Conference Coverage

Compared with the standard 3-week regimen, a 1-week hypofractionated regimen of adjuvant whole-breast radiotherapy had similar efficacy and safety at 5 years of follow-up, according to the U.K. FAST-Forward trial.

The trial was designed to compare the standard regimen (40 Gy in 15 fractions over 3 weeks) with a higher-dose hypofractionated regimen (27 Gy in 5 fractions over 5 days) and a lower-dose hypofractionated regimen (26 Gy in 5 fractions over 5 days) in women who had undergone surgery for early invasive breast cancer.

The 5-year rate of ipsilateral breast tumor relapse was similar with all regimens – 2.1% with the 40-Gy regimen, 1.7% with the 27-Gy regimen, and 1.4% with the 26-Gy regimen. The 26-Gy regimen also had similar safety as the 40-Gy regimen.

These results were presented at the European Society for Radiology and Oncology 2020 Online Congress by Joanne S. Haviland, MSc, of the Institute of Cancer Research in London. Results were also published in The Lancet.

Ms. Haviland said that hypofractionated regimens are attractive because of their shorter overall treatment times, which translate to greater convenience and lower treatment costs.

The historic 5-week regimen (50 Gy in 25 fractions) has been replaced by a 3-week regimen (40 Gy in 15 fractions) in the United Kingdom and elsewhere, and ongoing efforts are exploring whether further hypofractionation can be achieved without compromising efficacy and safety.

“The FAST-Forward trial was the next step on from testing hypofractionated schedules evaluated in earlier trials, including the START trials in the early 2000s and the FAST trial, which published its 10-year results earlier this year,” Ms. Haviland explained.

FAST-Forward enrolled 4,096 women who had undergone breast-conserving surgery or mastectomy for early invasive breast cancer. The patients were randomized into the aforementioned groups for adjuvant whole-breast or chest-wall radiotherapy: 40 Gy in 15 fractions over 3 weeks, 27 Gy in 5 fractions over 5 days, or 26 Gy in 5 fractions over 5 days. Boosts were permitted for all regimens.
 

Relapse, safety, and patient reports

The median follow-up was 6 years. The 5-year rate of ipsilateral breast tumor relapse was 2.1% with the 40-Gy standard regimen, 1.7% with the 27-Gy hypofractionated regimen, and 1.4% with the 26-Gy hypofractionated regimen.

The upper bound of the 95% confidence interval for the difference comparing the hypofractionated regimens against the standard fell well within the 1.6% excess predefined for noninferiority for both the 27-Gy regimen and the 26-Gy regimen (0.9% and 0.3%, respectively).

The hazard ratio for ipsilateral breast tumor relapse, compared with the standard regimen, was 0.86 for the 27-Gy hypofractionated regimen and 0.67 for the 26-Gy hypofractionated regimen.

In terms of safety, the 5-year rate of late adverse effects of the breast or chest wall – distortion, shrinkage, induration, telangiectasia, or edema – rated as “moderate” or “marked” by clinicians was 10% with the standard regimen, 15% with the 27-Gy regimen (relative risk, 1.55 ; P < .001), and 12% with the 26-Gy regimen (RR, 1.19; P = .17).

Over the entire follow-up, women had significantly higher odds of all moderate or marked individual late adverse effects (except discomfort) with the 27-Gy regimen versus the standard regimen, whereas their odds were significantly higher only for induration and edema with the 26-Gy regimen.

However, absolute rates and risk differences between groups were small, Ms. Haviland pointed out. For example, the most common moderate or marked late adverse effect with the standard regimen was breast shrinkage, seen in 5% of patients, followed by discomfort, seen in 4%.

Patient-assessed change in breast appearance and shrinkage did not differ significantly across groups. But women in the 27-Gy group were more likely than peers in the standard regimen group to report a moderate or marked increase in breast hardness/firmness (21% vs. 14%; P = .008), and women in both the 27-Gy and 26-Gy groups were more likely to report moderate or marked breast swelling (5%; P = .007 and 4%; P = .02, respectively, vs. 2%).
 

A new standard

“We have shown noninferiority in terms of local tumor control for both 5-fraction schedules, compared with the control group of 40 Gy in 15 fractions,” Ms. Haviland summarized. “Late adverse effects in normal tissues were similar after 26 Gy in 5 fractions to 40 Gy in 15 fractions, and although rates were higher for the 27-Gy schedule, we noted that these are consistent with the historic standard of 50 Gy in 25 fractions.”

“There are obvious benefits to patients and health care systems of shorter radiotherapy treatments, particularly at the current time, and in fact, the COVID pandemic has accelerated uptake of the 26-Gy schedule around the world,” she added. “At a recent consensus meeting organized by the Royal College of Radiologists, the U.K. adopted the 26-Gy schedule as a new standard, also integrating this with partial breast irradiation, in close collaboration with the U.K. IMPORT Low trial.”

“This is very important work. I think this is one of the most important trials in the past few years. It has really changed practice,” commented session co-chair Ben Slotman, MD, PhD, of Vrije Universiteit Medical Center, Amsterdam, and AMC Amsterdam, who was not involved the trial.

Dr. Slotman wondered how extensive uptake of the new hypofractionated regimen has been. “I know it’s being used in the U.K. and the Netherlands, but do you have any idea about the rest of Europe? What do we need to make it the new standard?”

“I think there has been uptake in other countries in Europe and elsewhere around the world as well,” Ms. Haviland replied. But feedback suggests adoption has been tempered because of reservations related to the regimen’s safety in certain patient subgroups.

“We haven’t found any cause for concern in the subgroups, and also backed up by meta-analysis in the many patients randomized in the START trials,” she noted. “So I think there is very convincing evidence that it is safe as a new standard.”

FAST-Forward was sponsored by the Institute of Cancer Research and funded by the National Institute for Health Research Health Technology Assessment Programme. Ms. Haviland disclosed no conflicts of interest. Dr. Slotman has relationships with ViewRay and Varian Medical Systems.

SOURCE: Haviland J et al. ESTRO 2020, Abstract OC-0610.

Compared with the standard 3-week regimen, a 1-week hypofractionated regimen of adjuvant whole-breast radiotherapy had similar efficacy and safety at 5 years of follow-up, according to the U.K. FAST-Forward trial.

The trial was designed to compare the standard regimen (40 Gy in 15 fractions over 3 weeks) with a higher-dose hypofractionated regimen (27 Gy in 5 fractions over 5 days) and a lower-dose hypofractionated regimen (26 Gy in 5 fractions over 5 days) in women who had undergone surgery for early invasive breast cancer.

The 5-year rate of ipsilateral breast tumor relapse was similar with all regimens – 2.1% with the 40-Gy regimen, 1.7% with the 27-Gy regimen, and 1.4% with the 26-Gy regimen. The 26-Gy regimen also had similar safety as the 40-Gy regimen.

These results were presented at the European Society for Radiology and Oncology 2020 Online Congress by Joanne S. Haviland, MSc, of the Institute of Cancer Research in London. Results were also published in The Lancet.

Ms. Haviland said that hypofractionated regimens are attractive because of their shorter overall treatment times, which translate to greater convenience and lower treatment costs.

The historic 5-week regimen (50 Gy in 25 fractions) has been replaced by a 3-week regimen (40 Gy in 15 fractions) in the United Kingdom and elsewhere, and ongoing efforts are exploring whether further hypofractionation can be achieved without compromising efficacy and safety.

“The FAST-Forward trial was the next step on from testing hypofractionated schedules evaluated in earlier trials, including the START trials in the early 2000s and the FAST trial, which published its 10-year results earlier this year,” Ms. Haviland explained.

FAST-Forward enrolled 4,096 women who had undergone breast-conserving surgery or mastectomy for early invasive breast cancer. The patients were randomized into the aforementioned groups for adjuvant whole-breast or chest-wall radiotherapy: 40 Gy in 15 fractions over 3 weeks, 27 Gy in 5 fractions over 5 days, or 26 Gy in 5 fractions over 5 days. Boosts were permitted for all regimens.
 

Relapse, safety, and patient reports

The median follow-up was 6 years. The 5-year rate of ipsilateral breast tumor relapse was 2.1% with the 40-Gy standard regimen, 1.7% with the 27-Gy hypofractionated regimen, and 1.4% with the 26-Gy hypofractionated regimen.

The upper bound of the 95% confidence interval for the difference comparing the hypofractionated regimens against the standard fell well within the 1.6% excess predefined for noninferiority for both the 27-Gy regimen and the 26-Gy regimen (0.9% and 0.3%, respectively).

The hazard ratio for ipsilateral breast tumor relapse, compared with the standard regimen, was 0.86 for the 27-Gy hypofractionated regimen and 0.67 for the 26-Gy hypofractionated regimen.

In terms of safety, the 5-year rate of late adverse effects of the breast or chest wall – distortion, shrinkage, induration, telangiectasia, or edema – rated as “moderate” or “marked” by clinicians was 10% with the standard regimen, 15% with the 27-Gy regimen (relative risk, 1.55 ; P < .001), and 12% with the 26-Gy regimen (RR, 1.19; P = .17).

Over the entire follow-up, women had significantly higher odds of all moderate or marked individual late adverse effects (except discomfort) with the 27-Gy regimen versus the standard regimen, whereas their odds were significantly higher only for induration and edema with the 26-Gy regimen.

However, absolute rates and risk differences between groups were small, Ms. Haviland pointed out. For example, the most common moderate or marked late adverse effect with the standard regimen was breast shrinkage, seen in 5% of patients, followed by discomfort, seen in 4%.

Patient-assessed change in breast appearance and shrinkage did not differ significantly across groups. But women in the 27-Gy group were more likely than peers in the standard regimen group to report a moderate or marked increase in breast hardness/firmness (21% vs. 14%; P = .008), and women in both the 27-Gy and 26-Gy groups were more likely to report moderate or marked breast swelling (5%; P = .007 and 4%; P = .02, respectively, vs. 2%).
 

A new standard

“We have shown noninferiority in terms of local tumor control for both 5-fraction schedules, compared with the control group of 40 Gy in 15 fractions,” Ms. Haviland summarized. “Late adverse effects in normal tissues were similar after 26 Gy in 5 fractions to 40 Gy in 15 fractions, and although rates were higher for the 27-Gy schedule, we noted that these are consistent with the historic standard of 50 Gy in 25 fractions.”

“There are obvious benefits to patients and health care systems of shorter radiotherapy treatments, particularly at the current time, and in fact, the COVID pandemic has accelerated uptake of the 26-Gy schedule around the world,” she added. “At a recent consensus meeting organized by the Royal College of Radiologists, the U.K. adopted the 26-Gy schedule as a new standard, also integrating this with partial breast irradiation, in close collaboration with the U.K. IMPORT Low trial.”

“This is very important work. I think this is one of the most important trials in the past few years. It has really changed practice,” commented session co-chair Ben Slotman, MD, PhD, of Vrije Universiteit Medical Center, Amsterdam, and AMC Amsterdam, who was not involved the trial.

Dr. Slotman wondered how extensive uptake of the new hypofractionated regimen has been. “I know it’s being used in the U.K. and the Netherlands, but do you have any idea about the rest of Europe? What do we need to make it the new standard?”

“I think there has been uptake in other countries in Europe and elsewhere around the world as well,” Ms. Haviland replied. But feedback suggests adoption has been tempered because of reservations related to the regimen’s safety in certain patient subgroups.

“We haven’t found any cause for concern in the subgroups, and also backed up by meta-analysis in the many patients randomized in the START trials,” she noted. “So I think there is very convincing evidence that it is safe as a new standard.”

FAST-Forward was sponsored by the Institute of Cancer Research and funded by the National Institute for Health Research Health Technology Assessment Programme. Ms. Haviland disclosed no conflicts of interest. Dr. Slotman has relationships with ViewRay and Varian Medical Systems.

SOURCE: Haviland J et al. ESTRO 2020, Abstract OC-0610.

Compared with the standard 3-week regimen, a 1-week hypofractionated regimen of adjuvant whole-breast radiotherapy had similar efficacy and safety at 5 years of follow-up, according to the U.K. FAST-Forward trial.

The trial was designed to compare the standard regimen (40 Gy in 15 fractions over 3 weeks) with a higher-dose hypofractionated regimen (27 Gy in 5 fractions over 5 days) and a lower-dose hypofractionated regimen (26 Gy in 5 fractions over 5 days) in women who had undergone surgery for early invasive breast cancer.

The 5-year rate of ipsilateral breast tumor relapse was similar with all regimens – 2.1% with the 40-Gy regimen, 1.7% with the 27-Gy regimen, and 1.4% with the 26-Gy regimen. The 26-Gy regimen also had similar safety as the 40-Gy regimen.

These results were presented at the European Society for Radiology and Oncology 2020 Online Congress by Joanne S. Haviland, MSc, of the Institute of Cancer Research in London. Results were also published in The Lancet.

Ms. Haviland said that hypofractionated regimens are attractive because of their shorter overall treatment times, which translate to greater convenience and lower treatment costs.

The historic 5-week regimen (50 Gy in 25 fractions) has been replaced by a 3-week regimen (40 Gy in 15 fractions) in the United Kingdom and elsewhere, and ongoing efforts are exploring whether further hypofractionation can be achieved without compromising efficacy and safety.

“The FAST-Forward trial was the next step on from testing hypofractionated schedules evaluated in earlier trials, including the START trials in the early 2000s and the FAST trial, which published its 10-year results earlier this year,” Ms. Haviland explained.

FAST-Forward enrolled 4,096 women who had undergone breast-conserving surgery or mastectomy for early invasive breast cancer. The patients were randomized into the aforementioned groups for adjuvant whole-breast or chest-wall radiotherapy: 40 Gy in 15 fractions over 3 weeks, 27 Gy in 5 fractions over 5 days, or 26 Gy in 5 fractions over 5 days. Boosts were permitted for all regimens.
 

Relapse, safety, and patient reports

The median follow-up was 6 years. The 5-year rate of ipsilateral breast tumor relapse was 2.1% with the 40-Gy standard regimen, 1.7% with the 27-Gy hypofractionated regimen, and 1.4% with the 26-Gy hypofractionated regimen.

The upper bound of the 95% confidence interval for the difference comparing the hypofractionated regimens against the standard fell well within the 1.6% excess predefined for noninferiority for both the 27-Gy regimen and the 26-Gy regimen (0.9% and 0.3%, respectively).

The hazard ratio for ipsilateral breast tumor relapse, compared with the standard regimen, was 0.86 for the 27-Gy hypofractionated regimen and 0.67 for the 26-Gy hypofractionated regimen.

In terms of safety, the 5-year rate of late adverse effects of the breast or chest wall – distortion, shrinkage, induration, telangiectasia, or edema – rated as “moderate” or “marked” by clinicians was 10% with the standard regimen, 15% with the 27-Gy regimen (relative risk, 1.55 ; P < .001), and 12% with the 26-Gy regimen (RR, 1.19; P = .17).

Over the entire follow-up, women had significantly higher odds of all moderate or marked individual late adverse effects (except discomfort) with the 27-Gy regimen versus the standard regimen, whereas their odds were significantly higher only for induration and edema with the 26-Gy regimen.

However, absolute rates and risk differences between groups were small, Ms. Haviland pointed out. For example, the most common moderate or marked late adverse effect with the standard regimen was breast shrinkage, seen in 5% of patients, followed by discomfort, seen in 4%.

Patient-assessed change in breast appearance and shrinkage did not differ significantly across groups. But women in the 27-Gy group were more likely than peers in the standard regimen group to report a moderate or marked increase in breast hardness/firmness (21% vs. 14%; P = .008), and women in both the 27-Gy and 26-Gy groups were more likely to report moderate or marked breast swelling (5%; P = .007 and 4%; P = .02, respectively, vs. 2%).
 

A new standard

“We have shown noninferiority in terms of local tumor control for both 5-fraction schedules, compared with the control group of 40 Gy in 15 fractions,” Ms. Haviland summarized. “Late adverse effects in normal tissues were similar after 26 Gy in 5 fractions to 40 Gy in 15 fractions, and although rates were higher for the 27-Gy schedule, we noted that these are consistent with the historic standard of 50 Gy in 25 fractions.”

“There are obvious benefits to patients and health care systems of shorter radiotherapy treatments, particularly at the current time, and in fact, the COVID pandemic has accelerated uptake of the 26-Gy schedule around the world,” she added. “At a recent consensus meeting organized by the Royal College of Radiologists, the U.K. adopted the 26-Gy schedule as a new standard, also integrating this with partial breast irradiation, in close collaboration with the U.K. IMPORT Low trial.”

“This is very important work. I think this is one of the most important trials in the past few years. It has really changed practice,” commented session co-chair Ben Slotman, MD, PhD, of Vrije Universiteit Medical Center, Amsterdam, and AMC Amsterdam, who was not involved the trial.

Dr. Slotman wondered how extensive uptake of the new hypofractionated regimen has been. “I know it’s being used in the U.K. and the Netherlands, but do you have any idea about the rest of Europe? What do we need to make it the new standard?”

“I think there has been uptake in other countries in Europe and elsewhere around the world as well,” Ms. Haviland replied. But feedback suggests adoption has been tempered because of reservations related to the regimen’s safety in certain patient subgroups.

“We haven’t found any cause for concern in the subgroups, and also backed up by meta-analysis in the many patients randomized in the START trials,” she noted. “So I think there is very convincing evidence that it is safe as a new standard.”

FAST-Forward was sponsored by the Institute of Cancer Research and funded by the National Institute for Health Research Health Technology Assessment Programme. Ms. Haviland disclosed no conflicts of interest. Dr. Slotman has relationships with ViewRay and Varian Medical Systems.

SOURCE: Haviland J et al. ESTRO 2020, Abstract OC-0610.

Full-field ablative laser resurfacing may be an “oldie but a goodie” technique, but it remains a gold standard for skin rejuvenation, according to Brian S. Biesman, MD.

