A new study suggests that the 0.25-mg/kg dose of the thrombolytic tenecteplase (TNK) is just as good at facilitating reperfusion of the blocked artery in patients with ischemic large-vessel stroke prior to planned thrombectomy as the higher 0.4-mg/kg dose.
 

The EXTEND-IA TNK Part 2 trial was presented today at the American Stroke Association’s International Stroke Conference (ISC) 2020 in Los Angeles and was published online simultaneously (JAMA. 2020 Feb 20. doi: 10.1001/jama.2020.1511).

“We found the 0.4-mg/kg dose was no better than 0.25 mg/kg. There was absolutely no perceptible difference, so it appears that 0.25 mg/kg is enough,” lead investigator Bruce Campbell, MBBS, PhD, said in an interview.

“Our study was conducted in patients with large-vessel occlusions heading for thrombectomy, but I think the results can be extrapolated to patients with smaller occlusions too,” he added.

The study also showed that one-fifth of patients given tenecteplase experienced reperfusion before thrombectomy was performed. The percentage rose to one-third among patients from rural areas, whose longer times in transport led to an increase in the time between thrombolysis and thrombectomy.

“I think these data are as good as we’re going to get on the optimal dose of TNK. Our endpoint was reperfusion rates – a good, solid biological marker of benefit – but if a difference in clinical outcomes is wanted, that would take a trial of several thousand patients, which is never likely to be done,” said Dr. Campbell, who is from the Department of Neurology at the Royal Melbourne Hospital, Australia.

The researchers note that tenecteplase has a practical advantage over alteplase in that it is given as a bolus injection, whereas alteplase is given as bolus followed by a 1-hour infusion.

Results from the first EXTEND-IA TNK study suggested that tenecteplase 0.25 mg/kg produced higher reperfusion rates than alteplase (N Engl J Med. 2018;378:1573-82). However, the larger NOR-TEST study found no difference in efficacy or safety between a 0.4-mg/kg dose of tenecteplase and alteplase in patients with mild stroke (Lancet Neurol. 2017 Oct;16[10]:781-8).

TNK use in stroke varies around the world. The drug is not licensed for use in stroke anywhere, which Dr. Campbell attributes to a lack of incentive for the manufacturer, Genentech/Boehringer Ingelheim. That company also markets alteplase, the main thrombolytic used in stroke.

But many countries have now included TNK in their stroke guidelines, Dr. Campbell noted. “This has only recently occurred in the U.S., where it has a 2b recommendation, and the dose recommendations are somewhat confusing, advocating 0.25 mg/kg in large-vessel occlusions [as was used in the first EXTEND IA study] and 0.4 mg/kg in non–large vessel occlusions [from the NOR-TEST trial].

“This makes no biological sense whatsoever, recommending a higher dose for smaller occlusions, but that is just a literal translation of the design of the two major studies. I’m hoping our current results will help clarify the dosage issue and that might encourage more use of TNK altogether,” he commented.

For the current study, conducted in Australia and New Zealand, 300 patients who had experienced ischemic large-vessel stroke within 4.5 hours of symptom onset and who were scheduled for endovascular thrombectomy were randomly assigned to receive open-label thrombolysis with tenecteplase 0.4 mg/kg or 0.25 mg/kg.

The primary outcome, reperfusion of greater than 50% of the involved ischemic territory prior to thrombectomy, occurred in 19.3% of both groups. There was also no difference in any of the functional-outcome secondary endpoints or all-cause mortality between the two doses.

“While we didn’t find any extra benefit of the 0.4-mg/kg dose over the 0.25-mg/kg dose, we also didn’t find any extra harm, and this gives us reassurance in the emergency situation if the weight of the patient is overestimated; then we have a window of safety,” Dr. Campbell commented. “While there was a nonsignificant numerical increase in intracranial hemorrhage in the 0.4-mg/kg group, the excess bleeds were caused by puncturing of the vessels during thrombectomy, so I don’t think we can blame the TNK dose for that.

Better reperfusion than with alteplase?

Noting that the original EXTEND-IA TNK study showed higher reperfusion rates with tenecteplase vs alteplase and a trend toward better outcomes on the mRS scale, Campbell reported that a pooled analysis of the TNK results from the current study with those from the first study confirmed these findings.

“We found a doubling in the rate of reperfusion with TNK vs. alteplase, and the [modified Rankin Scale] shift analysis remained positive,” he said.

“I think we say with confidence that TNK is at least as good as alteplase and probably better, but further studies comparing the two agents are ongoing,” he added.

Of note, for the 41 patients from rural areas in the current study, in whom the time from thrombolysis to thrombectomy was longer (152 min vs. 41 min for patients from urban areas), reperfusion rates were higher (34% vs 17%), and there was no difference in dosage between the two groups.

Commenting on these latest results in an interview, Nicola Logallo, MD, of Haukeland University Hospital, Bergen, Norway, who was part of the NOR-TEST trial, said: “There is some evidence supporting the use of TNK 0.4 mg/kg in mild stroke patients, based mainly on the results from the NOR-TEST trial, and the use of TNK 0.25 mg/kg in patients undergoing thrombectomy, based on Dr. Campbell’s previous EXTEND-TNK trial. Dr. Campbell’s new study confirms that probably the higher dose of TNK does not add any advantages in terms of clinical outcome.”

Hemorrhagic complications appear to be similar in the two groups, Dr. Logallo said. “Overall, the 0.25-mg/kg TNK dose could therefore be considered as the most convenient and sensible, at least in patients undergoing thrombectomy. When it comes to the remaining stroke patients receiving thrombolysis, it remains unclear which is the best dose, but studies such as TASTE, NOR-TEST 2, AcT, and ATTEST-2 will hopefully answer this question within the next years.”

Also commenting on the study, Michael Hill, MD, professor of neurology at University of Calgary, Alberta, Canada, said the results “confirm that a good proportion of patients given TNK reperfuse before the angiogram and clarifies the dose. This is useful information.”

Dr. Hill said TNK is used routinely in some countries – mainly in Australia and Norway, where the studies have been conducted – but there is now a movement toward use of TNK in North America, too.

“Studies so far suggest that it could be more effective than alteplase, and as it is more fibrin specific, it could be safer. It is also easier to give with a bolus dose, but perhaps the biggest driver might be that it is cheaper than alteplase. Momentum is building, and many leading investigators are now conducting new studies with TNK with several more studies coming out in the next year or so,” Dr. Hill added.

