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Automated Risk Assessment Tool Reduces Antibiotic Prescribing Rates
An algorithm-driven risk assessment embedded in an electronic health record (EHR) helped clinicians reduce inappropriate broad-spectrum antibiotic prescribing by 17.4% and 28.4% in patients with UTIs and pneumonia, respectively, according to two related studies published in JAMA.
The randomized control trials included more than 200,000 adult patients with non–life threatening pneumonia or urinary tract infections (UTIs) in 59 hospitals owned by HCA Healthcare across the country.
Researchers analyzed baseline prescribing behaviors over an 18-month period starting in April 2017, and data from a 15-month period of implementation of the new antibiotic system starting in April 2019.
, according to lead author Shruti K. Gohil, MD, MPH, associate medical director of epidemiology and infection prevention, infectious diseases at the University of California Irvine School of Medicine.
“When a patient comes in with pneumonia or a UTI, it’s precisely because we are concerned that our patients have a multidrug-resistant organism that we end up using broad-spectrum antibiotics,” she said.
Despite growing awareness of the need to reduce unnecessary antibiotic use, clinicians have still been slow to adopt a more conservative approach to prescribing, Dr. Gohil said.
“What physicians have been needing is something to hang their hat on, to be able to say, ‘Okay, well, this one’s a low-risk person,’ ” Dr. Gohil said.
The trials compared the impact of routine antibiotic activities with a stewardship bundle, called INSPIRE (Intelligent Stewardship Prompts to Improve Real-time Empiric Antibiotic Selection).
Both groups received educational materials, quarterly coaching calls, prospective evaluations for antibiotic use, and were required to select a reason for prescribing an antibiotic.
But prescribers in the intervention group took part in monthly coaching calls and feedback reports. In addition, if a clinician ordered a broad-spectrum antibiotic to treat pneumonia or a UTI outside of the intensive care unit within 72 hours of admission, an EHR prompt would pop up. The pop-up suggested a standard-spectrum antibiotic instead if patient risk for developing a multidrug-resistant (MDRO) version of either condition was less than 10%.
An algorithm used data from the EHR calculated risk, using factors like patient demographics and history and MDRO infection at the community and hospital level.
Prescribing rates were based on the number of days a patient received a broad-spectrum antibiotic during the first 72 hours of hospitalization.
For the UTI intervention group, rates dropped by 17.4% (rate ratio [RR], 0.83; 95% CI, 0.77-0.89; P < .001), and 28.4% reduction in the pneumonia group (RR, 0.72; 95% CI, 0.66-0.78; P < .001).
“We cannot know which element — prompt, education, or feedback — worked, but the data suggests that the prompt was the main driver,” Dr. Gohil said.
“In antibiotic stewardship, we have learned not only that doctors want to do the right thing, but that we as stewards need to make it easy for them do the right thing,” said Paul Pottinger, MD, professor of medicine at the Division of Allergy and Infectious Diseases at the University of Washington Medical Center in Seattle.
The prompt “is your easy button,” said Dr. Pottinger, who was not involved with either study. “The researchers made it simple, fast, and straightforward, so people don’t have to think about it too much.”
The studies showed similar safety outcomes for the control and intervention groups. Among patients with a UTI, those in the control group were transferred to the ICU after an average of 6.6 days compared to 7 days in the intervention group. Among patients with pneumonia, the average days to ICU transfer were 6.5 for the control group and 7.1 for the intervention group.
“This study is a proof of concept that physicians want to do the right thing and are willing to trust this information,” Dr. Pottinger said. “And this also shows us that this tool can be refined and made even more precise over time.”
The study was funded by the US Centers for Disease Control and Prevention and was led by the University of California Irvine, Harvard Pilgrim Healthcare Institute, and HCA Healthcare System. Various authors report funding and support from entities outside the submitted work. The full list can be found with the original articles.
A version of this article appeared on Medscape.com.
An algorithm-driven risk assessment embedded in an electronic health record (EHR) helped clinicians reduce inappropriate broad-spectrum antibiotic prescribing by 17.4% and 28.4% in patients with UTIs and pneumonia, respectively, according to two related studies published in JAMA.
The randomized control trials included more than 200,000 adult patients with non–life threatening pneumonia or urinary tract infections (UTIs) in 59 hospitals owned by HCA Healthcare across the country.
Researchers analyzed baseline prescribing behaviors over an 18-month period starting in April 2017, and data from a 15-month period of implementation of the new antibiotic system starting in April 2019.
, according to lead author Shruti K. Gohil, MD, MPH, associate medical director of epidemiology and infection prevention, infectious diseases at the University of California Irvine School of Medicine.
“When a patient comes in with pneumonia or a UTI, it’s precisely because we are concerned that our patients have a multidrug-resistant organism that we end up using broad-spectrum antibiotics,” she said.
Despite growing awareness of the need to reduce unnecessary antibiotic use, clinicians have still been slow to adopt a more conservative approach to prescribing, Dr. Gohil said.
“What physicians have been needing is something to hang their hat on, to be able to say, ‘Okay, well, this one’s a low-risk person,’ ” Dr. Gohil said.
The trials compared the impact of routine antibiotic activities with a stewardship bundle, called INSPIRE (Intelligent Stewardship Prompts to Improve Real-time Empiric Antibiotic Selection).
Both groups received educational materials, quarterly coaching calls, prospective evaluations for antibiotic use, and were required to select a reason for prescribing an antibiotic.
But prescribers in the intervention group took part in monthly coaching calls and feedback reports. In addition, if a clinician ordered a broad-spectrum antibiotic to treat pneumonia or a UTI outside of the intensive care unit within 72 hours of admission, an EHR prompt would pop up. The pop-up suggested a standard-spectrum antibiotic instead if patient risk for developing a multidrug-resistant (MDRO) version of either condition was less than 10%.
An algorithm used data from the EHR calculated risk, using factors like patient demographics and history and MDRO infection at the community and hospital level.
Prescribing rates were based on the number of days a patient received a broad-spectrum antibiotic during the first 72 hours of hospitalization.
For the UTI intervention group, rates dropped by 17.4% (rate ratio [RR], 0.83; 95% CI, 0.77-0.89; P < .001), and 28.4% reduction in the pneumonia group (RR, 0.72; 95% CI, 0.66-0.78; P < .001).
“We cannot know which element — prompt, education, or feedback — worked, but the data suggests that the prompt was the main driver,” Dr. Gohil said.
“In antibiotic stewardship, we have learned not only that doctors want to do the right thing, but that we as stewards need to make it easy for them do the right thing,” said Paul Pottinger, MD, professor of medicine at the Division of Allergy and Infectious Diseases at the University of Washington Medical Center in Seattle.
The prompt “is your easy button,” said Dr. Pottinger, who was not involved with either study. “The researchers made it simple, fast, and straightforward, so people don’t have to think about it too much.”
The studies showed similar safety outcomes for the control and intervention groups. Among patients with a UTI, those in the control group were transferred to the ICU after an average of 6.6 days compared to 7 days in the intervention group. Among patients with pneumonia, the average days to ICU transfer were 6.5 for the control group and 7.1 for the intervention group.
“This study is a proof of concept that physicians want to do the right thing and are willing to trust this information,” Dr. Pottinger said. “And this also shows us that this tool can be refined and made even more precise over time.”
The study was funded by the US Centers for Disease Control and Prevention and was led by the University of California Irvine, Harvard Pilgrim Healthcare Institute, and HCA Healthcare System. Various authors report funding and support from entities outside the submitted work. The full list can be found with the original articles.
A version of this article appeared on Medscape.com.
An algorithm-driven risk assessment embedded in an electronic health record (EHR) helped clinicians reduce inappropriate broad-spectrum antibiotic prescribing by 17.4% and 28.4% in patients with UTIs and pneumonia, respectively, according to two related studies published in JAMA.
The randomized control trials included more than 200,000 adult patients with non–life threatening pneumonia or urinary tract infections (UTIs) in 59 hospitals owned by HCA Healthcare across the country.
Researchers analyzed baseline prescribing behaviors over an 18-month period starting in April 2017, and data from a 15-month period of implementation of the new antibiotic system starting in April 2019.
, according to lead author Shruti K. Gohil, MD, MPH, associate medical director of epidemiology and infection prevention, infectious diseases at the University of California Irvine School of Medicine.
“When a patient comes in with pneumonia or a UTI, it’s precisely because we are concerned that our patients have a multidrug-resistant organism that we end up using broad-spectrum antibiotics,” she said.
Despite growing awareness of the need to reduce unnecessary antibiotic use, clinicians have still been slow to adopt a more conservative approach to prescribing, Dr. Gohil said.
“What physicians have been needing is something to hang their hat on, to be able to say, ‘Okay, well, this one’s a low-risk person,’ ” Dr. Gohil said.
The trials compared the impact of routine antibiotic activities with a stewardship bundle, called INSPIRE (Intelligent Stewardship Prompts to Improve Real-time Empiric Antibiotic Selection).
Both groups received educational materials, quarterly coaching calls, prospective evaluations for antibiotic use, and were required to select a reason for prescribing an antibiotic.
But prescribers in the intervention group took part in monthly coaching calls and feedback reports. In addition, if a clinician ordered a broad-spectrum antibiotic to treat pneumonia or a UTI outside of the intensive care unit within 72 hours of admission, an EHR prompt would pop up. The pop-up suggested a standard-spectrum antibiotic instead if patient risk for developing a multidrug-resistant (MDRO) version of either condition was less than 10%.
An algorithm used data from the EHR calculated risk, using factors like patient demographics and history and MDRO infection at the community and hospital level.
Prescribing rates were based on the number of days a patient received a broad-spectrum antibiotic during the first 72 hours of hospitalization.
For the UTI intervention group, rates dropped by 17.4% (rate ratio [RR], 0.83; 95% CI, 0.77-0.89; P < .001), and 28.4% reduction in the pneumonia group (RR, 0.72; 95% CI, 0.66-0.78; P < .001).
“We cannot know which element — prompt, education, or feedback — worked, but the data suggests that the prompt was the main driver,” Dr. Gohil said.
“In antibiotic stewardship, we have learned not only that doctors want to do the right thing, but that we as stewards need to make it easy for them do the right thing,” said Paul Pottinger, MD, professor of medicine at the Division of Allergy and Infectious Diseases at the University of Washington Medical Center in Seattle.
The prompt “is your easy button,” said Dr. Pottinger, who was not involved with either study. “The researchers made it simple, fast, and straightforward, so people don’t have to think about it too much.”
The studies showed similar safety outcomes for the control and intervention groups. Among patients with a UTI, those in the control group were transferred to the ICU after an average of 6.6 days compared to 7 days in the intervention group. Among patients with pneumonia, the average days to ICU transfer were 6.5 for the control group and 7.1 for the intervention group.
“This study is a proof of concept that physicians want to do the right thing and are willing to trust this information,” Dr. Pottinger said. “And this also shows us that this tool can be refined and made even more precise over time.”
The study was funded by the US Centers for Disease Control and Prevention and was led by the University of California Irvine, Harvard Pilgrim Healthcare Institute, and HCA Healthcare System. Various authors report funding and support from entities outside the submitted work. The full list can be found with the original articles.
A version of this article appeared on Medscape.com.
Study Demonstrates Faster Recovery, Less Pain After Facial Resurfacing With 2910-nm Laser
BALTIMORE — A — while causing less discomfort and downtime compared with conventional fractional lasers, a small single-center study showed.
The study enrolled 15 patients who had three treatment sessions with the 2910-nm laser. “It’s highly customizable,” the study’s lead author, Taryn Murray, MD, a dermatologist at Cleveland Clinic, told this news organization. “It has a really fast time in healing compared to traditional abatable lasers; the healing time is 5-7 days vs several weeks.” Dr. Murray presented the results at the annual meeting of the American Society for Laser Medicine and Surgery (ASLMS).
The Technology Behind the Laser
The 2910-nm erbium-doped fluoride glass fiber laser is a mid-infrared ablative fractional device that operates at peak water absorption. It’s designed to cause minimal residual thermal damage, resulting in less discomfort, shorter downtime, and potentially fewer side effects than conventional ablative lasers, Dr. Murray said.
Because of the way the pulses are delivered, “it’s far less painful than traditional fractional ablative lasers, so you can use mainly topical numbing; you don’t need nerve blocks, you don’t have to infiltrate lidocaine, you don’t have to put the patient under anesthesia,” she said.
“Because of the wavelength, how pulses are delivered and how customizable the settings are, it’s safer to use in darker skin types,” and the density, depth, and the amount of coagulation applied into the skin are customizable, Dr. Murray added.
The laser also delivers pulses in a different way than the conventional 2940-nm erbium and CO2 lasers, she explained. “Traditional lasers do it all in one pulse. This laser uses micropulses with relaxation time in between pulses, so the body interprets it as less painful and allows pressure and steam to escape out of the channel, which results in faster healing.”
The study patients had topical anesthetic cream applied to their faces 45-60 minutes before the procedure. Multiple passes were made using both superficial and deep laser modes. The average patient age was 65.7 years, and Fitzpatrick skin types included I (n = 3), II (n = 3), III (n = 7), and IV (n = 2). On a scale of 0-10, the average level of discomfort was 4.9, and the average patient satisfaction after three treatments was 4.8, Dr. Murray said.
For cosmetic improvement, the study used the 5-point Global Aesthetic Improvement Scale (GAIS). Blinded reviewers evaluated digital images and determined an average GAIS score of 3.2 for overall appearance, 2.9 for wrinkles, 3.6 for pigment, 3.1 for skin texture, and 2.6 for skin laxity.
When the patients themselves reviewed the digital images, the average GAIS score was 3.8 for overall appearance.
Side effects, said Dr. Murray, were transient, with edema and soft-tissue crusting lasting 3-5 days and erythema resolving in 1-2 weeks on average. One case of postinflammatory hyperpigmentation (PIH) did arise, which was linked to allergic contact dermatitis from the healing ointment. That patient stayed in the study and had complete resolution of the PIH.
Study Stands Out
A number of studies of the 2910-nm erbium-doped fluoride glass fiber laser have emerged over the past half year, Ritu Swali, MD, who was an American Society of Dermatologic Surgery fellow at a practice in Houston, said in an interview at the meeting. But this one stands out because of the evidence surrounding its use.
Most people are using this laser for facial resurfacing, “and we want to know that we have a technology ... with shorter downtime and easier wound care and just more comfort,” she said.
She noted that with conventional lasers, most patients get nerve blocks and some even opt for general anesthesia. “To be able to do the levels of facial resurfacing [Dr. Murray] is doing without having to do all of that pain management is pretty amazing,” Dr. Swali added.
The speed of the procedure and the relatively short downtime are also noteworthy, she said. “The huge advantage is having so much less pain from the procedure itself, so you’re able to do it faster because they’re tolerating it so well and you’re not having to take breaks,” she said.
As for downtime, Dr. Swali added, “these patients are coming in on a Thursday and they are back up and running by Monday,” as opposed to weeks that is typical with a conventional laser. This laser platform also avoids the pigmentation problems that can come with continuing and aggressive treatment with conventional lasers, she said.
Dr. Murray disclosed relationships with Acclaro Medical, the manufacturer of the laser. Dr. Swali has no relationships to disclose.
A version of this article first appeared on Medscape.com.
BALTIMORE — A — while causing less discomfort and downtime compared with conventional fractional lasers, a small single-center study showed.
The study enrolled 15 patients who had three treatment sessions with the 2910-nm laser. “It’s highly customizable,” the study’s lead author, Taryn Murray, MD, a dermatologist at Cleveland Clinic, told this news organization. “It has a really fast time in healing compared to traditional abatable lasers; the healing time is 5-7 days vs several weeks.” Dr. Murray presented the results at the annual meeting of the American Society for Laser Medicine and Surgery (ASLMS).
The Technology Behind the Laser
The 2910-nm erbium-doped fluoride glass fiber laser is a mid-infrared ablative fractional device that operates at peak water absorption. It’s designed to cause minimal residual thermal damage, resulting in less discomfort, shorter downtime, and potentially fewer side effects than conventional ablative lasers, Dr. Murray said.
Because of the way the pulses are delivered, “it’s far less painful than traditional fractional ablative lasers, so you can use mainly topical numbing; you don’t need nerve blocks, you don’t have to infiltrate lidocaine, you don’t have to put the patient under anesthesia,” she said.
“Because of the wavelength, how pulses are delivered and how customizable the settings are, it’s safer to use in darker skin types,” and the density, depth, and the amount of coagulation applied into the skin are customizable, Dr. Murray added.
