine Lai, MD, MPH, of the University of Pennsylvania, Philadelphia, said in an interview.
Alan Fahnestock, a 68-year-old retired telecommunications specialist in north-central Washington state, is one of the fortunate patients.
He was diagnosed with CML in 2004 after he underwent a thoracic CT scan in light of his tobacco use. “My GP found something odd in my lungs and referred me to a pulmonologist, who couldn’t figure it out either. He transmitted blood samples to my eventual hematologist/oncologist,” Mr. Fahnestock said in an interview. “It’s not clear to me that anybody ever figured out what the ‘oddity’ was. It has since apparently gone away. But the oncologist ran all the tests and came up with CML.”
Mr. Fahnestock hadn’t noticed any symptoms, although “this is, perhaps, because I tend not to pay a lot of attention to such things, having abused my body fairly severely over the years and having been borderline anemic since I was a kid. I don’t really expect to feel great and am a bit of a fatalist: I just get on with things until I no longer can.”
His physician prescribed Gleevec. “I had no particularly notable side effects, and carried on with my life pretty much as if nothing had happened,” Mr. Fahnestock said. He stayed on the drug for almost 20 years.
CML rooted in chromosome swap
It’s not clear exactly what causes CML, although the Mayo Clinic says most cases are linked to an abnormal, extra-short “Philadelphia chromosome,” created when two chromosomes swap material. This happens after birth.
Mr. Fahnestock thinks he happened to develop a random mutation. He also wonders if his work stints in the former Soviet Union in Vladivostok, “where the Soviet nuclear submarine fleet was decomposing,” and in Kiev, Ukraine, “which is not all that far from Chernobyl,” may be responsible.
Most patients, like Mr. Fahnestock, are men. Males will account for about 5,190 of the cases diagnosed in 2023, according to the American Cancer Society, compared to 3,740 in females.
Mr. Fahnestock’s CML diagnosis came at a fairly young age, when he was in his 40s. The average patient is diagnosed at 64. But it’s not unusual that he experienced no apparent symptoms when the cancer was found. In fact, that’s the norm.
Most patients with the disease – which is diagnosed in about 8,900 patients in the United States each year – are asymptomatic or have mild symptoms, Dr. Lai said. Their disease is discovered when “an elevated white count is found on routine blood work,” she said.
“The other group of patients typically present with very elevated white blood cell counts and splenomegaly with symptoms of fatigue and other constitutional symptoms. When the WBC count is very high, it is important to rule out transformation to accelerated or blast phase and also rule out an acute leukemia.”
Polymerase chain reaction is an especially important test during diagnosis, Dr. Atallah said, since it provides baseline data about the cancer that can be tracked.
TKIs: Mainstay of treatment
Four drugs are FDA approved for initial treatment of CML: imatinib (Gleevec), the second-generation TKIs dasatinib (Sprycel) and the third-generation TKI nilotinib (Tasigna). The third-generation TKIs bosutinib (Bosulif) and ponatinib (Iclusig) are approved for use as first-line treatments for patients who cannot tolerate the other drugs or are resistant to them.
The first-in-class drug asciminib (Scemblix), approved by the FDA in 2021, is a third-line drug for patients who failed treatment with two other TKIs and certain patients with the T315I mutation.
Dr. Lai said that it’s crucial to avoid side effects as much as possible “since the goal is for patients to be compliant and take the pill every day and not miss doses.” In younger patients, “I typically choose a second-generation TKI as my first choice, since there is a higher likelihood of getting into a deep molecular remission more quickly. If treatment-free remission is something a patient is interested in, a second-generation TKI is more likely to make this happen.”
According to Dr. Atallah, about half of patients end up using more than one drug because their initial choices either don’t work or cause intolerable side effects. Nevertheless, Dr. Lai noted: “Overall, patients do extremely well if compliant with their medication.”
Exceptions include the noncompliant and patients with more aggressive disease, like an accelerated or a blast phase, she said. For the latter patients, “allogenic bone marrow transplant should be considered once the patient is in remission.”
In remission, consider drug omission
How should patients be monitored if they are doing well?
“In general, I tend to follow patients monthly for the first six months after starting therapy, to make sure they are tolerating it well and to help manage side effects,” Dr. Lai said. “After that, I follow once every three months, and then often space out visits depending on whether they hit their molecular milestones and how long they’re in remission.”