The EXTEND-IA TNK Part 2 trial was supported by grants from the National Health and Medical Research Council of Australia and the National Heart Foundation of Australia. Campbell reports receiving grants from both institutions during the conduct of the study.
 

This article first appeared on Medscape.com.

A new study suggests that the 0.25-mg/kg dose of the thrombolytic tenecteplase (TNK) is just as good at facilitating reperfusion of the blocked artery in patients with ischemic large-vessel stroke prior to planned thrombectomy as the higher 0.4-mg/kg dose.
 

The EXTEND-IA TNK Part 2 trial was presented today at the American Stroke Association’s International Stroke Conference (ISC) 2020 in Los Angeles and was published online simultaneously (JAMA. 2020 Feb 20. doi: 10.1001/jama.2020.1511).

“We found the 0.4-mg/kg dose was no better than 0.25 mg/kg. There was absolutely no perceptible difference, so it appears that 0.25 mg/kg is enough,” lead investigator Bruce Campbell, MBBS, PhD, said in an interview.

“Our study was conducted in patients with large-vessel occlusions heading for thrombectomy, but I think the results can be extrapolated to patients with smaller occlusions too,” he added.

The study also showed that one-fifth of patients given tenecteplase experienced reperfusion before thrombectomy was performed. The percentage rose to one-third among patients from rural areas, whose longer times in transport led to an increase in the time between thrombolysis and thrombectomy.

“I think these data are as good as we’re going to get on the optimal dose of TNK. Our endpoint was reperfusion rates – a good, solid biological marker of benefit – but if a difference in clinical outcomes is wanted, that would take a trial of several thousand patients, which is never likely to be done,” said Dr. Campbell, who is from the Department of Neurology at the Royal Melbourne Hospital, Australia.

The researchers note that tenecteplase has a practical advantage over alteplase in that it is given as a bolus injection, whereas alteplase is given as bolus followed by a 1-hour infusion.

Results from the first EXTEND-IA TNK study suggested that tenecteplase 0.25 mg/kg produced higher reperfusion rates than alteplase (N Engl J Med. 2018;378:1573-82). However, the larger NOR-TEST study found no difference in efficacy or safety between a 0.4-mg/kg dose of tenecteplase and alteplase in patients with mild stroke (Lancet Neurol. 2017 Oct;16[10]:781-8).

TNK use in stroke varies around the world. The drug is not licensed for use in stroke anywhere, which Dr. Campbell attributes to a lack of incentive for the manufacturer, Genentech/Boehringer Ingelheim. That company also markets alteplase, the main thrombolytic used in stroke.

But many countries have now included TNK in their stroke guidelines, Dr. Campbell noted. “This has only recently occurred in the U.S., where it has a 2b recommendation, and the dose recommendations are somewhat confusing, advocating 0.25 mg/kg in large-vessel occlusions [as was used in the first EXTEND IA study] and 0.4 mg/kg in non–large vessel occlusions [from the NOR-TEST trial].

“This makes no biological sense whatsoever, recommending a higher dose for smaller occlusions, but that is just a literal translation of the design of the two major studies. I’m hoping our current results will help clarify the dosage issue and that might encourage more use of TNK altogether,” he commented.

For the current study, conducted in Australia and New Zealand, 300 patients who had experienced ischemic large-vessel stroke within 4.5 hours of symptom onset and who were scheduled for endovascular thrombectomy were randomly assigned to receive open-label thrombolysis with tenecteplase 0.4 mg/kg or 0.25 mg/kg.

The primary outcome, reperfusion of greater than 50% of the involved ischemic territory prior to thrombectomy, occurred in 19.3% of both groups. There was also no difference in any of the functional-outcome secondary endpoints or all-cause mortality between the two doses.

“While we didn’t find any extra benefit of the 0.4-mg/kg dose over the 0.25-mg/kg dose, we also didn’t find any extra harm, and this gives us reassurance in the emergency situation if the weight of the patient is overestimated; then we have a window of safety,” Dr. Campbell commented. “While there was a nonsignificant numerical increase in intracranial hemorrhage in the 0.4-mg/kg group, the excess bleeds were caused by puncturing of the vessels during thrombectomy, so I don’t think we can blame the TNK dose for that.

Better reperfusion than with alteplase?

Noting that the original EXTEND-IA TNK study showed higher reperfusion rates with tenecteplase vs alteplase and a trend toward better outcomes on the mRS scale, Campbell reported that a pooled analysis of the TNK results from the current study with those from the first study confirmed these findings.

“We found a doubling in the rate of reperfusion with TNK vs. alteplase, and the [modified Rankin Scale] shift analysis remained positive,” he said.

“I think we say with confidence that TNK is at least as good as alteplase and probably better, but further studies comparing the two agents are ongoing,” he added.

Of note, for the 41 patients from rural areas in the current study, in whom the time from thrombolysis to thrombectomy was longer (152 min vs. 41 min for patients from urban areas), reperfusion rates were higher (34% vs 17%), and there was no difference in dosage between the two groups.

Commenting on these latest results in an interview, Nicola Logallo, MD, of Haukeland University Hospital, Bergen, Norway, who was part of the NOR-TEST trial, said: “There is some evidence supporting the use of TNK 0.4 mg/kg in mild stroke patients, based mainly on the results from the NOR-TEST trial, and the use of TNK 0.25 mg/kg in patients undergoing thrombectomy, based on Dr. Campbell’s previous EXTEND-TNK trial. Dr. Campbell’s new study confirms that probably the higher dose of TNK does not add any advantages in terms of clinical outcome.”

Hemorrhagic complications appear to be similar in the two groups, Dr. Logallo said. “Overall, the 0.25-mg/kg TNK dose could therefore be considered as the most convenient and sensible, at least in patients undergoing thrombectomy. When it comes to the remaining stroke patients receiving thrombolysis, it remains unclear which is the best dose, but studies such as TASTE, NOR-TEST 2, AcT, and ATTEST-2 will hopefully answer this question within the next years.”

Also commenting on the study, Michael Hill, MD, professor of neurology at University of Calgary, Alberta, Canada, said the results “confirm that a good proportion of patients given TNK reperfuse before the angiogram and clarifies the dose. This is useful information.”