“When performing laser skin resurfacing, our goal is to match the degree of injury to the needs of the patient we’re treating,” Dr. Biesman, an oculofacial plastic surgeon who practices in Nashville, Tenn., said during a virtual course on laser and aesthetic skin therapy.

“If we’re treating a 35-year-old with minimal photoaging, we don’t need to use full-field resurfacing. By the same token, a 60-year-old who’s never had anything but sun exposure is not going to do well with nonablative fractional resurfacing or other modalities that produce only modest changes,” he noted. “Full ablative resurfacing is a useful tool that can be used to treat a variety of patients. We can tailor each treatment to the individual patient. We can simply dial the energy up or down and adjust the density.”

Full-field laser ablation removes the epidermis as well as a part of the dermis, and the degree of dermal injury varies depending on the relative aggressiveness of the treatment. “We can treat very superficially in the dermis or we can do deep dermal treatments,” he said at the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine.

“The residual thermal injury will vary to some degree, depending on our treatment parameters. It does cause immediate collagen contracture. It also stimulates a process of neocollagenesis.”

Two main lasers used for full-field treatments are the erbium:YAG laser and the CO₂ laser at wavelengths of 2,940 nm and 10,600 nm, respectively. “The erbium:YAG is far more highly absorbed by water, by a factor of about 13,” he said. “But both of these wavelengths can be used successfully as long as you understand the physics behind them.”

The short-pulsed erbium:YAG laser ablates effectively, producing about a 10 mcm zone of thermal injury. “That’s not going to induce much by the way of remodeling, but it will be effective in removing tissue from the superficial layers of the skin,” said Dr. Biesman, who is a past president of the American Society for Laser Medicine and Surgery. “There’s also an absorption peak for collagen, so if you’re treating a scar, this laser can be highly effective.”

The CO₂ laser creates more residual thermal injury during full-field resurfacing, compared with the short-pulsed erbium:YAG laser. The long-pulsed erbium:YAG laser can be used in both short- and long-pulsed modes and is more ablative than the CO₂ laser when used in short-pulsed mode. When used in long-pulse mode, it makes it possible to produce results “very similar to CO₂ in terms of the thermal injury profile,” he said. “It’s a versatile device. So, the CO₂ in its native mode produces more thermal injury, while the erbium:YAG laser is more ablative. Both can be used effectively for facial skin rejuvenation.”

Full-field laser resurfacing requires local infiltration with lidocaine 1% or 2% with epinephrine or general anesthesia. “This is not a treatment that you can do comfortably under topical anesthesia, even if you’re using cold air unless you are doing treatments essentially confined to the epidermis and superficial dermis,” Dr. Biesman said. “When working around the eyes or on the face you need to use ocular protection with metal ocular shields. There’s no two ways about it. There is no scenario in which you’re doing an ablative resurfacing around the eye where you don’t use metal corneal shields.”

Energy and density levels can be fine-tuned in order to optimize treatment. For deep rhytides in the perioral region or on the forehead or lateral cheeks, clinicians may choose to treat at a higher density, while rhytides located in other areas may respond well to treatments at a lower density. Relative danger zones include the eyelids in general, especially the medial lower eyelid, as well as the upper lip. “These are the areas that are most prone to developing scarring,” he said.

For the upper eyelids, Dr. Biesman treats from the lashes to the upper brow. “It’s important to protect the lashes and treat from the lower-lid margin all the way down to the orbital rim. I debride relatively aggressively. I want to debride all the eschar created by the first pass and come back with a second pass. I sometimes will decrease the density on the second pass, depending on the type of tissue response that I see. If I see a dramatic response on the second pass I will definitely decrease the density.” He uses Aquaphor to protect the eyebrows. “It’s difficult to do that on the lashes. For the lashes, I usually use a wet tongue blade and keep the lid on stretch as I do my treatments.”

Dr. Biesman recommends feathering to blend full-field treatments with the neck. This means bringing treatments below the mandible. “There are times when we want to conservatively treat the neck,” he said. “The neck does not recover nearly as well after ablative resurfacing as the face does due to the fact that there’s probably about 90% fewer sebaceous glands and hair follicles in the neck relative to the face.”

In Dr. Biesman’s opinion, the important perioperative preparation is counseling the patient, including setting realistic expectations and devising a plan for wound care. “They can expect 7-10 days to heal, depending on the area we’re treating and the relative aggressiveness of the planned treatment,” he said. For patients with a history of herpes simplex virus type 1, he recommends antiviral treatment prior to the procedure. “If you do encounter a herpetic infection postoperatively, you may not see typical clinical signs of blistering as the epidermis has been removed.”

Dr. Biesman uses both antiviral and antibiotic prophylaxis prior to full-field treatments. “The literature by and large says that antibiotic/antiviral prophylaxis is not required prior to full-face ablation,” he said. “The reason I choose to is that I have had some issues with community-acquired MRSA infections. Because it’s so ubiquitous these days, I typically do prescribe an agent that gives good MRSA coverage.”

As for wound care, the literature differs on open versus closed techniques. Dr. Biesman favors using Aquaphor for the first week or so and seeing patients back on posttreatment day 2, “who by that time are usually beyond the inflammatory phase of wound healing,” he said. “A lot of the initial oozing has stopped by then. We clean that off any dried exudate in the office very carefully. We debride gently with warm-water soaks and I like to use PRP [platelet-rich plasma]. There is literature to support the role of PRP in wound healing.”

Even in the most experienced hands, complications can occur from full-field laser resurfacing, including bacterial, viral, or fungal infections. Other potential complications include persistent erythema, hypopigmentation, hyperpigmentation, scarring, and ectropion. “Knowledge of treatment parameters, endpoints, and wound healing is required for safe and successful outcomes,” Dr. Biesman said.

He reported having no relevant disclosures related to his presentation.

dbrunk@mdedge.com

Full-field ablative laser resurfacing may be an “oldie but a goodie” technique, but it remains a gold standard for skin rejuvenation, according to Brian S. Biesman, MD.

“When performing laser skin resurfacing, our goal is to match the degree of injury to the needs of the patient we’re treating,” Dr. Biesman, an oculofacial plastic surgeon who practices in Nashville, Tenn., said during a virtual course on laser and aesthetic skin therapy.

“If we’re treating a 35-year-old with minimal photoaging, we don’t need to use full-field resurfacing. By the same token, a 60-year-old who’s never had anything but sun exposure is not going to do well with nonablative fractional resurfacing or other modalities that produce only modest changes,” he noted. “Full ablative resurfacing is a useful tool that can be used to treat a variety of patients. We can tailor each treatment to the individual patient. We can simply dial the energy up or down and adjust the density.”

Full-field laser ablation removes the epidermis as well as a part of the dermis, and the degree of dermal injury varies depending on the relative aggressiveness of the treatment. “We can treat very superficially in the dermis or we can do deep dermal treatments,” he said at the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine.

“The residual thermal injury will vary to some degree, depending on our treatment parameters. It does cause immediate collagen contracture. It also stimulates a process of neocollagenesis.”

Two main lasers used for full-field treatments are the erbium:YAG laser and the CO₂ laser at wavelengths of 2,940 nm and 10,600 nm, respectively. “The erbium:YAG is far more highly absorbed by water, by a factor of about 13,” he said. “But both of these wavelengths can be used successfully as long as you understand the physics behind them.”

The short-pulsed erbium:YAG laser ablates effectively, producing about a 10 mcm zone of thermal injury. “That’s not going to induce much by the way of remodeling, but it will be effective in removing tissue from the superficial layers of the skin,” said Dr. Biesman, who is a past president of the American Society for Laser Medicine and Surgery. “There’s also an absorption peak for collagen, so if you’re treating a scar, this laser can be highly effective.”

The CO₂ laser creates more residual thermal injury during full-field resurfacing, compared with the short-pulsed erbium:YAG laser. The long-pulsed erbium:YAG laser can be used in both short- and long-pulsed modes and is more ablative than the CO₂ laser when used in short-pulsed mode. When used in long-pulse mode, it makes it possible to produce results “very similar to CO₂ in terms of the thermal injury profile,” he said. “It’s a versatile device. So, the CO₂ in its native mode produces more thermal injury, while the erbium:YAG laser is more ablative. Both can be used effectively for facial skin rejuvenation.”

Full-field laser resurfacing requires local infiltration with lidocaine 1% or 2% with epinephrine or general anesthesia. “This is not a treatment that you can do comfortably under topical anesthesia, even if you’re using cold air unless you are doing treatments essentially confined to the epidermis and superficial dermis,” Dr. Biesman said. “When working around the eyes or on the face you need to use ocular protection with metal ocular shields. There’s no two ways about it. There is no scenario in which you’re doing an ablative resurfacing around the eye where you don’t use metal corneal shields.”

Energy and density levels can be fine-tuned in order to optimize treatment. For deep rhytides in the perioral region or on the forehead or lateral cheeks, clinicians may choose to treat at a higher density, while rhytides located in other areas may respond well to treatments at a lower density. Relative danger zones include the eyelids in general, especially the medial lower eyelid, as well as the upper lip. “These are the areas that are most prone to developing scarring,” he said.

For the upper eyelids, Dr. Biesman treats from the lashes to the upper brow. “It’s important to protect the lashes and treat from the lower-lid margin all the way down to the orbital rim. I debride relatively aggressively. I want to debride all the eschar created by the first pass and come back with a second pass. I sometimes will decrease the density on the second pass, depending on the type of tissue response that I see. If I see a dramatic response on the second pass I will definitely decrease the density.” He uses Aquaphor to protect the eyebrows. “It’s difficult to do that on the lashes. For the lashes, I usually use a wet tongue blade and keep the lid on stretch as I do my treatments.”

Dr. Biesman recommends feathering to blend full-field treatments with the neck. This means bringing treatments below the mandible. “There are times when we want to conservatively treat the neck,” he said. “The neck does not recover nearly as well after ablative resurfacing as the face does due to the fact that there’s probably about 90% fewer sebaceous glands and hair follicles in the neck relative to the face.”

In Dr. Biesman’s opinion, the important perioperative preparation is counseling the patient, including setting realistic expectations and devising a plan for wound care. “They can expect 7-10 days to heal, depending on the area we’re treating and the relative aggressiveness of the planned treatment,” he said. For patients with a history of herpes simplex virus type 1, he recommends antiviral treatment prior to the procedure. “If you do encounter a herpetic infection postoperatively, you may not see typical clinical signs of blistering as the epidermis has been removed.”

Dr. Biesman uses both antiviral and antibiotic prophylaxis prior to full-field treatments. “The literature by and large says that antibiotic/antiviral prophylaxis is not required prior to full-face ablation,” he said. “The reason I choose to is that I have had some issues with community-acquired MRSA infections. Because it’s so ubiquitous these days, I typically do prescribe an agent that gives good MRSA coverage.”

As for wound care, the literature differs on open versus closed techniques. Dr. Biesman favors using Aquaphor for the first week or so and seeing patients back on posttreatment day 2, “who by that time are usually beyond the inflammatory phase of wound healing,” he said. “A lot of the initial oozing has stopped by then. We clean that off any dried exudate in the office very carefully. We debride gently with warm-water soaks and I like to use PRP [platelet-rich plasma]. There is literature to support the role of PRP in wound healing.”

Even in the most experienced hands, complications can occur from full-field laser resurfacing, including bacterial, viral, or fungal infections. Other potential complications include persistent erythema, hypopigmentation, hyperpigmentation, scarring, and ectropion. “Knowledge of treatment parameters, endpoints, and wound healing is required for safe and successful outcomes,” Dr. Biesman said.

He reported having no relevant disclosures related to his presentation.

dbrunk@mdedge.com

Full-field ablative laser resurfacing may be an “oldie but a goodie” technique, but it remains a gold standard for skin rejuvenation, according to Brian S. Biesman, MD.

“When performing laser skin resurfacing, our goal is to match the degree of injury to the needs of the patient we’re treating,” Dr. Biesman, an oculofacial plastic surgeon who practices in Nashville, Tenn., said during a virtual course on laser and aesthetic skin therapy.

“If we’re treating a 35-year-old with minimal photoaging, we don’t need to use full-field resurfacing. By the same token, a 60-year-old who’s never had anything but sun exposure is not going to do well with nonablative fractional resurfacing or other modalities that produce only modest changes,” he noted. “Full ablative resurfacing is a useful tool that can be used to treat a variety of patients. We can tailor each treatment to the individual patient. We can simply dial the energy up or down and adjust the density.”

Full-field laser ablation removes the epidermis as well as a part of the dermis, and the degree of dermal injury varies depending on the relative aggressiveness of the treatment. “We can treat very superficially in the dermis or we can do deep dermal treatments,” he said at the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine.

“The residual thermal injury will vary to some degree, depending on our treatment parameters. It does cause immediate collagen contracture. It also stimulates a process of neocollagenesis.”

Two main lasers used for full-field treatments are the erbium:YAG laser and the CO₂ laser at wavelengths of 2,940 nm and 10,600 nm, respectively. “The erbium:YAG is far more highly absorbed by water, by a factor of about 13,” he said. “But both of these wavelengths can be used successfully as long as you understand the physics behind them.”

The short-pulsed erbium:YAG laser ablates effectively, producing about a 10 mcm zone of thermal injury. “That’s not going to induce much by the way of remodeling, but it will be effective in removing tissue from the superficial layers of the skin,” said Dr. Biesman, who is a past president of the American Society for Laser Medicine and Surgery. “There’s also an absorption peak for collagen, so if you’re treating a scar, this laser can be highly effective.”

The CO₂ laser creates more residual thermal injury during full-field resurfacing, compared with the short-pulsed erbium:YAG laser. The long-pulsed erbium:YAG laser can be used in both short- and long-pulsed modes and is more ablative than the CO₂ laser when used in short-pulsed mode. When used in long-pulse mode, it makes it possible to produce results “very similar to CO₂ in terms of the thermal injury profile,” he said. “It’s a versatile device. So, the CO₂ in its native mode produces more thermal injury, while the erbium:YAG laser is more ablative. Both can be used effectively for facial skin rejuvenation.”

Full-field laser resurfacing requires local infiltration with lidocaine 1% or 2% with epinephrine or general anesthesia. “This is not a treatment that you can do comfortably under topical anesthesia, even if you’re using cold air unless you are doing treatments essentially confined to the epidermis and superficial dermis,” Dr. Biesman said. “When working around the eyes or on the face you need to use ocular protection with metal ocular shields. There’s no two ways about it. There is no scenario in which you’re doing an ablative resurfacing around the eye where you don’t use metal corneal shields.”

Energy and density levels can be fine-tuned in order to optimize treatment. For deep rhytides in the perioral region or on the forehead or lateral cheeks, clinicians may choose to treat at a higher density, while rhytides located in other areas may respond well to treatments at a lower density. Relative danger zones include the eyelids in general, especially the medial lower eyelid, as well as the upper lip. “These are the areas that are most prone to developing scarring,” he said.

For the upper eyelids, Dr. Biesman treats from the lashes to the upper brow. “It’s important to protect the lashes and treat from the lower-lid margin all the way down to the orbital rim. I debride relatively aggressively. I want to debride all the eschar created by the first pass and come back with a second pass. I sometimes will decrease the density on the second pass, depending on the type of tissue response that I see. If I see a dramatic response on the second pass I will definitely decrease the density.” He uses Aquaphor to protect the eyebrows. “It’s difficult to do that on the lashes. For the lashes, I usually use a wet tongue blade and keep the lid on stretch as I do my treatments.”

Dr. Biesman recommends feathering to blend full-field treatments with the neck. This means bringing treatments below the mandible. “There are times when we want to conservatively treat the neck,” he said. “The neck does not recover nearly as well after ablative resurfacing as the face does due to the fact that there’s probably about 90% fewer sebaceous glands and hair follicles in the neck relative to the face.”

In Dr. Biesman’s opinion, the important perioperative preparation is counseling the patient, including setting realistic expectations and devising a plan for wound care. “They can expect 7-10 days to heal, depending on the area we’re treating and the relative aggressiveness of the planned treatment,” he said. For patients with a history of herpes simplex virus type 1, he recommends antiviral treatment prior to the procedure. “If you do encounter a herpetic infection postoperatively, you may not see typical clinical signs of blistering as the epidermis has been removed.”

Dr. Biesman uses both antiviral and antibiotic prophylaxis prior to full-field treatments. “The literature by and large says that antibiotic/antiviral prophylaxis is not required prior to full-face ablation,” he said. “The reason I choose to is that I have had some issues with community-acquired MRSA infections. Because it’s so ubiquitous these days, I typically do prescribe an agent that gives good MRSA coverage.”

As for wound care, the literature differs on open versus closed techniques. Dr. Biesman favors using Aquaphor for the first week or so and seeing patients back on posttreatment day 2, “who by that time are usually beyond the inflammatory phase of wound healing,” he said. “A lot of the initial oozing has stopped by then. We clean that off any dried exudate in the office very carefully. We debride gently with warm-water soaks and I like to use PRP [platelet-rich plasma]. There is literature to support the role of PRP in wound healing.”

Even in the most experienced hands, complications can occur from full-field laser resurfacing, including bacterial, viral, or fungal infections. Other potential complications include persistent erythema, hypopigmentation, hyperpigmentation, scarring, and ectropion. “Knowledge of treatment parameters, endpoints, and wound healing is required for safe and successful outcomes,” Dr. Biesman said.

He reported having no relevant disclosures related to his presentation.

dbrunk@mdedge.com

Patients with breast cancer want accurate information on the risk of their cancer recurring once they have completed treatment.

“I would like to know the true stats of how many breast cancers come back no matter what the hell we do for treatment,” comments a typical post on a breast cancer patient bulletin board.

But those statistics have not been available from a robust population-based source.