The laser also delivers pulses in a different way than the conventional 2940-nm erbium and CO2 lasers, she explained. “Traditional lasers do it all in one pulse. This laser uses micropulses with relaxation time in between pulses, so the body interprets it as less painful and allows pressure and steam to escape out of the channel, which results in faster healing.”
The study patients had topical anesthetic cream applied to their faces 45-60 minutes before the procedure. Multiple passes were made using both superficial and deep laser modes. The average patient age was 65.7 years, and Fitzpatrick skin types included I (n = 3), II (n = 3), III (n = 7), and IV (n = 2). On a scale of 0-10, the average level of discomfort was 4.9, and the average patient satisfaction after three treatments was 4.8, Dr. Murray said.
For cosmetic improvement, the study used the 5-point Global Aesthetic Improvement Scale (GAIS). Blinded reviewers evaluated digital images and determined an average GAIS score of 3.2 for overall appearance, 2.9 for wrinkles, 3.6 for pigment, 3.1 for skin texture, and 2.6 for skin laxity.
When the patients themselves reviewed the digital images, the average GAIS score was 3.8 for overall appearance.
Side effects, said Dr. Murray, were transient, with edema and soft-tissue crusting lasting 3-5 days and erythema resolving in 1-2 weeks on average. One case of postinflammatory hyperpigmentation (PIH) did arise, which was linked to allergic contact dermatitis from the healing ointment. That patient stayed in the study and had complete resolution of the PIH.
Study Stands Out
A number of studies of the 2910-nm erbium-doped fluoride glass fiber laser have emerged over the past half year, Ritu Swali, MD, who was an American Society of Dermatologic Surgery fellow at a practice in Houston, said in an interview at the meeting. But this one stands out because of the evidence surrounding its use.
Most people are using this laser for facial resurfacing, “and we want to know that we have a technology ... with shorter downtime and easier wound care and just more comfort,” she said.
She noted that with conventional lasers, most patients get nerve blocks and some even opt for general anesthesia. “To be able to do the levels of facial resurfacing [Dr. Murray] is doing without having to do all of that pain management is pretty amazing,” Dr. Swali added.
The speed of the procedure and the relatively short downtime are also noteworthy, she said. “The huge advantage is having so much less pain from the procedure itself, so you’re able to do it faster because they’re tolerating it so well and you’re not having to take breaks,” she said.
As for downtime, Dr. Swali added, “these patients are coming in on a Thursday and they are back up and running by Monday,” as opposed to weeks that is typical with a conventional laser. This laser platform also avoids the pigmentation problems that can come with continuing and aggressive treatment with conventional lasers, she said.
Dr. Murray disclosed relationships with Acclaro Medical, the manufacturer of the laser. Dr. Swali has no relationships to disclose.
A version of this article first appeared on Medscape.com.
BALTIMORE — A — while causing less discomfort and downtime compared with conventional fractional lasers, a small single-center study showed.
The study enrolled 15 patients who had three treatment sessions with the 2910-nm laser. “It’s highly customizable,” the study’s lead author, Taryn Murray, MD, a dermatologist at Cleveland Clinic, told this news organization. “It has a really fast time in healing compared to traditional abatable lasers; the healing time is 5-7 days vs several weeks.” Dr. Murray presented the results at the annual meeting of the American Society for Laser Medicine and Surgery (ASLMS).
The Technology Behind the Laser
The 2910-nm erbium-doped fluoride glass fiber laser is a mid-infrared ablative fractional device that operates at peak water absorption. It’s designed to cause minimal residual thermal damage, resulting in less discomfort, shorter downtime, and potentially fewer side effects than conventional ablative lasers, Dr. Murray said.
Because of the way the pulses are delivered, “it’s far less painful than traditional fractional ablative lasers, so you can use mainly topical numbing; you don’t need nerve blocks, you don’t have to infiltrate lidocaine, you don’t have to put the patient under anesthesia,” she said.
“Because of the wavelength, how pulses are delivered and how customizable the settings are, it’s safer to use in darker skin types,” and the density, depth, and the amount of coagulation applied into the skin are customizable, Dr. Murray added.
The laser also delivers pulses in a different way than the conventional 2940-nm erbium and CO2 lasers, she explained. “Traditional lasers do it all in one pulse. This laser uses micropulses with relaxation time in between pulses, so the body interprets it as less painful and allows pressure and steam to escape out of the channel, which results in faster healing.”
The study patients had topical anesthetic cream applied to their faces 45-60 minutes before the procedure. Multiple passes were made using both superficial and deep laser modes. The average patient age was 65.7 years, and Fitzpatrick skin types included I (n = 3), II (n = 3), III (n = 7), and IV (n = 2). On a scale of 0-10, the average level of discomfort was 4.9, and the average patient satisfaction after three treatments was 4.8, Dr. Murray said.
For cosmetic improvement, the study used the 5-point Global Aesthetic Improvement Scale (GAIS). Blinded reviewers evaluated digital images and determined an average GAIS score of 3.2 for overall appearance, 2.9 for wrinkles, 3.6 for pigment, 3.1 for skin texture, and 2.6 for skin laxity.
When the patients themselves reviewed the digital images, the average GAIS score was 3.8 for overall appearance.
Side effects, said Dr. Murray, were transient, with edema and soft-tissue crusting lasting 3-5 days and erythema resolving in 1-2 weeks on average. One case of postinflammatory hyperpigmentation (PIH) did arise, which was linked to allergic contact dermatitis from the healing ointment. That patient stayed in the study and had complete resolution of the PIH.
Study Stands Out
A number of studies of the 2910-nm erbium-doped fluoride glass fiber laser have emerged over the past half year, Ritu Swali, MD, who was an American Society of Dermatologic Surgery fellow at a practice in Houston, said in an interview at the meeting. But this one stands out because of the evidence surrounding its use.
Most people are using this laser for facial resurfacing, “and we want to know that we have a technology ... with shorter downtime and easier wound care and just more comfort,” she said.
She noted that with conventional lasers, most patients get nerve blocks and some even opt for general anesthesia. “To be able to do the levels of facial resurfacing [Dr. Murray] is doing without having to do all of that pain management is pretty amazing,” Dr. Swali added.
The speed of the procedure and the relatively short downtime are also noteworthy, she said. “The huge advantage is having so much less pain from the procedure itself, so you’re able to do it faster because they’re tolerating it so well and you’re not having to take breaks,” she said.
As for downtime, Dr. Swali added, “these patients are coming in on a Thursday and they are back up and running by Monday,” as opposed to weeks that is typical with a conventional laser. This laser platform also avoids the pigmentation problems that can come with continuing and aggressive treatment with conventional lasers, she said.
Dr. Murray disclosed relationships with Acclaro Medical, the manufacturer of the laser. Dr. Swali has no relationships to disclose.
A version of this article first appeared on Medscape.com.
FROM ASLMS 2024
‘We Need to Rethink Our Options’: Lung Cancer Recurrence
This transcript has been edited for clarity.
Hello. It’s Mark Kris reporting back after attending the New York Lung Cancer Foundation Summit here in New York. A large amount of discussion went on, but as usual, I was most interested in the perioperative space.
In previous videos, I’ve talked about this ongoing discussion of whether you should operate and give adjuvant therapy or give neoadjuvant therapy, and I’ve addressed that already. One thing I want to bring up – and as we move off of that argument, which frankly doesn’t have an answer today, with neoadjuvant therapy, having all the data to support it – is
I was taught early on by my surgical mentors that the issue here was systemic control. While they could do very successful surgery to get high levels of local control, they could not control systemic disease. Sadly, the tools we had early on with chemotherapy were just not good enough. Suddenly, we have better tools to control systemic spread. In the past, the vast majority of occurrences were systemic; they’re now local.
What I think we need to do as a group of practitioners trying to deal with the problems getting in the way of curing our patients is look at what the issue is now. Frankly, the big issue now, as systemic therapy has controlled metastatic disease, is recurrence in the chest.
We give adjuvant osimertinib. Please remember what the numbers are. In the osimertinib arm, of the 11 recurrences reported in the European Society for Medical Oncology presentation a few years back, nine of them were in the chest or mediastinal nodes. In the arm that got no osimertinib afterward, there were 46 recurrences, and 32 of those 46 recurrences were in the chest, either the lung or mediastinal nodes. Therefore, 74% of the recurrences are suddenly in the chest. What’s the issue here?
The issue is we need to find strategies to give better disease control in the chest, as we have made inroads in controlling systemic disease with the targeted therapies in the endothelial growth factor receptor space, and very likely the checkpoint inhibitors, too, as that data kind of filters out. We need to think about how better to get local control.
I think rather than continue to get into this argument of neoadjuvant vs adjuvant, we should move to what’s really hurting our patients. Again, the data I quoted you was from the ADAURA trial, which was adjuvant therapy, and I’m sure the neoadjuvant is going to show the same thing. It’s better systemic therapy but now, more trouble in the chest.
How are we going to deal with that? I’d like to throw out one strategy, and that is to rethink the role of radiation in these patients. Again, if the problem is local in the chest, lung, and lymph nodes, we have to think about local therapy. Yes, we’re not recommending it routinely for everybody, but now that we have better systemic control, we need to rethink our options. The obvious one to rethink is about giving radiotherapy.
We should also use what we learned in the earlier trials, which is that there is harm in giving excessive radiation to the heart. If you avoid the heart, you avoid the harm. We have better planning strategies for stereotactic body radiotherapy and more traditional radiation, and of course, we have proton therapy as well.
As we continue to struggle with the idea of that patient with stage II or III disease, whether to give adjuvant vs neoadjuvant therapy, please remember to consider their risk in 2024. Their risk for first recurrence is in the chest.
What are we going to do to better control disease in the chest? We have a challenge. I’m sure we can meet it if we put our heads together.
Dr. Kris is professor of medicine at Weill Cornell Medical College, and attending physician, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York. He disclosed ties with AstraZeneca, Roche/Genentech, Ariad Pharmaceuticals, Pfizer, and PUMA.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
Hello. It’s Mark Kris reporting back after attending the New York Lung Cancer Foundation Summit here in New York. A large amount of discussion went on, but as usual, I was most interested in the perioperative space.
In previous videos, I’ve talked about this ongoing discussion of whether you should operate and give adjuvant therapy or give neoadjuvant therapy, and I’ve addressed that already. One thing I want to bring up – and as we move off of that argument, which frankly doesn’t have an answer today, with neoadjuvant therapy, having all the data to support it – is
I was taught early on by my surgical mentors that the issue here was systemic control. While they could do very successful surgery to get high levels of local control, they could not control systemic disease. Sadly, the tools we had early on with chemotherapy were just not good enough. Suddenly, we have better tools to control systemic spread. In the past, the vast majority of occurrences were systemic; they’re now local.
What I think we need to do as a group of practitioners trying to deal with the problems getting in the way of curing our patients is look at what the issue is now. Frankly, the big issue now, as systemic therapy has controlled metastatic disease, is recurrence in the chest.
We give adjuvant osimertinib. Please remember what the numbers are. In the osimertinib arm, of the 11 recurrences reported in the European Society for Medical Oncology presentation a few years back, nine of them were in the chest or mediastinal nodes. In the arm that got no osimertinib afterward, there were 46 recurrences, and 32 of those 46 recurrences were in the chest, either the lung or mediastinal nodes. Therefore, 74% of the recurrences are suddenly in the chest. What’s the issue here?
The issue is we need to find strategies to give better disease control in the chest, as we have made inroads in controlling systemic disease with the targeted therapies in the endothelial growth factor receptor space, and very likely the checkpoint inhibitors, too, as that data kind of filters out. We need to think about how better to get local control.
I think rather than continue to get into this argument of neoadjuvant vs adjuvant, we should move to what’s really hurting our patients. Again, the data I quoted you was from the ADAURA trial, which was adjuvant therapy, and I’m sure the neoadjuvant is going to show the same thing. It’s better systemic therapy but now, more trouble in the chest.
How are we going to deal with that? I’d like to throw out one strategy, and that is to rethink the role of radiation in these patients. Again, if the problem is local in the chest, lung, and lymph nodes, we have to think about local therapy. Yes, we’re not recommending it routinely for everybody, but now that we have better systemic control, we need to rethink our options. The obvious one to rethink is about giving radiotherapy.
We should also use what we learned in the earlier trials, which is that there is harm in giving excessive radiation to the heart. If you avoid the heart, you avoid the harm. We have better planning strategies for stereotactic body radiotherapy and more traditional radiation, and of course, we have proton therapy as well.
As we continue to struggle with the idea of that patient with stage II or III disease, whether to give adjuvant vs neoadjuvant therapy, please remember to consider their risk in 2024. Their risk for first recurrence is in the chest.
What are we going to do to better control disease in the chest? We have a challenge. I’m sure we can meet it if we put our heads together.
Dr. Kris is professor of medicine at Weill Cornell Medical College, and attending physician, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York. He disclosed ties with AstraZeneca, Roche/Genentech, Ariad Pharmaceuticals, Pfizer, and PUMA.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
Hello. It’s Mark Kris reporting back after attending the New York Lung Cancer Foundation Summit here in New York. A large amount of discussion went on, but as usual, I was most interested in the perioperative space.
In previous videos, I’ve talked about this ongoing discussion of whether you should operate and give adjuvant therapy or give neoadjuvant therapy, and I’ve addressed that already. One thing I want to bring up – and as we move off of that argument, which frankly doesn’t have an answer today, with neoadjuvant therapy, having all the data to support it – is
I was taught early on by my surgical mentors that the issue here was systemic control. While they could do very successful surgery to get high levels of local control, they could not control systemic disease. Sadly, the tools we had early on with chemotherapy were just not good enough. Suddenly, we have better tools to control systemic spread. In the past, the vast majority of occurrences were systemic; they’re now local.
What I think we need to do as a group of practitioners trying to deal with the problems getting in the way of curing our patients is look at what the issue is now. Frankly, the big issue now, as systemic therapy has controlled metastatic disease, is recurrence in the chest.
We give adjuvant osimertinib. Please remember what the numbers are. In the osimertinib arm, of the 11 recurrences reported in the European Society for Medical Oncology presentation a few years back, nine of them were in the chest or mediastinal nodes. In the arm that got no osimertinib afterward, there were 46 recurrences, and 32 of those 46 recurrences were in the chest, either the lung or mediastinal nodes. Therefore, 74% of the recurrences are suddenly in the chest. What’s the issue here?
The issue is we need to find strategies to give better disease control in the chest, as we have made inroads in controlling systemic disease with the targeted therapies in the endothelial growth factor receptor space, and very likely the checkpoint inhibitors, too, as that data kind of filters out. We need to think about how better to get local control.
I think rather than continue to get into this argument of neoadjuvant vs adjuvant, we should move to what’s really hurting our patients. Again, the data I quoted you was from the ADAURA trial, which was adjuvant therapy, and I’m sure the neoadjuvant is going to show the same thing. It’s better systemic therapy but now, more trouble in the chest.
How are we going to deal with that? I’d like to throw out one strategy, and that is to rethink the role of radiation in these patients. Again, if the problem is local in the chest, lung, and lymph nodes, we have to think about local therapy. Yes, we’re not recommending it routinely for everybody, but now that we have better systemic control, we need to rethink our options. The obvious one to rethink is about giving radiotherapy.
We should also use what we learned in the earlier trials, which is that there is harm in giving excessive radiation to the heart. If you avoid the heart, you avoid the harm. We have better planning strategies for stereotactic body radiotherapy and more traditional radiation, and of course, we have proton therapy as well.
As we continue to struggle with the idea of that patient with stage II or III disease, whether to give adjuvant vs neoadjuvant therapy, please remember to consider their risk in 2024. Their risk for first recurrence is in the chest.
What are we going to do to better control disease in the chest? We have a challenge. I’m sure we can meet it if we put our heads together.
Dr. Kris is professor of medicine at Weill Cornell Medical College, and attending physician, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York. He disclosed ties with AstraZeneca, Roche/Genentech, Ariad Pharmaceuticals, Pfizer, and PUMA.
A version of this article appeared on Medscape.com.
First Results From Laser-Related Adverse Events Registry Reported
BALTIMORE — A relatively . But the process of reporting AEs to the registry needs to be made easier to attract more cases and provide a more complete picture of complications after dermatologic procedures, a researcher and observer said.
The Cutaneous Procedures Adverse Events Reporting Registry (CAPER) was established in 2021 to track AEs from dermatologic procedures. Since then, it has logged a total of 81 cases and 147 AEs from 27 unique procedures, Eric Koza, MD, a postdoctoral research fellow in the Department of Dermatology at Northwestern University, Chicago, reported at the annual conference of the American Society for Laser Medicine and Surgery.
“The takeaways from this project is that 20 laser and energy device treatments have been reported to the registry, half of which were nonablative laser treatments,” Dr. Koza said in presenting the results. “Of the adverse events reported, nonphysicians and non-dermatologic physicians were more likely to be associated with severe or persistent adverse events.”