Dr. Hill said TNK is used routinely in some countries – mainly in Australia and Norway, where the studies have been conducted – but there is now a movement toward use of TNK in North America, too.

“Studies so far suggest that it could be more effective than alteplase, and as it is more fibrin specific, it could be safer. It is also easier to give with a bolus dose, but perhaps the biggest driver might be that it is cheaper than alteplase. Momentum is building, and many leading investigators are now conducting new studies with TNK with several more studies coming out in the next year or so,” Dr. Hill added.

The EXTEND-IA TNK Part 2 trial was supported by grants from the National Health and Medical Research Council of Australia and the National Heart Foundation of Australia. Campbell reports receiving grants from both institutions during the conduct of the study.
 

This article first appeared on Medscape.com.

A new study suggests that the 0.25-mg/kg dose of the thrombolytic tenecteplase (TNK) is just as good at facilitating reperfusion of the blocked artery in patients with ischemic large-vessel stroke prior to planned thrombectomy as the higher 0.4-mg/kg dose.
 

The EXTEND-IA TNK Part 2 trial was presented today at the American Stroke Association’s International Stroke Conference (ISC) 2020 in Los Angeles and was published online simultaneously (JAMA. 2020 Feb 20. doi: 10.1001/jama.2020.1511).

“We found the 0.4-mg/kg dose was no better than 0.25 mg/kg. There was absolutely no perceptible difference, so it appears that 0.25 mg/kg is enough,” lead investigator Bruce Campbell, MBBS, PhD, said in an interview.

“Our study was conducted in patients with large-vessel occlusions heading for thrombectomy, but I think the results can be extrapolated to patients with smaller occlusions too,” he added.

The study also showed that one-fifth of patients given tenecteplase experienced reperfusion before thrombectomy was performed. The percentage rose to one-third among patients from rural areas, whose longer times in transport led to an increase in the time between thrombolysis and thrombectomy.

“I think these data are as good as we’re going to get on the optimal dose of TNK. Our endpoint was reperfusion rates – a good, solid biological marker of benefit – but if a difference in clinical outcomes is wanted, that would take a trial of several thousand patients, which is never likely to be done,” said Dr. Campbell, who is from the Department of Neurology at the Royal Melbourne Hospital, Australia.

The researchers note that tenecteplase has a practical advantage over alteplase in that it is given as a bolus injection, whereas alteplase is given as bolus followed by a 1-hour infusion.

Results from the first EXTEND-IA TNK study suggested that tenecteplase 0.25 mg/kg produced higher reperfusion rates than alteplase (N Engl J Med. 2018;378:1573-82). However, the larger NOR-TEST study found no difference in efficacy or safety between a 0.4-mg/kg dose of tenecteplase and alteplase in patients with mild stroke (Lancet Neurol. 2017 Oct;16[10]:781-8).

TNK use in stroke varies around the world. The drug is not licensed for use in stroke anywhere, which Dr. Campbell attributes to a lack of incentive for the manufacturer, Genentech/Boehringer Ingelheim. That company also markets alteplase, the main thrombolytic used in stroke.

But many countries have now included TNK in their stroke guidelines, Dr. Campbell noted. “This has only recently occurred in the U.S., where it has a 2b recommendation, and the dose recommendations are somewhat confusing, advocating 0.25 mg/kg in large-vessel occlusions [as was used in the first EXTEND IA study] and 0.4 mg/kg in non–large vessel occlusions [from the NOR-TEST trial].

“This makes no biological sense whatsoever, recommending a higher dose for smaller occlusions, but that is just a literal translation of the design of the two major studies. I’m hoping our current results will help clarify the dosage issue and that might encourage more use of TNK altogether,” he commented.

For the current study, conducted in Australia and New Zealand, 300 patients who had experienced ischemic large-vessel stroke within 4.5 hours of symptom onset and who were scheduled for endovascular thrombectomy were randomly assigned to receive open-label thrombolysis with tenecteplase 0.4 mg/kg or 0.25 mg/kg.

The primary outcome, reperfusion of greater than 50% of the involved ischemic territory prior to thrombectomy, occurred in 19.3% of both groups. There was also no difference in any of the functional-outcome secondary endpoints or all-cause mortality between the two doses.

“While we didn’t find any extra benefit of the 0.4-mg/kg dose over the 0.25-mg/kg dose, we also didn’t find any extra harm, and this gives us reassurance in the emergency situation if the weight of the patient is overestimated; then we have a window of safety,” Dr. Campbell commented. “While there was a nonsignificant numerical increase in intracranial hemorrhage in the 0.4-mg/kg group, the excess bleeds were caused by puncturing of the vessels during thrombectomy, so I don’t think we can blame the TNK dose for that.

Better reperfusion than with alteplase?

Noting that the original EXTEND-IA TNK study showed higher reperfusion rates with tenecteplase vs alteplase and a trend toward better outcomes on the mRS scale, Campbell reported that a pooled analysis of the TNK results from the current study with those from the first study confirmed these findings.

“We found a doubling in the rate of reperfusion with TNK vs. alteplase, and the [modified Rankin Scale] shift analysis remained positive,” he said.

“I think we say with confidence that TNK is at least as good as alteplase and probably better, but further studies comparing the two agents are ongoing,” he added.

Of note, for the 41 patients from rural areas in the current study, in whom the time from thrombolysis to thrombectomy was longer (152 min vs. 41 min for patients from urban areas), reperfusion rates were higher (34% vs 17%), and there was no difference in dosage between the two groups.

Commenting on these latest results in an interview, Nicola Logallo, MD, of Haukeland University Hospital, Bergen, Norway, who was part of the NOR-TEST trial, said: “There is some evidence supporting the use of TNK 0.4 mg/kg in mild stroke patients, based mainly on the results from the NOR-TEST trial, and the use of TNK 0.25 mg/kg in patients undergoing thrombectomy, based on Dr. Campbell’s previous EXTEND-TNK trial. Dr. Campbell’s new study confirms that probably the higher dose of TNK does not add any advantages in terms of clinical outcome.”

Hemorrhagic complications appear to be similar in the two groups, Dr. Logallo said. “Overall, the 0.25-mg/kg TNK dose could therefore be considered as the most convenient and sensible, at least in patients undergoing thrombectomy. When it comes to the remaining stroke patients receiving thrombolysis, it remains unclear which is the best dose, but studies such as TASTE, NOR-TEST 2, AcT, and ATTEST-2 will hopefully answer this question within the next years.”