In certain cases, patients may be taken off medication. The most recent National Comprehensive Cancer Network guidelines for treatment of CML, published in 2021, say that “discontinuation of TKI therapy (with close monitoring) is feasible in carefully selected, consenting patients” with early stage CML who’ve reached remission, defined as deep molecular response (DMR) of at least MR 4.0 for at least 2 years.
The guidelines caution that disease recurrence appears in “approximately 40%-60% of patients who discontinue TKI therapy after achieving DMR experience recurrence within 12 months of treatment cessation, in some cases as early as one month after discontinuation of TKI therapy.”
Still, the guidelines add that “resumption of TKI therapy immediately after recurrence results in the achievement of DMR in almost all patients.”
Dr. Atallah said stopping medication can be especially helpful for patients who grapple with side effects such as fatigue, diarrhea, and muscle aches. Some patients who take the drugs fear losing their health insurance and facing sky-high drug expenses. In 2018, average daily TKI costs for patients with CML were over $350, a 2020 report found.
Many patients were prescribed hugely expensive second-line treatments rather than inexpensive generic imatinib, the report said, despite “no evidence that later-generation TKIs provide superior progression free or overall survival.”
Many patients, however, refuse to consider stopping their medication, Dr. Atallah said. More data about treatment-free remission is needed, and the 21 U.S. academic medical centers in the H. Jean Khoury Cure CML Consortium are gathering information about patient outcomes.
Mr. Fahnestock is a fan of treatment-free remission. He stopped taking Gleevec about 2 years ago on the advice of his physician after he reached undetectable levels of disease.
“It was sort of a nonevent, really, with no discernible physical effects beyond exacerbation of the osteoarthritis in my hands,” he said. According to him, it’s not clear if this effect is linked to his eliminating the medication.
“I also vaguely hoped I’d feel better, even though I’d never been able to nail down any deleterious side effects,” he said. “No such luck, as it happens.”
Blood work has indicated no resurgence of the disease, and Mr. Fahnestock continues to volunteer as a rural firefighter.
“In general, I’m apparently reasonably healthy for my age, despite my folly [in younger years], and firefighting requires me to stay in reasonable shape,” he said. “I’ve recently been made aware of minor kidney issues and prediabetes. But, hell, I’m genetically scheduled to croak within 5 years or so, so why worry?”
National survival statistics in CML vary by factors such as gender and age, as a 2021 study revealed, and men have worse outcomes. Still, there’s a good chance Mr. Fahnestock won’t need to worry about CML ever again.
Dr. Atallah disclosed research support from Novartis and Takeda and has served both of those firms and Bristol-Myers Squibb as a consultant advisor. Dr. Lai discloses tied with Bristol-Myers Squibb, Jazz, Genentech, Novartis, Abbvie, Daiichi Sankyo, Astellas, MacroGenics, Servier, and Taiho. Mr. Fahnestock has no disclosures.
When imatinib (Gleevec) appeared on the market just over 2 decades ago, it revolutionized the treatment of chronic myelogenous leukemia (CML) and transformed it from a grim diagnosis into a largely treatable form of blood cancer. New generations of tyrosine kinase inhibitors (TKIs) have continued to expand options for patients, and many can look forward to normal lifespans.
But these medications cause side effects and can be expensive. Long-term data doesn’t exist for the newer therapies, so no one knows whether they can harm patients over time. None of this is particularly unusual for medications to treat chronic illness, but now there’s a twist:
“Our focus has changed because the results of treatment are so good,” hematologist-oncologist Ehab L. Atallah, MD, of the Medical College of Wisconsin, Milwaukee, said in an interview. “We’re trying to get people off their medication.”
Still, research estimates that only 20% of patients with CML will be eligible for treatment discontinuation and benefit from it in the long term. As a result, the wide majority of patients will need to be on drugs indefinitely.
Gleevec: A new age dawns
In the early 1990s, before the era of TKIs, the 5-year relative survival rate from CML was just 27%, and the 10-year rate was only 9.5%, according to a 2008 report. “If someone showed up with CML, their only option was to go to a bone marrow transplant. About half survived the transplant, and half of those had significant complications from it,” Dr. Atallah said. According to him, just about everyone who didn’t get transplantation would go on to die.
Then came Gleevec, which received Food and Drug Administration approval in 2001. It ushered in the era of “targeted” cancer treatment by specifically killing CML cells, instead of relying on traditional chemotherapy’s carpet-bombing approach.
“Gleevec and other TKIs have revolutionized how CML is treated, and patients are now living normal lives,” hematologist-oncologist Catherine Lai, MD, MPH, of the University of Pennsylvania, Philadelphia, said in an interview.