The American Society for Dermatologic Surgery Association and the Northwestern University Department of Dermatology launched CAPER. Previously, Dr. Koza said, AEs were typically reported only through the Food and Drug Administration’s AE reporting system. He noted that CAPER is the only voluntary national reporting registry for AEs from dermatologic procedures.
What the Registry Shows So Far
The registry matched 72 of the 81 cases with type of provider, with dermatologist-conducted procedures (51, 70.8%) comprising the majority, followed by nonphysician-conducted procedures (14, 19.4%) and nondermatologist physician–conducted procedures (7, 9.7%).
Of the 81 total cases, the following reports were related to laser and energy device treatments: 12 (14.3%) from nonablative laser treatments, five (6%) from light treatments, and three (3.6%) from ablative laser treatments, Dr. Koza said.
Among nonablative laser treatments, the most common AE was blistering (six reports, 50%). Scar, pain, and hypopigmentation accounted for two cases each (16.67%). Dermatologists performed seven of these cases (58.3%); nonphysicians, four (33.3%); and a non-dermatologist physician, one (8.3%).
For intense pulsed-light treatments, burns were the most common AEs (three reports, 60%), with swelling and inflammation each accounting for one case (20%). Three of these cases (75%) were confirmed to have been performed by nonphysicians.
The ablative laser treatment AEs included one case each of hypopigmentation, scar, and erythema. Two of the three cases were confirmed to have been performed by dermatologists.
Dr. Koza acknowledged the low number of cases is a limitation of this analysis of registry reports. A future goal for CAPER is to publicize it more, he said. “The registry is only 3 years old,” he told this news organization. “Hopefully, we can get more data as time goes on. We’ve been getting more and more each year.” CAPER adapted data entry forms used in other registries.
Submitting a case to the registry takes about 15 minutes of the provider’s time, Dr. Koza said. “We can streamline that to make it easier for people to submit their adverse events,” he said in an interview.
Only registry staff have access to the reports, and when reported, the data “is de-identified and any identifying information pertaining to the patient or reporter is removed,” according to a statement on the CAPER website.
‘Needs a Little Help’
Jennifer Lin, MD, a dermatologist at Brigham and Women’s Hospital and Dana-Farber Cancer Institute in Boston, who was at the meeting, commented on the onerous reporting process and the “low” enrollment. “It’s such an important initiative and with everyone over-logging e-mails, a 15-minute entry just is not going to cut it,” she told this news organization.
For providers, reporting AEs is stressful, she said. “As it is, it’s hard to voluntarily submit an adverse event,” Dr. Lin continued. “There’s a feeling of shame. Hospitals require it in order to monitor adverse events, but there’s no monitoring when you’re out in your own private practice.”
“The idea is excellent, but I think to facilitate better enrollment, the word has to get out at all these meetings” and make it easier to submit cases, Dr. Lin added. “It’s a good idea, but it needs a little help.”
Information on submitting AE reports to CAPER is available on the CAPER website.
Dr. Koza and Dr. Lin had no relevant relationships to disclose.
A version of this article first appeared on Medscape.com.
BALTIMORE — A relatively . But the process of reporting AEs to the registry needs to be made easier to attract more cases and provide a more complete picture of complications after dermatologic procedures, a researcher and observer said.
The Cutaneous Procedures Adverse Events Reporting Registry (CAPER) was established in 2021 to track AEs from dermatologic procedures. Since then, it has logged a total of 81 cases and 147 AEs from 27 unique procedures, Eric Koza, MD, a postdoctoral research fellow in the Department of Dermatology at Northwestern University, Chicago, reported at the annual conference of the American Society for Laser Medicine and Surgery.
“The takeaways from this project is that 20 laser and energy device treatments have been reported to the registry, half of which were nonablative laser treatments,” Dr. Koza said in presenting the results. “Of the adverse events reported, nonphysicians and non-dermatologic physicians were more likely to be associated with severe or persistent adverse events.”
The American Society for Dermatologic Surgery Association and the Northwestern University Department of Dermatology launched CAPER. Previously, Dr. Koza said, AEs were typically reported only through the Food and Drug Administration’s AE reporting system. He noted that CAPER is the only voluntary national reporting registry for AEs from dermatologic procedures.
What the Registry Shows So Far
The registry matched 72 of the 81 cases with type of provider, with dermatologist-conducted procedures (51, 70.8%) comprising the majority, followed by nonphysician-conducted procedures (14, 19.4%) and nondermatologist physician–conducted procedures (7, 9.7%).
Of the 81 total cases, the following reports were related to laser and energy device treatments: 12 (14.3%) from nonablative laser treatments, five (6%) from light treatments, and three (3.6%) from ablative laser treatments, Dr. Koza said.
Among nonablative laser treatments, the most common AE was blistering (six reports, 50%). Scar, pain, and hypopigmentation accounted for two cases each (16.67%). Dermatologists performed seven of these cases (58.3%); nonphysicians, four (33.3%); and a non-dermatologist physician, one (8.3%).
For intense pulsed-light treatments, burns were the most common AEs (three reports, 60%), with swelling and inflammation each accounting for one case (20%). Three of these cases (75%) were confirmed to have been performed by nonphysicians.
The ablative laser treatment AEs included one case each of hypopigmentation, scar, and erythema. Two of the three cases were confirmed to have been performed by dermatologists.
Dr. Koza acknowledged the low number of cases is a limitation of this analysis of registry reports. A future goal for CAPER is to publicize it more, he said. “The registry is only 3 years old,” he told this news organization. “Hopefully, we can get more data as time goes on. We’ve been getting more and more each year.” CAPER adapted data entry forms used in other registries.
Submitting a case to the registry takes about 15 minutes of the provider’s time, Dr. Koza said. “We can streamline that to make it easier for people to submit their adverse events,” he said in an interview.
Only registry staff have access to the reports, and when reported, the data “is de-identified and any identifying information pertaining to the patient or reporter is removed,” according to a statement on the CAPER website.
‘Needs a Little Help’
Jennifer Lin, MD, a dermatologist at Brigham and Women’s Hospital and Dana-Farber Cancer Institute in Boston, who was at the meeting, commented on the onerous reporting process and the “low” enrollment. “It’s such an important initiative and with everyone over-logging e-mails, a 15-minute entry just is not going to cut it,” she told this news organization.
For providers, reporting AEs is stressful, she said. “As it is, it’s hard to voluntarily submit an adverse event,” Dr. Lin continued. “There’s a feeling of shame. Hospitals require it in order to monitor adverse events, but there’s no monitoring when you’re out in your own private practice.”
“The idea is excellent, but I think to facilitate better enrollment, the word has to get out at all these meetings” and make it easier to submit cases, Dr. Lin added. “It’s a good idea, but it needs a little help.”
Information on submitting AE reports to CAPER is available on the CAPER website.
Dr. Koza and Dr. Lin had no relevant relationships to disclose.
A version of this article first appeared on Medscape.com.
BALTIMORE — A relatively . But the process of reporting AEs to the registry needs to be made easier to attract more cases and provide a more complete picture of complications after dermatologic procedures, a researcher and observer said.
The Cutaneous Procedures Adverse Events Reporting Registry (CAPER) was established in 2021 to track AEs from dermatologic procedures. Since then, it has logged a total of 81 cases and 147 AEs from 27 unique procedures, Eric Koza, MD, a postdoctoral research fellow in the Department of Dermatology at Northwestern University, Chicago, reported at the annual conference of the American Society for Laser Medicine and Surgery.
“The takeaways from this project is that 20 laser and energy device treatments have been reported to the registry, half of which were nonablative laser treatments,” Dr. Koza said in presenting the results. “Of the adverse events reported, nonphysicians and non-dermatologic physicians were more likely to be associated with severe or persistent adverse events.”
The American Society for Dermatologic Surgery Association and the Northwestern University Department of Dermatology launched CAPER. Previously, Dr. Koza said, AEs were typically reported only through the Food and Drug Administration’s AE reporting system. He noted that CAPER is the only voluntary national reporting registry for AEs from dermatologic procedures.
What the Registry Shows So Far
The registry matched 72 of the 81 cases with type of provider, with dermatologist-conducted procedures (51, 70.8%) comprising the majority, followed by nonphysician-conducted procedures (14, 19.4%) and nondermatologist physician–conducted procedures (7, 9.7%).
Of the 81 total cases, the following reports were related to laser and energy device treatments: 12 (14.3%) from nonablative laser treatments, five (6%) from light treatments, and three (3.6%) from ablative laser treatments, Dr. Koza said.
Among nonablative laser treatments, the most common AE was blistering (six reports, 50%). Scar, pain, and hypopigmentation accounted for two cases each (16.67%). Dermatologists performed seven of these cases (58.3%); nonphysicians, four (33.3%); and a non-dermatologist physician, one (8.3%).
For intense pulsed-light treatments, burns were the most common AEs (three reports, 60%), with swelling and inflammation each accounting for one case (20%). Three of these cases (75%) were confirmed to have been performed by nonphysicians.
The ablative laser treatment AEs included one case each of hypopigmentation, scar, and erythema. Two of the three cases were confirmed to have been performed by dermatologists.
Dr. Koza acknowledged the low number of cases is a limitation of this analysis of registry reports. A future goal for CAPER is to publicize it more, he said. “The registry is only 3 years old,” he told this news organization. “Hopefully, we can get more data as time goes on. We’ve been getting more and more each year.” CAPER adapted data entry forms used in other registries.
Submitting a case to the registry takes about 15 minutes of the provider’s time, Dr. Koza said. “We can streamline that to make it easier for people to submit their adverse events,” he said in an interview.
Only registry staff have access to the reports, and when reported, the data “is de-identified and any identifying information pertaining to the patient or reporter is removed,” according to a statement on the CAPER website.
‘Needs a Little Help’
Jennifer Lin, MD, a dermatologist at Brigham and Women’s Hospital and Dana-Farber Cancer Institute in Boston, who was at the meeting, commented on the onerous reporting process and the “low” enrollment. “It’s such an important initiative and with everyone over-logging e-mails, a 15-minute entry just is not going to cut it,” she told this news organization.
For providers, reporting AEs is stressful, she said. “As it is, it’s hard to voluntarily submit an adverse event,” Dr. Lin continued. “There’s a feeling of shame. Hospitals require it in order to monitor adverse events, but there’s no monitoring when you’re out in your own private practice.”
“The idea is excellent, but I think to facilitate better enrollment, the word has to get out at all these meetings” and make it easier to submit cases, Dr. Lin added. “It’s a good idea, but it needs a little help.”
Information on submitting AE reports to CAPER is available on the CAPER website.
Dr. Koza and Dr. Lin had no relevant relationships to disclose.
A version of this article first appeared on Medscape.com.
FROM ASLMS 2024
A Welcome Trade-off
At the end of March, in an anniversary no one but I noticed, I passed 4 years since I’d last rounded at the hospital.
It’s hard to comprehend that. I was at the hospital regularly for the first 22 years of my career, though admittedly it had dwindled from daily (1998-2011) to 1-2 weekends a month at the end.
Looking back, I still don’t miss it, and have no desire to go back. That’s not to say I don’t keep up on inpatient neurology, in case circumstances change, but at this point, honestly, I don’t want to. I’ve become accustomed to my non-hospital world, no late-night consults, no weekends spent rounding, no taking separate cars to restaurants or family events in case I get called in.
There are certainly things I miss about it. As odd as it may seem (and as much as I’d complain about it) I liked the wee hours of the really late night and early morning. It was quieter. Less chasing patients to tests or therapy. Pleasant idle chatter with staff and the few others docs around. Sitting at the computer and trying to think out a case on the fly. There was always junk food lying around.
But at this point in my life I’ll take the quiet of being home and my routine office hours. I know when my office day starts and ends. Aside from the occasional stop at Costco, I won’t be going anywhere else on my way home. I still get the occasional after-hours call, but none that require me to run to the ER.
On Fridays I’m glad the week is over, and don’t dread the 5:00 answering service switchover, or my call partner giving me the patient list.
There’s some revenue lost in the deal, but I’ll still take the trade-off.
It’s not like I ever had some grand plan to leave the hospital — I actually had thought I’d be there, at least occasionally, until retirement. But here I am.
Not to say there aren’t docs my age (and older) who still do it. Certainly our experience makes us good at it. But younger docs are closer to residency, which is primarily inpatient, so it’s an easier transition for many.
They probably have more energy, too.
Dr. Block has a solo neurology practice in Scottsdale, Arizona.
At the end of March, in an anniversary no one but I noticed, I passed 4 years since I’d last rounded at the hospital.
It’s hard to comprehend that. I was at the hospital regularly for the first 22 years of my career, though admittedly it had dwindled from daily (1998-2011) to 1-2 weekends a month at the end.
Looking back, I still don’t miss it, and have no desire to go back. That’s not to say I don’t keep up on inpatient neurology, in case circumstances change, but at this point, honestly, I don’t want to. I’ve become accustomed to my non-hospital world, no late-night consults, no weekends spent rounding, no taking separate cars to restaurants or family events in case I get called in.
There are certainly things I miss about it. As odd as it may seem (and as much as I’d complain about it) I liked the wee hours of the really late night and early morning. It was quieter. Less chasing patients to tests or therapy. Pleasant idle chatter with staff and the few others docs around. Sitting at the computer and trying to think out a case on the fly. There was always junk food lying around.
But at this point in my life I’ll take the quiet of being home and my routine office hours. I know when my office day starts and ends. Aside from the occasional stop at Costco, I won’t be going anywhere else on my way home. I still get the occasional after-hours call, but none that require me to run to the ER.
On Fridays I’m glad the week is over, and don’t dread the 5:00 answering service switchover, or my call partner giving me the patient list.
There’s some revenue lost in the deal, but I’ll still take the trade-off.
It’s not like I ever had some grand plan to leave the hospital — I actually had thought I’d be there, at least occasionally, until retirement. But here I am.
Not to say there aren’t docs my age (and older) who still do it. Certainly our experience makes us good at it. But younger docs are closer to residency, which is primarily inpatient, so it’s an easier transition for many.
They probably have more energy, too.
Dr. Block has a solo neurology practice in Scottsdale, Arizona.
At the end of March, in an anniversary no one but I noticed, I passed 4 years since I’d last rounded at the hospital.
It’s hard to comprehend that. I was at the hospital regularly for the first 22 years of my career, though admittedly it had dwindled from daily (1998-2011) to 1-2 weekends a month at the end.
Looking back, I still don’t miss it, and have no desire to go back. That’s not to say I don’t keep up on inpatient neurology, in case circumstances change, but at this point, honestly, I don’t want to. I’ve become accustomed to my non-hospital world, no late-night consults, no weekends spent rounding, no taking separate cars to restaurants or family events in case I get called in.
There are certainly things I miss about it. As odd as it may seem (and as much as I’d complain about it) I liked the wee hours of the really late night and early morning. It was quieter. Less chasing patients to tests or therapy. Pleasant idle chatter with staff and the few others docs around. Sitting at the computer and trying to think out a case on the fly. There was always junk food lying around.
But at this point in my life I’ll take the quiet of being home and my routine office hours. I know when my office day starts and ends. Aside from the occasional stop at Costco, I won’t be going anywhere else on my way home. I still get the occasional after-hours call, but none that require me to run to the ER.
On Fridays I’m glad the week is over, and don’t dread the 5:00 answering service switchover, or my call partner giving me the patient list.
There’s some revenue lost in the deal, but I’ll still take the trade-off.
It’s not like I ever had some grand plan to leave the hospital — I actually had thought I’d be there, at least occasionally, until retirement. But here I am.
Not to say there aren’t docs my age (and older) who still do it. Certainly our experience makes us good at it. But younger docs are closer to residency, which is primarily inpatient, so it’s an easier transition for many.
They probably have more energy, too.
Dr. Block has a solo neurology practice in Scottsdale, Arizona.
Commentary: Comparisons Among PsA Therapies, May 2024
Bimekizumab is a novel biologic therapy that inhibits interleukin (IL)–17A and IL-17F and is efficacious in the treatment of psoriasis, PsA, and axial spondyloarthritis. In the absence of a formal head-to-head study, matching-adjusted indirect comparison is a method to evaluate comparative effectiveness. Warren and colleagues ran a study that included biological DMARD-naive patients and patients with inadequate response to tumor necrosis factor inhibitors (TNFi-IR) with PsA who received bimekizumab (160 mg every 4 weeks; 431 and 267 patients, respectively) and guselkumab (100 mg every 4 weeks or every 8 weeks; 495 and 189 patients, respectively). They demonstrate that in biological DMARD-naive patients, bimekizumab was associated with a greater likelihood of achieving ≥70% improvement in American College of Rheumatology (ACR) response and minimal disease activity outcome at week 52 compared with guselkumab. Similar outcomes were observed in the TNFi-IR subgroup. Thus, bimekizumab may be more effective than guselkumab in PsA. Formal head-to-head studies comparing bimekizumab vs guselkumab are required.