Also commenting on the study, Michael Hill, MD, professor of neurology at University of Calgary, Alberta, Canada, said the results “confirm that a good proportion of patients given TNK reperfuse before the angiogram and clarifies the dose. This is useful information.”

Dr. Hill said TNK is used routinely in some countries – mainly in Australia and Norway, where the studies have been conducted – but there is now a movement toward use of TNK in North America, too.

“Studies so far suggest that it could be more effective than alteplase, and as it is more fibrin specific, it could be safer. It is also easier to give with a bolus dose, but perhaps the biggest driver might be that it is cheaper than alteplase. Momentum is building, and many leading investigators are now conducting new studies with TNK with several more studies coming out in the next year or so,” Dr. Hill added.

The EXTEND-IA TNK Part 2 trial was supported by grants from the National Health and Medical Research Council of Australia and the National Heart Foundation of Australia. Campbell reports receiving grants from both institutions during the conduct of the study.
 

This article first appeared on Medscape.com.

Adolescent and young adult cancer survivors have higher standardized mortality ratios (SMRs) than the general population but lower ratios than childhood cancer survivors, according to data from the Childhood Cancer Survivor Study.

Xavier_S/Thinkstock

At a median follow-up of 21 years, the SMR for all-cause mortality was 5.9 among survivors aged 15-20 years and 6.2 among diagnosis-matched children under 15 years, compared with expected rates at the same ages in the general population. For health-related causes – excluding primary cancer recurrence or progression but including late effects of cancer therapy – the SMRs were 4.8 in the older group and 6.8 in the younger group.

Eugene Suh, MD, of Loyola University Chicago Medical Center, Maywood, Ill., and colleagues reported these results in Lancet Oncology.

The difference between the older and younger survivors (n = 5,804 in each group) was most evident at least 20 years after cancer diagnosis, the authors noted.

For both groups, but more so for childhood cancer survivors, the risk of developing any chronic health condition and any grade 3-5 health condition was greater than for siblings of the same age who did not have cancer (hazard ratios, 4.2 for adolescents/young adults and 5.6 for childhood survivors). The same was true for grade 3-5 cardiac conditions (HRs, 4.3 and 5.6, respectively), endocrine conditions (HRs, 3.9 and 6.4, respectively), and musculoskeletal conditions (HRs, 6.5 and 8.0, respectively).

These findings, which confirm those of previous studies suggesting that younger children might be more vulnerable to the adverse effects of cancer treatment, “underscore that focused efforts are needed to ensure early-adolescent and young adult cancer survivors are receiving recommended risk-based care, with a focus on high-risk cancer screening, to reduce morbidity and premature mortality,” the researchers concluded, noting that “studies to date indicate that adherence to such high-risk screening is poor.”

In a related editorial, Päivi Lähteenmäki, MD, PhD, of University of Turku (Finland) and Turku University Hospital, wrote that these findings warrant long-term follow-up of adolescent and young adult cancer survivors. She also argued that the results “might not be fully generalizable to patients treated today who might be on different treatment regimens to those treated in previous decades” and that “[m]ore prospectively collected objective data focusing on survivors ... are needed.”

Accurate characterization of patients at high risk who would benefit from a tailored screening program is most important, and identifying underlying genetic or molecular factors that confer higher risk for late sequelae would be useful for “planning approaches to survivorship,” Dr. Lähteenmäki added.

This study was funded by the National Cancer Institute and American Lebanese-Syrian Associated Charities. Dr. Suh and Dr. Lähteenmäki reported having no competing interests.

sworcester@mdedge.com

SOURCES: Suh E et al. Lancet Oncology. 2020 Feb 14. doi: 10.1016/S1470-2045(19)30800-9;Lähteenmäki P. Lancet Oncol. 2020 Feb 14. doi: 10.106/S1470-2045(19)30858-7.

Adolescent and young adult cancer survivors have higher standardized mortality ratios (SMRs) than the general population but lower ratios than childhood cancer survivors, according to data from the Childhood Cancer Survivor Study.

Xavier_S/Thinkstock

At a median follow-up of 21 years, the SMR for all-cause mortality was 5.9 among survivors aged 15-20 years and 6.2 among diagnosis-matched children under 15 years, compared with expected rates at the same ages in the general population. For health-related causes – excluding primary cancer recurrence or progression but including late effects of cancer therapy – the SMRs were 4.8 in the older group and 6.8 in the younger group.

Eugene Suh, MD, of Loyola University Chicago Medical Center, Maywood, Ill., and colleagues reported these results in Lancet Oncology.

The difference between the older and younger survivors (n = 5,804 in each group) was most evident at least 20 years after cancer diagnosis, the authors noted.

For both groups, but more so for childhood cancer survivors, the risk of developing any chronic health condition and any grade 3-5 health condition was greater than for siblings of the same age who did not have cancer (hazard ratios, 4.2 for adolescents/young adults and 5.6 for childhood survivors). The same was true for grade 3-5 cardiac conditions (HRs, 4.3 and 5.6, respectively), endocrine conditions (HRs, 3.9 and 6.4, respectively), and musculoskeletal conditions (HRs, 6.5 and 8.0, respectively).

These findings, which confirm those of previous studies suggesting that younger children might be more vulnerable to the adverse effects of cancer treatment, “underscore that focused efforts are needed to ensure early-adolescent and young adult cancer survivors are receiving recommended risk-based care, with a focus on high-risk cancer screening, to reduce morbidity and premature mortality,” the researchers concluded, noting that “studies to date indicate that adherence to such high-risk screening is poor.”

In a related editorial, Päivi Lähteenmäki, MD, PhD, of University of Turku (Finland) and Turku University Hospital, wrote that these findings warrant long-term follow-up of adolescent and young adult cancer survivors. She also argued that the results “might not be fully generalizable to patients treated today who might be on different treatment regimens to those treated in previous decades” and that “[m]ore prospectively collected objective data focusing on survivors ... are needed.”

Accurate characterization of patients at high risk who would benefit from a tailored screening program is most important, and identifying underlying genetic or molecular factors that confer higher risk for late sequelae would be useful for “planning approaches to survivorship,” Dr. Lähteenmäki added.