Alan Fahnestock, a 68-year-old retired telecommunications specialist in north-central Washington state, is one of the fortunate patients.
He was diagnosed with CML in 2004 after he underwent a thoracic CT scan in light of his tobacco use. “My GP found something odd in my lungs and referred me to a pulmonologist, who couldn’t figure it out either. He transmitted blood samples to my eventual hematologist/oncologist,” Mr. Fahnestock said in an interview. “It’s not clear to me that anybody ever figured out what the ‘oddity’ was. It has since apparently gone away. But the oncologist ran all the tests and came up with CML.”
Mr. Fahnestock hadn’t noticed any symptoms, although “this is, perhaps, because I tend not to pay a lot of attention to such things, having abused my body fairly severely over the years and having been borderline anemic since I was a kid. I don’t really expect to feel great and am a bit of a fatalist: I just get on with things until I no longer can.”
His physician prescribed Gleevec. “I had no particularly notable side effects, and carried on with my life pretty much as if nothing had happened,” Mr. Fahnestock said. He stayed on the drug for almost 20 years.
CML rooted in chromosome swap
It’s not clear exactly what causes CML, although the Mayo Clinic says most cases are linked to an abnormal, extra-short “Philadelphia chromosome,” created when two chromosomes swap material. This happens after birth.
Mr. Fahnestock thinks he happened to develop a random mutation. He also wonders if his work stints in the former Soviet Union in Vladivostok, “where the Soviet nuclear submarine fleet was decomposing,” and in Kiev, Ukraine, “which is not all that far from Chernobyl,” may be responsible.
Most patients, like Mr. Fahnestock, are men. Males will account for about 5,190 of the cases diagnosed in 2023, according to the American Cancer Society, compared to 3,740 in females.
Mr. Fahnestock’s CML diagnosis came at a fairly young age, when he was in his 40s. The average patient is diagnosed at 64. But it’s not unusual that he experienced no apparent symptoms when the cancer was found. In fact, that’s the norm.
Most patients with the disease – which is diagnosed in about 8,900 patients in the United States each year – are asymptomatic or have mild symptoms, Dr. Lai said. Their disease is discovered when “an elevated white count is found on routine blood work,” she said.
“The other group of patients typically present with very elevated white blood cell counts and splenomegaly with symptoms of fatigue and other constitutional symptoms. When the WBC count is very high, it is important to rule out transformation to accelerated or blast phase and also rule out an acute leukemia.”
Polymerase chain reaction is an especially important test during diagnosis, Dr. Atallah said, since it provides baseline data about the cancer that can be tracked.
TKIs: Mainstay of treatment
Four drugs are FDA approved for initial treatment of CML: imatinib (Gleevec), the second-generation TKIs dasatinib (Sprycel) and the third-generation TKI nilotinib (Tasigna). The third-generation TKIs bosutinib (Bosulif) and ponatinib (Iclusig) are approved for use as first-line treatments for patients who cannot tolerate the other drugs or are resistant to them.
The first-in-class drug asciminib (Scemblix), approved by the FDA in 2021, is a third-line drug for patients who failed treatment with two other TKIs and certain patients with the T315I mutation.
Dr. Lai said that it’s crucial to avoid side effects as much as possible “since the goal is for patients to be compliant and take the pill every day and not miss doses.” In younger patients, “I typically choose a second-generation TKI as my first choice, since there is a higher likelihood of getting into a deep molecular remission more quickly. If treatment-free remission is something a patient is interested in, a second-generation TKI is more likely to make this happen.”
According to Dr. Atallah, about half of patients end up using more than one drug because their initial choices either don’t work or cause intolerable side effects. Nevertheless, Dr. Lai noted: “Overall, patients do extremely well if compliant with their medication.”
Exceptions include the noncompliant and patients with more aggressive disease, like an accelerated or a blast phase, she said. For the latter patients, “allogenic bone marrow transplant should be considered once the patient is in remission.”
In remission, consider drug omission
How should patients be monitored if they are doing well?
“In general, I tend to follow patients monthly for the first six months after starting therapy, to make sure they are tolerating it well and to help manage side effects,” Dr. Lai said. “After that, I follow once every three months, and then often space out visits depending on whether they hit their molecular milestones and how long they’re in remission.”
In certain cases, patients may be taken off medication. The most recent National Comprehensive Cancer Network guidelines for treatment of CML, published in 2021, say that “discontinuation of TKI therapy (with close monitoring) is feasible in carefully selected, consenting patients” with early stage CML who’ve reached remission, defined as deep molecular response (DMR) of at least MR 4.0 for at least 2 years.