With the availability of multiple targeted therapies for PsA, choosing the most effective and safe drug for a patient is difficult, especially in the absence of many head-to-head clinical trials. To help address this problem, Lin and Ren conducted a network meta-analysis of head-to-head active comparison studies in PsA. They included 17 studies in their analysis and demonstrated that Janus kinase inhibitors had the highest probability of achieving ACR 20/50/70 response. Treatment with IL-17A inhibitors was more likely than TNFi therapy to lead to resolution of enthesitis and dactylitis and achieving combined ACR 50 and Psoriasis Area Severity Index 100 response. Patients receiving phosphodiesterase 4 inhibitors were least likely to have adverse events. They conclude that when both efficacy and safety are considered, IL-17A inhibitors may be the better agent for initial therapy for PsA. IL-17A inhibitors are indeed safe and efficacious in PsA; more direct head-to-head comparisons as well as strategy trials are required to determine choice of first and subsequent therapy in PsA.
Infections are the most important adverse effects of targeted therapies. The risk for infection in PsA in real-world settings is not well known. In a cohort study that included 12,071 patients with PsA from the French national health insurance database who were new users of targeted therapies (adalimumab, etanercept, golimumab, certolizumab pegol, infliximab, secukinumab, ixekizumab, ustekinumab, and tofacitinib), Bastard and colleagues demonstrated that the incidence of serious infections in users of targeted therapies was 17.0 per 1000 person-years. Compared with new users of adalimumab, the risk for serious infections was significantly lower in new users of etanercept (weighted hazard ratio [wHR] 0.72; 95% CI 0.53-0.97) and ustekinumab (wHR 0.57; 95% CI 0.35-0.93). Thus, the overall risk for serious infections is low, with etanercept and ustekinumab being safer treatment options than adalimumab.
Bimekizumab is a novel biologic therapy that inhibits interleukin (IL)–17A and IL-17F and is efficacious in the treatment of psoriasis, PsA, and axial spondyloarthritis. In the absence of a formal head-to-head study, matching-adjusted indirect comparison is a method to evaluate comparative effectiveness. Warren and colleagues ran a study that included biological DMARD-naive patients and patients with inadequate response to tumor necrosis factor inhibitors (TNFi-IR) with PsA who received bimekizumab (160 mg every 4 weeks; 431 and 267 patients, respectively) and guselkumab (100 mg every 4 weeks or every 8 weeks; 495 and 189 patients, respectively). They demonstrate that in biological DMARD-naive patients, bimekizumab was associated with a greater likelihood of achieving ≥70% improvement in American College of Rheumatology (ACR) response and minimal disease activity outcome at week 52 compared with guselkumab. Similar outcomes were observed in the TNFi-IR subgroup. Thus, bimekizumab may be more effective than guselkumab in PsA. Formal head-to-head studies comparing bimekizumab vs guselkumab are required.
With the availability of multiple targeted therapies for PsA, choosing the most effective and safe drug for a patient is difficult, especially in the absence of many head-to-head clinical trials. To help address this problem, Lin and Ren conducted a network meta-analysis of head-to-head active comparison studies in PsA. They included 17 studies in their analysis and demonstrated that Janus kinase inhibitors had the highest probability of achieving ACR 20/50/70 response. Treatment with IL-17A inhibitors was more likely than TNFi therapy to lead to resolution of enthesitis and dactylitis and achieving combined ACR 50 and Psoriasis Area Severity Index 100 response. Patients receiving phosphodiesterase 4 inhibitors were least likely to have adverse events. They conclude that when both efficacy and safety are considered, IL-17A inhibitors may be the better agent for initial therapy for PsA. IL-17A inhibitors are indeed safe and efficacious in PsA; more direct head-to-head comparisons as well as strategy trials are required to determine choice of first and subsequent therapy in PsA.
Infections are the most important adverse effects of targeted therapies. The risk for infection in PsA in real-world settings is not well known. In a cohort study that included 12,071 patients with PsA from the French national health insurance database who were new users of targeted therapies (adalimumab, etanercept, golimumab, certolizumab pegol, infliximab, secukinumab, ixekizumab, ustekinumab, and tofacitinib), Bastard and colleagues demonstrated that the incidence of serious infections in users of targeted therapies was 17.0 per 1000 person-years. Compared with new users of adalimumab, the risk for serious infections was significantly lower in new users of etanercept (weighted hazard ratio [wHR] 0.72; 95% CI 0.53-0.97) and ustekinumab (wHR 0.57; 95% CI 0.35-0.93). Thus, the overall risk for serious infections is low, with etanercept and ustekinumab being safer treatment options than adalimumab.
Bimekizumab is a novel biologic therapy that inhibits interleukin (IL)–17A and IL-17F and is efficacious in the treatment of psoriasis, PsA, and axial spondyloarthritis. In the absence of a formal head-to-head study, matching-adjusted indirect comparison is a method to evaluate comparative effectiveness. Warren and colleagues ran a study that included biological DMARD-naive patients and patients with inadequate response to tumor necrosis factor inhibitors (TNFi-IR) with PsA who received bimekizumab (160 mg every 4 weeks; 431 and 267 patients, respectively) and guselkumab (100 mg every 4 weeks or every 8 weeks; 495 and 189 patients, respectively). They demonstrate that in biological DMARD-naive patients, bimekizumab was associated with a greater likelihood of achieving ≥70% improvement in American College of Rheumatology (ACR) response and minimal disease activity outcome at week 52 compared with guselkumab. Similar outcomes were observed in the TNFi-IR subgroup. Thus, bimekizumab may be more effective than guselkumab in PsA. Formal head-to-head studies comparing bimekizumab vs guselkumab are required.
With the availability of multiple targeted therapies for PsA, choosing the most effective and safe drug for a patient is difficult, especially in the absence of many head-to-head clinical trials. To help address this problem, Lin and Ren conducted a network meta-analysis of head-to-head active comparison studies in PsA. They included 17 studies in their analysis and demonstrated that Janus kinase inhibitors had the highest probability of achieving ACR 20/50/70 response. Treatment with IL-17A inhibitors was more likely than TNFi therapy to lead to resolution of enthesitis and dactylitis and achieving combined ACR 50 and Psoriasis Area Severity Index 100 response. Patients receiving phosphodiesterase 4 inhibitors were least likely to have adverse events. They conclude that when both efficacy and safety are considered, IL-17A inhibitors may be the better agent for initial therapy for PsA. IL-17A inhibitors are indeed safe and efficacious in PsA; more direct head-to-head comparisons as well as strategy trials are required to determine choice of first and subsequent therapy in PsA.
Infections are the most important adverse effects of targeted therapies. The risk for infection in PsA in real-world settings is not well known. In a cohort study that included 12,071 patients with PsA from the French national health insurance database who were new users of targeted therapies (adalimumab, etanercept, golimumab, certolizumab pegol, infliximab, secukinumab, ixekizumab, ustekinumab, and tofacitinib), Bastard and colleagues demonstrated that the incidence of serious infections in users of targeted therapies was 17.0 per 1000 person-years. Compared with new users of adalimumab, the risk for serious infections was significantly lower in new users of etanercept (weighted hazard ratio [wHR] 0.72; 95% CI 0.53-0.97) and ustekinumab (wHR 0.57; 95% CI 0.35-0.93). Thus, the overall risk for serious infections is low, with etanercept and ustekinumab being safer treatment options than adalimumab.
Can Rectal Cancer Patients Benefit from Deintensification of Treatment?
New and evolving research in locally advanced rectal cancer suggests that selective use of treatments in some patients can achieve outcomes similar to those of standard regimens, according to the chair of the Department of Radiation Oncology at Duke University School of Medicine, Durham, North Carolina.
Total neoadjuvant therapy (TNT) is the standard treatment that involves systemic chemotherapy and radiation therapy before surgery for patients with locally advanced rectal cancer, Christopher G. Willett, MD, explained, in an interview. However, recent clinical trials support several strategies for “deintensification” of TNT for patients with locally advanced rectal cancer, he said.
Some patients may not require surgery or radiation therapy, or they may not require any treatment modalities including radiation therapy, chemotherapy, and surgery, Dr. Willett continued.
However, “these patients require close surveillance post treatment to identify any recurrence that may require salvage treatment,” he added.
During a presentation at the 2024 National Comprehensive Cancer Network Annual Conference, Dr. Willett primarily discussed the following three strategies for deintensifying overall therapy for locally advanced rectal cancer:
- Selective surgical omission for patients with rectal cancer having a complete clinical response after TNT with close surveillance following treatment.
- Selective omission of radiation therapy for patients with surgery such as sphincter-sparing surgery.
- Selective omission of all treatment modalities (radiation therapy, chemotherapy and surgery).
Does Watch and Wait Work?
Selective surgical omission, also known as a “watch and wait” or nonoperative management (NOM), involves treating patients with chemotherapy or a combination of chemo and radiation therapy but without surgery, Dr. Willett said during his presentation at the meeting.
Data from the OPRA trial published in the Journal of Clinical Oncology showed that 36% of patients who started on NOM developed tumor regrowth, most of which occurred in the first 2-3 years. Five-year disease-free survival rates were similar in patients who had total mesorectal excision (TME) upfront and those who had salvage TME procedures after tumor regrowth (61% and 62%, respectively). An update to the OPRA trial showed that the clinical outcomes persisted, and the results suggest no significant differences in disease-free survival between upfront surgery vs. watch and wait, Dr. Willett said.
Does Selective Omission of Radiotherapy Work?
Selective omission of radiotherapy is another option for reducing the overall treatment burden in patients with locally advanced rectal cancer, Dr. Willett. For these patients, who are at relatively low risk for recurrence, radiation along with surgery may not be needed.
Data from the FOWARC trial, published in the Journal of Clinical Oncology in 2016 and 2019, included 495 patients from 15 centers in China. In the randomized trial, the researchers found no significant difference in the primary outcome of disease-free survival between patients assigned in a 1:1:1 ratio to three arms:
- FOLFOX chemotherapy alone (a combination of chemotherapy drugs including folinic acid, fluorouracil, and oxaliplatin).
- FOLFOX plus chemoradiation.
- FU (fluorouracil)/LV (leucovorin calcium) plus chemoradiation.
Although the data were ultimately inconclusive because of potential staging bias, the findings were “promising for recommending radiation omission in these patients,” Dr. Willett said.
The larger PROSPECT study published in The New England Journal of Medicine in 2023 was similarly encouraging, he said. In this trial, 1194 patients with locally advanced rectal cancer were randomized to FOLFOX or chemoradiation prior to sphincter-sparing surgery. The two groups showed similar 5-year estimated overall survival, complete resection (R0), and pathological complete response.
“These further data support the idea that we don’t need radiotherapy anymore,” Dr. Willett said.
PROSPECT was “a very well-done trial” that also showed important patient reported outcomes, he said. At 12 months after surgery, patients in the chemoradiation group had higher scores on fatigue and neuropathy measures, but less than 15% were severe. Sexual function scores for men and women were worse in the chemoradiation group, although overall health-related quality-of-life scores were not significantly different between the groups, he noted.
Does Dropping Everything But Immunotherapy Work?
Research is very preliminary, but a small study of 12 patients with mismatch repair-deficit (MMRd) locally advanced rectal cancer published in The New England Journal of Medicine “lends optimism” to a personalized treatment approach via a programmed death 1 (PD-1) blockade, Dr. Willett said. The “small, but impressive numbers” showed that all 12 patients treated with dostarlimab only (an anti-PD-1 monoclonal antibody) had durable disease control at a follow-up of 6-24 months.
This option is feasible for patients with MMRd locally advanced rectal cancer, Dr. Willett said in an interview. “Patients treated with only dostarlimab (a PD-1 inhibitor) had excellent outcomes and did not require radiation therapy, chemotherapy, and surgery. This is potentially a new paradigm of treatment for MMRd rectal cancer.”
What are the Clinical Implications and Next Steps?
Patients should be carefully evaluated and selected for treatment approaches by experienced multidisciplinary teams with vigilant posttreatment surveillance, including history and physical exam, endoscopy, computed tomography (CT) of the chest, and abdomen and pelvic magnetic resonance imaging (MRI), Dr. Willett said in the interview.
Data on the treatment of patients with MMRd rectal cancer using dostarlimab and other immune checkpoint inhibitors are preliminary; more patients and further follow-up are required, he said. This treatment is applicable to only 5%-10% of patients with rectal cancer, he continued.
“There is a need for biomarkers such as circulating tumor DNA to further aid in selection and monitoring of patients with rectal cancer,” Dr. Willett said.
Other preliminary research is examining circulating tumor DNA analysis to guide adjuvant treatment for patients with resected stage II colon cancer, he noted in his presentation. Currently, ctDNA-driven therapy is not recommended by the NCCN, but more research is needed to determine whether this strategy might be applied to decision-making in rectal cancer patients, especially with watch and wait/nonoperative strategies, he said.
What Are the Takeaways for Deintensifying Treatment of Rectal Cancer?
The global continuum of rectal cancer clinical trials has provided significant evidence that, for select patients, the deintensification of treatment strategies may result in the avoidance of radiation and even avoidance of surgery, which can profoundly improve long-term quality of life, Al B. Benson III, MD, said in an interview.
“A critical takeaway message for clinicians who are determining which individual patient might benefit from a less intensive regimen to treat locally advanced rectal cancer is to first have a multidisciplinary consensus which should encompass review of a rectal MRI, pathology, chest and abdominal imaging, colonoscopy, as well as the patient’s clinical status including comorbidities,” said Dr. Benson, who served as chair of the NCCN Guidelines Panel for Colon/Rectal/Anal Cancers and Small Intestine Adenocarcinoma.
“The location of the rectal tumor (distal versus proximal) and clinical TNM stage also will inform the discussion as to which of the potential total neoadjuvant therapy regimens would be most optimal to reduce the risk of local recurrence and maintain long-term quality of life for the individual patient,” explained Dr. Benson, professor of medicine at Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Chicago.
The effectiveness of less intense treatment for rectal cancer remains a work in progress, Dr. Benson said in an interview. “There is much we still do not know, such as the optimal selection of patients and the durability of this approach over time.”
Patients who undergo watch and wait require intensive follow-up, including sigmoidoscopy, digital rectal exam, and rectal MRI, to detect any evidence of local recurrence that would warrant further intervention, including possible radiation and surgery, he said. A highly skilled multidisciplinary team is a must for individuals who are potential candidates for a less intense treatment regimen, he emphasized.
The treatment of locally advanced rectal cancer continues to evolve, but there is no question that TNT has transformed patient outcomes, including the ability to deintensify treatment for select patients, Dr. Benson said.
However, many research gaps remain, Dr. Benson said in an interview. “For the MSI/dMMR patient who has achieved a complete response from immunotherapy we will need more long-term data to determine the durability of a complete clinical response and long-term avoidance of other interventions including radiation, chemotherapy and surgery.
“The wait and watch strategy for the much more common MSS patient also will require much longer follow-up to determine which patients are destined to recur and which are not,” he added.
“The introduction of monitoring with ctDNA determination over time offers an opportunity to streamline surveillance of patients who have completed combination therapy and for those undergoing watch and wait; however, much more information is required to determine which of the various ctDNA assays are most optimal, and the frequency and duration of ctDNA determination that will lend this approach as a standard of care,” Dr. Benson said.
Dr. Willett and Dr. Benson had no financial conflicts to disclose.
New and evolving research in locally advanced rectal cancer suggests that selective use of treatments in some patients can achieve outcomes similar to those of standard regimens, according to the chair of the Department of Radiation Oncology at Duke University School of Medicine, Durham, North Carolina.
Total neoadjuvant therapy (TNT) is the standard treatment that involves systemic chemotherapy and radiation therapy before surgery for patients with locally advanced rectal cancer, Christopher G. Willett, MD, explained, in an interview. However, recent clinical trials support several strategies for “deintensification” of TNT for patients with locally advanced rectal cancer, he said.
Some patients may not require surgery or radiation therapy, or they may not require any treatment modalities including radiation therapy, chemotherapy, and surgery, Dr. Willett continued.
However, “these patients require close surveillance post treatment to identify any recurrence that may require salvage treatment,” he added.
During a presentation at the 2024 National Comprehensive Cancer Network Annual Conference, Dr. Willett primarily discussed the following three strategies for deintensifying overall therapy for locally advanced rectal cancer:
- Selective surgical omission for patients with rectal cancer having a complete clinical response after TNT with close surveillance following treatment.