This study was funded by the National Cancer Institute and American Lebanese-Syrian Associated Charities. Dr. Suh and Dr. Lähteenmäki reported having no competing interests.

sworcester@mdedge.com

SOURCES: Suh E et al. Lancet Oncology. 2020 Feb 14. doi: 10.1016/S1470-2045(19)30800-9;Lähteenmäki P. Lancet Oncol. 2020 Feb 14. doi: 10.106/S1470-2045(19)30858-7.

Adolescent and young adult cancer survivors have higher standardized mortality ratios (SMRs) than the general population but lower ratios than childhood cancer survivors, according to data from the Childhood Cancer Survivor Study.

Xavier_S/Thinkstock

At a median follow-up of 21 years, the SMR for all-cause mortality was 5.9 among survivors aged 15-20 years and 6.2 among diagnosis-matched children under 15 years, compared with expected rates at the same ages in the general population. For health-related causes – excluding primary cancer recurrence or progression but including late effects of cancer therapy – the SMRs were 4.8 in the older group and 6.8 in the younger group.

Eugene Suh, MD, of Loyola University Chicago Medical Center, Maywood, Ill., and colleagues reported these results in Lancet Oncology.

The difference between the older and younger survivors (n = 5,804 in each group) was most evident at least 20 years after cancer diagnosis, the authors noted.

For both groups, but more so for childhood cancer survivors, the risk of developing any chronic health condition and any grade 3-5 health condition was greater than for siblings of the same age who did not have cancer (hazard ratios, 4.2 for adolescents/young adults and 5.6 for childhood survivors). The same was true for grade 3-5 cardiac conditions (HRs, 4.3 and 5.6, respectively), endocrine conditions (HRs, 3.9 and 6.4, respectively), and musculoskeletal conditions (HRs, 6.5 and 8.0, respectively).

These findings, which confirm those of previous studies suggesting that younger children might be more vulnerable to the adverse effects of cancer treatment, “underscore that focused efforts are needed to ensure early-adolescent and young adult cancer survivors are receiving recommended risk-based care, with a focus on high-risk cancer screening, to reduce morbidity and premature mortality,” the researchers concluded, noting that “studies to date indicate that adherence to such high-risk screening is poor.”

In a related editorial, Päivi Lähteenmäki, MD, PhD, of University of Turku (Finland) and Turku University Hospital, wrote that these findings warrant long-term follow-up of adolescent and young adult cancer survivors. She also argued that the results “might not be fully generalizable to patients treated today who might be on different treatment regimens to those treated in previous decades” and that “[m]ore prospectively collected objective data focusing on survivors ... are needed.”

Accurate characterization of patients at high risk who would benefit from a tailored screening program is most important, and identifying underlying genetic or molecular factors that confer higher risk for late sequelae would be useful for “planning approaches to survivorship,” Dr. Lähteenmäki added.

This study was funded by the National Cancer Institute and American Lebanese-Syrian Associated Charities. Dr. Suh and Dr. Lähteenmäki reported having no competing interests.

sworcester@mdedge.com

SOURCES: Suh E et al. Lancet Oncology. 2020 Feb 14. doi: 10.1016/S1470-2045(19)30800-9;Lähteenmäki P. Lancet Oncol. 2020 Feb 14. doi: 10.106/S1470-2045(19)30858-7.

For more than a decade, most physicians have paid a steady amount for medical liability insurance. But that price stability appears to be ending, according to a recent analysis.

In 2019, more than 25% of medical liability insurance premiums rose for internists, ob.gyns., and surgeons, a review by the Medical Liability Monitor (MLM) found. The MLM survey, published annually, analyzes premium data from major malpractice insurers based on mature, claims-made policies with $1 million/$3 million limits for internists, general surgeons, and ob.gyns.

The increases mark a shift in the long-stable market and suggest rising premiums in the future, said Michael Matray, editor for the Medical Liability Monitor.

“It’s my impression that rates will increase again in [2020]. It’s almost a foregone conclusion,” he said in an interview. “We can expect more firming within the market.”

Most of the premium increases in 2019 were small – between 0.1% and 10%, Mr. Matray said. At the same time, close to 70% of premium rates were flat in 2019 and about 5% of premium rates decreased, according to the survey, released in late 2019.

Comparatively, about 58% of premium rates were flat from 2007 to 2014, about 30% of rates went down during that time frame, and 12% of rates went up. From 2015 to 2018, nearly 76% of rates were steady, 10% went down, and 15% of rates increased, according to the latest analysis. 2019 was the first time since 2006 that more than 25% of premium rates rose, the survey noted.

“This is a normal cycle for the insurance industry – years of feast, followed by years of famine. Eventually companies reach a point where they feel enough pain and one response is to raise rates,” said Alyssa Gittleman, a coauthor of the survey and senior associate in the insurance research department at Conning, an investment management firm for the insurance industry.

“We could also point out many of the rate increases reported in the survey came from the larger [medical professional liability] companies. These companies are well capitalized, and the fact that they are raising rates could be a bellwether that a hard market is coming. However, as we said in the survey, it will probably take another 12-24 months before we know for certain,” she added.
 

Location, location, location

Physicians continue to pay vastly different premiums depending on where they practice. Ob.gyns. in eastern New York for example, paid about $201,000 in 2019, while their Minnesota colleagues paid about $16,500. Internists in southern Florida, meanwhile, paid about $49,000 in 2019, while their counterparts in northern California paid about $4,100. General surgeons in southern Florida paid about $195,000 for malpractice insurance, while some Wisconsin general surgeons paid about $11,000.

“Medical malpractice rates are determined locally, that’s why we don’t give state averages or national averages [in the survey],” Mr. Matray said. “It’s all determined by malpractice claims history within that territory and how aggressive the plaintiffs bar is in those areas.”

Two states – Arizona and Pennsylvania – experienced exceptional rate decreases in 2019. In Arizona, The Doctors Company lowered their rates by more than 60% for internists, general surgeons, and ob.gyns. In Pennsylvania, which operates a patient compensation fund, The Doctors Company decreased its rates between 20% and 46% for each of the three specialties. The insurer reported it made the decreases to align its rates with other insurers in those states, according to the survey. The Doctors Company did not respond to messages seeking comment for this article.