The guidelines caution that disease recurrence appears in “approximately 40%-60% of patients who discontinue TKI therapy after achieving DMR experience recurrence within 12 months of treatment cessation, in some cases as early as one month after discontinuation of TKI therapy.”
Still, the guidelines add that “resumption of TKI therapy immediately after recurrence results in the achievement of DMR in almost all patients.”
Dr. Atallah said stopping medication can be especially helpful for patients who grapple with side effects such as fatigue, diarrhea, and muscle aches. Some patients who take the drugs fear losing their health insurance and facing sky-high drug expenses. In 2018, average daily TKI costs for patients with CML were over $350, a 2020 report found.
Many patients were prescribed hugely expensive second-line treatments rather than inexpensive generic imatinib, the report said, despite “no evidence that later-generation TKIs provide superior progression free or overall survival.”
Many patients, however, refuse to consider stopping their medication, Dr. Atallah said. More data about treatment-free remission is needed, and the 21 U.S. academic medical centers in the H. Jean Khoury Cure CML Consortium are gathering information about patient outcomes.
Mr. Fahnestock is a fan of treatment-free remission. He stopped taking Gleevec about 2 years ago on the advice of his physician after he reached undetectable levels of disease.
“It was sort of a nonevent, really, with no discernible physical effects beyond exacerbation of the osteoarthritis in my hands,” he said. According to him, it’s not clear if this effect is linked to his eliminating the medication.
“I also vaguely hoped I’d feel better, even though I’d never been able to nail down any deleterious side effects,” he said. “No such luck, as it happens.”
Blood work has indicated no resurgence of the disease, and Mr. Fahnestock continues to volunteer as a rural firefighter.
“In general, I’m apparently reasonably healthy for my age, despite my folly [in younger years], and firefighting requires me to stay in reasonable shape,” he said. “I’ve recently been made aware of minor kidney issues and prediabetes. But, hell, I’m genetically scheduled to croak within 5 years or so, so why worry?”
National survival statistics in CML vary by factors such as gender and age, as a 2021 study revealed, and men have worse outcomes. Still, there’s a good chance Mr. Fahnestock won’t need to worry about CML ever again.
Dr. Atallah disclosed research support from Novartis and Takeda and has served both of those firms and Bristol-Myers Squibb as a consultant advisor. Dr. Lai discloses tied with Bristol-Myers Squibb, Jazz, Genentech, Novartis, Abbvie, Daiichi Sankyo, Astellas, MacroGenics, Servier, and Taiho. Mr. Fahnestock has no disclosures.
Surgeon’s license suspension spotlights hazards, ethics of live-streaming surgeries
potentially endangering patients. The surgeon has a large social media following.
In November, the State Medical Board of Ohio temporarily suspended the license of Katherine Roxanne Grawe, MD, who practices in the wealthy Columbus suburb of Powell.
Among other accusations of misconduct, the board stated that “during some videos/live-streams you engage in dialogue to respond to viewers’ online questions while the surgical procedure remains actively ongoing.”
One patient needed emergency treatment following liposuction and was diagnosed with a perforated bowel and serious bacterial infection.
“Despite liposuction being a blind surgery that requires awareness of the tip of the cannula to avoid injury, your attention to the camera meant at those moments you were not looking at the patient or palpating the location of the tip of the cannula,” the medical board said.
Neither Dr. Grawe nor her attorney responded to requests for comment.
Dr. Grawe, known as “Dr. Roxy,” has a popular TikTok account – now set to private – with 841,600 followers and 14.6 million likes. She has another 123,000 followers on her Instagram account, also now private.
The Columbus Dispatch reported that Dr. Grawe had previously been warned to protect patient privacy on social media. The board has yet to make a final decision regarding her license.
According to Columbus TV station WSYX, she said in a TikTok video, “We show our surgeries every single day on Snapchat. Patients get to decide if they want to be part of it. And if you do, you can watch your own surgery.”
The TV station quoted former patients who described surgical complications. One said: “I went to her because, I thought, from all of her social media that she uplifted women. That she helped women empower themselves. But she didn’t.”
Dallas plastic surgeon Rod J. Rohrich, MD, who has written about social-media best practices and has 430,000 followers on Instagram, said in an interview that many surgeons have been reprimanded by state medical boards for being distracted by social media during procedures.
“It is best not to do live-streaming unless it is an educational event to demonstrate techniques and technology with full informed consent of the patient. It should be a very well-rehearsed event for education,” he said.