Now, there is hope that they will – at last – be collected.

A new pilot project at the National Cancer Institute is setting out to collect that information, although the researchers say it is a “long-term goal” that will take a few years.

But it has already been a long time coming. The mother lode of all U.S. cancer data, the NCI’s Surveillance, Epidemiology, and End Results (SEER) Program, started collecting cancer data in 1973.

“When they began to capture cancer data, the focus was primarily on the incidence of cancer, the different types of cancer, and survival,” explained Esmeralda Ramirez-Pena, PhD, MPH, cancer prevention fellow at the NCI.

“Later, SEER expanded to include subgroups of various cancers and different stages at diagnosis,” she added.

But this database has never included information on cancer recurrence.

In a 2017 press statement, the NCI commented: “Collecting recurrence data has been challenging for cancer registries because recurrence can be diagnosed through diverse methods and in a variety of locations.”
 

New project

The NCI now has a “long-term goal” to implement additional “data elements” into SEER that will allow calculation of breast cancer recurrences, said Dr. Ramirez-Pena.

The Breast Cancer Recurrence Project, a pilot program funded via an NCI–Department of Energy collaboration, “will take a couple of years,” she said.

She presented some details of the new project as a poster at the recent San Antonio Breast Cancer Symposium 2020.

“SEER has added data elements over time,” she said, and this latest move will – at last – include information on breast cancer recurrence.
 

Why the change now?

“There’s been so much interest [in breast cancer recurrence]. It’s a top cause of cancer death in the United States and globally. The urgent need is evident,” she explained.

Breast cancer advocates have long been calling for SEER to count recurrence, including metastatic recurrence.

Katherine O’Brien, a breast cancer “metser” from Chicago, is credited with especially turning the heat up on the NCI.

In 2015, Ms. O’Brien spearheaded the creation of an online petition on the website change.org, calling on the NCI’s SEER, the Centers for Disease Control and Prevention, and all state cancer registries to start counting all people living with metastatic breast cancer, including those whose early-stage disease progressed. The petition, which is now closed, collected nearly 12,000 signatures.
 

Tracking recurrences

In the new project, cancer recurrence is defined as a cancer that was treated, reduced to undetectable levels, and later returned either locally, regionally, or distantly.

Tracking recurrence is not a simple matter because posttreatment surveillance to detect it includes clinical exams, biomarker testing, pathologic studies, molecular testing, imaging, and patient-reported symptoms and because recurrence frequency varies by subtype of breast cancer and TNM classification. Additionally, recurrence may depend on age at diagnosis, a variety of risk factors, treatment type, and access to quality of care.

“It’s likely there are many elements that influence recurrence,” said Dr. Ramirez-Pena.

To get a handle on the complexity, the NCI needs to first identify which data are needed to tally recurrence and the frequency at which they are collected, explained Dr. Ramirez-Pena. To do so, she and her coinvestigators conducted a systematic review of phase 3 clinical trials of early-stage breast cancer.

On their own, such trials are not sufficient to provide recurrence estimates at the population level because they lack diversity, represent fewer than 5% of all cancer patients, and the study period may not be long enough to capture recurrences for long-latency breast cancers, such as estrogen receptor–positive malignancies.

Nonetheless, these clinical trials provide a starting place.

The investigators identified 444 early-stage clinical trials. They stratified participants by subtype and tumor characteristics, which will enable analysis of risk-group and treatment-dependent differences in recurrence.

The changing science of breast cancer makes this work a challenge, the investigators said. For example, in clinical trials from the early 1990s through the early 2000s, receptor status and subtyping was not commonly reported, and some treatment endpoints were added during the past few years.

“Our next step will be to extract recurrence rates from these trials so we can eventually provide individualized information about recurrence risk to survivors,” Dr. Ramirez-Pena said, describing the big-picture aims.

The Breast Cancer Recurrence Project is collaborating with external agencies, such as the International Agency for Research on Cancer and Public Health England, in fine-tuning data elements, because “recurrence is not captured well globally either,” said Dr. Ramirez-Pena.

The study was supported by NCI.

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

Patients with breast cancer want accurate information on the risk of their cancer recurring once they have completed treatment.

“I would like to know the true stats of how many breast cancers come back no matter what the hell we do for treatment,” comments a typical post on a breast cancer patient bulletin board.

But those statistics have not been available from a robust population-based source.

Now, there is hope that they will – at last – be collected.

A new pilot project at the National Cancer Institute is setting out to collect that information, although the researchers say it is a “long-term goal” that will take a few years.

But it has already been a long time coming. The mother lode of all U.S. cancer data, the NCI’s Surveillance, Epidemiology, and End Results (SEER) Program, started collecting cancer data in 1973.

“When they began to capture cancer data, the focus was primarily on the incidence of cancer, the different types of cancer, and survival,” explained Esmeralda Ramirez-Pena, PhD, MPH, cancer prevention fellow at the NCI.

“Later, SEER expanded to include subgroups of various cancers and different stages at diagnosis,” she added.

But this database has never included information on cancer recurrence.

In a 2017 press statement, the NCI commented: “Collecting recurrence data has been challenging for cancer registries because recurrence can be diagnosed through diverse methods and in a variety of locations.”
 

New project

The NCI now has a “long-term goal” to implement additional “data elements” into SEER that will allow calculation of breast cancer recurrences, said Dr. Ramirez-Pena.

The Breast Cancer Recurrence Project, a pilot program funded via an NCI–Department of Energy collaboration, “will take a couple of years,” she said.

She presented some details of the new project as a poster at the recent San Antonio Breast Cancer Symposium 2020.

“SEER has added data elements over time,” she said, and this latest move will – at last – include information on breast cancer recurrence.
 

Why the change now?

“There’s been so much interest [in breast cancer recurrence]. It’s a top cause of cancer death in the United States and globally. The urgent need is evident,” she explained.

Breast cancer advocates have long been calling for SEER to count recurrence, including metastatic recurrence.

Katherine O’Brien, a breast cancer “metser” from Chicago, is credited with especially turning the heat up on the NCI.

In 2015, Ms. O’Brien spearheaded the creation of an online petition on the website change.org, calling on the NCI’s SEER, the Centers for Disease Control and Prevention, and all state cancer registries to start counting all people living with metastatic breast cancer, including those whose early-stage disease progressed. The petition, which is now closed, collected nearly 12,000 signatures.
 

Tracking recurrences

In the new project, cancer recurrence is defined as a cancer that was treated, reduced to undetectable levels, and later returned either locally, regionally, or distantly.

Tracking recurrence is not a simple matter because posttreatment surveillance to detect it includes clinical exams, biomarker testing, pathologic studies, molecular testing, imaging, and patient-reported symptoms and because recurrence frequency varies by subtype of breast cancer and TNM classification. Additionally, recurrence may depend on age at diagnosis, a variety of risk factors, treatment type, and access to quality of care.

“It’s likely there are many elements that influence recurrence,” said Dr. Ramirez-Pena.

To get a handle on the complexity, the NCI needs to first identify which data are needed to tally recurrence and the frequency at which they are collected, explained Dr. Ramirez-Pena. To do so, she and her coinvestigators conducted a systematic review of phase 3 clinical trials of early-stage breast cancer.

On their own, such trials are not sufficient to provide recurrence estimates at the population level because they lack diversity, represent fewer than 5% of all cancer patients, and the study period may not be long enough to capture recurrences for long-latency breast cancers, such as estrogen receptor–positive malignancies.

Nonetheless, these clinical trials provide a starting place.

The investigators identified 444 early-stage clinical trials. They stratified participants by subtype and tumor characteristics, which will enable analysis of risk-group and treatment-dependent differences in recurrence.

The changing science of breast cancer makes this work a challenge, the investigators said. For example, in clinical trials from the early 1990s through the early 2000s, receptor status and subtyping was not commonly reported, and some treatment endpoints were added during the past few years.

“Our next step will be to extract recurrence rates from these trials so we can eventually provide individualized information about recurrence risk to survivors,” Dr. Ramirez-Pena said, describing the big-picture aims.

The Breast Cancer Recurrence Project is collaborating with external agencies, such as the International Agency for Research on Cancer and Public Health England, in fine-tuning data elements, because “recurrence is not captured well globally either,” said Dr. Ramirez-Pena.

The study was supported by NCI.

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

Patients with breast cancer want accurate information on the risk of their cancer recurring once they have completed treatment.

“I would like to know the true stats of how many breast cancers come back no matter what the hell we do for treatment,” comments a typical post on a breast cancer patient bulletin board.

But those statistics have not been available from a robust population-based source.

Now, there is hope that they will – at last – be collected.

A new pilot project at the National Cancer Institute is setting out to collect that information, although the researchers say it is a “long-term goal” that will take a few years.

But it has already been a long time coming. The mother lode of all U.S. cancer data, the NCI’s Surveillance, Epidemiology, and End Results (SEER) Program, started collecting cancer data in 1973.

“When they began to capture cancer data, the focus was primarily on the incidence of cancer, the different types of cancer, and survival,” explained Esmeralda Ramirez-Pena, PhD, MPH, cancer prevention fellow at the NCI.

“Later, SEER expanded to include subgroups of various cancers and different stages at diagnosis,” she added.

But this database has never included information on cancer recurrence.

In a 2017 press statement, the NCI commented: “Collecting recurrence data has been challenging for cancer registries because recurrence can be diagnosed through diverse methods and in a variety of locations.”
 

New project

The NCI now has a “long-term goal” to implement additional “data elements” into SEER that will allow calculation of breast cancer recurrences, said Dr. Ramirez-Pena.

The Breast Cancer Recurrence Project, a pilot program funded via an NCI–Department of Energy collaboration, “will take a couple of years,” she said.

She presented some details of the new project as a poster at the recent San Antonio Breast Cancer Symposium 2020.

“SEER has added data elements over time,” she said, and this latest move will – at last – include information on breast cancer recurrence.
 

Why the change now?

“There’s been so much interest [in breast cancer recurrence]. It’s a top cause of cancer death in the United States and globally. The urgent need is evident,” she explained.

Breast cancer advocates have long been calling for SEER to count recurrence, including metastatic recurrence.

Katherine O’Brien, a breast cancer “metser” from Chicago, is credited with especially turning the heat up on the NCI.

In 2015, Ms. O’Brien spearheaded the creation of an online petition on the website change.org, calling on the NCI’s SEER, the Centers for Disease Control and Prevention, and all state cancer registries to start counting all people living with metastatic breast cancer, including those whose early-stage disease progressed. The petition, which is now closed, collected nearly 12,000 signatures.
 

Tracking recurrences

In the new project, cancer recurrence is defined as a cancer that was treated, reduced to undetectable levels, and later returned either locally, regionally, or distantly.

Tracking recurrence is not a simple matter because posttreatment surveillance to detect it includes clinical exams, biomarker testing, pathologic studies, molecular testing, imaging, and patient-reported symptoms and because recurrence frequency varies by subtype of breast cancer and TNM classification. Additionally, recurrence may depend on age at diagnosis, a variety of risk factors, treatment type, and access to quality of care.

“It’s likely there are many elements that influence recurrence,” said Dr. Ramirez-Pena.

To get a handle on the complexity, the NCI needs to first identify which data are needed to tally recurrence and the frequency at which they are collected, explained Dr. Ramirez-Pena. To do so, she and her coinvestigators conducted a systematic review of phase 3 clinical trials of early-stage breast cancer.

On their own, such trials are not sufficient to provide recurrence estimates at the population level because they lack diversity, represent fewer than 5% of all cancer patients, and the study period may not be long enough to capture recurrences for long-latency breast cancers, such as estrogen receptor–positive malignancies.

Nonetheless, these clinical trials provide a starting place.

The investigators identified 444 early-stage clinical trials. They stratified participants by subtype and tumor characteristics, which will enable analysis of risk-group and treatment-dependent differences in recurrence.

The changing science of breast cancer makes this work a challenge, the investigators said. For example, in clinical trials from the early 1990s through the early 2000s, receptor status and subtyping was not commonly reported, and some treatment endpoints were added during the past few years.

“Our next step will be to extract recurrence rates from these trials so we can eventually provide individualized information about recurrence risk to survivors,” Dr. Ramirez-Pena said, describing the big-picture aims.

The Breast Cancer Recurrence Project is collaborating with external agencies, such as the International Agency for Research on Cancer and Public Health England, in fine-tuning data elements, because “recurrence is not captured well globally either,” said Dr. Ramirez-Pena.

The study was supported by NCI.

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

Deucravacitinib, a first-in-class oral selective tyrosine kinase 2 inhibitor, shows considerable promise as a potential novel treatment for psoriasis and a range of other chronic inflammatory diseases, Bruce E. Strober, MD, PhD, said at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

Deucravacitinib solely blocks tyrosine kinase 2 (TYK2) signaling without touching Janus kinase (JAK) 1, 2, or 3. In so doing, it inhibits several cytokines important for inflammation: interleukin-12, IL-13, and interferon-alpha and -beta. Yet it doesn’t affect the numerous pathways mediated by JAKs 1-3, many of which relate to growth and development of cell lineages, including production of erythropoietin, thrombopoietin, granulocyte-macrophage colony-stimulating factor, prolactin, growth hormone, and leptin. These deucravacitinib characteristics should translate into fewer off-target side effects than with oral JAK inhibitors.

“The promise of TYK2 inhibition that’s brought to you by deucravacitinib is there will be no laboratory monitoring and the effects will be narrow in blocking inflammation,” said Dr. Strober, a dermatologist at Yale University, New Haven, Conn., and in private practice in Cromwell, Conn.

He highlighted the positive results of a randomized, phase 2, dose-ranging study conducted in 267 patients with moderate or severe plaque psoriasis. Participants had an average baseline Psoriasis Area and Severity Index (PASI) score of 19, with a Dermatology Life Quality Index score of about 12. At the top dose of 12 mg once daily, 75% of patients achieved a PASI 75 response at week 12, and 44% reached a PASI 90, as did 69% and 44%, respectively, who were on deucravacitinib at 3 mg twice daily. Those are collective efficacy numbers similar to adalimumab (Humira) or ustekinumab (Stelara).

Deucravacitinib may provide efficacy “like one of our second-tier biological therapies, yet it will be oral,” Dr. Strober commented.

Importantly, no laboratory abnormalities were detected in this trial. Only mild side effects were documented, most prominently acne, which occurred in dose-dependent fashion in 2% of patients on 3 mg of deucravacitinib twice daily and 4% at 12 mg once daily.

“The treatment of the acne that is elicited by this drug is yet to be fully described, but I’m sure we’ll learn the best approaches, given that acne is in our wheel house,” the dermatologist added.

Bristol-Myers Squibb has announced positive results from the pivotal phase 3 POETYK PSO-1 trial. Deucravacitinib at 6 mg once daily met both of its coprimary efficacy endpoints in the study, which included 666 patients with moderate to severe psoriasis. The TYK 2 inhibitor demonstrated superiority to both placebo and oral apremilast (Otezla) at week 16. The company said the safety profile was consistent with the phase 2 results, and that the full details of the phase 3 trial will be presented next year at a major medical meeting.

In addition, positive phase 2 results were reported for deucravacitinib in the treatment of psoriatic arthritis in a randomized trial presented at the fall 2020 meeting of the American College of Rheumatology. Deucravacitinib is also under study for lupus and inflammatory bowel disease.

Dr. Strober, an active clinical trialist, reported serving as a consultant to more than two dozen pharmaceutical companies, including Bristol-Myers Squibb.

MedscapeLive and this news organization are owned by the same parent company.

bjancin@mdedge.com

Deucravacitinib, a first-in-class oral selective tyrosine kinase 2 inhibitor, shows considerable promise as a potential novel treatment for psoriasis and a range of other chronic inflammatory diseases, Bruce E. Strober, MD, PhD, said at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

Deucravacitinib solely blocks tyrosine kinase 2 (TYK2) signaling without touching Janus kinase (JAK) 1, 2, or 3. In so doing, it inhibits several cytokines important for inflammation: interleukin-12, IL-13, and interferon-alpha and -beta. Yet it doesn’t affect the numerous pathways mediated by JAKs 1-3, many of which relate to growth and development of cell lineages, including production of erythropoietin, thrombopoietin, granulocyte-macrophage colony-stimulating factor, prolactin, growth hormone, and leptin. These deucravacitinib characteristics should translate into fewer off-target side effects than with oral JAK inhibitors.

“The promise of TYK2 inhibition that’s brought to you by deucravacitinib is there will be no laboratory monitoring and the effects will be narrow in blocking inflammation,” said Dr. Strober, a dermatologist at Yale University, New Haven, Conn., and in private practice in Cromwell, Conn.

He highlighted the positive results of a randomized, phase 2, dose-ranging study conducted in 267 patients with moderate or severe plaque psoriasis. Participants had an average baseline Psoriasis Area and Severity Index (PASI) score of 19, with a Dermatology Life Quality Index score of about 12. At the top dose of 12 mg once daily, 75% of patients achieved a PASI 75 response at week 12, and 44% reached a PASI 90, as did 69% and 44%, respectively, who were on deucravacitinib at 3 mg twice daily. Those are collective efficacy numbers similar to adalimumab (Humira) or ustekinumab (Stelara).

Deucravacitinib may provide efficacy “like one of our second-tier biological therapies, yet it will be oral,” Dr. Strober commented.

Importantly, no laboratory abnormalities were detected in this trial. Only mild side effects were documented, most prominently acne, which occurred in dose-dependent fashion in 2% of patients on 3 mg of deucravacitinib twice daily and 4% at 12 mg once daily.

“The treatment of the acne that is elicited by this drug is yet to be fully described, but I’m sure we’ll learn the best approaches, given that acne is in our wheel house,” the dermatologist added.