When individual companies greatly increase or greatly decrease rates in a given state, it’s generally to bring their rates in line with those of larger companies in the market, said Bill Burns, a coauthor of the MLM report and a vice president in the insurance research department at Conning. In 2018, The Doctors Company held about 2% of the market in Arizona, and the company held about 1% of the Pennsylvania market, he noted.

“These decreases, which get them in line with the larger writers, should tighten up the range of rates in those states,” Mr. Burns said in an interview. “To sell the product, they’re going to have be close to the competition.”

For a clear picture of the overall premium landscape, the survey authors analyzed the data both with and without the exceptional rate decreases in Arizona and Pennsylvania. Regionally – excluding the exceptional decreases – the average premium rate increase was 2% in the Midwest, 1.4% in the Northeast, 1.1% in the South, and 0.3% in the West.

For all three specialties surveyed, premiums rose slightly in 2019, with surgeons experiencing the largest increase. Internists saw a nearly 1% average rate increase, ob.gyns. experienced a 0.5% rise, and surgeons experienced a 2.3% rate increase, the survey found. For doctors in the seven states that have patient compensation funds, internists experienced a nearly 2.1% average rate increase, ob.gyns. saw a 1.4% rise, and surgeons experienced a 2.1% rate increase. (These data sets exclude the exceptional rate decreases in Arizona and Pennsylvania.)

The change in rates for general surgery could mean more claims are being filed against surgeons or that the cost of claims are rising, Mr. Burns said.

“The differences are not terribly significant, but suggest something is happening with general surgery,” he said.
 

Why are rates on the rise?

A number of factors are behind the changing medical liability insurance market, said Brian Atchinson, president and CEO for the Medical Professional Liability Association (MPL Association), a trade association for medical liability insurers.

While the frequency of claims against physicians has remained flat for an extended period of time, the cost of managing those claims has continued to increase, he said.

“Medical liability insurers insuring physicians and other clinicians, they need to defend every claim that they believe warrants defense,” Mr. Atchinson said in an interview. “When the medical treatment provided is within the appropriate standards, even though there may be claims or lawsuits, every one of those [cases] can be very expensive to defend.”

Other contributers to the increasing rates include the trend of high-dollar settlements and judgments, particularly in the hospital space, Mr. Atchinson noted. Such large payouts are generally tied to hospital and health system claims, but they still affect the broader medical liability insurance marketplace, he said.

Additionally, a growing number of medical liability tort reform measures enacted over the last 20 years are being eliminated, Mr. Atchinson said. In June 2019, the Kansas Supreme Court for instance, struck down the state’s cap on damages for noneconomic injuries in medical liability cases. In a 2017 ruling, the Pennsylvania Supreme Court changed the state’s statue of limitations for medical malpractice wrongful death claims from 2 years from the time of the patient’s injury to 2 years from the time of the patient’s death.

When legislatures change state laws and courts invalidate protections against nonmeritorious lawsuits, the actions can have serious consequences for physicians and companies operating in those states, Mr. Atchinson said.

“These [changes] will all ultimately work their way into the rates that physicians are paying,” he said.

agallegos@mdedge.com

For more than a decade, most physicians have paid a steady amount for medical liability insurance. But that price stability appears to be ending, according to a recent analysis.

In 2019, more than 25% of medical liability insurance premiums rose for internists, ob.gyns., and surgeons, a review by the Medical Liability Monitor (MLM) found. The MLM survey, published annually, analyzes premium data from major malpractice insurers based on mature, claims-made policies with $1 million/$3 million limits for internists, general surgeons, and ob.gyns.

The increases mark a shift in the long-stable market and suggest rising premiums in the future, said Michael Matray, editor for the Medical Liability Monitor.

“It’s my impression that rates will increase again in [2020]. It’s almost a foregone conclusion,” he said in an interview. “We can expect more firming within the market.”

Most of the premium increases in 2019 were small – between 0.1% and 10%, Mr. Matray said. At the same time, close to 70% of premium rates were flat in 2019 and about 5% of premium rates decreased, according to the survey, released in late 2019.

Comparatively, about 58% of premium rates were flat from 2007 to 2014, about 30% of rates went down during that time frame, and 12% of rates went up. From 2015 to 2018, nearly 76% of rates were steady, 10% went down, and 15% of rates increased, according to the latest analysis. 2019 was the first time since 2006 that more than 25% of premium rates rose, the survey noted.

“This is a normal cycle for the insurance industry – years of feast, followed by years of famine. Eventually companies reach a point where they feel enough pain and one response is to raise rates,” said Alyssa Gittleman, a coauthor of the survey and senior associate in the insurance research department at Conning, an investment management firm for the insurance industry.

“We could also point out many of the rate increases reported in the survey came from the larger [medical professional liability] companies. These companies are well capitalized, and the fact that they are raising rates could be a bellwether that a hard market is coming. However, as we said in the survey, it will probably take another 12-24 months before we know for certain,” she added.
 

Location, location, location

Physicians continue to pay vastly different premiums depending on where they practice. Ob.gyns. in eastern New York for example, paid about $201,000 in 2019, while their Minnesota colleagues paid about $16,500. Internists in southern Florida, meanwhile, paid about $49,000 in 2019, while their counterparts in northern California paid about $4,100. General surgeons in southern Florida paid about $195,000 for malpractice insurance, while some Wisconsin general surgeons paid about $11,000.

“Medical malpractice rates are determined locally, that’s why we don’t give state averages or national averages [in the survey],” Mr. Matray said. “It’s all determined by malpractice claims history within that territory and how aggressive the plaintiffs bar is in those areas.”

Two states – Arizona and Pennsylvania – experienced exceptional rate decreases in 2019. In Arizona, The Doctors Company lowered their rates by more than 60% for internists, general surgeons, and ob.gyns. In Pennsylvania, which operates a patient compensation fund, The Doctors Company decreased its rates between 20% and 46% for each of the three specialties. The insurer reported it made the decreases to align its rates with other insurers in those states, according to the survey. The Doctors Company did not respond to messages seeking comment for this article.

When individual companies greatly increase or greatly decrease rates in a given state, it’s generally to bring their rates in line with those of larger companies in the market, said Bill Burns, a coauthor of the MLM report and a vice president in the insurance research department at Conning. In 2018, The Doctors Company held about 2% of the market in Arizona, and the company held about 1% of the Pennsylvania market, he noted.