- Selective omission of radiation therapy for patients with surgery such as sphincter-sparing surgery.
- Selective omission of all treatment modalities (radiation therapy, chemotherapy and surgery).
Does Watch and Wait Work?
Selective surgical omission, also known as a “watch and wait” or nonoperative management (NOM), involves treating patients with chemotherapy or a combination of chemo and radiation therapy but without surgery, Dr. Willett said during his presentation at the meeting.
Data from the OPRA trial published in the Journal of Clinical Oncology showed that 36% of patients who started on NOM developed tumor regrowth, most of which occurred in the first 2-3 years. Five-year disease-free survival rates were similar in patients who had total mesorectal excision (TME) upfront and those who had salvage TME procedures after tumor regrowth (61% and 62%, respectively). An update to the OPRA trial showed that the clinical outcomes persisted, and the results suggest no significant differences in disease-free survival between upfront surgery vs. watch and wait, Dr. Willett said.
Does Selective Omission of Radiotherapy Work?
Selective omission of radiotherapy is another option for reducing the overall treatment burden in patients with locally advanced rectal cancer, Dr. Willett. For these patients, who are at relatively low risk for recurrence, radiation along with surgery may not be needed.
Data from the FOWARC trial, published in the Journal of Clinical Oncology in 2016 and 2019, included 495 patients from 15 centers in China. In the randomized trial, the researchers found no significant difference in the primary outcome of disease-free survival between patients assigned in a 1:1:1 ratio to three arms:
- FOLFOX chemotherapy alone (a combination of chemotherapy drugs including folinic acid, fluorouracil, and oxaliplatin).
- FOLFOX plus chemoradiation.
- FU (fluorouracil)/LV (leucovorin calcium) plus chemoradiation.
Although the data were ultimately inconclusive because of potential staging bias, the findings were “promising for recommending radiation omission in these patients,” Dr. Willett said.
The larger PROSPECT study published in The New England Journal of Medicine in 2023 was similarly encouraging, he said. In this trial, 1194 patients with locally advanced rectal cancer were randomized to FOLFOX or chemoradiation prior to sphincter-sparing surgery. The two groups showed similar 5-year estimated overall survival, complete resection (R0), and pathological complete response.
“These further data support the idea that we don’t need radiotherapy anymore,” Dr. Willett said.
PROSPECT was “a very well-done trial” that also showed important patient reported outcomes, he said. At 12 months after surgery, patients in the chemoradiation group had higher scores on fatigue and neuropathy measures, but less than 15% were severe. Sexual function scores for men and women were worse in the chemoradiation group, although overall health-related quality-of-life scores were not significantly different between the groups, he noted.
Does Dropping Everything But Immunotherapy Work?
Research is very preliminary, but a small study of 12 patients with mismatch repair-deficit (MMRd) locally advanced rectal cancer published in The New England Journal of Medicine “lends optimism” to a personalized treatment approach via a programmed death 1 (PD-1) blockade, Dr. Willett said. The “small, but impressive numbers” showed that all 12 patients treated with dostarlimab only (an anti-PD-1 monoclonal antibody) had durable disease control at a follow-up of 6-24 months.
This option is feasible for patients with MMRd locally advanced rectal cancer, Dr. Willett said in an interview. “Patients treated with only dostarlimab (a PD-1 inhibitor) had excellent outcomes and did not require radiation therapy, chemotherapy, and surgery. This is potentially a new paradigm of treatment for MMRd rectal cancer.”
What are the Clinical Implications and Next Steps?
Patients should be carefully evaluated and selected for treatment approaches by experienced multidisciplinary teams with vigilant posttreatment surveillance, including history and physical exam, endoscopy, computed tomography (CT) of the chest, and abdomen and pelvic magnetic resonance imaging (MRI), Dr. Willett said in the interview.
Data on the treatment of patients with MMRd rectal cancer using dostarlimab and other immune checkpoint inhibitors are preliminary; more patients and further follow-up are required, he said. This treatment is applicable to only 5%-10% of patients with rectal cancer, he continued.
“There is a need for biomarkers such as circulating tumor DNA to further aid in selection and monitoring of patients with rectal cancer,” Dr. Willett said.
Other preliminary research is examining circulating tumor DNA analysis to guide adjuvant treatment for patients with resected stage II colon cancer, he noted in his presentation. Currently, ctDNA-driven therapy is not recommended by the NCCN, but more research is needed to determine whether this strategy might be applied to decision-making in rectal cancer patients, especially with watch and wait/nonoperative strategies, he said.
What Are the Takeaways for Deintensifying Treatment of Rectal Cancer?
The global continuum of rectal cancer clinical trials has provided significant evidence that, for select patients, the deintensification of treatment strategies may result in the avoidance of radiation and even avoidance of surgery, which can profoundly improve long-term quality of life, Al B. Benson III, MD, said in an interview.
“A critical takeaway message for clinicians who are determining which individual patient might benefit from a less intensive regimen to treat locally advanced rectal cancer is to first have a multidisciplinary consensus which should encompass review of a rectal MRI, pathology, chest and abdominal imaging, colonoscopy, as well as the patient’s clinical status including comorbidities,” said Dr. Benson, who served as chair of the NCCN Guidelines Panel for Colon/Rectal/Anal Cancers and Small Intestine Adenocarcinoma.
“The location of the rectal tumor (distal versus proximal) and clinical TNM stage also will inform the discussion as to which of the potential total neoadjuvant therapy regimens would be most optimal to reduce the risk of local recurrence and maintain long-term quality of life for the individual patient,” explained Dr. Benson, professor of medicine at Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Chicago.
The effectiveness of less intense treatment for rectal cancer remains a work in progress, Dr. Benson said in an interview. “There is much we still do not know, such as the optimal selection of patients and the durability of this approach over time.”
Patients who undergo watch and wait require intensive follow-up, including sigmoidoscopy, digital rectal exam, and rectal MRI, to detect any evidence of local recurrence that would warrant further intervention, including possible radiation and surgery, he said. A highly skilled multidisciplinary team is a must for individuals who are potential candidates for a less intense treatment regimen, he emphasized.
The treatment of locally advanced rectal cancer continues to evolve, but there is no question that TNT has transformed patient outcomes, including the ability to deintensify treatment for select patients, Dr. Benson said.
However, many research gaps remain, Dr. Benson said in an interview. “For the MSI/dMMR patient who has achieved a complete response from immunotherapy we will need more long-term data to determine the durability of a complete clinical response and long-term avoidance of other interventions including radiation, chemotherapy and surgery.
“The wait and watch strategy for the much more common MSS patient also will require much longer follow-up to determine which patients are destined to recur and which are not,” he added.
“The introduction of monitoring with ctDNA determination over time offers an opportunity to streamline surveillance of patients who have completed combination therapy and for those undergoing watch and wait; however, much more information is required to determine which of the various ctDNA assays are most optimal, and the frequency and duration of ctDNA determination that will lend this approach as a standard of care,” Dr. Benson said.
Dr. Willett and Dr. Benson had no financial conflicts to disclose.
New and evolving research in locally advanced rectal cancer suggests that selective use of treatments in some patients can achieve outcomes similar to those of standard regimens, according to the chair of the Department of Radiation Oncology at Duke University School of Medicine, Durham, North Carolina.
Total neoadjuvant therapy (TNT) is the standard treatment that involves systemic chemotherapy and radiation therapy before surgery for patients with locally advanced rectal cancer, Christopher G. Willett, MD, explained, in an interview. However, recent clinical trials support several strategies for “deintensification” of TNT for patients with locally advanced rectal cancer, he said.
Some patients may not require surgery or radiation therapy, or they may not require any treatment modalities including radiation therapy, chemotherapy, and surgery, Dr. Willett continued.
However, “these patients require close surveillance post treatment to identify any recurrence that may require salvage treatment,” he added.
During a presentation at the 2024 National Comprehensive Cancer Network Annual Conference, Dr. Willett primarily discussed the following three strategies for deintensifying overall therapy for locally advanced rectal cancer:
- Selective surgical omission for patients with rectal cancer having a complete clinical response after TNT with close surveillance following treatment.
- Selective omission of radiation therapy for patients with surgery such as sphincter-sparing surgery.
- Selective omission of all treatment modalities (radiation therapy, chemotherapy and surgery).
Does Watch and Wait Work?
Selective surgical omission, also known as a “watch and wait” or nonoperative management (NOM), involves treating patients with chemotherapy or a combination of chemo and radiation therapy but without surgery, Dr. Willett said during his presentation at the meeting.
Data from the OPRA trial published in the Journal of Clinical Oncology showed that 36% of patients who started on NOM developed tumor regrowth, most of which occurred in the first 2-3 years. Five-year disease-free survival rates were similar in patients who had total mesorectal excision (TME) upfront and those who had salvage TME procedures after tumor regrowth (61% and 62%, respectively). An update to the OPRA trial showed that the clinical outcomes persisted, and the results suggest no significant differences in disease-free survival between upfront surgery vs. watch and wait, Dr. Willett said.
Does Selective Omission of Radiotherapy Work?
Selective omission of radiotherapy is another option for reducing the overall treatment burden in patients with locally advanced rectal cancer, Dr. Willett. For these patients, who are at relatively low risk for recurrence, radiation along with surgery may not be needed.
Data from the FOWARC trial, published in the Journal of Clinical Oncology in 2016 and 2019, included 495 patients from 15 centers in China. In the randomized trial, the researchers found no significant difference in the primary outcome of disease-free survival between patients assigned in a 1:1:1 ratio to three arms:
- FOLFOX chemotherapy alone (a combination of chemotherapy drugs including folinic acid, fluorouracil, and oxaliplatin).
- FOLFOX plus chemoradiation.
- FU (fluorouracil)/LV (leucovorin calcium) plus chemoradiation.
Although the data were ultimately inconclusive because of potential staging bias, the findings were “promising for recommending radiation omission in these patients,” Dr. Willett said.
The larger PROSPECT study published in The New England Journal of Medicine in 2023 was similarly encouraging, he said. In this trial, 1194 patients with locally advanced rectal cancer were randomized to FOLFOX or chemoradiation prior to sphincter-sparing surgery. The two groups showed similar 5-year estimated overall survival, complete resection (R0), and pathological complete response.
“These further data support the idea that we don’t need radiotherapy anymore,” Dr. Willett said.
PROSPECT was “a very well-done trial” that also showed important patient reported outcomes, he said. At 12 months after surgery, patients in the chemoradiation group had higher scores on fatigue and neuropathy measures, but less than 15% were severe. Sexual function scores for men and women were worse in the chemoradiation group, although overall health-related quality-of-life scores were not significantly different between the groups, he noted.
Does Dropping Everything But Immunotherapy Work?
Research is very preliminary, but a small study of 12 patients with mismatch repair-deficit (MMRd) locally advanced rectal cancer published in The New England Journal of Medicine “lends optimism” to a personalized treatment approach via a programmed death 1 (PD-1) blockade, Dr. Willett said. The “small, but impressive numbers” showed that all 12 patients treated with dostarlimab only (an anti-PD-1 monoclonal antibody) had durable disease control at a follow-up of 6-24 months.
This option is feasible for patients with MMRd locally advanced rectal cancer, Dr. Willett said in an interview. “Patients treated with only dostarlimab (a PD-1 inhibitor) had excellent outcomes and did not require radiation therapy, chemotherapy, and surgery. This is potentially a new paradigm of treatment for MMRd rectal cancer.”
What are the Clinical Implications and Next Steps?
Patients should be carefully evaluated and selected for treatment approaches by experienced multidisciplinary teams with vigilant posttreatment surveillance, including history and physical exam, endoscopy, computed tomography (CT) of the chest, and abdomen and pelvic magnetic resonance imaging (MRI), Dr. Willett said in the interview.
Data on the treatment of patients with MMRd rectal cancer using dostarlimab and other immune checkpoint inhibitors are preliminary; more patients and further follow-up are required, he said. This treatment is applicable to only 5%-10% of patients with rectal cancer, he continued.
“There is a need for biomarkers such as circulating tumor DNA to further aid in selection and monitoring of patients with rectal cancer,” Dr. Willett said.
Other preliminary research is examining circulating tumor DNA analysis to guide adjuvant treatment for patients with resected stage II colon cancer, he noted in his presentation. Currently, ctDNA-driven therapy is not recommended by the NCCN, but more research is needed to determine whether this strategy might be applied to decision-making in rectal cancer patients, especially with watch and wait/nonoperative strategies, he said.
What Are the Takeaways for Deintensifying Treatment of Rectal Cancer?
The global continuum of rectal cancer clinical trials has provided significant evidence that, for select patients, the deintensification of treatment strategies may result in the avoidance of radiation and even avoidance of surgery, which can profoundly improve long-term quality of life, Al B. Benson III, MD, said in an interview.
“A critical takeaway message for clinicians who are determining which individual patient might benefit from a less intensive regimen to treat locally advanced rectal cancer is to first have a multidisciplinary consensus which should encompass review of a rectal MRI, pathology, chest and abdominal imaging, colonoscopy, as well as the patient’s clinical status including comorbidities,” said Dr. Benson, who served as chair of the NCCN Guidelines Panel for Colon/Rectal/Anal Cancers and Small Intestine Adenocarcinoma.
“The location of the rectal tumor (distal versus proximal) and clinical TNM stage also will inform the discussion as to which of the potential total neoadjuvant therapy regimens would be most optimal to reduce the risk of local recurrence and maintain long-term quality of life for the individual patient,” explained Dr. Benson, professor of medicine at Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Chicago.
The effectiveness of less intense treatment for rectal cancer remains a work in progress, Dr. Benson said in an interview. “There is much we still do not know, such as the optimal selection of patients and the durability of this approach over time.”
Patients who undergo watch and wait require intensive follow-up, including sigmoidoscopy, digital rectal exam, and rectal MRI, to detect any evidence of local recurrence that would warrant further intervention, including possible radiation and surgery, he said. A highly skilled multidisciplinary team is a must for individuals who are potential candidates for a less intense treatment regimen, he emphasized.
The treatment of locally advanced rectal cancer continues to evolve, but there is no question that TNT has transformed patient outcomes, including the ability to deintensify treatment for select patients, Dr. Benson said.
However, many research gaps remain, Dr. Benson said in an interview. “For the MSI/dMMR patient who has achieved a complete response from immunotherapy we will need more long-term data to determine the durability of a complete clinical response and long-term avoidance of other interventions including radiation, chemotherapy and surgery.
“The wait and watch strategy for the much more common MSS patient also will require much longer follow-up to determine which patients are destined to recur and which are not,” he added.
“The introduction of monitoring with ctDNA determination over time offers an opportunity to streamline surveillance of patients who have completed combination therapy and for those undergoing watch and wait; however, much more information is required to determine which of the various ctDNA assays are most optimal, and the frequency and duration of ctDNA determination that will lend this approach as a standard of care,” Dr. Benson said.
Dr. Willett and Dr. Benson had no financial conflicts to disclose.
FROM NCCN 2024
Commentary: Studies Often Do Not Answer Clinical Questions in AD, May 2024
In "Atopic Dermatitis in Early Childhood and Risk of Inflammatory Bowel Disease: A Scandinavian Birth Cohort Study," Lerchova and colleagues found a statistically significant increased risk for inflammatory bowel disease (IBD) in children with atopic dermatitis. The study had a large patient population, giving it the power to identify very small differences. The researchers found increased risks for IBD, Crohn's disease, and ulcerative colitis (UC) in children with atopic dermatitis; UC had the greatest relative risk. But I don't think this risk was clinically meaningful. About 2 in every 1000 children with atopic dermatitis had UC, whereas about 1 in every 1000 children without atopic dermatitis had UC. Even if the increased absolute risk of 1 in 1000 children was due to atopic dermatitis and not to other factors, I don't think it justifies the authors' conclusion that "these findings might be useful in identifying at-risk individuals for IBD."
Sometimes reviewing articles makes me feel like a crotchety old man. A study by Guttman-Yassky and colleagues, "Targeting IL-13 With Tralokinumab Normalizes Type 2 Inflammation in Atopic Dermatitis Both Early and at 2 Years," didn't seem to test any specific hypothesis. The researchers just looked at a variety of inflammation markers in patients with atopic dermatitis treated with tralokinumab, an interleukin-13 (IL-13) antagonist. In these patients, as expected, the atopic dermatitis improved; so did the inflammatory markers. Did we learn anything clinically useful? I don't think so. We already know that IL-13 is important in atopic dermatitis because when we block IL-13, atopic dermatitis improves.