Bristol-Myers Squibb has announced positive results from the pivotal phase 3 POETYK PSO-1 trial. Deucravacitinib at 6 mg once daily met both of its coprimary efficacy endpoints in the study, which included 666 patients with moderate to severe psoriasis. The TYK 2 inhibitor demonstrated superiority to both placebo and oral apremilast (Otezla) at week 16. The company said the safety profile was consistent with the phase 2 results, and that the full details of the phase 3 trial will be presented next year at a major medical meeting.

In addition, positive phase 2 results were reported for deucravacitinib in the treatment of psoriatic arthritis in a randomized trial presented at the fall 2020 meeting of the American College of Rheumatology. Deucravacitinib is also under study for lupus and inflammatory bowel disease.

Dr. Strober, an active clinical trialist, reported serving as a consultant to more than two dozen pharmaceutical companies, including Bristol-Myers Squibb.

MedscapeLive and this news organization are owned by the same parent company.

bjancin@mdedge.com

Deucravacitinib, a first-in-class oral selective tyrosine kinase 2 inhibitor, shows considerable promise as a potential novel treatment for psoriasis and a range of other chronic inflammatory diseases, Bruce E. Strober, MD, PhD, said at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

Deucravacitinib solely blocks tyrosine kinase 2 (TYK2) signaling without touching Janus kinase (JAK) 1, 2, or 3. In so doing, it inhibits several cytokines important for inflammation: interleukin-12, IL-13, and interferon-alpha and -beta. Yet it doesn’t affect the numerous pathways mediated by JAKs 1-3, many of which relate to growth and development of cell lineages, including production of erythropoietin, thrombopoietin, granulocyte-macrophage colony-stimulating factor, prolactin, growth hormone, and leptin. These deucravacitinib characteristics should translate into fewer off-target side effects than with oral JAK inhibitors.

“The promise of TYK2 inhibition that’s brought to you by deucravacitinib is there will be no laboratory monitoring and the effects will be narrow in blocking inflammation,” said Dr. Strober, a dermatologist at Yale University, New Haven, Conn., and in private practice in Cromwell, Conn.

He highlighted the positive results of a randomized, phase 2, dose-ranging study conducted in 267 patients with moderate or severe plaque psoriasis. Participants had an average baseline Psoriasis Area and Severity Index (PASI) score of 19, with a Dermatology Life Quality Index score of about 12. At the top dose of 12 mg once daily, 75% of patients achieved a PASI 75 response at week 12, and 44% reached a PASI 90, as did 69% and 44%, respectively, who were on deucravacitinib at 3 mg twice daily. Those are collective efficacy numbers similar to adalimumab (Humira) or ustekinumab (Stelara).

Deucravacitinib may provide efficacy “like one of our second-tier biological therapies, yet it will be oral,” Dr. Strober commented.

Importantly, no laboratory abnormalities were detected in this trial. Only mild side effects were documented, most prominently acne, which occurred in dose-dependent fashion in 2% of patients on 3 mg of deucravacitinib twice daily and 4% at 12 mg once daily.

“The treatment of the acne that is elicited by this drug is yet to be fully described, but I’m sure we’ll learn the best approaches, given that acne is in our wheel house,” the dermatologist added.

Bristol-Myers Squibb has announced positive results from the pivotal phase 3 POETYK PSO-1 trial. Deucravacitinib at 6 mg once daily met both of its coprimary efficacy endpoints in the study, which included 666 patients with moderate to severe psoriasis. The TYK 2 inhibitor demonstrated superiority to both placebo and oral apremilast (Otezla) at week 16. The company said the safety profile was consistent with the phase 2 results, and that the full details of the phase 3 trial will be presented next year at a major medical meeting.

In addition, positive phase 2 results were reported for deucravacitinib in the treatment of psoriatic arthritis in a randomized trial presented at the fall 2020 meeting of the American College of Rheumatology. Deucravacitinib is also under study for lupus and inflammatory bowel disease.

Dr. Strober, an active clinical trialist, reported serving as a consultant to more than two dozen pharmaceutical companies, including Bristol-Myers Squibb.

MedscapeLive and this news organization are owned by the same parent company.

bjancin@mdedge.com

Patients with moderate to severe atopic dermatitis (AD) affecting between 10% and 50% of their body surface area (BSA) account for the majority of responders to baricitinib 2 mg, results from an analysis of phase 3 data showed.

“This proposed clinical tailoring approach for baricitinib 2 mg allows for treatment of patients who are more likely to respond to therapy and rapid decision on discontinuation of treatment for those who are not likely to benefit from baricitinib 2 mg,” Eric L. Simpson, MD, said during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis virtual symposium.

Baricitinib is an oral, reversible and selective Janus kinase 1/JAK2 inhibitor that is approved in Europe for the treatment of moderate to severe AD in adults who are candidates for systemic therapy. In the United States, it is approved for treating rheumatoid arthritis, and is currently under Food and Drug Administration review in the United States for AD.

For the current analysis, Dr. Simpson, professor of dermatology at Oregon Health & Science University, Portland, and colleagues set out to identify responders to baricitinib 2 mg using a tailored approach based on baseline BSA affected and early clinical improvement in the phase 3 monotherapy trial BREEZE-AD5. The trial enrolled 440 patients: 147 to placebo, 147 to baricitinib 1 mg once daily, and 146 to baricitinib 2 mg once daily. The primary endpoint was Eczema Area and Severity Index (EASI)–75 at week 16.

“Understanding which patients can benefit most from this treatment was our goal,” Dr. Simpson said. “By tailoring your therapy, you can significantly improve the patient experience, increase the cost-effectiveness of a therapy, and you can ensure that only patients who are likely to benefit are exposed to a drug.”

The researchers used a classification and regression tree algorithm that identified baseline BSA as the strongest predictor of EASI-75 response at week 16. A BSA cutoff of 50% was established as the optimal cutoff for sensitivity and negative predictive value. Results for EASI-75 and Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) scores of 0 or 1 were confirmed using a BSA of 10%-50% at baseline to predict response, compared with a BSA or greater than 50% at baseline.

Sensitivity analyses revealed that about 90% of patients with an EASI-75 response were in the BSA 10%-50% group. Conversely, among patients with a BSA greater than 50%, the negative predictive value was greater than 90%, “so there’s a 90% chance you’re not going to hit that EASI-75 at week 16 if your BSA is greater than 50%,” Dr. Simpson explained. “The same holds true for vIGA-AD, so that 50% cutoff is important for understanding whether someone is going to respond or not.”

On the EASI-75, 38% of patients in the BSA 10%-50% group responded to baricitinib at week 16, compared with 10% in the BSA greater than 50% group. A similar association was observed on the vIGA-AD, where 32% of patients in the BSA 10%-50% group responded to baricitinib at week 16, compared with 5% in the BSA greater than 50% group.

When stratified by early response assessed at week 4, based on a 4-point improvement or greater on the Itch Numeric Rating Scale, 55% of those patients became EASI-75 responders, compared with 17% who were not. A similar association was observed by early response assessed at week 8.

“Due to the rapid onset of response, clinical assessment of patients after 4-8 weeks of initiation of baricitinib 2 mg treatment provided a positive feedback to patients who are likely to benefit from long-term therapy,” Dr. Simpson said. “This analysis may allow for a precision-medicine approach to therapy in moderate to severe AD.”

The study was supported by Eli Lilly, and was under license from Incyte. Dr. Simpson reported serving as an investigator for and consultant to numerous pharmaceutical companies.

dbrunk@mdedge.com

Patients with moderate to severe atopic dermatitis (AD) affecting between 10% and 50% of their body surface area (BSA) account for the majority of responders to baricitinib 2 mg, results from an analysis of phase 3 data showed.

“This proposed clinical tailoring approach for baricitinib 2 mg allows for treatment of patients who are more likely to respond to therapy and rapid decision on discontinuation of treatment for those who are not likely to benefit from baricitinib 2 mg,” Eric L. Simpson, MD, said during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis virtual symposium.

Baricitinib is an oral, reversible and selective Janus kinase 1/JAK2 inhibitor that is approved in Europe for the treatment of moderate to severe AD in adults who are candidates for systemic therapy. In the United States, it is approved for treating rheumatoid arthritis, and is currently under Food and Drug Administration review in the United States for AD.

For the current analysis, Dr. Simpson, professor of dermatology at Oregon Health & Science University, Portland, and colleagues set out to identify responders to baricitinib 2 mg using a tailored approach based on baseline BSA affected and early clinical improvement in the phase 3 monotherapy trial BREEZE-AD5. The trial enrolled 440 patients: 147 to placebo, 147 to baricitinib 1 mg once daily, and 146 to baricitinib 2 mg once daily. The primary endpoint was Eczema Area and Severity Index (EASI)–75 at week 16.

“Understanding which patients can benefit most from this treatment was our goal,” Dr. Simpson said. “By tailoring your therapy, you can significantly improve the patient experience, increase the cost-effectiveness of a therapy, and you can ensure that only patients who are likely to benefit are exposed to a drug.”

The researchers used a classification and regression tree algorithm that identified baseline BSA as the strongest predictor of EASI-75 response at week 16. A BSA cutoff of 50% was established as the optimal cutoff for sensitivity and negative predictive value. Results for EASI-75 and Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) scores of 0 or 1 were confirmed using a BSA of 10%-50% at baseline to predict response, compared with a BSA or greater than 50% at baseline.

Sensitivity analyses revealed that about 90% of patients with an EASI-75 response were in the BSA 10%-50% group. Conversely, among patients with a BSA greater than 50%, the negative predictive value was greater than 90%, “so there’s a 90% chance you’re not going to hit that EASI-75 at week 16 if your BSA is greater than 50%,” Dr. Simpson explained. “The same holds true for vIGA-AD, so that 50% cutoff is important for understanding whether someone is going to respond or not.”

On the EASI-75, 38% of patients in the BSA 10%-50% group responded to baricitinib at week 16, compared with 10% in the BSA greater than 50% group. A similar association was observed on the vIGA-AD, where 32% of patients in the BSA 10%-50% group responded to baricitinib at week 16, compared with 5% in the BSA greater than 50% group.

When stratified by early response assessed at week 4, based on a 4-point improvement or greater on the Itch Numeric Rating Scale, 55% of those patients became EASI-75 responders, compared with 17% who were not. A similar association was observed by early response assessed at week 8.

“Due to the rapid onset of response, clinical assessment of patients after 4-8 weeks of initiation of baricitinib 2 mg treatment provided a positive feedback to patients who are likely to benefit from long-term therapy,” Dr. Simpson said. “This analysis may allow for a precision-medicine approach to therapy in moderate to severe AD.”

The study was supported by Eli Lilly, and was under license from Incyte. Dr. Simpson reported serving as an investigator for and consultant to numerous pharmaceutical companies.

dbrunk@mdedge.com

Patients with moderate to severe atopic dermatitis (AD) affecting between 10% and 50% of their body surface area (BSA) account for the majority of responders to baricitinib 2 mg, results from an analysis of phase 3 data showed.

“This proposed clinical tailoring approach for baricitinib 2 mg allows for treatment of patients who are more likely to respond to therapy and rapid decision on discontinuation of treatment for those who are not likely to benefit from baricitinib 2 mg,” Eric L. Simpson, MD, said during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis virtual symposium.

Baricitinib is an oral, reversible and selective Janus kinase 1/JAK2 inhibitor that is approved in Europe for the treatment of moderate to severe AD in adults who are candidates for systemic therapy. In the United States, it is approved for treating rheumatoid arthritis, and is currently under Food and Drug Administration review in the United States for AD.

For the current analysis, Dr. Simpson, professor of dermatology at Oregon Health & Science University, Portland, and colleagues set out to identify responders to baricitinib 2 mg using a tailored approach based on baseline BSA affected and early clinical improvement in the phase 3 monotherapy trial BREEZE-AD5. The trial enrolled 440 patients: 147 to placebo, 147 to baricitinib 1 mg once daily, and 146 to baricitinib 2 mg once daily. The primary endpoint was Eczema Area and Severity Index (EASI)–75 at week 16.

“Understanding which patients can benefit most from this treatment was our goal,” Dr. Simpson said. “By tailoring your therapy, you can significantly improve the patient experience, increase the cost-effectiveness of a therapy, and you can ensure that only patients who are likely to benefit are exposed to a drug.”

The researchers used a classification and regression tree algorithm that identified baseline BSA as the strongest predictor of EASI-75 response at week 16. A BSA cutoff of 50% was established as the optimal cutoff for sensitivity and negative predictive value. Results for EASI-75 and Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) scores of 0 or 1 were confirmed using a BSA of 10%-50% at baseline to predict response, compared with a BSA or greater than 50% at baseline.

Sensitivity analyses revealed that about 90% of patients with an EASI-75 response were in the BSA 10%-50% group. Conversely, among patients with a BSA greater than 50%, the negative predictive value was greater than 90%, “so there’s a 90% chance you’re not going to hit that EASI-75 at week 16 if your BSA is greater than 50%,” Dr. Simpson explained. “The same holds true for vIGA-AD, so that 50% cutoff is important for understanding whether someone is going to respond or not.”

On the EASI-75, 38% of patients in the BSA 10%-50% group responded to baricitinib at week 16, compared with 10% in the BSA greater than 50% group. A similar association was observed on the vIGA-AD, where 32% of patients in the BSA 10%-50% group responded to baricitinib at week 16, compared with 5% in the BSA greater than 50% group.

When stratified by early response assessed at week 4, based on a 4-point improvement or greater on the Itch Numeric Rating Scale, 55% of those patients became EASI-75 responders, compared with 17% who were not. A similar association was observed by early response assessed at week 8.

“Due to the rapid onset of response, clinical assessment of patients after 4-8 weeks of initiation of baricitinib 2 mg treatment provided a positive feedback to patients who are likely to benefit from long-term therapy,” Dr. Simpson said. “This analysis may allow for a precision-medicine approach to therapy in moderate to severe AD.”

The study was supported by Eli Lilly, and was under license from Incyte. Dr. Simpson reported serving as an investigator for and consultant to numerous pharmaceutical companies.

dbrunk@mdedge.com

Trigger avoidance is a common cornerstone of management for all patients with atopic dermatitis (AD), but implementing the strategy is easier said than done.

“Guidelines on trigger avoidance are written as if it’s easy to do,” Jonathan I. Silverberg, MD, PhD, MPH, said during the Revolutionizing Atopic Dermatitis virtual symposium. “It turns out that trigger avoidance is really complicated.”

He and his colleagues conducted a study of most common triggers for itch based on a prospective dermatology practice–based study of 587 adults with AD . About two-thirds (65%) reported one or more itch trigger in the past week and 36% had three or more itch triggers in the past week. The two most common triggers were stress (35%) and sweat (31%).

“To me, this is provocative, because this is not how I was trained in residency,” said Dr. Silverberg, director of clinical research in the division of dermatology at George Washington University, Washington. “I was trained that it’s all about excess showering, dry air, or cold temperature. Those are important, but the most common triggers are stress and sweat.”

AD triggers are also commonly linked to seasonality. “If you ask patients when their AD is worse, sometimes it’s winter,” he said. “Sometimes it’s spring. Sometimes it’s summer. It turns out that there is a distinct set of triggers that are associated with AD seasonality.” Wintertime worsening of disease is associated with cold temperature and weather change, he continued, while springtime worsening of disease is often linked to weather change and dry air. Common summertime triggers for flares include hot temperature, heat, sweat, weather change, sunlight, humid air, and dry air. “In the fall, the weather change again comes up as a trigger. Humid air does as well.”

In their prospective study, Dr. Silverberg and colleagues found that 90% of those who had at least three itch triggers reported 3 months or less of AD remission in the past year, “meaning that 90% are reporting persistent disease when they have multiple itch triggers,” he said. In addition, 78% reported two or more flares per year and 61% reported that AD is worse during certain seasons.

Potential mitigation strategies for stress include stress management, biofeedback, meditation, relaxation training, and mindfulness. “These don’t necessarily require expensive psychotherapy,” he said. Freely available iPhone apps can be incorporated into daily practice, such as Calm, Relax with Andrew Johnson, Nature Sounds Relax and Sleep, Breathe2Relax, and Headspace.

Many AD patients are sedentary and avoid vigorous physical activity owing to heat and sweat as triggers. Simple solutions include exercising in a cooler temperature environment, “not just using fans,” he said. “Take a quick shower right after working out and consider pre- and/or post treatment with topical medication.”

High temperature and sweating can be problematic at bedtime, he continued. Even if the indoor temperature is 70° F, that might jump to 85° F or 90° F under a thick blanket. “That heat can trigger itch and may cause sweating, which can trigger itch,” said Dr. Silverberg, who has AD and is director of patch testing at George Washington University. Potential solutions include using a lighter blanket, lowering the indoor temperature, and wearing breathable pajamas.

Dryness, another common AD trigger, can be secondary to a combination of low outdoor and/or indoor humidity. “Lower outdoor humidity is a particular problem in the wintertime, because cold air doesn’t hold moisture as well,” he said. “That’s why the air feels much dryer in the wintertime. There’s also a problem of indoor heating and cooling. Sometimes central air systems can lower humidity to the point where it’s bone dry.”

In an effort to determine the impact of specific climatic factors on the U.S. prevalence of AD, Dr. Silverberg and colleagues conducted a study using a merged analysis of the 2007 National Survey of Children’s Health from a representative sample of 91,642 children aged 0-17 years and 2006-2007 measurements from the National Climate Data Center and Weather Service. They found that childhood AD prevalence was increased in geographical areas that use more indoor heat and cooling and had lower outdoor humidity. “So, we see that there’s a direct correlate of this dryness issue that is leading to more AD throughout the U.S.,” he said.

Practical solutions to mitigate the effect of dry air on AD include opening windows to allow entry of moist air, “which can be particularly helpful in residences that are overheated,” he said. “I deal with this a lot in patients who live in dormitories. Use humidifiers to add moisture back into the air. Aim for 40%-50% indoor humidity to avoid mold and dust mites. It’s better to use demineralized water to reduce bacterial growth. This can be helpful for aeroallergies. Of note, there are really no well-done studies that have examined the efficacy of humidifiers in AD, but based on our anecdotal experience, this is a good way to go.”