“These decreases, which get them in line with the larger writers, should tighten up the range of rates in those states,” Mr. Burns said in an interview. “To sell the product, they’re going to have be close to the competition.”

For a clear picture of the overall premium landscape, the survey authors analyzed the data both with and without the exceptional rate decreases in Arizona and Pennsylvania. Regionally – excluding the exceptional decreases – the average premium rate increase was 2% in the Midwest, 1.4% in the Northeast, 1.1% in the South, and 0.3% in the West.

For all three specialties surveyed, premiums rose slightly in 2019, with surgeons experiencing the largest increase. Internists saw a nearly 1% average rate increase, ob.gyns. experienced a 0.5% rise, and surgeons experienced a 2.3% rate increase, the survey found. For doctors in the seven states that have patient compensation funds, internists experienced a nearly 2.1% average rate increase, ob.gyns. saw a 1.4% rise, and surgeons experienced a 2.1% rate increase. (These data sets exclude the exceptional rate decreases in Arizona and Pennsylvania.)

The change in rates for general surgery could mean more claims are being filed against surgeons or that the cost of claims are rising, Mr. Burns said.

“The differences are not terribly significant, but suggest something is happening with general surgery,” he said.
 

Why are rates on the rise?

A number of factors are behind the changing medical liability insurance market, said Brian Atchinson, president and CEO for the Medical Professional Liability Association (MPL Association), a trade association for medical liability insurers.

While the frequency of claims against physicians has remained flat for an extended period of time, the cost of managing those claims has continued to increase, he said.

“Medical liability insurers insuring physicians and other clinicians, they need to defend every claim that they believe warrants defense,” Mr. Atchinson said in an interview. “When the medical treatment provided is within the appropriate standards, even though there may be claims or lawsuits, every one of those [cases] can be very expensive to defend.”

Other contributers to the increasing rates include the trend of high-dollar settlements and judgments, particularly in the hospital space, Mr. Atchinson noted. Such large payouts are generally tied to hospital and health system claims, but they still affect the broader medical liability insurance marketplace, he said.

Additionally, a growing number of medical liability tort reform measures enacted over the last 20 years are being eliminated, Mr. Atchinson said. In June 2019, the Kansas Supreme Court for instance, struck down the state’s cap on damages for noneconomic injuries in medical liability cases. In a 2017 ruling, the Pennsylvania Supreme Court changed the state’s statue of limitations for medical malpractice wrongful death claims from 2 years from the time of the patient’s injury to 2 years from the time of the patient’s death.

When legislatures change state laws and courts invalidate protections against nonmeritorious lawsuits, the actions can have serious consequences for physicians and companies operating in those states, Mr. Atchinson said.

“These [changes] will all ultimately work their way into the rates that physicians are paying,” he said.

agallegos@mdedge.com

For more than a decade, most physicians have paid a steady amount for medical liability insurance. But that price stability appears to be ending, according to a recent analysis.

In 2019, more than 25% of medical liability insurance premiums rose for internists, ob.gyns., and surgeons, a review by the Medical Liability Monitor (MLM) found. The MLM survey, published annually, analyzes premium data from major malpractice insurers based on mature, claims-made policies with $1 million/$3 million limits for internists, general surgeons, and ob.gyns.

The increases mark a shift in the long-stable market and suggest rising premiums in the future, said Michael Matray, editor for the Medical Liability Monitor.

“It’s my impression that rates will increase again in [2020]. It’s almost a foregone conclusion,” he said in an interview. “We can expect more firming within the market.”

Most of the premium increases in 2019 were small – between 0.1% and 10%, Mr. Matray said. At the same time, close to 70% of premium rates were flat in 2019 and about 5% of premium rates decreased, according to the survey, released in late 2019.

Comparatively, about 58% of premium rates were flat from 2007 to 2014, about 30% of rates went down during that time frame, and 12% of rates went up. From 2015 to 2018, nearly 76% of rates were steady, 10% went down, and 15% of rates increased, according to the latest analysis. 2019 was the first time since 2006 that more than 25% of premium rates rose, the survey noted.

“This is a normal cycle for the insurance industry – years of feast, followed by years of famine. Eventually companies reach a point where they feel enough pain and one response is to raise rates,” said Alyssa Gittleman, a coauthor of the survey and senior associate in the insurance research department at Conning, an investment management firm for the insurance industry.

“We could also point out many of the rate increases reported in the survey came from the larger [medical professional liability] companies. These companies are well capitalized, and the fact that they are raising rates could be a bellwether that a hard market is coming. However, as we said in the survey, it will probably take another 12-24 months before we know for certain,” she added.
 

Location, location, location

Physicians continue to pay vastly different premiums depending on where they practice. Ob.gyns. in eastern New York for example, paid about $201,000 in 2019, while their Minnesota colleagues paid about $16,500. Internists in southern Florida, meanwhile, paid about $49,000 in 2019, while their counterparts in northern California paid about $4,100. General surgeons in southern Florida paid about $195,000 for malpractice insurance, while some Wisconsin general surgeons paid about $11,000.

“Medical malpractice rates are determined locally, that’s why we don’t give state averages or national averages [in the survey],” Mr. Matray said. “It’s all determined by malpractice claims history within that territory and how aggressive the plaintiffs bar is in those areas.”

Two states – Arizona and Pennsylvania – experienced exceptional rate decreases in 2019. In Arizona, The Doctors Company lowered their rates by more than 60% for internists, general surgeons, and ob.gyns. In Pennsylvania, which operates a patient compensation fund, The Doctors Company decreased its rates between 20% and 46% for each of the three specialties. The insurer reported it made the decreases to align its rates with other insurers in those states, according to the survey. The Doctors Company did not respond to messages seeking comment for this article.

When individual companies greatly increase or greatly decrease rates in a given state, it’s generally to bring their rates in line with those of larger companies in the market, said Bill Burns, a coauthor of the MLM report and a vice president in the insurance research department at Conning. In 2018, The Doctors Company held about 2% of the market in Arizona, and the company held about 1% of the Pennsylvania market, he noted.

“These decreases, which get them in line with the larger writers, should tighten up the range of rates in those states,” Mr. Burns said in an interview. “To sell the product, they’re going to have be close to the competition.”