Vitamin D supplementation doesn't appear to improve atopic dermatitis, as reported by Borzutzky and colleagues in "Effect of Weekly Vitamin D Supplementation on the Severity of Atopic Dermatitis and Type 2 Immunity Biomarkers in Children: A Randomized Controlled Trial." A group of 101 children with atopic dermatitis were randomly assigned to receive oral vitamin D supplementation or placebo. The two groups improved to a similar extent. If you know me, you know I'm wondering whether they took the medication. It appears that they did, because at baseline most of the children were vitamin D deficient, and vitamin D levels improved greatly in the group treated with vitamin D but not in the placebo group.
Journals such as the Journal of the American Academy of Dermatology should require articles to report absolute risk. In "Risk of Lymphoma in Patients With Atopic Dermatitis: A Case-Control Study in the All of Us Database," Powers and colleagues tell us that atopic dermatitis is associated with a statistically significantly increased risk for lymphoma. This means that increased risk wasn't likely due to chance alone. The article says nothing, as far as I could tell, about how big the risk is. Does everyone get lymphoma? Or is it a one in a million risk? Without knowing the absolute risk, the relative risk doesn't tell us whether there is a clinically meaningful increased risk or not. I suspect the increased risk is small. If the incidence of lymphoma is about 2 in 10,000 and peripheral T-cell lymphomas (PTCL) account for 10% of those, even a fourfold increase in the risk for PTCL (the form of lymphoma with the highest relative risk) would not amount to much.
Traidl and colleagues report in "Treatment of Moderate-to-Severe Atopic Dermatitis With Baricitinib: Results From an Interim Analysis of the TREATgermany Registry" that the Janus kinase inhibitor baricitinib makes atopic dermatitis better.
In "Dupilumab Therapy for Atopic Dermatitis Is Associated With Increased Risk of Cutaneous T Cell Lymphoma," Hasan and colleagues report that "it requires 738 prescriptions of dupilumab to produce one case of CTCL [cutaneous T-cell lymphoma]." It seems that this finding could easily be due to 1 in 738 people with a rash thought to be severe atopic dermatitis needing dupilumab having CTCL, not atopic dermatitis, to begin with. If we were to wonder whether dupilumab causes CTCL, perhaps it would be better to study asthma patients treated with or without dupilumab.
In "Atopic Dermatitis in Early Childhood and Risk of Inflammatory Bowel Disease: A Scandinavian Birth Cohort Study," Lerchova and colleagues found a statistically significant increased risk for inflammatory bowel disease (IBD) in children with atopic dermatitis. The study had a large patient population, giving it the power to identify very small differences. The researchers found increased risks for IBD, Crohn's disease, and ulcerative colitis (UC) in children with atopic dermatitis; UC had the greatest relative risk. But I don't think this risk was clinically meaningful. About 2 in every 1000 children with atopic dermatitis had UC, whereas about 1 in every 1000 children without atopic dermatitis had UC. Even if the increased absolute risk of 1 in 1000 children was due to atopic dermatitis and not to other factors, I don't think it justifies the authors' conclusion that "these findings might be useful in identifying at-risk individuals for IBD."
Sometimes reviewing articles makes me feel like a crotchety old man. A study by Guttman-Yassky and colleagues, "Targeting IL-13 With Tralokinumab Normalizes Type 2 Inflammation in Atopic Dermatitis Both Early and at 2 Years," didn't seem to test any specific hypothesis. The researchers just looked at a variety of inflammation markers in patients with atopic dermatitis treated with tralokinumab, an interleukin-13 (IL-13) antagonist. In these patients, as expected, the atopic dermatitis improved; so did the inflammatory markers. Did we learn anything clinically useful? I don't think so. We already know that IL-13 is important in atopic dermatitis because when we block IL-13, atopic dermatitis improves.
Vitamin D supplementation doesn't appear to improve atopic dermatitis, as reported by Borzutzky and colleagues in "Effect of Weekly Vitamin D Supplementation on the Severity of Atopic Dermatitis and Type 2 Immunity Biomarkers in Children: A Randomized Controlled Trial." A group of 101 children with atopic dermatitis were randomly assigned to receive oral vitamin D supplementation or placebo. The two groups improved to a similar extent. If you know me, you know I'm wondering whether they took the medication. It appears that they did, because at baseline most of the children were vitamin D deficient, and vitamin D levels improved greatly in the group treated with vitamin D but not in the placebo group.
Journals such as the Journal of the American Academy of Dermatology should require articles to report absolute risk. In "Risk of Lymphoma in Patients With Atopic Dermatitis: A Case-Control Study in the All of Us Database," Powers and colleagues tell us that atopic dermatitis is associated with a statistically significantly increased risk for lymphoma. This means that increased risk wasn't likely due to chance alone. The article says nothing, as far as I could tell, about how big the risk is. Does everyone get lymphoma? Or is it a one in a million risk? Without knowing the absolute risk, the relative risk doesn't tell us whether there is a clinically meaningful increased risk or not. I suspect the increased risk is small. If the incidence of lymphoma is about 2 in 10,000 and peripheral T-cell lymphomas (PTCL) account for 10% of those, even a fourfold increase in the risk for PTCL (the form of lymphoma with the highest relative risk) would not amount to much.
Traidl and colleagues report in "Treatment of Moderate-to-Severe Atopic Dermatitis With Baricitinib: Results From an Interim Analysis of the TREATgermany Registry" that the Janus kinase inhibitor baricitinib makes atopic dermatitis better.
In "Dupilumab Therapy for Atopic Dermatitis Is Associated With Increased Risk of Cutaneous T Cell Lymphoma," Hasan and colleagues report that "it requires 738 prescriptions of dupilumab to produce one case of CTCL [cutaneous T-cell lymphoma]." It seems that this finding could easily be due to 1 in 738 people with a rash thought to be severe atopic dermatitis needing dupilumab having CTCL, not atopic dermatitis, to begin with. If we were to wonder whether dupilumab causes CTCL, perhaps it would be better to study asthma patients treated with or without dupilumab.
In "Atopic Dermatitis in Early Childhood and Risk of Inflammatory Bowel Disease: A Scandinavian Birth Cohort Study," Lerchova and colleagues found a statistically significant increased risk for inflammatory bowel disease (IBD) in children with atopic dermatitis. The study had a large patient population, giving it the power to identify very small differences. The researchers found increased risks for IBD, Crohn's disease, and ulcerative colitis (UC) in children with atopic dermatitis; UC had the greatest relative risk. But I don't think this risk was clinically meaningful. About 2 in every 1000 children with atopic dermatitis had UC, whereas about 1 in every 1000 children without atopic dermatitis had UC. Even if the increased absolute risk of 1 in 1000 children was due to atopic dermatitis and not to other factors, I don't think it justifies the authors' conclusion that "these findings might be useful in identifying at-risk individuals for IBD."
Sometimes reviewing articles makes me feel like a crotchety old man. A study by Guttman-Yassky and colleagues, "Targeting IL-13 With Tralokinumab Normalizes Type 2 Inflammation in Atopic Dermatitis Both Early and at 2 Years," didn't seem to test any specific hypothesis. The researchers just looked at a variety of inflammation markers in patients with atopic dermatitis treated with tralokinumab, an interleukin-13 (IL-13) antagonist. In these patients, as expected, the atopic dermatitis improved; so did the inflammatory markers. Did we learn anything clinically useful? I don't think so. We already know that IL-13 is important in atopic dermatitis because when we block IL-13, atopic dermatitis improves.
Vitamin D supplementation doesn't appear to improve atopic dermatitis, as reported by Borzutzky and colleagues in "Effect of Weekly Vitamin D Supplementation on the Severity of Atopic Dermatitis and Type 2 Immunity Biomarkers in Children: A Randomized Controlled Trial." A group of 101 children with atopic dermatitis were randomly assigned to receive oral vitamin D supplementation or placebo. The two groups improved to a similar extent. If you know me, you know I'm wondering whether they took the medication. It appears that they did, because at baseline most of the children were vitamin D deficient, and vitamin D levels improved greatly in the group treated with vitamin D but not in the placebo group.
Journals such as the Journal of the American Academy of Dermatology should require articles to report absolute risk. In "Risk of Lymphoma in Patients With Atopic Dermatitis: A Case-Control Study in the All of Us Database," Powers and colleagues tell us that atopic dermatitis is associated with a statistically significantly increased risk for lymphoma. This means that increased risk wasn't likely due to chance alone. The article says nothing, as far as I could tell, about how big the risk is. Does everyone get lymphoma? Or is it a one in a million risk? Without knowing the absolute risk, the relative risk doesn't tell us whether there is a clinically meaningful increased risk or not. I suspect the increased risk is small. If the incidence of lymphoma is about 2 in 10,000 and peripheral T-cell lymphomas (PTCL) account for 10% of those, even a fourfold increase in the risk for PTCL (the form of lymphoma with the highest relative risk) would not amount to much.
Traidl and colleagues report in "Treatment of Moderate-to-Severe Atopic Dermatitis With Baricitinib: Results From an Interim Analysis of the TREATgermany Registry" that the Janus kinase inhibitor baricitinib makes atopic dermatitis better.
In "Dupilumab Therapy for Atopic Dermatitis Is Associated With Increased Risk of Cutaneous T Cell Lymphoma," Hasan and colleagues report that "it requires 738 prescriptions of dupilumab to produce one case of CTCL [cutaneous T-cell lymphoma]." It seems that this finding could easily be due to 1 in 738 people with a rash thought to be severe atopic dermatitis needing dupilumab having CTCL, not atopic dermatitis, to begin with. If we were to wonder whether dupilumab causes CTCL, perhaps it would be better to study asthma patients treated with or without dupilumab.
Are Direct-to-Consumer Microbiome Tests Clinically Useful?
Companies selling gut microbiome tests directly to consumers offer up a variety of claims to promote their products.
“We analyze the trillions of microbes in your gut microflora and craft a unique formula for your unique gut needs,” one says. “Get actionable dietary, supplement, and lifestyle recommendations from our microbiome experts based on your results, tailored to mom and baby’s biomarkers. ... Any family member like dads or siblings are welcome too,” says another.
The companies assert that they can improve gut health by offering individuals personalized treatments based on their gut microbiome test results. The trouble is, no provider, company, or technology can reliably do that yet.
Clinical Implications, Not Applications
The microbiome is the “constellation of microorganisms that call the human body home,” including many strains of bacteria, fungi, and viruses. That constellation comprises some 39 trillion cells.
Although knowledge is increasing on the oral, cutaneous, and vaginal microbiomes, the gut microbiome is arguably the most studied. However, while research is increasingly demonstrating that the gut microbiome has clinical implications, much work needs to be done before reliable applications based on that research are available.
But , Erik C. von Rosenvinge, MD, AGAF, a professor at the University of Maryland School of Medicine and chief of gastroenterology at the VA Maryland Health Care System, Baltimore, said in an interview.
“If you go to their websites, even if it’s not stated overtly, these companies at least give the impression that they’re providing actionable, useful information,” he said. “The sites recommend microbiome testing, and often supplements, probiotics, or other products that they sell. And consumers are told they need to be tested again once they start taking any of these products to see if they’re receiving any benefit.”
Dr. von Rosenvinge and colleagues authored a recent article in Science arguing that DTC microbiome tests “lack analytical and clinical validity” — and yet regulation of the industry has been “generally ignored.” They identified 31 companies globally, 17 of which are based in the United States, claiming to have products and/or services aimed at changing the intestinal microbiome.
Unreliable, Unregulated
The lack of reliability has been shown by experts who have tested the tests.
“People have taken the same stool sample, sent it to multiple companies, and gotten different results back,” Dr. von Rosenvinge said. “People also have taken a stool sample and sent it to the same company under two different names and received two different results. If the test is unreliable at its foundational level, it’s hard to use it in any clinical way.”
Test users’ methods and the companies’ procedures can affect the results, Dina Kao, MD, a professor at the University of Alberta, Edmonton, Alberta, Canada, said in an interview.
“So many biases can be introduced at every single step of the way, starting from how the stool sample was collected and how it’s preserved or not being preserved, because that can introduce a lot of noise that would change the analyses. Which primer they’re using to amplify the signals and which bioinformatic pipeline they use are also important,” said Dr. Kao, who presented at the recent Gut Microbiota for Health World Summit, organized by the American Gastroenterological Association (AGA) and the European Society of Neurogastroenterology and Motility (ESNM).
Different investigators and companies use different technologies, so it’s very difficult to compare them and to create a standard, said Mahmoud Ghannoum, PhD, a professor in the dermatology and pathology departments at Case Western Reserve University School of Medicine and director of the Center for Medical Mycology at University Hospitals in Cleveland.
The complexity of the gut microbiome makes test standardization more difficult than it is when just one organism is involved, Dr. Ghannoum, who chaired the antifungal subcommittee at the Clinical and Laboratory Standards Institute, said in an interview.
“Even though many researchers are focusing on bacteria, we also have fungi and viruses. We need standardization of methods for testing these organisms if we want to have regulations,” said Dr. Ghannoum, a cofounder of BIOHM, a microbiome company that offers nondiagnostic tests and markets a variety of probiotics, prebiotics, and immunity supplements. BIOHM is one of the 31 companies identified by Dr. von Rosenvinge and colleagues, as noted above.
Dr. Ghannoum believes that taking a systematic approach could facilitate standardization and, ultimately, regulation of the DTC microbiome testing products. He and his colleagues described such an approach by outlining the stages for designing probiotics capable of modulating the microbiome in chronic diseases, using Crohn’s disease as a model. Their strategy involved the following steps:
- Using primary microbiome data to identify, by abundance, the microorganisms underlying dysbiosis.
- Gaining insight into the interactions among the identified pathogens.
- Conducting a correlation analysis to identify potential lead probiotic strains that antagonize these pathogens and discovering metabolites that can interrupt their interactions.
- Creating a prototype formulation for testing.
- Validating the efficacy of the candidate formulation via preclinical in vitro and in vivo testing.
- Conducting clinical testing.
Dr. Ghannoum recommends that companies use a similar process “to provide evidence that what they are doing will be helpful, not only for them but also for the reputation of the whole industry.”
Potential Pitfalls
Whether test results from commercial companies are positioned as wellness aids or diagnostic tools, providing advice based on the results “is where the danger can really come in,” Dr. Kao said. “There is still so much we don’t know about which microbial signatures are associated with each condition.”
“Even when we have a solution, like the Crohn’s exclusion diet, a physician doesn’t know enough of the nuances to give advice to a patient,” she said. “That really should be done under the guidance of an expert dietitian. And if a company is selling probiotics, I personally feel that’s not ethical. I’m pretty sure there’s always going to be some kind of conflict of interest.”
Supplements and probiotics are generally safe, but negative consequences can occur, Dr. von Rosenvinge noted.
“We occasionally see people who end up with liver problems as a result of certain supplements, and rarely, probiotics have been associated with infections from those organisms, usually in those with a compromised immune system,” he said.
Other risks include people taking supplements or probiotics when they actually have a medically treatable condition or delays in diagnosis of a potentially serious underlying condition, such as colon cancer, he said. Some patients may stop taking their traditional medication in favor of taking supplements or may experience a drug-supplement interaction if they take both.
What to Tell Patients
“Doctors should be advising against this testing for their patients,” gastroenterologist Colleen R. Kelly, MD, AGAF, Brigham and Women’s Hospital, Boston, said in an interview. “I explain to patients that these tests are not validated and are clinically meaningless data and not worth the money. There is a reason they are not covered by insurance.
“Recommendations to purchase probiotics or supplements manufactured by the testing company to ‘restore a balanced or healthy microbiome’ clearly seem like a scam,” she added. “I believe some of these companies are capitalizing on patients who are desperate for answers to explain chronic symptoms, such as bloating in irritable bowel syndrome.”
Dr. von Rosenvinge said that the message to patients “is that the science isn’t there yet to support using the results of these tests in a meaningful way. We believe the microbiome is very important in health and disease, but the tests themselves in their current state are not as reliable and reproducible as we would like.”
When patients come in with test results, the first question a clinician should ask is what led them to seek out this type of information in the first place, Dr. von Rosenvinge said.
“Our patient focus groups suggested that many have not gotten clear, satisfactory answers from traditional medicine,” he said. “We don’t have a single test that says, yes, you have irritable bowel syndrome, or no, you don’t. We might suggest things that are helpful for some people and are less helpful for others.”
Dr. Kelly said she worries that “there are snake oil salesmen and cons out there who will gladly take your money. These may be smart people, capable of doing very high-level testing, and even producing very detailed and accurate results, but that doesn’t mean we know what to do with them.”
She hopes to see a microbiome-based diagnostic test in the future, particularly if the ability to therapeutically manipulate the gut microbiome in various diseases becomes a reality.