Cold temperatures and trigger intense itch, even in the setting of high humidity. “For me personally, this is one of my most brutal triggers,” Dr. Silverberg said. “When I’m in a place with extremes of cold, I get a rapid onset of itch, a mix of itch and pain, particularly on the dorsal hands. For solutions, you can encourage patients to avoid extremely low temperatures, to bundle up, and to potentially use hand warmers or other heating devices.”

Clothing can be a trigger as well, especially tight-fitting clothes, hot and nonbreathable clothes, and large-diameter wool, which has been shown to induce itching and irritation. Mitigation strategies include wearing loose-fitting, lightweight, nonirritating fabric. “Traditional cotton and silk fabrics have mixed evidence in improving AD but are generally safe,” he said. “Ultra- or superfine merino wool has been shown to be nonpruritic. There is sparse evidence to support chemically treated/coated clothing for AD, but this may be an emerging area.”

Dr. Silverberg pointed out variability of cultural perspectives and preferences for bathing practices, including temperature, duration, frequency, optimal bathing products, and the use of loofahs and other scrubbing products. “This stems from different perceptions of what it means to be clean, and how dry our skin should feel after a shower,” he said. “Many clinicians and patients were taught that regular bathing is harmful in AD. It turns out that’s not true.”

In a recently published systematic review and meta-analysis of 13 studies, he and his colleagues examined efficacy outcomes of different bathing/showering regimens in AD. All 13 studies showed numerically reduced AD severity with any bathing regimen in at least one time point. Numerical decreases over time were observed for body surface area (BSA), Eczema Area and Severity Index (EASI), and/or SCORAD measures for daily and less than daily bathing, with or without application of emollients or topical corticosteroids. In random effects regression models, taking baths more than or less than seven times per week were not associated with significant differences of Cohen’s D scores for EASI, SCORAD, or BSA. “The take-home message here is, let your AD patients bathe,” Dr. Silverberg said. “Bathing is good. It can be channeled to help the eczema, but it has to be done the right way.”

Patients should be counseled to use nonirritating cleansers and shampoos, avoid excessively long baths/showers, avoid excessively hot baths/showers, avoid excessive rubbing or scrubbing of skin, and to apply emollients and/or topical corticosteroids immediately after the bath/shower.

PROMIS Itch-Triggers is a simple and feasible checklist to screen for the most common itch triggers in AD in clinical practice (patients are asked to check off which of the following have caused their itch in the previous 7 days: cold temperature, hot temperature, heat, sweat, tight clothing, fragrances, boredom, talking about itch, stress, weather change, sunlight, humid air, dry air). “It takes less than 1 minute to complete,” he said. “Additional testing with skin patch and/or prick testing may be warranted to identify allergenic triggers.”

Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies. He is also a speaker for Regeneron and Sanofi and has received a grant from Galderma.

dbrunk@mdedge.com

Trigger avoidance is a common cornerstone of management for all patients with atopic dermatitis (AD), but implementing the strategy is easier said than done.

“Guidelines on trigger avoidance are written as if it’s easy to do,” Jonathan I. Silverberg, MD, PhD, MPH, said during the Revolutionizing Atopic Dermatitis virtual symposium. “It turns out that trigger avoidance is really complicated.”

He and his colleagues conducted a study of most common triggers for itch based on a prospective dermatology practice–based study of 587 adults with AD . About two-thirds (65%) reported one or more itch trigger in the past week and 36% had three or more itch triggers in the past week. The two most common triggers were stress (35%) and sweat (31%).

“To me, this is provocative, because this is not how I was trained in residency,” said Dr. Silverberg, director of clinical research in the division of dermatology at George Washington University, Washington. “I was trained that it’s all about excess showering, dry air, or cold temperature. Those are important, but the most common triggers are stress and sweat.”

AD triggers are also commonly linked to seasonality. “If you ask patients when their AD is worse, sometimes it’s winter,” he said. “Sometimes it’s spring. Sometimes it’s summer. It turns out that there is a distinct set of triggers that are associated with AD seasonality.” Wintertime worsening of disease is associated with cold temperature and weather change, he continued, while springtime worsening of disease is often linked to weather change and dry air. Common summertime triggers for flares include hot temperature, heat, sweat, weather change, sunlight, humid air, and dry air. “In the fall, the weather change again comes up as a trigger. Humid air does as well.”

In their prospective study, Dr. Silverberg and colleagues found that 90% of those who had at least three itch triggers reported 3 months or less of AD remission in the past year, “meaning that 90% are reporting persistent disease when they have multiple itch triggers,” he said. In addition, 78% reported two or more flares per year and 61% reported that AD is worse during certain seasons.

Potential mitigation strategies for stress include stress management, biofeedback, meditation, relaxation training, and mindfulness. “These don’t necessarily require expensive psychotherapy,” he said. Freely available iPhone apps can be incorporated into daily practice, such as Calm, Relax with Andrew Johnson, Nature Sounds Relax and Sleep, Breathe2Relax, and Headspace.

Many AD patients are sedentary and avoid vigorous physical activity owing to heat and sweat as triggers. Simple solutions include exercising in a cooler temperature environment, “not just using fans,” he said. “Take a quick shower right after working out and consider pre- and/or post treatment with topical medication.”

High temperature and sweating can be problematic at bedtime, he continued. Even if the indoor temperature is 70° F, that might jump to 85° F or 90° F under a thick blanket. “That heat can trigger itch and may cause sweating, which can trigger itch,” said Dr. Silverberg, who has AD and is director of patch testing at George Washington University. Potential solutions include using a lighter blanket, lowering the indoor temperature, and wearing breathable pajamas.

Dryness, another common AD trigger, can be secondary to a combination of low outdoor and/or indoor humidity. “Lower outdoor humidity is a particular problem in the wintertime, because cold air doesn’t hold moisture as well,” he said. “That’s why the air feels much dryer in the wintertime. There’s also a problem of indoor heating and cooling. Sometimes central air systems can lower humidity to the point where it’s bone dry.”

In an effort to determine the impact of specific climatic factors on the U.S. prevalence of AD, Dr. Silverberg and colleagues conducted a study using a merged analysis of the 2007 National Survey of Children’s Health from a representative sample of 91,642 children aged 0-17 years and 2006-2007 measurements from the National Climate Data Center and Weather Service. They found that childhood AD prevalence was increased in geographical areas that use more indoor heat and cooling and had lower outdoor humidity. “So, we see that there’s a direct correlate of this dryness issue that is leading to more AD throughout the U.S.,” he said.

Practical solutions to mitigate the effect of dry air on AD include opening windows to allow entry of moist air, “which can be particularly helpful in residences that are overheated,” he said. “I deal with this a lot in patients who live in dormitories. Use humidifiers to add moisture back into the air. Aim for 40%-50% indoor humidity to avoid mold and dust mites. It’s better to use demineralized water to reduce bacterial growth. This can be helpful for aeroallergies. Of note, there are really no well-done studies that have examined the efficacy of humidifiers in AD, but based on our anecdotal experience, this is a good way to go.”

Cold temperatures and trigger intense itch, even in the setting of high humidity. “For me personally, this is one of my most brutal triggers,” Dr. Silverberg said. “When I’m in a place with extremes of cold, I get a rapid onset of itch, a mix of itch and pain, particularly on the dorsal hands. For solutions, you can encourage patients to avoid extremely low temperatures, to bundle up, and to potentially use hand warmers or other heating devices.”

Clothing can be a trigger as well, especially tight-fitting clothes, hot and nonbreathable clothes, and large-diameter wool, which has been shown to induce itching and irritation. Mitigation strategies include wearing loose-fitting, lightweight, nonirritating fabric. “Traditional cotton and silk fabrics have mixed evidence in improving AD but are generally safe,” he said. “Ultra- or superfine merino wool has been shown to be nonpruritic. There is sparse evidence to support chemically treated/coated clothing for AD, but this may be an emerging area.”

Dr. Silverberg pointed out variability of cultural perspectives and preferences for bathing practices, including temperature, duration, frequency, optimal bathing products, and the use of loofahs and other scrubbing products. “This stems from different perceptions of what it means to be clean, and how dry our skin should feel after a shower,” he said. “Many clinicians and patients were taught that regular bathing is harmful in AD. It turns out that’s not true.”

In a recently published systematic review and meta-analysis of 13 studies, he and his colleagues examined efficacy outcomes of different bathing/showering regimens in AD. All 13 studies showed numerically reduced AD severity with any bathing regimen in at least one time point. Numerical decreases over time were observed for body surface area (BSA), Eczema Area and Severity Index (EASI), and/or SCORAD measures for daily and less than daily bathing, with or without application of emollients or topical corticosteroids. In random effects regression models, taking baths more than or less than seven times per week were not associated with significant differences of Cohen’s D scores for EASI, SCORAD, or BSA. “The take-home message here is, let your AD patients bathe,” Dr. Silverberg said. “Bathing is good. It can be channeled to help the eczema, but it has to be done the right way.”

Patients should be counseled to use nonirritating cleansers and shampoos, avoid excessively long baths/showers, avoid excessively hot baths/showers, avoid excessive rubbing or scrubbing of skin, and to apply emollients and/or topical corticosteroids immediately after the bath/shower.

PROMIS Itch-Triggers is a simple and feasible checklist to screen for the most common itch triggers in AD in clinical practice (patients are asked to check off which of the following have caused their itch in the previous 7 days: cold temperature, hot temperature, heat, sweat, tight clothing, fragrances, boredom, talking about itch, stress, weather change, sunlight, humid air, dry air). “It takes less than 1 minute to complete,” he said. “Additional testing with skin patch and/or prick testing may be warranted to identify allergenic triggers.”

Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies. He is also a speaker for Regeneron and Sanofi and has received a grant from Galderma.

dbrunk@mdedge.com

Trigger avoidance is a common cornerstone of management for all patients with atopic dermatitis (AD), but implementing the strategy is easier said than done.

“Guidelines on trigger avoidance are written as if it’s easy to do,” Jonathan I. Silverberg, MD, PhD, MPH, said during the Revolutionizing Atopic Dermatitis virtual symposium. “It turns out that trigger avoidance is really complicated.”

He and his colleagues conducted a study of most common triggers for itch based on a prospective dermatology practice–based study of 587 adults with AD . About two-thirds (65%) reported one or more itch trigger in the past week and 36% had three or more itch triggers in the past week. The two most common triggers were stress (35%) and sweat (31%).

“To me, this is provocative, because this is not how I was trained in residency,” said Dr. Silverberg, director of clinical research in the division of dermatology at George Washington University, Washington. “I was trained that it’s all about excess showering, dry air, or cold temperature. Those are important, but the most common triggers are stress and sweat.”

AD triggers are also commonly linked to seasonality. “If you ask patients when their AD is worse, sometimes it’s winter,” he said. “Sometimes it’s spring. Sometimes it’s summer. It turns out that there is a distinct set of triggers that are associated with AD seasonality.” Wintertime worsening of disease is associated with cold temperature and weather change, he continued, while springtime worsening of disease is often linked to weather change and dry air. Common summertime triggers for flares include hot temperature, heat, sweat, weather change, sunlight, humid air, and dry air. “In the fall, the weather change again comes up as a trigger. Humid air does as well.”

In their prospective study, Dr. Silverberg and colleagues found that 90% of those who had at least three itch triggers reported 3 months or less of AD remission in the past year, “meaning that 90% are reporting persistent disease when they have multiple itch triggers,” he said. In addition, 78% reported two or more flares per year and 61% reported that AD is worse during certain seasons.

Potential mitigation strategies for stress include stress management, biofeedback, meditation, relaxation training, and mindfulness. “These don’t necessarily require expensive psychotherapy,” he said. Freely available iPhone apps can be incorporated into daily practice, such as Calm, Relax with Andrew Johnson, Nature Sounds Relax and Sleep, Breathe2Relax, and Headspace.

Many AD patients are sedentary and avoid vigorous physical activity owing to heat and sweat as triggers. Simple solutions include exercising in a cooler temperature environment, “not just using fans,” he said. “Take a quick shower right after working out and consider pre- and/or post treatment with topical medication.”

High temperature and sweating can be problematic at bedtime, he continued. Even if the indoor temperature is 70° F, that might jump to 85° F or 90° F under a thick blanket. “That heat can trigger itch and may cause sweating, which can trigger itch,” said Dr. Silverberg, who has AD and is director of patch testing at George Washington University. Potential solutions include using a lighter blanket, lowering the indoor temperature, and wearing breathable pajamas.

Dryness, another common AD trigger, can be secondary to a combination of low outdoor and/or indoor humidity. “Lower outdoor humidity is a particular problem in the wintertime, because cold air doesn’t hold moisture as well,” he said. “That’s why the air feels much dryer in the wintertime. There’s also a problem of indoor heating and cooling. Sometimes central air systems can lower humidity to the point where it’s bone dry.”

In an effort to determine the impact of specific climatic factors on the U.S. prevalence of AD, Dr. Silverberg and colleagues conducted a study using a merged analysis of the 2007 National Survey of Children’s Health from a representative sample of 91,642 children aged 0-17 years and 2006-2007 measurements from the National Climate Data Center and Weather Service. They found that childhood AD prevalence was increased in geographical areas that use more indoor heat and cooling and had lower outdoor humidity. “So, we see that there’s a direct correlate of this dryness issue that is leading to more AD throughout the U.S.,” he said.

Practical solutions to mitigate the effect of dry air on AD include opening windows to allow entry of moist air, “which can be particularly helpful in residences that are overheated,” he said. “I deal with this a lot in patients who live in dormitories. Use humidifiers to add moisture back into the air. Aim for 40%-50% indoor humidity to avoid mold and dust mites. It’s better to use demineralized water to reduce bacterial growth. This can be helpful for aeroallergies. Of note, there are really no well-done studies that have examined the efficacy of humidifiers in AD, but based on our anecdotal experience, this is a good way to go.”

Cold temperatures and trigger intense itch, even in the setting of high humidity. “For me personally, this is one of my most brutal triggers,” Dr. Silverberg said. “When I’m in a place with extremes of cold, I get a rapid onset of itch, a mix of itch and pain, particularly on the dorsal hands. For solutions, you can encourage patients to avoid extremely low temperatures, to bundle up, and to potentially use hand warmers or other heating devices.”

Clothing can be a trigger as well, especially tight-fitting clothes, hot and nonbreathable clothes, and large-diameter wool, which has been shown to induce itching and irritation. Mitigation strategies include wearing loose-fitting, lightweight, nonirritating fabric. “Traditional cotton and silk fabrics have mixed evidence in improving AD but are generally safe,” he said. “Ultra- or superfine merino wool has been shown to be nonpruritic. There is sparse evidence to support chemically treated/coated clothing for AD, but this may be an emerging area.”

Dr. Silverberg pointed out variability of cultural perspectives and preferences for bathing practices, including temperature, duration, frequency, optimal bathing products, and the use of loofahs and other scrubbing products. “This stems from different perceptions of what it means to be clean, and how dry our skin should feel after a shower,” he said. “Many clinicians and patients were taught that regular bathing is harmful in AD. It turns out that’s not true.”

In a recently published systematic review and meta-analysis of 13 studies, he and his colleagues examined efficacy outcomes of different bathing/showering regimens in AD. All 13 studies showed numerically reduced AD severity with any bathing regimen in at least one time point. Numerical decreases over time were observed for body surface area (BSA), Eczema Area and Severity Index (EASI), and/or SCORAD measures for daily and less than daily bathing, with or without application of emollients or topical corticosteroids. In random effects regression models, taking baths more than or less than seven times per week were not associated with significant differences of Cohen’s D scores for EASI, SCORAD, or BSA. “The take-home message here is, let your AD patients bathe,” Dr. Silverberg said. “Bathing is good. It can be channeled to help the eczema, but it has to be done the right way.”

Patients should be counseled to use nonirritating cleansers and shampoos, avoid excessively long baths/showers, avoid excessively hot baths/showers, avoid excessive rubbing or scrubbing of skin, and to apply emollients and/or topical corticosteroids immediately after the bath/shower.

PROMIS Itch-Triggers is a simple and feasible checklist to screen for the most common itch triggers in AD in clinical practice (patients are asked to check off which of the following have caused their itch in the previous 7 days: cold temperature, hot temperature, heat, sweat, tight clothing, fragrances, boredom, talking about itch, stress, weather change, sunlight, humid air, dry air). “It takes less than 1 minute to complete,” he said. “Additional testing with skin patch and/or prick testing may be warranted to identify allergenic triggers.”

Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies. He is also a speaker for Regeneron and Sanofi and has received a grant from Galderma.

dbrunk@mdedge.com

Dupilumab treatment with concomitant topical corticosteroids provided rapid and sustained improvement in itch intensity and frequency in children aged 6-11 years with severe atopic dermatitis.

The findings come from a post hoc analysis of a phase 3 trial known as LIBERTY AD PEDS (NCT03345914) that Gil Yosipovitch, MD, presented during a late-breaking research session at the Revolutionizing Atopic Dermatitis virtual symposium.

By week 16, a higher weekly proportion of dupilumab-treated patients achieved a 2-point or more improvement in worst itch score, compared with placebo (72% in the 300-mg q4w group vs. 74% in the 200-mg q2w group; P less than or equal to .001). The same association held true for the daily proportion of dupilumab-treated patients who achieved a 4-point or more improvement in worst itch score, compared with placebo (54% vs. 61%; P less than or equal to .001).

Next, the researchers evaluated the proportion of patients reporting the number of days with itchy skin over the previous 7 days as assessed from the Patient-Oriented Eczema Measure (POEM) itch item question: “Over the last week, on how many days has your child’s skin been itchy because of their eczema?” By week 16, the majority of children treated with dupilumab achieved a reduction of days experiencing itch from every day at baseline to at most 2 days, with some improvement to zero days per week.