Nurses also have been disciplined for inappropriate posts on social media. In December 2022, an Atlanta hospital announced that four nurses were no longer on the job after they appeared in a TikTok video in scrubs and revealed their “icks” regarding obstetric care.
“My ick is when you ask me how much the baby weighs,” one worker said in the video, “and it’s still ... in your hands.”
Plastic surgeon Christian J. Vercler, MD, of the University of Michigan, Ann Arbor, who’s studied social-media guidelines for surgeons, said in an interview that plastic surgery content on TikTok has “blown up” in recent years.
“Five years or so ago, it was Snapchat where I saw a lot of inappropriate things posted by surgeons,” Dr. Vercler said in an interview. “That may still be happening on Snapchat, but I actually don’t ever use that platform anymore, and neither do my trainees.”
Dr. Vercler cautioned colleagues to consider their motivations for live-streaming surgery and to think about whether they can fully focus on the patient.
“There are many potential distractions in the OR. We get pages, phone calls, nurses asking us questions, anesthesiologists trying to talk to us. Social media is just one more thing competing for the surgeon’s attention,” he said. “Every surgeon should strive to eliminate unnecessary or unavoidable distractions, so the question becomes, ‘who is best being served by me focusing my attention on recording this operation on someone’s phone so we can post it on social media? Is it the patient?’ ”
Dr. Vercler added, “There are many, many plastic surgeons using social media as the powerful platform that it is to build their brands, to connect with potential patients, and to educate the public about what they do. I believe that most are doing this in a way that is respectful to patients and doesn’t exploit patients for the surgeon’s benefit.
“Unfortunately,” he concluded, “there are some who do see patients as merely instruments by which they can achieve fame, notoriety, and wealth.”
Dr. Rohrich and Dr. Vercler disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
potentially endangering patients. The surgeon has a large social media following.
In November, the State Medical Board of Ohio temporarily suspended the license of Katherine Roxanne Grawe, MD, who practices in the wealthy Columbus suburb of Powell.
Among other accusations of misconduct, the board stated that “during some videos/live-streams you engage in dialogue to respond to viewers’ online questions while the surgical procedure remains actively ongoing.”
One patient needed emergency treatment following liposuction and was diagnosed with a perforated bowel and serious bacterial infection.
“Despite liposuction being a blind surgery that requires awareness of the tip of the cannula to avoid injury, your attention to the camera meant at those moments you were not looking at the patient or palpating the location of the tip of the cannula,” the medical board said.
Neither Dr. Grawe nor her attorney responded to requests for comment.
Dr. Grawe, known as “Dr. Roxy,” has a popular TikTok account – now set to private – with 841,600 followers and 14.6 million likes. She has another 123,000 followers on her Instagram account, also now private.
The Columbus Dispatch reported that Dr. Grawe had previously been warned to protect patient privacy on social media. The board has yet to make a final decision regarding her license.
According to Columbus TV station WSYX, she said in a TikTok video, “We show our surgeries every single day on Snapchat. Patients get to decide if they want to be part of it. And if you do, you can watch your own surgery.”
The TV station quoted former patients who described surgical complications. One said: “I went to her because, I thought, from all of her social media that she uplifted women. That she helped women empower themselves. But she didn’t.”
Dallas plastic surgeon Rod J. Rohrich, MD, who has written about social-media best practices and has 430,000 followers on Instagram, said in an interview that many surgeons have been reprimanded by state medical boards for being distracted by social media during procedures.
“It is best not to do live-streaming unless it is an educational event to demonstrate techniques and technology with full informed consent of the patient. It should be a very well-rehearsed event for education,” he said.
Nurses also have been disciplined for inappropriate posts on social media. In December 2022, an Atlanta hospital announced that four nurses were no longer on the job after they appeared in a TikTok video in scrubs and revealed their “icks” regarding obstetric care.
“My ick is when you ask me how much the baby weighs,” one worker said in the video, “and it’s still ... in your hands.”
Plastic surgeon Christian J. Vercler, MD, of the University of Michigan, Ann Arbor, who’s studied social-media guidelines for surgeons, said in an interview that plastic surgery content on TikTok has “blown up” in recent years.
“Five years or so ago, it was Snapchat where I saw a lot of inappropriate things posted by surgeons,” Dr. Vercler said in an interview. “That may still be happening on Snapchat, but I actually don’t ever use that platform anymore, and neither do my trainees.”
Dr. Vercler cautioned colleagues to consider their motivations for live-streaming surgery and to think about whether they can fully focus on the patient.