Educate Clinicians, Companies
More education is needed on the subject, so we can become “microbial clinicians,” Dr. Kao said.
“The microbiome never came up when I was going through my medical education,” she said. But we, and the next generation of physicians, “need to at least be able to understand the basics.
“Hopefully, one day, we will be in a position where we can have meaningful interpretations of the test results and make some kind of meaningful dietary interventions,” Dr. Kao added.
As for clinicians who are currently ordering these tests and products directly from the DTC companies, Dr. Kao said, “I roll my eyes.”
Dr. Ghannoum reiterated that companies offering microbiome tests and products also need to be educated and encouraged to use systematic approaches to product development and interpretation.
“Companies should be open to calls from clinicians and be ready to explain findings on a report, as well as the basis for any recommendations,” he said.
Dr. von Rosenvinge, Dr. Kao, and Dr. Kelly had no relevant conflicts of interest. Dr. Ghannoum is a cofounder of BIOHM.
A version of this article appeared on Medscape.com.
Companies selling gut microbiome tests directly to consumers offer up a variety of claims to promote their products.
“We analyze the trillions of microbes in your gut microflora and craft a unique formula for your unique gut needs,” one says. “Get actionable dietary, supplement, and lifestyle recommendations from our microbiome experts based on your results, tailored to mom and baby’s biomarkers. ... Any family member like dads or siblings are welcome too,” says another.
The companies assert that they can improve gut health by offering individuals personalized treatments based on their gut microbiome test results. The trouble is, no provider, company, or technology can reliably do that yet.
Clinical Implications, Not Applications
The microbiome is the “constellation of microorganisms that call the human body home,” including many strains of bacteria, fungi, and viruses. That constellation comprises some 39 trillion cells.
Although knowledge is increasing on the oral, cutaneous, and vaginal microbiomes, the gut microbiome is arguably the most studied. However, while research is increasingly demonstrating that the gut microbiome has clinical implications, much work needs to be done before reliable applications based on that research are available.
But , Erik C. von Rosenvinge, MD, AGAF, a professor at the University of Maryland School of Medicine and chief of gastroenterology at the VA Maryland Health Care System, Baltimore, said in an interview.
“If you go to their websites, even if it’s not stated overtly, these companies at least give the impression that they’re providing actionable, useful information,” he said. “The sites recommend microbiome testing, and often supplements, probiotics, or other products that they sell. And consumers are told they need to be tested again once they start taking any of these products to see if they’re receiving any benefit.”
Dr. von Rosenvinge and colleagues authored a recent article in Science arguing that DTC microbiome tests “lack analytical and clinical validity” — and yet regulation of the industry has been “generally ignored.” They identified 31 companies globally, 17 of which are based in the United States, claiming to have products and/or services aimed at changing the intestinal microbiome.
Unreliable, Unregulated
The lack of reliability has been shown by experts who have tested the tests.
“People have taken the same stool sample, sent it to multiple companies, and gotten different results back,” Dr. von Rosenvinge said. “People also have taken a stool sample and sent it to the same company under two different names and received two different results. If the test is unreliable at its foundational level, it’s hard to use it in any clinical way.”
Test users’ methods and the companies’ procedures can affect the results, Dina Kao, MD, a professor at the University of Alberta, Edmonton, Alberta, Canada, said in an interview.
“So many biases can be introduced at every single step of the way, starting from how the stool sample was collected and how it’s preserved or not being preserved, because that can introduce a lot of noise that would change the analyses. Which primer they’re using to amplify the signals and which bioinformatic pipeline they use are also important,” said Dr. Kao, who presented at the recent Gut Microbiota for Health World Summit, organized by the American Gastroenterological Association (AGA) and the European Society of Neurogastroenterology and Motility (ESNM).
Different investigators and companies use different technologies, so it’s very difficult to compare them and to create a standard, said Mahmoud Ghannoum, PhD, a professor in the dermatology and pathology departments at Case Western Reserve University School of Medicine and director of the Center for Medical Mycology at University Hospitals in Cleveland.
The complexity of the gut microbiome makes test standardization more difficult than it is when just one organism is involved, Dr. Ghannoum, who chaired the antifungal subcommittee at the Clinical and Laboratory Standards Institute, said in an interview.
“Even though many researchers are focusing on bacteria, we also have fungi and viruses. We need standardization of methods for testing these organisms if we want to have regulations,” said Dr. Ghannoum, a cofounder of BIOHM, a microbiome company that offers nondiagnostic tests and markets a variety of probiotics, prebiotics, and immunity supplements. BIOHM is one of the 31 companies identified by Dr. von Rosenvinge and colleagues, as noted above.
Dr. Ghannoum believes that taking a systematic approach could facilitate standardization and, ultimately, regulation of the DTC microbiome testing products. He and his colleagues described such an approach by outlining the stages for designing probiotics capable of modulating the microbiome in chronic diseases, using Crohn’s disease as a model. Their strategy involved the following steps:
- Using primary microbiome data to identify, by abundance, the microorganisms underlying dysbiosis.
- Gaining insight into the interactions among the identified pathogens.
- Conducting a correlation analysis to identify potential lead probiotic strains that antagonize these pathogens and discovering metabolites that can interrupt their interactions.
- Creating a prototype formulation for testing.
- Validating the efficacy of the candidate formulation via preclinical in vitro and in vivo testing.
- Conducting clinical testing.
Dr. Ghannoum recommends that companies use a similar process “to provide evidence that what they are doing will be helpful, not only for them but also for the reputation of the whole industry.”
Potential Pitfalls
Whether test results from commercial companies are positioned as wellness aids or diagnostic tools, providing advice based on the results “is where the danger can really come in,” Dr. Kao said. “There is still so much we don’t know about which microbial signatures are associated with each condition.”
“Even when we have a solution, like the Crohn’s exclusion diet, a physician doesn’t know enough of the nuances to give advice to a patient,” she said. “That really should be done under the guidance of an expert dietitian. And if a company is selling probiotics, I personally feel that’s not ethical. I’m pretty sure there’s always going to be some kind of conflict of interest.”
Supplements and probiotics are generally safe, but negative consequences can occur, Dr. von Rosenvinge noted.
“We occasionally see people who end up with liver problems as a result of certain supplements, and rarely, probiotics have been associated with infections from those organisms, usually in those with a compromised immune system,” he said.
Other risks include people taking supplements or probiotics when they actually have a medically treatable condition or delays in diagnosis of a potentially serious underlying condition, such as colon cancer, he said. Some patients may stop taking their traditional medication in favor of taking supplements or may experience a drug-supplement interaction if they take both.
What to Tell Patients
“Doctors should be advising against this testing for their patients,” gastroenterologist Colleen R. Kelly, MD, AGAF, Brigham and Women’s Hospital, Boston, said in an interview. “I explain to patients that these tests are not validated and are clinically meaningless data and not worth the money. There is a reason they are not covered by insurance.
“Recommendations to purchase probiotics or supplements manufactured by the testing company to ‘restore a balanced or healthy microbiome’ clearly seem like a scam,” she added. “I believe some of these companies are capitalizing on patients who are desperate for answers to explain chronic symptoms, such as bloating in irritable bowel syndrome.”
Dr. von Rosenvinge said that the message to patients “is that the science isn’t there yet to support using the results of these tests in a meaningful way. We believe the microbiome is very important in health and disease, but the tests themselves in their current state are not as reliable and reproducible as we would like.”
When patients come in with test results, the first question a clinician should ask is what led them to seek out this type of information in the first place, Dr. von Rosenvinge said.
“Our patient focus groups suggested that many have not gotten clear, satisfactory answers from traditional medicine,” he said. “We don’t have a single test that says, yes, you have irritable bowel syndrome, or no, you don’t. We might suggest things that are helpful for some people and are less helpful for others.”
Dr. Kelly said she worries that “there are snake oil salesmen and cons out there who will gladly take your money. These may be smart people, capable of doing very high-level testing, and even producing very detailed and accurate results, but that doesn’t mean we know what to do with them.”
She hopes to see a microbiome-based diagnostic test in the future, particularly if the ability to therapeutically manipulate the gut microbiome in various diseases becomes a reality.
Educate Clinicians, Companies
More education is needed on the subject, so we can become “microbial clinicians,” Dr. Kao said.
“The microbiome never came up when I was going through my medical education,” she said. But we, and the next generation of physicians, “need to at least be able to understand the basics.
“Hopefully, one day, we will be in a position where we can have meaningful interpretations of the test results and make some kind of meaningful dietary interventions,” Dr. Kao added.
As for clinicians who are currently ordering these tests and products directly from the DTC companies, Dr. Kao said, “I roll my eyes.”
Dr. Ghannoum reiterated that companies offering microbiome tests and products also need to be educated and encouraged to use systematic approaches to product development and interpretation.
“Companies should be open to calls from clinicians and be ready to explain findings on a report, as well as the basis for any recommendations,” he said.
Dr. von Rosenvinge, Dr. Kao, and Dr. Kelly had no relevant conflicts of interest. Dr. Ghannoum is a cofounder of BIOHM.
A version of this article appeared on Medscape.com.
Companies selling gut microbiome tests directly to consumers offer up a variety of claims to promote their products.
“We analyze the trillions of microbes in your gut microflora and craft a unique formula for your unique gut needs,” one says. “Get actionable dietary, supplement, and lifestyle recommendations from our microbiome experts based on your results, tailored to mom and baby’s biomarkers. ... Any family member like dads or siblings are welcome too,” says another.
The companies assert that they can improve gut health by offering individuals personalized treatments based on their gut microbiome test results. The trouble is, no provider, company, or technology can reliably do that yet.
Clinical Implications, Not Applications
The microbiome is the “constellation of microorganisms that call the human body home,” including many strains of bacteria, fungi, and viruses. That constellation comprises some 39 trillion cells.
Although knowledge is increasing on the oral, cutaneous, and vaginal microbiomes, the gut microbiome is arguably the most studied. However, while research is increasingly demonstrating that the gut microbiome has clinical implications, much work needs to be done before reliable applications based on that research are available.
But , Erik C. von Rosenvinge, MD, AGAF, a professor at the University of Maryland School of Medicine and chief of gastroenterology at the VA Maryland Health Care System, Baltimore, said in an interview.
“If you go to their websites, even if it’s not stated overtly, these companies at least give the impression that they’re providing actionable, useful information,” he said. “The sites recommend microbiome testing, and often supplements, probiotics, or other products that they sell. And consumers are told they need to be tested again once they start taking any of these products to see if they’re receiving any benefit.”
Dr. von Rosenvinge and colleagues authored a recent article in Science arguing that DTC microbiome tests “lack analytical and clinical validity” — and yet regulation of the industry has been “generally ignored.” They identified 31 companies globally, 17 of which are based in the United States, claiming to have products and/or services aimed at changing the intestinal microbiome.
Unreliable, Unregulated
The lack of reliability has been shown by experts who have tested the tests.
“People have taken the same stool sample, sent it to multiple companies, and gotten different results back,” Dr. von Rosenvinge said. “People also have taken a stool sample and sent it to the same company under two different names and received two different results. If the test is unreliable at its foundational level, it’s hard to use it in any clinical way.”
Test users’ methods and the companies’ procedures can affect the results, Dina Kao, MD, a professor at the University of Alberta, Edmonton, Alberta, Canada, said in an interview.
“So many biases can be introduced at every single step of the way, starting from how the stool sample was collected and how it’s preserved or not being preserved, because that can introduce a lot of noise that would change the analyses. Which primer they’re using to amplify the signals and which bioinformatic pipeline they use are also important,” said Dr. Kao, who presented at the recent Gut Microbiota for Health World Summit, organized by the American Gastroenterological Association (AGA) and the European Society of Neurogastroenterology and Motility (ESNM).
Different investigators and companies use different technologies, so it’s very difficult to compare them and to create a standard, said Mahmoud Ghannoum, PhD, a professor in the dermatology and pathology departments at Case Western Reserve University School of Medicine and director of the Center for Medical Mycology at University Hospitals in Cleveland.
The complexity of the gut microbiome makes test standardization more difficult than it is when just one organism is involved, Dr. Ghannoum, who chaired the antifungal subcommittee at the Clinical and Laboratory Standards Institute, said in an interview.
“Even though many researchers are focusing on bacteria, we also have fungi and viruses. We need standardization of methods for testing these organisms if we want to have regulations,” said Dr. Ghannoum, a cofounder of BIOHM, a microbiome company that offers nondiagnostic tests and markets a variety of probiotics, prebiotics, and immunity supplements. BIOHM is one of the 31 companies identified by Dr. von Rosenvinge and colleagues, as noted above.
Dr. Ghannoum believes that taking a systematic approach could facilitate standardization and, ultimately, regulation of the DTC microbiome testing products. He and his colleagues described such an approach by outlining the stages for designing probiotics capable of modulating the microbiome in chronic diseases, using Crohn’s disease as a model. Their strategy involved the following steps:
- Using primary microbiome data to identify, by abundance, the microorganisms underlying dysbiosis.
- Gaining insight into the interactions among the identified pathogens.
- Conducting a correlation analysis to identify potential lead probiotic strains that antagonize these pathogens and discovering metabolites that can interrupt their interactions.
- Creating a prototype formulation for testing.
- Validating the efficacy of the candidate formulation via preclinical in vitro and in vivo testing.
- Conducting clinical testing.
Dr. Ghannoum recommends that companies use a similar process “to provide evidence that what they are doing will be helpful, not only for them but also for the reputation of the whole industry.”
Potential Pitfalls
Whether test results from commercial companies are positioned as wellness aids or diagnostic tools, providing advice based on the results “is where the danger can really come in,” Dr. Kao said. “There is still so much we don’t know about which microbial signatures are associated with each condition.”
“Even when we have a solution, like the Crohn’s exclusion diet, a physician doesn’t know enough of the nuances to give advice to a patient,” she said. “That really should be done under the guidance of an expert dietitian. And if a company is selling probiotics, I personally feel that’s not ethical. I’m pretty sure there’s always going to be some kind of conflict of interest.”
Supplements and probiotics are generally safe, but negative consequences can occur, Dr. von Rosenvinge noted.
“We occasionally see people who end up with liver problems as a result of certain supplements, and rarely, probiotics have been associated with infections from those organisms, usually in those with a compromised immune system,” he said.
Other risks include people taking supplements or probiotics when they actually have a medically treatable condition or delays in diagnosis of a potentially serious underlying condition, such as colon cancer, he said. Some patients may stop taking their traditional medication in favor of taking supplements or may experience a drug-supplement interaction if they take both.
What to Tell Patients
“Doctors should be advising against this testing for their patients,” gastroenterologist Colleen R. Kelly, MD, AGAF, Brigham and Women’s Hospital, Boston, said in an interview. “I explain to patients that these tests are not validated and are clinically meaningless data and not worth the money. There is a reason they are not covered by insurance.
“Recommendations to purchase probiotics or supplements manufactured by the testing company to ‘restore a balanced or healthy microbiome’ clearly seem like a scam,” she added. “I believe some of these companies are capitalizing on patients who are desperate for answers to explain chronic symptoms, such as bloating in irritable bowel syndrome.”
Dr. von Rosenvinge said that the message to patients “is that the science isn’t there yet to support using the results of these tests in a meaningful way. We believe the microbiome is very important in health and disease, but the tests themselves in their current state are not as reliable and reproducible as we would like.”
When patients come in with test results, the first question a clinician should ask is what led them to seek out this type of information in the first place, Dr. von Rosenvinge said.
“Our patient focus groups suggested that many have not gotten clear, satisfactory answers from traditional medicine,” he said. “We don’t have a single test that says, yes, you have irritable bowel syndrome, or no, you don’t. We might suggest things that are helpful for some people and are less helpful for others.”
Dr. Kelly said she worries that “there are snake oil salesmen and cons out there who will gladly take your money. These may be smart people, capable of doing very high-level testing, and even producing very detailed and accurate results, but that doesn’t mean we know what to do with them.”
She hopes to see a microbiome-based diagnostic test in the future, particularly if the ability to therapeutically manipulate the gut microbiome in various diseases becomes a reality.
Educate Clinicians, Companies
More education is needed on the subject, so we can become “microbial clinicians,” Dr. Kao said.
“The microbiome never came up when I was going through my medical education,” she said. But we, and the next generation of physicians, “need to at least be able to understand the basics.
“Hopefully, one day, we will be in a position where we can have meaningful interpretations of the test results and make some kind of meaningful dietary interventions,” Dr. Kao added.
As for clinicians who are currently ordering these tests and products directly from the DTC companies, Dr. Kao said, “I roll my eyes.”
Dr. Ghannoum reiterated that companies offering microbiome tests and products also need to be educated and encouraged to use systematic approaches to product development and interpretation.