“Overall, in the LIBERTY AD PEDS trial, dupilumab was well tolerated and data were consistent with the known dupilumab safety profile observed in adults and adolescents,” Dr. Yosipovitch said. “Injection site reactions and conjunctivitis were more common with dupilumab. Infections and AD exacerbations were more common with placebo.”

The study was sponsored by Sanofi and Regeneron Pharmaceuticals. Dr. Yosipovitch and coauthors reporting having received financial grants and research grants from numerous pharmaceutical companies.

dbrunk@mdedge.com

Dupilumab treatment with concomitant topical corticosteroids provided rapid and sustained improvement in itch intensity and frequency in children aged 6-11 years with severe atopic dermatitis.

The findings come from a post hoc analysis of a phase 3 trial known as LIBERTY AD PEDS (NCT03345914) that Gil Yosipovitch, MD, presented during a late-breaking research session at the Revolutionizing Atopic Dermatitis virtual symposium.

By week 16, a higher weekly proportion of dupilumab-treated patients achieved a 2-point or more improvement in worst itch score, compared with placebo (72% in the 300-mg q4w group vs. 74% in the 200-mg q2w group; P less than or equal to .001). The same association held true for the daily proportion of dupilumab-treated patients who achieved a 4-point or more improvement in worst itch score, compared with placebo (54% vs. 61%; P less than or equal to .001).

Next, the researchers evaluated the proportion of patients reporting the number of days with itchy skin over the previous 7 days as assessed from the Patient-Oriented Eczema Measure (POEM) itch item question: “Over the last week, on how many days has your child’s skin been itchy because of their eczema?” By week 16, the majority of children treated with dupilumab achieved a reduction of days experiencing itch from every day at baseline to at most 2 days, with some improvement to zero days per week.

“Overall, in the LIBERTY AD PEDS trial, dupilumab was well tolerated and data were consistent with the known dupilumab safety profile observed in adults and adolescents,” Dr. Yosipovitch said. “Injection site reactions and conjunctivitis were more common with dupilumab. Infections and AD exacerbations were more common with placebo.”

The study was sponsored by Sanofi and Regeneron Pharmaceuticals. Dr. Yosipovitch and coauthors reporting having received financial grants and research grants from numerous pharmaceutical companies.

dbrunk@mdedge.com

Dupilumab treatment with concomitant topical corticosteroids provided rapid and sustained improvement in itch intensity and frequency in children aged 6-11 years with severe atopic dermatitis.

The findings come from a post hoc analysis of a phase 3 trial known as LIBERTY AD PEDS (NCT03345914) that Gil Yosipovitch, MD, presented during a late-breaking research session at the Revolutionizing Atopic Dermatitis virtual symposium.

By week 16, a higher weekly proportion of dupilumab-treated patients achieved a 2-point or more improvement in worst itch score, compared with placebo (72% in the 300-mg q4w group vs. 74% in the 200-mg q2w group; P less than or equal to .001). The same association held true for the daily proportion of dupilumab-treated patients who achieved a 4-point or more improvement in worst itch score, compared with placebo (54% vs. 61%; P less than or equal to .001).

Next, the researchers evaluated the proportion of patients reporting the number of days with itchy skin over the previous 7 days as assessed from the Patient-Oriented Eczema Measure (POEM) itch item question: “Over the last week, on how many days has your child’s skin been itchy because of their eczema?” By week 16, the majority of children treated with dupilumab achieved a reduction of days experiencing itch from every day at baseline to at most 2 days, with some improvement to zero days per week.

“Overall, in the LIBERTY AD PEDS trial, dupilumab was well tolerated and data were consistent with the known dupilumab safety profile observed in adults and adolescents,” Dr. Yosipovitch said. “Injection site reactions and conjunctivitis were more common with dupilumab. Infections and AD exacerbations were more common with placebo.”

The study was sponsored by Sanofi and Regeneron Pharmaceuticals. Dr. Yosipovitch and coauthors reporting having received financial grants and research grants from numerous pharmaceutical companies.

dbrunk@mdedge.com

Chronic leg ulcers of all types feature a significant inflammatory component for which medical compression therapy is absolutely the best form of anti-inflammatory therapy, Elena Conde Montero, MD, PhD, asserted at the virtual annual congress of the European Academy of Dermatology and Venereology.

In addition to delving into the finer points of compression therapy, she offered other clinical pearls for the treatment of chronic leg ulcers. These included the use of autologous punch grafting to reduce pain as well as promote healing, when to employ adjunctive negative pressure therapy, and the benefits of liquid sevoflurane for highly effective topical analgesia during wound cleansing and debridement.
 

Compression therapy

“If no contraindications exist, compression therapy is the best antihypertensive and anti-inflammatory treatment for all leg ulcers, not only venous leg ulcers,” according to Dr. Conde, a dermatologist at Infanta Leonor University Hospital in Madrid.

The list of absolute contraindications to compression treatment is brief, as highlighted in a recent international consensus statement. The expert writing panel named only four: severe peripheral artery disease, the presence of an epifascial arterial bypass, severe cardiac insufficiency, and true allergy to compression material.

Compression therapy provides multiple salutary effects. These include reduced capillary filtration of fluids to tissue, decreased swelling, enhanced tissue remodeling, better lymphatic drainage, reduced inflammatory cell counts, and increased arterial flow.

“This means that people with mild arterial disease will benefit from active compression because perfusion will improve,” Dr. Conde said.

Similarly, leg ulcers secondary to pyoderma gangrenosum will benefit from the anti-inflammatory effects of compression therapy in conjunction with standard immunotherapy, added the dermatologist, who coauthored a recent publication by the European Wound Management Association entitled “Atypical Wounds: Best Clinical Practices and Challenges.”

Four broad types of compression therapy are available: compression stockings, short-stretch bandages, multicomponent bandage systems, and self-adjusting compression wrap devices. The best clinical outcomes are achieved by individualized selection of a compression method based upon patient characteristics.

Short-stretch, low-elasticity bandages – such as the classic Unna boot loaded with zinc paste and topical corticosteroids – are well suited for patients with large leg ulcers. These bandages feature high working pressures during muscle contraction. They also provide low resting pressures, which is advantageous in patients with peripheral artery disease. The major disadvantage of short-stretch bandages is the need for frequent dressing changes by a nurse or other trained professional, since the compression is quickly lost as an unwanted consequence of the welcome reduction in swelling.

Multicomponent bandage systems feature two to four layers of bandages of differing stiffness, as well as padding material and in many cases pressure indicators. These bandages can often be worn for up to a week without needing to be changed, since they maintain adequate pressure long term. “These are very easy to use by nonexperts,” Dr. Conde noted.

A caveat regarding both short-stretch bandages and the multicomponent bandage systems: before applying them, it’s important to pad at-risk areas against injury caused by high pressures. These high-risk areas include the Achilles tendon, the pretibial region, and the lateral foot.

Self-adjusting compression systems are comprised of strips of short-stretch, low-elasticity fabric, which wrap around the leg and are fixed with Velcro closures. Dr. Conde hailed these devices as “a great innovation in compression therapy, without doubt.” Their major advantage is ease of application and removal by the patient. They are best-suited for treatment of small ulcers in patients who find it difficult to use compression stockings because of obesity or osteoarthritis, in patients who can’t tolerate such stockings because they have peripheral artery disease and the stockings’ high resting pressure is uncomfortable, or in individuals ill-suited for compression bandages because they lack adequate access to nursing care for the required frequent dressing changes.

Compression stockings are a good option for small ulcers. It’s easier for patients to wear shoes with compression stockings and thereby engage in normal everyday activities than with short-stretch bandages. A tip: Many patients find it arduous to don and remove a high-compression stocking that achieves the recommended pressure of 30-40 mm Hg at the point of transition between the Achilles tendon and the calf muscle, but the same effect can be achieved by overlapping two easier-to-use lower-compression stockings.

Punch grafting

This simple, cost-effective outpatient procedure was first described as a means of enhancing wound healing 150 years ago. The method involves utilizing a scalpel, curette, or punch to obtain a series of thin split-thickness skin grafts that contain epidermis and dermis down to the superficial papillary dermis. The grafts, usually harvested from the anterior thigh, are placed on the wound. This is followed by at least 5 days of local pressure and rest to promote graft uptake.

Sequential punch grafting is an excellent option for particularly challenging chronic ulcers, including Martorell hypertensive ischemic leg ulcers and other arteriolopathic ulcers in the elderly.

“Sequential punch grafting of wounds is very common in our clinics, especially for wounds that lack perfect grafting conditions,” Dr. Conde said.

She considers Martorell hypertensive ischemic leg ulcers to be underdiagnosed and undertreated. The Martorell leg ulcer is an exceedingly painful, rapidly progressive ischemic lesion, or bilateral lesions, with inflamed irregular margins. The disorder is caused by obstruction of subcutaneous arterioles in the absence of signs of vasculitis, and generally occurs in older individuals who have had well-controlled hypertension for many years. Diabetes, obesity, dyslipidemia, and peripheral artery disease are common comorbid conditions. The most common form of treatment – bioactive dressings in a moist environment – produces unsatisfactory results because it doesn’t address the inflammatory process.

Dr. Conde and coworkers have published the full details of how they achieved complete healing of Martorell hypertensive ischemic leg ulcers 3-8 weeks after punch grafting in three affected patients, all of whom presented with pain scores of 10/10 refractory even to opioid analgesics. The punch grafting was preceded by 15 days of topical corticosteroids and low-elasticity compression bandages in order to create adequate granulation tissue in the wound bed, which had the added benefit of achieving a 2- to 3-point reduction in pain scores even before the surgical procedure.

The pain-reducing effect of punch grafting isn’t as well appreciated as the wound-healing effect. Dr. Conde was first author of a recent study in which investigators systematically measured pain reduction in 136 patients with hard-to-heal leg ulcers of various etiologies treated with punch grafting. Nearly three-quarters of those who presented with painful ulcers were pain free after punch grafting, and the rest experienced greater than 70% pain reduction.

Pain suppression wasn’t dependent upon the percentage of graft uptake in this study. That’s because, as long as the wound isn’t overcleaned during dressing changes, even grafts that haven’t attached to the wound will release growth factors that promote wound healing, Dr. Conde explained.
 

Adjunctive negative pressure therapy

Portable vacuum-based negative pressure therapy devices are easy to use as a means to promote punch graft uptake. Negative pressure is best employed as an adjunct to punch grafting in suboptimal wound beds, longstanding ulcers, in patients with previous graft failure, or in challenging anatomic locations, such as the Achilles tendon or ankle. Dr. Conde has found the combination of punch grafting and negative pressure therapy especially helpful in patients with clinically inactive pyoderma gangrenosum.

Topical sevoflurane for analgesia

Most of the literature on topical sevoflurane for ulcer care has been published by Spanish researchers, but this form of analgesia deserves much more widespread use, according to Dr. Conde.

Sevoflurane is most often used as a gas in general anesthesia. In liquid form, however, it not only has a rapid, long-lasting analgesic effect when applied to painful leg ulcers, it also promotes healing because it is both antibacterial and a vasodilator. So before performing a potentially painful ulcer or wound cleaning, Dr. Conde recommended protecting perilesional skin with petroleum jelly, then irrigating the ulcer site with liquid sevoflurane. After that, it’s advisable to wait just 5-10 minutes before proceeding.

“It takes effect in much less time than EMLA cream,” she noted.

In one study of 30 adults aged over age 65 years with painful chronic venous ulcers refractory to conventional analgesics who underwent ulcer cleaning supported by topical sevoflurane at a dose of roughly 1 mL/cm² of ulcer area every 2 days for a month, Spanish investigators documented onset of analgesic effect in 2-7 minutes, with a duration of 8-18 hours. The researchers found that the use of backup conventional analgesics ranging from acetaminophen to opioids was diminished. Side effects were limited to mild, transient itching and redness.

Dr. Conde reported having no financial conflicts of interest regarding her presentation.

bjancin@mdedge.com

Chronic leg ulcers of all types feature a significant inflammatory component for which medical compression therapy is absolutely the best form of anti-inflammatory therapy, Elena Conde Montero, MD, PhD, asserted at the virtual annual congress of the European Academy of Dermatology and Venereology.

In addition to delving into the finer points of compression therapy, she offered other clinical pearls for the treatment of chronic leg ulcers. These included the use of autologous punch grafting to reduce pain as well as promote healing, when to employ adjunctive negative pressure therapy, and the benefits of liquid sevoflurane for highly effective topical analgesia during wound cleansing and debridement.
 

Compression therapy

“If no contraindications exist, compression therapy is the best antihypertensive and anti-inflammatory treatment for all leg ulcers, not only venous leg ulcers,” according to Dr. Conde, a dermatologist at Infanta Leonor University Hospital in Madrid.

The list of absolute contraindications to compression treatment is brief, as highlighted in a recent international consensus statement. The expert writing panel named only four: severe peripheral artery disease, the presence of an epifascial arterial bypass, severe cardiac insufficiency, and true allergy to compression material.

Compression therapy provides multiple salutary effects. These include reduced capillary filtration of fluids to tissue, decreased swelling, enhanced tissue remodeling, better lymphatic drainage, reduced inflammatory cell counts, and increased arterial flow.

“This means that people with mild arterial disease will benefit from active compression because perfusion will improve,” Dr. Conde said.

Similarly, leg ulcers secondary to pyoderma gangrenosum will benefit from the anti-inflammatory effects of compression therapy in conjunction with standard immunotherapy, added the dermatologist, who coauthored a recent publication by the European Wound Management Association entitled “Atypical Wounds: Best Clinical Practices and Challenges.”

Four broad types of compression therapy are available: compression stockings, short-stretch bandages, multicomponent bandage systems, and self-adjusting compression wrap devices. The best clinical outcomes are achieved by individualized selection of a compression method based upon patient characteristics.

Short-stretch, low-elasticity bandages – such as the classic Unna boot loaded with zinc paste and topical corticosteroids – are well suited for patients with large leg ulcers. These bandages feature high working pressures during muscle contraction. They also provide low resting pressures, which is advantageous in patients with peripheral artery disease. The major disadvantage of short-stretch bandages is the need for frequent dressing changes by a nurse or other trained professional, since the compression is quickly lost as an unwanted consequence of the welcome reduction in swelling.

Multicomponent bandage systems feature two to four layers of bandages of differing stiffness, as well as padding material and in many cases pressure indicators. These bandages can often be worn for up to a week without needing to be changed, since they maintain adequate pressure long term. “These are very easy to use by nonexperts,” Dr. Conde noted.

A caveat regarding both short-stretch bandages and the multicomponent bandage systems: before applying them, it’s important to pad at-risk areas against injury caused by high pressures. These high-risk areas include the Achilles tendon, the pretibial region, and the lateral foot.

Self-adjusting compression systems are comprised of strips of short-stretch, low-elasticity fabric, which wrap around the leg and are fixed with Velcro closures. Dr. Conde hailed these devices as “a great innovation in compression therapy, without doubt.” Their major advantage is ease of application and removal by the patient. They are best-suited for treatment of small ulcers in patients who find it difficult to use compression stockings because of obesity or osteoarthritis, in patients who can’t tolerate such stockings because they have peripheral artery disease and the stockings’ high resting pressure is uncomfortable, or in individuals ill-suited for compression bandages because they lack adequate access to nursing care for the required frequent dressing changes.

Compression stockings are a good option for small ulcers. It’s easier for patients to wear shoes with compression stockings and thereby engage in normal everyday activities than with short-stretch bandages. A tip: Many patients find it arduous to don and remove a high-compression stocking that achieves the recommended pressure of 30-40 mm Hg at the point of transition between the Achilles tendon and the calf muscle, but the same effect can be achieved by overlapping two easier-to-use lower-compression stockings.

Punch grafting

This simple, cost-effective outpatient procedure was first described as a means of enhancing wound healing 150 years ago. The method involves utilizing a scalpel, curette, or punch to obtain a series of thin split-thickness skin grafts that contain epidermis and dermis down to the superficial papillary dermis. The grafts, usually harvested from the anterior thigh, are placed on the wound. This is followed by at least 5 days of local pressure and rest to promote graft uptake.

Sequential punch grafting is an excellent option for particularly challenging chronic ulcers, including Martorell hypertensive ischemic leg ulcers and other arteriolopathic ulcers in the elderly.

“Sequential punch grafting of wounds is very common in our clinics, especially for wounds that lack perfect grafting conditions,” Dr. Conde said.

She considers Martorell hypertensive ischemic leg ulcers to be underdiagnosed and undertreated. The Martorell leg ulcer is an exceedingly painful, rapidly progressive ischemic lesion, or bilateral lesions, with inflamed irregular margins. The disorder is caused by obstruction of subcutaneous arterioles in the absence of signs of vasculitis, and generally occurs in older individuals who have had well-controlled hypertension for many years. Diabetes, obesity, dyslipidemia, and peripheral artery disease are common comorbid conditions. The most common form of treatment – bioactive dressings in a moist environment – produces unsatisfactory results because it doesn’t address the inflammatory process.

Dr. Conde and coworkers have published the full details of how they achieved complete healing of Martorell hypertensive ischemic leg ulcers 3-8 weeks after punch grafting in three affected patients, all of whom presented with pain scores of 10/10 refractory even to opioid analgesics. The punch grafting was preceded by 15 days of topical corticosteroids and low-elasticity compression bandages in order to create adequate granulation tissue in the wound bed, which had the added benefit of achieving a 2- to 3-point reduction in pain scores even before the surgical procedure.