“There are many potential distractions in the OR. We get pages, phone calls, nurses asking us questions, anesthesiologists trying to talk to us. Social media is just one more thing competing for the surgeon’s attention,” he said. “Every surgeon should strive to eliminate unnecessary or unavoidable distractions, so the question becomes, ‘who is best being served by me focusing my attention on recording this operation on someone’s phone so we can post it on social media? Is it the patient?’ ”
Dr. Vercler added, “There are many, many plastic surgeons using social media as the powerful platform that it is to build their brands, to connect with potential patients, and to educate the public about what they do. I believe that most are doing this in a way that is respectful to patients and doesn’t exploit patients for the surgeon’s benefit.
“Unfortunately,” he concluded, “there are some who do see patients as merely instruments by which they can achieve fame, notoriety, and wealth.”
Dr. Rohrich and Dr. Vercler disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
potentially endangering patients. The surgeon has a large social media following.
In November, the State Medical Board of Ohio temporarily suspended the license of Katherine Roxanne Grawe, MD, who practices in the wealthy Columbus suburb of Powell.
Among other accusations of misconduct, the board stated that “during some videos/live-streams you engage in dialogue to respond to viewers’ online questions while the surgical procedure remains actively ongoing.”
One patient needed emergency treatment following liposuction and was diagnosed with a perforated bowel and serious bacterial infection.
“Despite liposuction being a blind surgery that requires awareness of the tip of the cannula to avoid injury, your attention to the camera meant at those moments you were not looking at the patient or palpating the location of the tip of the cannula,” the medical board said.
Neither Dr. Grawe nor her attorney responded to requests for comment.
Dr. Grawe, known as “Dr. Roxy,” has a popular TikTok account – now set to private – with 841,600 followers and 14.6 million likes. She has another 123,000 followers on her Instagram account, also now private.
The Columbus Dispatch reported that Dr. Grawe had previously been warned to protect patient privacy on social media. The board has yet to make a final decision regarding her license.
According to Columbus TV station WSYX, she said in a TikTok video, “We show our surgeries every single day on Snapchat. Patients get to decide if they want to be part of it. And if you do, you can watch your own surgery.”
The TV station quoted former patients who described surgical complications. One said: “I went to her because, I thought, from all of her social media that she uplifted women. That she helped women empower themselves. But she didn’t.”
Dallas plastic surgeon Rod J. Rohrich, MD, who has written about social-media best practices and has 430,000 followers on Instagram, said in an interview that many surgeons have been reprimanded by state medical boards for being distracted by social media during procedures.
“It is best not to do live-streaming unless it is an educational event to demonstrate techniques and technology with full informed consent of the patient. It should be a very well-rehearsed event for education,” he said.
Nurses also have been disciplined for inappropriate posts on social media. In December 2022, an Atlanta hospital announced that four nurses were no longer on the job after they appeared in a TikTok video in scrubs and revealed their “icks” regarding obstetric care.
“My ick is when you ask me how much the baby weighs,” one worker said in the video, “and it’s still ... in your hands.”
Plastic surgeon Christian J. Vercler, MD, of the University of Michigan, Ann Arbor, who’s studied social-media guidelines for surgeons, said in an interview that plastic surgery content on TikTok has “blown up” in recent years.
“Five years or so ago, it was Snapchat where I saw a lot of inappropriate things posted by surgeons,” Dr. Vercler said in an interview. “That may still be happening on Snapchat, but I actually don’t ever use that platform anymore, and neither do my trainees.”
Dr. Vercler cautioned colleagues to consider their motivations for live-streaming surgery and to think about whether they can fully focus on the patient.
“There are many potential distractions in the OR. We get pages, phone calls, nurses asking us questions, anesthesiologists trying to talk to us. Social media is just one more thing competing for the surgeon’s attention,” he said. “Every surgeon should strive to eliminate unnecessary or unavoidable distractions, so the question becomes, ‘who is best being served by me focusing my attention on recording this operation on someone’s phone so we can post it on social media? Is it the patient?’ ”
Dr. Vercler added, “There are many, many plastic surgeons using social media as the powerful platform that it is to build their brands, to connect with potential patients, and to educate the public about what they do. I believe that most are doing this in a way that is respectful to patients and doesn’t exploit patients for the surgeon’s benefit.
“Unfortunately,” he concluded, “there are some who do see patients as merely instruments by which they can achieve fame, notoriety, and wealth.”
Dr. Rohrich and Dr. Vercler disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.