“Companies should be open to calls from clinicians and be ready to explain findings on a report, as well as the basis for any recommendations,” he said.
Dr. von Rosenvinge, Dr. Kao, and Dr. Kelly had no relevant conflicts of interest. Dr. Ghannoum is a cofounder of BIOHM.
A version of this article appeared on Medscape.com.
GLP-1s May Increase Post-Endoscopy Aspiration Pneumonia Risk
, according to a new large population-based study.
In June 2023, the American Society of Anesthesiologists (ASA) recommended holding GLP-1 RAs before an endoscopic or surgical procedure to reduce the risk for complications associated with anesthesia and delayed stomach emptying.
In response, the American Gastroenterological Association (AGA) published a rapid clinical practice update in November 2023 that found insufficient evidence to support patients stopping the medications before endoscopic procedures.
“It is known that GLP-1 RAs significantly reduce the motility of the stomach and small bowel. As more and more patients are being started on GLP-1 RAs at higher doses and longer half-life, the question became whether the current recommended fasting durations are enough to reasonably assume the stomach is empty prior to procedures that require sedation,” said senior author Ali Rezaie, MD, medical director of the GI Motility Program at Cedars-Sinai Medical Center in Los Angeles.
“We wanted to see if these medications in fact increased the chance of aspiration before the ASA suggestion went into effect,” he said. “However, this is not an easy task, as aspiration is a rare event and a large sample size is needed to confidently answer that question. That is why we evaluated nearly 1 million cases.”
The study was published online in Gastroenterology.
Analyzing GLP-1 RA Use
Dr. Rezaie and colleagues conducted a population-based, retrospective cohort study of the TriNetX dataset, which includes 114 million deidentified individual health records from 80 healthcare organizations. The research team analyzed nearly 1 million records for adult patients between ages 21 and 70 who underwent upper and lower endoscopies between January 2018 and December 2020.
The researchers defined GLP-1 RA users as those who had the medication for more than 6 months and two or more refills within 6 months before the procedure. They adjusted for 59 factors that could affect gut motility or aspiration risks, such as obesity, numerous chronic diseases, and dozens of medications. The primary outcome was aspiration pneumonia within a month after the procedure.
Among 963,184 patients who underwent endoscopy, 46,935 (4.9%) were considered GLP-1 RA users. Among those, 20,099 GLP-1 RA users met the inclusion criteria and had their results compared with non-GLP-1 RA users.
After propensity score matching for the 59 potential confounders, GLP-1 RA use had a higher incidence rate of aspiration pneumonia (0.83% vs 0.63%) and was associated with a significantly higher risk for aspiration pneumonia, with a hazard ratio (HR) of 1.33.
An even higher risk was seen among patients with propofol-assisted endoscopies (HR, 1.49) but not among those without propofol (HR, 1.31).
In a subgroup analysis based on endoscopy type, an elevated risk was observed among patients who underwent upper endoscopy (HR, 1.82) and combined upper and lower endoscopy (HR, 2.26) but not lower endoscopy (HR, 0.56).
“The results were not necessarily surprising given the mechanism of action of GLP-1 RAs. However, for the first time, this was shown with a clinically relevant outcome, such as aspiration pneumonia,” Dr. Rezaie said. “Aspiration during sedation can have devastating consequences, and the 0.2% difference in risk of aspiration can have a significant effect on healthcare as well.”
More than 20 million endoscopies are performed across the United States annually. Based on the assumption that about 3% of those patients are taking GLP-1 RAs, about 1200 aspiration cases per year can be prevented by raising awareness, he said.
Considering Next Steps
The varying risk profiles observed with separate sedation and endoscopy types point to a need for more tailored guidance in managing GLP-1 RA use before a procedure, the study authors wrote.
Although holding the medications before endoscopy may disrupt diabetes management, the potential increased risk for aspiration could justify a change in practice, particularly for upper endoscopy and propofol-associated procedures, they added.
At the same time, additional studies are needed to understand the optimal drug withholding windows before endoscopies and other procedures, they concluded.
“We will need more data on what is the optimal duration of holding GLP-1 RAs,” Dr. Rezaie said. “But given our data and current ASA guidance, stopping these medications prior to elective procedures is the safe thing to do.”
For now, AGA guidance remains the same as offered in the November 2023 update, suggesting an individual approach for each patient on a GLP-1 RA rather than a “blanket statement” on how to manage all patients taking these medications.
“Overall, I believe that this study is important, but we require more high-level data to inform clinical decision-making regarding patients using GLP-1 receptor agonists prior to gastrointestinal endoscopy,” said Andrew Y. Wang, MD, AGAF, chief of gastroenterology and hepatology and director of interventional endoscopy at the University of Virginia in Charlottesville.
Dr. Wang, who wasn’t involved with this study, coauthored the AGA rapid clinical practice update. He and colleagues advised continuing with a procedure as planned for patients on GLP-1 RAs who followed standard preprocedure fasting instructions and didn’t have nausea, vomiting, dyspepsia, or abdominal distention.
Among patients with symptoms that suggest retained gastric contents, rapid sequence intubation may be considered, though it may not be possible in ambulatory or office-based endoscopy settings, Dr. Wang and colleagues wrote. As another option in lieu of stopping GLP-1 RAs, patients can be placed on a liquid diet for 1 day before the procedure.
“While this study found a signal suggesting that patients using GLP-1 RAs had an increased risk of aspiration pneumonia within 1 month following upper endoscopy or combined upper and lower endoscopy, it does not inform us if having patients stop GLP-1 RAs before endoscopic procedures — especially for a single dose — will mitigate this potential risk,” Dr. Wang said.
“It was also interesting that these investigators found that patients taking GLP-1 RAs who underwent lower endoscopy alone were not at increased risk for aspiration pneumonia,” Dr. Wang noted.
The authors didn’t report a funding source and disclosed no potential conflicts. Dr. Wang reported no relevant disclosures.
A version of this article appeared on Medscape.com.
, according to a new large population-based study.
In June 2023, the American Society of Anesthesiologists (ASA) recommended holding GLP-1 RAs before an endoscopic or surgical procedure to reduce the risk for complications associated with anesthesia and delayed stomach emptying.
In response, the American Gastroenterological Association (AGA) published a rapid clinical practice update in November 2023 that found insufficient evidence to support patients stopping the medications before endoscopic procedures.
“It is known that GLP-1 RAs significantly reduce the motility of the stomach and small bowel. As more and more patients are being started on GLP-1 RAs at higher doses and longer half-life, the question became whether the current recommended fasting durations are enough to reasonably assume the stomach is empty prior to procedures that require sedation,” said senior author Ali Rezaie, MD, medical director of the GI Motility Program at Cedars-Sinai Medical Center in Los Angeles.
“We wanted to see if these medications in fact increased the chance of aspiration before the ASA suggestion went into effect,” he said. “However, this is not an easy task, as aspiration is a rare event and a large sample size is needed to confidently answer that question. That is why we evaluated nearly 1 million cases.”
The study was published online in Gastroenterology.
Analyzing GLP-1 RA Use
Dr. Rezaie and colleagues conducted a population-based, retrospective cohort study of the TriNetX dataset, which includes 114 million deidentified individual health records from 80 healthcare organizations. The research team analyzed nearly 1 million records for adult patients between ages 21 and 70 who underwent upper and lower endoscopies between January 2018 and December 2020.
The researchers defined GLP-1 RA users as those who had the medication for more than 6 months and two or more refills within 6 months before the procedure. They adjusted for 59 factors that could affect gut motility or aspiration risks, such as obesity, numerous chronic diseases, and dozens of medications. The primary outcome was aspiration pneumonia within a month after the procedure.
Among 963,184 patients who underwent endoscopy, 46,935 (4.9%) were considered GLP-1 RA users. Among those, 20,099 GLP-1 RA users met the inclusion criteria and had their results compared with non-GLP-1 RA users.
After propensity score matching for the 59 potential confounders, GLP-1 RA use had a higher incidence rate of aspiration pneumonia (0.83% vs 0.63%) and was associated with a significantly higher risk for aspiration pneumonia, with a hazard ratio (HR) of 1.33.
An even higher risk was seen among patients with propofol-assisted endoscopies (HR, 1.49) but not among those without propofol (HR, 1.31).
In a subgroup analysis based on endoscopy type, an elevated risk was observed among patients who underwent upper endoscopy (HR, 1.82) and combined upper and lower endoscopy (HR, 2.26) but not lower endoscopy (HR, 0.56).
“The results were not necessarily surprising given the mechanism of action of GLP-1 RAs. However, for the first time, this was shown with a clinically relevant outcome, such as aspiration pneumonia,” Dr. Rezaie said. “Aspiration during sedation can have devastating consequences, and the 0.2% difference in risk of aspiration can have a significant effect on healthcare as well.”
More than 20 million endoscopies are performed across the United States annually. Based on the assumption that about 3% of those patients are taking GLP-1 RAs, about 1200 aspiration cases per year can be prevented by raising awareness, he said.
Considering Next Steps
The varying risk profiles observed with separate sedation and endoscopy types point to a need for more tailored guidance in managing GLP-1 RA use before a procedure, the study authors wrote.
Although holding the medications before endoscopy may disrupt diabetes management, the potential increased risk for aspiration could justify a change in practice, particularly for upper endoscopy and propofol-associated procedures, they added.
At the same time, additional studies are needed to understand the optimal drug withholding windows before endoscopies and other procedures, they concluded.
“We will need more data on what is the optimal duration of holding GLP-1 RAs,” Dr. Rezaie said. “But given our data and current ASA guidance, stopping these medications prior to elective procedures is the safe thing to do.”
For now, AGA guidance remains the same as offered in the November 2023 update, suggesting an individual approach for each patient on a GLP-1 RA rather than a “blanket statement” on how to manage all patients taking these medications.
“Overall, I believe that this study is important, but we require more high-level data to inform clinical decision-making regarding patients using GLP-1 receptor agonists prior to gastrointestinal endoscopy,” said Andrew Y. Wang, MD, AGAF, chief of gastroenterology and hepatology and director of interventional endoscopy at the University of Virginia in Charlottesville.
Dr. Wang, who wasn’t involved with this study, coauthored the AGA rapid clinical practice update. He and colleagues advised continuing with a procedure as planned for patients on GLP-1 RAs who followed standard preprocedure fasting instructions and didn’t have nausea, vomiting, dyspepsia, or abdominal distention.
Among patients with symptoms that suggest retained gastric contents, rapid sequence intubation may be considered, though it may not be possible in ambulatory or office-based endoscopy settings, Dr. Wang and colleagues wrote. As another option in lieu of stopping GLP-1 RAs, patients can be placed on a liquid diet for 1 day before the procedure.
“While this study found a signal suggesting that patients using GLP-1 RAs had an increased risk of aspiration pneumonia within 1 month following upper endoscopy or combined upper and lower endoscopy, it does not inform us if having patients stop GLP-1 RAs before endoscopic procedures — especially for a single dose — will mitigate this potential risk,” Dr. Wang said.
“It was also interesting that these investigators found that patients taking GLP-1 RAs who underwent lower endoscopy alone were not at increased risk for aspiration pneumonia,” Dr. Wang noted.
The authors didn’t report a funding source and disclosed no potential conflicts. Dr. Wang reported no relevant disclosures.
A version of this article appeared on Medscape.com.
, according to a new large population-based study.
In June 2023, the American Society of Anesthesiologists (ASA) recommended holding GLP-1 RAs before an endoscopic or surgical procedure to reduce the risk for complications associated with anesthesia and delayed stomach emptying.
In response, the American Gastroenterological Association (AGA) published a rapid clinical practice update in November 2023 that found insufficient evidence to support patients stopping the medications before endoscopic procedures.
“It is known that GLP-1 RAs significantly reduce the motility of the stomach and small bowel. As more and more patients are being started on GLP-1 RAs at higher doses and longer half-life, the question became whether the current recommended fasting durations are enough to reasonably assume the stomach is empty prior to procedures that require sedation,” said senior author Ali Rezaie, MD, medical director of the GI Motility Program at Cedars-Sinai Medical Center in Los Angeles.
“We wanted to see if these medications in fact increased the chance of aspiration before the ASA suggestion went into effect,” he said. “However, this is not an easy task, as aspiration is a rare event and a large sample size is needed to confidently answer that question. That is why we evaluated nearly 1 million cases.”
The study was published online in Gastroenterology.
Analyzing GLP-1 RA Use
Dr. Rezaie and colleagues conducted a population-based, retrospective cohort study of the TriNetX dataset, which includes 114 million deidentified individual health records from 80 healthcare organizations. The research team analyzed nearly 1 million records for adult patients between ages 21 and 70 who underwent upper and lower endoscopies between January 2018 and December 2020.
The researchers defined GLP-1 RA users as those who had the medication for more than 6 months and two or more refills within 6 months before the procedure. They adjusted for 59 factors that could affect gut motility or aspiration risks, such as obesity, numerous chronic diseases, and dozens of medications. The primary outcome was aspiration pneumonia within a month after the procedure.
Among 963,184 patients who underwent endoscopy, 46,935 (4.9%) were considered GLP-1 RA users. Among those, 20,099 GLP-1 RA users met the inclusion criteria and had their results compared with non-GLP-1 RA users.
After propensity score matching for the 59 potential confounders, GLP-1 RA use had a higher incidence rate of aspiration pneumonia (0.83% vs 0.63%) and was associated with a significantly higher risk for aspiration pneumonia, with a hazard ratio (HR) of 1.33.
An even higher risk was seen among patients with propofol-assisted endoscopies (HR, 1.49) but not among those without propofol (HR, 1.31).
In a subgroup analysis based on endoscopy type, an elevated risk was observed among patients who underwent upper endoscopy (HR, 1.82) and combined upper and lower endoscopy (HR, 2.26) but not lower endoscopy (HR, 0.56).
“The results were not necessarily surprising given the mechanism of action of GLP-1 RAs. However, for the first time, this was shown with a clinically relevant outcome, such as aspiration pneumonia,” Dr. Rezaie said. “Aspiration during sedation can have devastating consequences, and the 0.2% difference in risk of aspiration can have a significant effect on healthcare as well.”
More than 20 million endoscopies are performed across the United States annually. Based on the assumption that about 3% of those patients are taking GLP-1 RAs, about 1200 aspiration cases per year can be prevented by raising awareness, he said.
Considering Next Steps
The varying risk profiles observed with separate sedation and endoscopy types point to a need for more tailored guidance in managing GLP-1 RA use before a procedure, the study authors wrote.
Although holding the medications before endoscopy may disrupt diabetes management, the potential increased risk for aspiration could justify a change in practice, particularly for upper endoscopy and propofol-associated procedures, they added.
At the same time, additional studies are needed to understand the optimal drug withholding windows before endoscopies and other procedures, they concluded.
“We will need more data on what is the optimal duration of holding GLP-1 RAs,” Dr. Rezaie said. “But given our data and current ASA guidance, stopping these medications prior to elective procedures is the safe thing to do.”
For now, AGA guidance remains the same as offered in the November 2023 update, suggesting an individual approach for each patient on a GLP-1 RA rather than a “blanket statement” on how to manage all patients taking these medications.
“Overall, I believe that this study is important, but we require more high-level data to inform clinical decision-making regarding patients using GLP-1 receptor agonists prior to gastrointestinal endoscopy,” said Andrew Y. Wang, MD, AGAF, chief of gastroenterology and hepatology and director of interventional endoscopy at the University of Virginia in Charlottesville.
Dr. Wang, who wasn’t involved with this study, coauthored the AGA rapid clinical practice update. He and colleagues advised continuing with a procedure as planned for patients on GLP-1 RAs who followed standard preprocedure fasting instructions and didn’t have nausea, vomiting, dyspepsia, or abdominal distention.
Among patients with symptoms that suggest retained gastric contents, rapid sequence intubation may be considered, though it may not be possible in ambulatory or office-based endoscopy settings, Dr. Wang and colleagues wrote. As another option in lieu of stopping GLP-1 RAs, patients can be placed on a liquid diet for 1 day before the procedure.
“While this study found a signal suggesting that patients using GLP-1 RAs had an increased risk of aspiration pneumonia within 1 month following upper endoscopy or combined upper and lower endoscopy, it does not inform us if having patients stop GLP-1 RAs before endoscopic procedures — especially for a single dose — will mitigate this potential risk,” Dr. Wang said.
“It was also interesting that these investigators found that patients taking GLP-1 RAs who underwent lower endoscopy alone were not at increased risk for aspiration pneumonia,” Dr. Wang noted.
The authors didn’t report a funding source and disclosed no potential conflicts. Dr. Wang reported no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM GASTROENTEROLOGY