The pain-reducing effect of punch grafting isn’t as well appreciated as the wound-healing effect. Dr. Conde was first author of a recent study in which investigators systematically measured pain reduction in 136 patients with hard-to-heal leg ulcers of various etiologies treated with punch grafting. Nearly three-quarters of those who presented with painful ulcers were pain free after punch grafting, and the rest experienced greater than 70% pain reduction.

Pain suppression wasn’t dependent upon the percentage of graft uptake in this study. That’s because, as long as the wound isn’t overcleaned during dressing changes, even grafts that haven’t attached to the wound will release growth factors that promote wound healing, Dr. Conde explained.
 

Adjunctive negative pressure therapy

Portable vacuum-based negative pressure therapy devices are easy to use as a means to promote punch graft uptake. Negative pressure is best employed as an adjunct to punch grafting in suboptimal wound beds, longstanding ulcers, in patients with previous graft failure, or in challenging anatomic locations, such as the Achilles tendon or ankle. Dr. Conde has found the combination of punch grafting and negative pressure therapy especially helpful in patients with clinically inactive pyoderma gangrenosum.

Topical sevoflurane for analgesia

Most of the literature on topical sevoflurane for ulcer care has been published by Spanish researchers, but this form of analgesia deserves much more widespread use, according to Dr. Conde.

Sevoflurane is most often used as a gas in general anesthesia. In liquid form, however, it not only has a rapid, long-lasting analgesic effect when applied to painful leg ulcers, it also promotes healing because it is both antibacterial and a vasodilator. So before performing a potentially painful ulcer or wound cleaning, Dr. Conde recommended protecting perilesional skin with petroleum jelly, then irrigating the ulcer site with liquid sevoflurane. After that, it’s advisable to wait just 5-10 minutes before proceeding.

“It takes effect in much less time than EMLA cream,” she noted.

In one study of 30 adults aged over age 65 years with painful chronic venous ulcers refractory to conventional analgesics who underwent ulcer cleaning supported by topical sevoflurane at a dose of roughly 1 mL/cm² of ulcer area every 2 days for a month, Spanish investigators documented onset of analgesic effect in 2-7 minutes, with a duration of 8-18 hours. The researchers found that the use of backup conventional analgesics ranging from acetaminophen to opioids was diminished. Side effects were limited to mild, transient itching and redness.

Dr. Conde reported having no financial conflicts of interest regarding her presentation.

bjancin@mdedge.com

Chronic leg ulcers of all types feature a significant inflammatory component for which medical compression therapy is absolutely the best form of anti-inflammatory therapy, Elena Conde Montero, MD, PhD, asserted at the virtual annual congress of the European Academy of Dermatology and Venereology.

In addition to delving into the finer points of compression therapy, she offered other clinical pearls for the treatment of chronic leg ulcers. These included the use of autologous punch grafting to reduce pain as well as promote healing, when to employ adjunctive negative pressure therapy, and the benefits of liquid sevoflurane for highly effective topical analgesia during wound cleansing and debridement.
 

Compression therapy

“If no contraindications exist, compression therapy is the best antihypertensive and anti-inflammatory treatment for all leg ulcers, not only venous leg ulcers,” according to Dr. Conde, a dermatologist at Infanta Leonor University Hospital in Madrid.

The list of absolute contraindications to compression treatment is brief, as highlighted in a recent international consensus statement. The expert writing panel named only four: severe peripheral artery disease, the presence of an epifascial arterial bypass, severe cardiac insufficiency, and true allergy to compression material.

Compression therapy provides multiple salutary effects. These include reduced capillary filtration of fluids to tissue, decreased swelling, enhanced tissue remodeling, better lymphatic drainage, reduced inflammatory cell counts, and increased arterial flow.

“This means that people with mild arterial disease will benefit from active compression because perfusion will improve,” Dr. Conde said.

Similarly, leg ulcers secondary to pyoderma gangrenosum will benefit from the anti-inflammatory effects of compression therapy in conjunction with standard immunotherapy, added the dermatologist, who coauthored a recent publication by the European Wound Management Association entitled “Atypical Wounds: Best Clinical Practices and Challenges.”

Four broad types of compression therapy are available: compression stockings, short-stretch bandages, multicomponent bandage systems, and self-adjusting compression wrap devices. The best clinical outcomes are achieved by individualized selection of a compression method based upon patient characteristics.

Short-stretch, low-elasticity bandages – such as the classic Unna boot loaded with zinc paste and topical corticosteroids – are well suited for patients with large leg ulcers. These bandages feature high working pressures during muscle contraction. They also provide low resting pressures, which is advantageous in patients with peripheral artery disease. The major disadvantage of short-stretch bandages is the need for frequent dressing changes by a nurse or other trained professional, since the compression is quickly lost as an unwanted consequence of the welcome reduction in swelling.

Multicomponent bandage systems feature two to four layers of bandages of differing stiffness, as well as padding material and in many cases pressure indicators. These bandages can often be worn for up to a week without needing to be changed, since they maintain adequate pressure long term. “These are very easy to use by nonexperts,” Dr. Conde noted.

A caveat regarding both short-stretch bandages and the multicomponent bandage systems: before applying them, it’s important to pad at-risk areas against injury caused by high pressures. These high-risk areas include the Achilles tendon, the pretibial region, and the lateral foot.

Self-adjusting compression systems are comprised of strips of short-stretch, low-elasticity fabric, which wrap around the leg and are fixed with Velcro closures. Dr. Conde hailed these devices as “a great innovation in compression therapy, without doubt.” Their major advantage is ease of application and removal by the patient. They are best-suited for treatment of small ulcers in patients who find it difficult to use compression stockings because of obesity or osteoarthritis, in patients who can’t tolerate such stockings because they have peripheral artery disease and the stockings’ high resting pressure is uncomfortable, or in individuals ill-suited for compression bandages because they lack adequate access to nursing care for the required frequent dressing changes.

Compression stockings are a good option for small ulcers. It’s easier for patients to wear shoes with compression stockings and thereby engage in normal everyday activities than with short-stretch bandages. A tip: Many patients find it arduous to don and remove a high-compression stocking that achieves the recommended pressure of 30-40 mm Hg at the point of transition between the Achilles tendon and the calf muscle, but the same effect can be achieved by overlapping two easier-to-use lower-compression stockings.

Punch grafting

This simple, cost-effective outpatient procedure was first described as a means of enhancing wound healing 150 years ago. The method involves utilizing a scalpel, curette, or punch to obtain a series of thin split-thickness skin grafts that contain epidermis and dermis down to the superficial papillary dermis. The grafts, usually harvested from the anterior thigh, are placed on the wound. This is followed by at least 5 days of local pressure and rest to promote graft uptake.

Sequential punch grafting is an excellent option for particularly challenging chronic ulcers, including Martorell hypertensive ischemic leg ulcers and other arteriolopathic ulcers in the elderly.

“Sequential punch grafting of wounds is very common in our clinics, especially for wounds that lack perfect grafting conditions,” Dr. Conde said.

She considers Martorell hypertensive ischemic leg ulcers to be underdiagnosed and undertreated. The Martorell leg ulcer is an exceedingly painful, rapidly progressive ischemic lesion, or bilateral lesions, with inflamed irregular margins. The disorder is caused by obstruction of subcutaneous arterioles in the absence of signs of vasculitis, and generally occurs in older individuals who have had well-controlled hypertension for many years. Diabetes, obesity, dyslipidemia, and peripheral artery disease are common comorbid conditions. The most common form of treatment – bioactive dressings in a moist environment – produces unsatisfactory results because it doesn’t address the inflammatory process.

Dr. Conde and coworkers have published the full details of how they achieved complete healing of Martorell hypertensive ischemic leg ulcers 3-8 weeks after punch grafting in three affected patients, all of whom presented with pain scores of 10/10 refractory even to opioid analgesics. The punch grafting was preceded by 15 days of topical corticosteroids and low-elasticity compression bandages in order to create adequate granulation tissue in the wound bed, which had the added benefit of achieving a 2- to 3-point reduction in pain scores even before the surgical procedure.

The pain-reducing effect of punch grafting isn’t as well appreciated as the wound-healing effect. Dr. Conde was first author of a recent study in which investigators systematically measured pain reduction in 136 patients with hard-to-heal leg ulcers of various etiologies treated with punch grafting. Nearly three-quarters of those who presented with painful ulcers were pain free after punch grafting, and the rest experienced greater than 70% pain reduction.

Pain suppression wasn’t dependent upon the percentage of graft uptake in this study. That’s because, as long as the wound isn’t overcleaned during dressing changes, even grafts that haven’t attached to the wound will release growth factors that promote wound healing, Dr. Conde explained.
 

Adjunctive negative pressure therapy

Portable vacuum-based negative pressure therapy devices are easy to use as a means to promote punch graft uptake. Negative pressure is best employed as an adjunct to punch grafting in suboptimal wound beds, longstanding ulcers, in patients with previous graft failure, or in challenging anatomic locations, such as the Achilles tendon or ankle. Dr. Conde has found the combination of punch grafting and negative pressure therapy especially helpful in patients with clinically inactive pyoderma gangrenosum.

Topical sevoflurane for analgesia

Most of the literature on topical sevoflurane for ulcer care has been published by Spanish researchers, but this form of analgesia deserves much more widespread use, according to Dr. Conde.

Sevoflurane is most often used as a gas in general anesthesia. In liquid form, however, it not only has a rapid, long-lasting analgesic effect when applied to painful leg ulcers, it also promotes healing because it is both antibacterial and a vasodilator. So before performing a potentially painful ulcer or wound cleaning, Dr. Conde recommended protecting perilesional skin with petroleum jelly, then irrigating the ulcer site with liquid sevoflurane. After that, it’s advisable to wait just 5-10 minutes before proceeding.

“It takes effect in much less time than EMLA cream,” she noted.

In one study of 30 adults aged over age 65 years with painful chronic venous ulcers refractory to conventional analgesics who underwent ulcer cleaning supported by topical sevoflurane at a dose of roughly 1 mL/cm² of ulcer area every 2 days for a month, Spanish investigators documented onset of analgesic effect in 2-7 minutes, with a duration of 8-18 hours. The researchers found that the use of backup conventional analgesics ranging from acetaminophen to opioids was diminished. Side effects were limited to mild, transient itching and redness.

Dr. Conde reported having no financial conflicts of interest regarding her presentation.

bjancin@mdedge.com

Dermoscopic evaluation for detection of hypomelanotic and amelanotic melanomas is less accurate than for pigmented melanomas, but its utility can be boosted by familiarity with a handful of dermoscopic features specific to melanomas lacking significant pigment, Steven Q. Wang, MD, said at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

These features emerged from a major study conducted on five continents by members of the International Dermoscopy Society. The investigators developed a simple, eight-variable model, which demonstrated a sensitivity of 70% and specificity of 56% for diagnosis of melanoma. And while that’s a markedly worse performance than when dermoscopy is used for detection of pigmented melanomas, where sensitivities in excess of 90% and specificities greater than 70% are typical, it’s nonetheless a significant improvement over naked-eye evaluation of these challenging pigment-deprived melanomas, noted Dr. Wang, director of dermatologic surgery and dermatology at Memorial Sloan Kettering Basking Ridge (N.J.)

Using the predictive model developed in the international study to evaluate lesions lacking pigment, a diagnosis of melanoma is made provided two conditions are met: The lesion can have no more than three milia-like cysts, and it has to possess one or more of seven positive dermoscopic findings. The strongest predictor of melanoma in the study was the presence of a blue-white veil, which in univariate analysis was associated with a 13-fold increased likelihood of melanoma.

The other positive predictors were irregularly shaped depigmentation, more than one shade of pink, predominant central vessels, irregularly sized or distributed brown dots or globules, multiple blue-gray dots, and dotted and linear irregular vessels.

Dr. Wang emphasized that, when dermoscopy and clinical skin examination of a featureless hypomelanotic or amelanotic lesion yield ambiguous findings, frequent vigilant follow-up is a viable strategy to detect early melanoma – provided the lesion is superficial.

“The reality is not all melanomas are the same. The superficial spreading melanomas and lentigo melanomas grow very, very slowly: less than 0.1 mm per month. Those are the types of lesions you can monitor. But there is one type of lesion you should never, ever monitor: nodular lesions. They are the type of lesions that can do your patient harm because nodular melanomas can grow really fast. So my key takeaway message is, if you see a nodule and you don’t know what it is, take it off,” the dermatologist said.

Dermoscopy in the hands of experienced users has repeatedly been shown to improve diagnostic accuracy by more than 25%. But there is an additional very important reason to embrace dermoscopy in daily clinical practice, according to Dr. Wang: “When you put the scope on an individual, you slow down the exam and patients feels like you’re paying more attention to them.”

That’s worthwhile because the No. 1 complaint voiced by patients who make their way to Sloan Kettering for a second opinion is that their prior skin examination by an outside physician wasn’t thorough. They’re often angry about it. And while it’s true that incorporating dermoscopy does make for a lengthier skin examination, the additional time involved is actually minimal. Dr. Wang cited a randomized, prospective, multicenter study which documented that the median time required to conduct a thorough complete skin examination without dermoscopy was 70 seconds versus 142 seconds with dermoscopy.

Dr. Wang reported having no financial conflicts regarding his presentation.

MedscapeLive and this news organization are owned by the same parent company.
 

bjancin@mdedge.com

Dermoscopic evaluation for detection of hypomelanotic and amelanotic melanomas is less accurate than for pigmented melanomas, but its utility can be boosted by familiarity with a handful of dermoscopic features specific to melanomas lacking significant pigment, Steven Q. Wang, MD, said at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

These features emerged from a major study conducted on five continents by members of the International Dermoscopy Society. The investigators developed a simple, eight-variable model, which demonstrated a sensitivity of 70% and specificity of 56% for diagnosis of melanoma. And while that’s a markedly worse performance than when dermoscopy is used for detection of pigmented melanomas, where sensitivities in excess of 90% and specificities greater than 70% are typical, it’s nonetheless a significant improvement over naked-eye evaluation of these challenging pigment-deprived melanomas, noted Dr. Wang, director of dermatologic surgery and dermatology at Memorial Sloan Kettering Basking Ridge (N.J.)

Using the predictive model developed in the international study to evaluate lesions lacking pigment, a diagnosis of melanoma is made provided two conditions are met: The lesion can have no more than three milia-like cysts, and it has to possess one or more of seven positive dermoscopic findings. The strongest predictor of melanoma in the study was the presence of a blue-white veil, which in univariate analysis was associated with a 13-fold increased likelihood of melanoma.

The other positive predictors were irregularly shaped depigmentation, more than one shade of pink, predominant central vessels, irregularly sized or distributed brown dots or globules, multiple blue-gray dots, and dotted and linear irregular vessels.

Dr. Wang emphasized that, when dermoscopy and clinical skin examination of a featureless hypomelanotic or amelanotic lesion yield ambiguous findings, frequent vigilant follow-up is a viable strategy to detect early melanoma – provided the lesion is superficial.

“The reality is not all melanomas are the same. The superficial spreading melanomas and lentigo melanomas grow very, very slowly: less than 0.1 mm per month. Those are the types of lesions you can monitor. But there is one type of lesion you should never, ever monitor: nodular lesions. They are the type of lesions that can do your patient harm because nodular melanomas can grow really fast. So my key takeaway message is, if you see a nodule and you don’t know what it is, take it off,” the dermatologist said.

Dermoscopy in the hands of experienced users has repeatedly been shown to improve diagnostic accuracy by more than 25%. But there is an additional very important reason to embrace dermoscopy in daily clinical practice, according to Dr. Wang: “When you put the scope on an individual, you slow down the exam and patients feels like you’re paying more attention to them.”

That’s worthwhile because the No. 1 complaint voiced by patients who make their way to Sloan Kettering for a second opinion is that their prior skin examination by an outside physician wasn’t thorough. They’re often angry about it. And while it’s true that incorporating dermoscopy does make for a lengthier skin examination, the additional time involved is actually minimal. Dr. Wang cited a randomized, prospective, multicenter study which documented that the median time required to conduct a thorough complete skin examination without dermoscopy was 70 seconds versus 142 seconds with dermoscopy.

Dr. Wang reported having no financial conflicts regarding his presentation.

MedscapeLive and this news organization are owned by the same parent company.
 

bjancin@mdedge.com

Dermoscopic evaluation for detection of hypomelanotic and amelanotic melanomas is less accurate than for pigmented melanomas, but its utility can be boosted by familiarity with a handful of dermoscopic features specific to melanomas lacking significant pigment, Steven Q. Wang, MD, said at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

These features emerged from a major study conducted on five continents by members of the International Dermoscopy Society. The investigators developed a simple, eight-variable model, which demonstrated a sensitivity of 70% and specificity of 56% for diagnosis of melanoma. And while that’s a markedly worse performance than when dermoscopy is used for detection of pigmented melanomas, where sensitivities in excess of 90% and specificities greater than 70% are typical, it’s nonetheless a significant improvement over naked-eye evaluation of these challenging pigment-deprived melanomas, noted Dr. Wang, director of dermatologic surgery and dermatology at Memorial Sloan Kettering Basking Ridge (N.J.)

Using the predictive model developed in the international study to evaluate lesions lacking pigment, a diagnosis of melanoma is made provided two conditions are met: The lesion can have no more than three milia-like cysts, and it has to possess one or more of seven positive dermoscopic findings. The strongest predictor of melanoma in the study was the presence of a blue-white veil, which in univariate analysis was associated with a 13-fold increased likelihood of melanoma.

The other positive predictors were irregularly shaped depigmentation, more than one shade of pink, predominant central vessels, irregularly sized or distributed brown dots or globules, multiple blue-gray dots, and dotted and linear irregular vessels.

Dr. Wang emphasized that, when dermoscopy and clinical skin examination of a featureless hypomelanotic or amelanotic lesion yield ambiguous findings, frequent vigilant follow-up is a viable strategy to detect early melanoma – provided the lesion is superficial.

“The reality is not all melanomas are the same. The superficial spreading melanomas and lentigo melanomas grow very, very slowly: less than 0.1 mm per month. Those are the types of lesions you can monitor. But there is one type of lesion you should never, ever monitor: nodular lesions. They are the type of lesions that can do your patient harm because nodular melanomas can grow really fast. So my key takeaway message is, if you see a nodule and you don’t know what it is, take it off,” the dermatologist said.

Dermoscopy in the hands of experienced users has repeatedly been shown to improve diagnostic accuracy by more than 25%. But there is an additional very important reason to embrace dermoscopy in daily clinical practice, according to Dr. Wang: “When you put the scope on an individual, you slow down the exam and patients feels like you’re paying more attention to them.”

That’s worthwhile because the No. 1 complaint voiced by patients who make their way to Sloan Kettering for a second opinion is that their prior skin examination by an outside physician wasn’t thorough. They’re often angry about it. And while it’s true that incorporating dermoscopy does make for a lengthier skin examination, the additional time involved is actually minimal. Dr. Wang cited a randomized, prospective, multicenter study which documented that the median time required to conduct a thorough complete skin examination without dermoscopy was 70 seconds versus 142 seconds with dermoscopy.

Dr. Wang reported having no financial conflicts regarding his presentation.

MedscapeLive and this news organization are owned by the same parent company.
 

bjancin@mdedge.com

MRI-guided adaptive brachytherapy yields promising long-term outcomes in locally advanced cervical cancer but needs refinement to reduce morbidity and improve efficacy for certain patients, the EMBRACE I study suggests.

At 5 years, the rate of local control was 92%, and overall survival was 74%. However, nodal and systemic control rates were inferior for node-positive and high-risk patients, and nearly 15% of patients experienced grade 3-5 treatment-related morbidity.

These results were reported at the European Society for Radiology and Oncology 2020 Online Congress.

Historically, brachytherapy dose has been fairly rigidly prescribed, based on dose points defined in two dimensions. By performing imaging before each brachytherapy implant, treatment parameters can be adapted to a patient’s anatomy, taking into account the positions of organs at risk and any tumor regression from prior treatment.

Richard Pötter, MD, emeritus professor at Medical University of Vienna, and colleagues tested MRI-guided adaptive brachytherapy in a multicenter cohort study.

The study’s disease outcome analysis included 1,341 women with cervical cancer of International Federation of Gynecology and Obstetrics stage IB–IVB (52% node positive) being treated with curative intent.

The women underwent definitive external beam radiotherapy (45-50 Gy, using either three-dimensional–conformal radiotherapy or intensity-modulated radiotherapy) with concurrent cisplatin chemotherapy, followed by MRI-guided adaptive brachytherapy based on MRI with the applicator in situ.

“There was no fixed dose prescription for brachytherapy, and there were no constraints for organs at risk,” Dr. Pötter explained. “But there was systematic joint reporting and contouring for the target and organs at risk, and also for doses and volumes.”

Nearly all patients were treated with adaptive MRI-based target and dose-volume and point parameters (99.1%), as well as with individualized multiparametric dose optimization (98.2%). The application technique was adapted, with intracavitary application alone used in 57% of patients, and both intracavitary and interstitial application in 43%.
 

Efficacy and toxicity

At a median follow-up of 51 months, 7.3% of patients had experienced a local failure, with 3.8% having an isolated local failure and 3.5% having synchronous nodal or systemic failure, Dr. Pötter reported.

The local failure rate was similar going from disease stage IB2 to IVA (8%-9%), even though the target volume more than doubled.

“This favorable result was due to an adaptation of dose, which was quite similar for the different stages and volumes. This is a major message of EMBRACE I,” Dr. Pötter commented.

The Kaplan-Meier–estimated 5-year rate of local control was 92% for the whole cohort. It was 98% in patients with stage IB1 disease and 91%-92% in patients with stage IB2–IVA disease.

The 5-year rate of overall survival was 74% for the entire cohort. It fell with stage, from 83% in patients with stage IB1 disease to 52% in patients with stage IVA disease.

For the entire population, the 5-year pelvic control rate was 87%, the 5-year cancer-specific survival was 79%, and the 5-year disease-free survival was 68%.

Overall, 14.6% of patients experienced grade 3-5 treatment-related morbidity at 5 years: 2.7% developed fistulas, 6.1% had vaginal toxicity, 6.5% had genitourinary toxicity, and 7.6% had gastrointestinal toxicity.
 

Room for improvement

“MRI-guided adaptive brachytherapy in locally advanced cervical cancer works in multicenter clinical practice, within such a study, with adaptation of the target and application technique, and multiparametric treatment planning and dose prescription,” Dr. Pötter summarized.

However, “the mature clinical outcomes appear challenging,” he added. Specifically, although the rate of local control was high, the rate of nodal control left room for improvement in node-positive patients, and the rates of systemic control and overall survival left room for improvement in high-risk patients.

In addition, “the grade 3-5 morbidity was limited per organ and per endpoint, but was considerable overall, and this asks for a reduction,” Dr. Pötter said.

Two of the areas needing improvement are being addressed in ongoing and planned research, according to Dr. Pötter. “The nodal part is already being addressed in EMBRACE II, intensifying treatment for node-positive patients through a simultaneous integrated boost and a very sophisticated probability planning concept, and also including more patients for paraaortic radiotherapy,” he elaborated. “For the systemic part, we have thought about [a study testing an] additional drug ... and there are thoughts for EMBRACE III to investigate such effect.”
 

A benchmark for brachytherapy

“This is the largest prospective cohort of patients treated with image-guided brachytherapy. The high rates of local control with long-term follow-up are impressive and speak to the clear value of high-quality brachytherapy,” commented Ann H. Klopp, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, who was not involved in this study.

With its consistent reporting of detailed dose and toxicity data, the study establishes a benchmark for brachytherapy worldwide, Dr. Klopp said. It also better informs treatment decision-making in cases where replacing brachytherapy with external beam techniques is being considered.

Although MRI guidance is increasingly being used in brachytherapy, the latest studies on patterns of care suggest that overall use is still low, according to Dr. Klopp.

“The challenges are primarily logistical,” she elaborated. “MRI-compatible applicators must be placed, and patients need to wait for the scans to be performed, which can take an hour or more. In addition, the times that patients get scanned can be unpredictable based on procedure times, which can create practical challenges for scheduling. In some cases, cost may also be a deterrent.

“The bar is high for brachytherapy. It’s an excellent treatment modality that provides very high rates of local control with very low toxicity when done optimally,” Dr. Klopp concluded. “I do think that this experience provides very convincing evidence that the best brachytherapy is image-guided and requires care to monitor normal tissue doses in order to reduce the risk of long-term toxicity.”

The study was supported by unrestricted grants from Elekta and Varian. Dr. Pötter and Dr. Klopp disclosed no conflicts of interest.

SOURCE: Pötter R et al. ESTRO 2020, Abstract OC-0437.

MRI-guided adaptive brachytherapy yields promising long-term outcomes in locally advanced cervical cancer but needs refinement to reduce morbidity and improve efficacy for certain patients, the EMBRACE I study suggests.

At 5 years, the rate of local control was 92%, and overall survival was 74%. However, nodal and systemic control rates were inferior for node-positive and high-risk patients, and nearly 15% of patients experienced grade 3-5 treatment-related morbidity.

These results were reported at the European Society for Radiology and Oncology 2020 Online Congress.

Historically, brachytherapy dose has been fairly rigidly prescribed, based on dose points defined in two dimensions. By performing imaging before each brachytherapy implant, treatment parameters can be adapted to a patient’s anatomy, taking into account the positions of organs at risk and any tumor regression from prior treatment.

Richard Pötter, MD, emeritus professor at Medical University of Vienna, and colleagues tested MRI-guided adaptive brachytherapy in a multicenter cohort study.

The study’s disease outcome analysis included 1,341 women with cervical cancer of International Federation of Gynecology and Obstetrics stage IB–IVB (52% node positive) being treated with curative intent.

The women underwent definitive external beam radiotherapy (45-50 Gy, using either three-dimensional–conformal radiotherapy or intensity-modulated radiotherapy) with concurrent cisplatin chemotherapy, followed by MRI-guided adaptive brachytherapy based on MRI with the applicator in situ.

“There was no fixed dose prescription for brachytherapy, and there were no constraints for organs at risk,” Dr. Pötter explained. “But there was systematic joint reporting and contouring for the target and organs at risk, and also for doses and volumes.”

Nearly all patients were treated with adaptive MRI-based target and dose-volume and point parameters (99.1%), as well as with individualized multiparametric dose optimization (98.2%). The application technique was adapted, with intracavitary application alone used in 57% of patients, and both intracavitary and interstitial application in 43%.
 

Efficacy and toxicity

At a median follow-up of 51 months, 7.3% of patients had experienced a local failure, with 3.8% having an isolated local failure and 3.5% having synchronous nodal or systemic failure, Dr. Pötter reported.

The local failure rate was similar going from disease stage IB2 to IVA (8%-9%), even though the target volume more than doubled.

“This favorable result was due to an adaptation of dose, which was quite similar for the different stages and volumes. This is a major message of EMBRACE I,” Dr. Pötter commented.

The Kaplan-Meier–estimated 5-year rate of local control was 92% for the whole cohort. It was 98% in patients with stage IB1 disease and 91%-92% in patients with stage IB2–IVA disease.

The 5-year rate of overall survival was 74% for the entire cohort. It fell with stage, from 83% in patients with stage IB1 disease to 52% in patients with stage IVA disease.

For the entire population, the 5-year pelvic control rate was 87%, the 5-year cancer-specific survival was 79%, and the 5-year disease-free survival was 68%.

Overall, 14.6% of patients experienced grade 3-5 treatment-related morbidity at 5 years: 2.7% developed fistulas, 6.1% had vaginal toxicity, 6.5% had genitourinary toxicity, and 7.6% had gastrointestinal toxicity.
 

Room for improvement

“MRI-guided adaptive brachytherapy in locally advanced cervical cancer works in multicenter clinical practice, within such a study, with adaptation of the target and application technique, and multiparametric treatment planning and dose prescription,” Dr. Pötter summarized.

However, “the mature clinical outcomes appear challenging,” he added. Specifically, although the rate of local control was high, the rate of nodal control left room for improvement in node-positive patients, and the rates of systemic control and overall survival left room for improvement in high-risk patients.

In addition, “the grade 3-5 morbidity was limited per organ and per endpoint, but was considerable overall, and this asks for a reduction,” Dr. Pötter said.

Two of the areas needing improvement are being addressed in ongoing and planned research, according to Dr. Pötter. “The nodal part is already being addressed in EMBRACE II, intensifying treatment for node-positive patients through a simultaneous integrated boost and a very sophisticated probability planning concept, and also including more patients for paraaortic radiotherapy,” he elaborated. “For the systemic part, we have thought about [a study testing an] additional drug ... and there are thoughts for EMBRACE III to investigate such effect.”
 

A benchmark for brachytherapy

“This is the largest prospective cohort of patients treated with image-guided brachytherapy. The high rates of local control with long-term follow-up are impressive and speak to the clear value of high-quality brachytherapy,” commented Ann H. Klopp, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, who was not involved in this study.

With its consistent reporting of detailed dose and toxicity data, the study establishes a benchmark for brachytherapy worldwide, Dr. Klopp said. It also better informs treatment decision-making in cases where replacing brachytherapy with external beam techniques is being considered.

Although MRI guidance is increasingly being used in brachytherapy, the latest studies on patterns of care suggest that overall use is still low, according to Dr. Klopp.

“The challenges are primarily logistical,” she elaborated. “MRI-compatible applicators must be placed, and patients need to wait for the scans to be performed, which can take an hour or more. In addition, the times that patients get scanned can be unpredictable based on procedure times, which can create practical challenges for scheduling. In some cases, cost may also be a deterrent.

“The bar is high for brachytherapy. It’s an excellent treatment modality that provides very high rates of local control with very low toxicity when done optimally,” Dr. Klopp concluded. “I do think that this experience provides very convincing evidence that the best brachytherapy is image-guided and requires care to monitor normal tissue doses in order to reduce the risk of long-term toxicity.”

The study was supported by unrestricted grants from Elekta and Varian. Dr. Pötter and Dr. Klopp disclosed no conflicts of interest.

SOURCE: Pötter R et al. ESTRO 2020, Abstract OC-0437.

MRI-guided adaptive brachytherapy yields promising long-term outcomes in locally advanced cervical cancer but needs refinement to reduce morbidity and improve efficacy for certain patients, the EMBRACE I study suggests.

At 5 years, the rate of local control was 92%, and overall survival was 74%. However, nodal and systemic control rates were inferior for node-positive and high-risk patients, and nearly 15% of patients experienced grade 3-5 treatment-related morbidity.

These results were reported at the European Society for Radiology and Oncology 2020 Online Congress.

Historically, brachytherapy dose has been fairly rigidly prescribed, based on dose points defined in two dimensions. By performing imaging before each brachytherapy implant, treatment parameters can be adapted to a patient’s anatomy, taking into account the positions of organs at risk and any tumor regression from prior treatment.

Richard Pötter, MD, emeritus professor at Medical University of Vienna, and colleagues tested MRI-guided adaptive brachytherapy in a multicenter cohort study.

The study’s disease outcome analysis included 1,341 women with cervical cancer of International Federation of Gynecology and Obstetrics stage IB–IVB (52% node positive) being treated with curative intent.

The women underwent definitive external beam radiotherapy (45-50 Gy, using either three-dimensional–conformal radiotherapy or intensity-modulated radiotherapy) with concurrent cisplatin chemotherapy, followed by MRI-guided adaptive brachytherapy based on MRI with the applicator in situ.

“There was no fixed dose prescription for brachytherapy, and there were no constraints for organs at risk,” Dr. Pötter explained. “But there was systematic joint reporting and contouring for the target and organs at risk, and also for doses and volumes.”

Nearly all patients were treated with adaptive MRI-based target and dose-volume and point parameters (99.1%), as well as with individualized multiparametric dose optimization (98.2%). The application technique was adapted, with intracavitary application alone used in 57% of patients, and both intracavitary and interstitial application in 43%.
 

Efficacy and toxicity

At a median follow-up of 51 months, 7.3% of patients had experienced a local failure, with 3.8% having an isolated local failure and 3.5% having synchronous nodal or systemic failure, Dr. Pötter reported.

The local failure rate was similar going from disease stage IB2 to IVA (8%-9%), even though the target volume more than doubled.

“This favorable result was due to an adaptation of dose, which was quite similar for the different stages and volumes. This is a major message of EMBRACE I,” Dr. Pötter commented.

The Kaplan-Meier–estimated 5-year rate of local control was 92% for the whole cohort. It was 98% in patients with stage IB1 disease and 91%-92% in patients with stage IB2–IVA disease.

The 5-year rate of overall survival was 74% for the entire cohort. It fell with stage, from 83% in patients with stage IB1 disease to 52% in patients with stage IVA disease.

For the entire population, the 5-year pelvic control rate was 87%, the 5-year cancer-specific survival was 79%, and the 5-year disease-free survival was 68%.

Overall, 14.6% of patients experienced grade 3-5 treatment-related morbidity at 5 years: 2.7% developed fistulas, 6.1% had vaginal toxicity, 6.5% had genitourinary toxicity, and 7.6% had gastrointestinal toxicity.
 

Room for improvement

“MRI-guided adaptive brachytherapy in locally advanced cervical cancer works in multicenter clinical practice, within such a study, with adaptation of the target and application technique, and multiparametric treatment planning and dose prescription,” Dr. Pötter summarized.

However, “the mature clinical outcomes appear challenging,” he added. Specifically, although the rate of local control was high, the rate of nodal control left room for improvement in node-positive patients, and the rates of systemic control and overall survival left room for improvement in high-risk patients.

In addition, “the grade 3-5 morbidity was limited per organ and per endpoint, but was considerable overall, and this asks for a reduction,” Dr. Pötter said.

Two of the areas needing improvement are being addressed in ongoing and planned research, according to Dr. Pötter. “The nodal part is already being addressed in EMBRACE II, intensifying treatment for node-positive patients through a simultaneous integrated boost and a very sophisticated probability planning concept, and also including more patients for paraaortic radiotherapy,” he elaborated. “For the systemic part, we have thought about [a study testing an] additional drug ... and there are thoughts for EMBRACE III to investigate such effect.”
 

A benchmark for brachytherapy

“This is the largest prospective cohort of patients treated with image-guided brachytherapy. The high rates of local control with long-term follow-up are impressive and speak to the clear value of high-quality brachytherapy,” commented Ann H. Klopp, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, who was not involved in this study.

With its consistent reporting of detailed dose and toxicity data, the study establishes a benchmark for brachytherapy worldwide, Dr. Klopp said. It also better informs treatment decision-making in cases where replacing brachytherapy with external beam techniques is being considered.

Although MRI guidance is increasingly being used in brachytherapy, the latest studies on patterns of care suggest that overall use is still low, according to Dr. Klopp.

“The challenges are primarily logistical,” she elaborated. “MRI-compatible applicators must be placed, and patients need to wait for the scans to be performed, which can take an hour or more. In addition, the times that patients get scanned can be unpredictable based on procedure times, which can create practical challenges for scheduling. In some cases, cost may also be a deterrent.

“The bar is high for brachytherapy. It’s an excellent treatment modality that provides very high rates of local control with very low toxicity when done optimally,” Dr. Klopp concluded. “I do think that this experience provides very convincing evidence that the best brachytherapy is image-guided and requires care to monitor normal tissue doses in order to reduce the risk of long-term toxicity.”

The study was supported by unrestricted grants from Elekta and Varian. Dr. Pötter and Dr. Klopp disclosed no conflicts of interest.

SOURCE: Pötter R et al. ESTRO 2020, Abstract OC-0437.