For a clear picture of the overall premium landscape, the survey authors analyzed the data both with and without the exceptional rate decreases in Arizona and Pennsylvania. Regionally – excluding the exceptional decreases – the average premium rate increase was 2% in the Midwest, 1.4% in the Northeast, 1.1% in the South, and 0.3% in the West.

For all three specialties surveyed, premiums rose slightly in 2019, with surgeons experiencing the largest increase. Internists saw a nearly 1% average rate increase, ob.gyns. experienced a 0.5% rise, and surgeons experienced a 2.3% rate increase, the survey found. For doctors in the seven states that have patient compensation funds, internists experienced a nearly 2.1% average rate increase, ob.gyns. saw a 1.4% rise, and surgeons experienced a 2.1% rate increase. (These data sets exclude the exceptional rate decreases in Arizona and Pennsylvania.)

The change in rates for general surgery could mean more claims are being filed against surgeons or that the cost of claims are rising, Mr. Burns said.

“The differences are not terribly significant, but suggest something is happening with general surgery,” he said.
 

Why are rates on the rise?

A number of factors are behind the changing medical liability insurance market, said Brian Atchinson, president and CEO for the Medical Professional Liability Association (MPL Association), a trade association for medical liability insurers.

While the frequency of claims against physicians has remained flat for an extended period of time, the cost of managing those claims has continued to increase, he said.

“Medical liability insurers insuring physicians and other clinicians, they need to defend every claim that they believe warrants defense,” Mr. Atchinson said in an interview. “When the medical treatment provided is within the appropriate standards, even though there may be claims or lawsuits, every one of those [cases] can be very expensive to defend.”

Other contributers to the increasing rates include the trend of high-dollar settlements and judgments, particularly in the hospital space, Mr. Atchinson noted. Such large payouts are generally tied to hospital and health system claims, but they still affect the broader medical liability insurance marketplace, he said.

Additionally, a growing number of medical liability tort reform measures enacted over the last 20 years are being eliminated, Mr. Atchinson said. In June 2019, the Kansas Supreme Court for instance, struck down the state’s cap on damages for noneconomic injuries in medical liability cases. In a 2017 ruling, the Pennsylvania Supreme Court changed the state’s statue of limitations for medical malpractice wrongful death claims from 2 years from the time of the patient’s injury to 2 years from the time of the patient’s death.

When legislatures change state laws and courts invalidate protections against nonmeritorious lawsuits, the actions can have serious consequences for physicians and companies operating in those states, Mr. Atchinson said.

“These [changes] will all ultimately work their way into the rates that physicians are paying,” he said.

agallegos@mdedge.com

The total number of hysterectomies performed during residency training has declined significantly since 2008, despite an increase in laparoscopic hysterectomies performed, according to a new analysis of data from graduating ob.gyn. residents that has implications for the structure of resident education.

U.S. Air Force photo by Staff Sgt. Ciara Gosier

The investigators abstracted case log data from the Accreditation Council for Graduate Medical Education (ACGME) database to assess trends in residents’ operative experience and found decreases in abdominal and vaginal cases but an increase in experience with laparoscopic hysterectomy.

The median number of abdominal hysterectomies performed per resident over 4 years of training decreased by 57% between 2002-2003 and 2017-2018 (from 85 cases to 37), and the median number of vaginal hysterectomies decreased by 36% (from 31 to 20 cases).

Laparoscopic hysterectomy increased by 115% from a median of 20 procedures in 2008-2009 to 43 in 2017-2018. Even so, the median total number of hysterectomies per resident decreased by 6%, from 112 to 105 procedures during those two time periods. (Data on total hysterectomy and laparoscopic hysterectomy were not collected by ACGME until 2008.)

While the absolute decrease in the total number of hysterectomies is “relatively small,” the trend “raises questions about what the appropriate number of hysterectomies per graduating resident should be,” Gregory M. Gressel, MD, MSc, of the Montefiore Medical Center, New York, and coauthors wrote in Obstetrics & Gynecology.

“These data point,” they wrote, “to the necessity of maximizing surgical exposure in the face of a declining availability of procedures and the importance of reflecting on which (and how many) procedures an obstetrics and gynecology resident needs to complete before entering clinical practice.”

The training numbers parallel an increased use of laparoscopic hysterectomy in the United States and other countries, as well as a well-documented decline in the total number of hysterectomies performed in the United States, the latter of which is driven largely by the availability and increasing use of alternatives to the procedure (such as hormone therapy, endometrial ablation, and uterine artery embolization).

Hysterectomy still is a “core procedure of gynecologic surgery,” however, and is “at the heart of surgical training in obstetrics and gynecology,” as surgical techniques developed from learning hysterectomy “are applied broadly in the pelvis,” Saketh R. Guntupalli, MD, wrote in an accompanying editorial.

Dr. Guntupalli, of the University of Colorado at Aurora, Denver, was involved in a survey of fellowship program directors, published in 2015, that found only 20% of first-year fellows were able to independently perform a vaginal hysterectomy and 46% to independently perform an abdominal hysterectomy (Obstet Gynecol. 2015;126:559-68).

This and other research suggest that fellowship training is “used to address deficiencies in residency training rather than to develop new, specialized surgical skills,” he wrote. Given a dearth of fellowship positions in ob.gyn., “it is impossible to adequately use those avenues to train the number of competent surgeons necessary to address the surgical needs of women’s health in the United States.”

To address such concerns, some residency programs have instituted resident tracking to direct more hysterectomy cases toward those residents who plan to pursue surgical subspecialties. The Cleveland Clinic, Dr. Guntupalli noted, has tried the latter approach “with success.”

An increase in the number of accredited training programs and a decrease in the number of residents per program also might help to improve surgical exposure for residents, Dr. Gressel and associates wrote. Over the 16-year study period, the number of graduating residents increased significantly (by 12 per year) and the number of residency programs decreased significantly (0.52 fewer programs per year).

Additionally, Dr. Guntupalli wrote, regulatory bodies may need to reevaluate how competencies are assessed, and whether minimal numbers of cases “continue to carry the same weight as they did in previous generations.”

In the study, one coauthor is a full-time employee of ACGME, and another receives funds as a director for the American Board of Obstetrics and Gynecology. The remaining authors had no relevant financial disclosures. There was no outside funding for the study. Dr. Guntupalli said he had no conflicts of interest.

SOURCES: Gressel GM et al. Obstet Gynecol. 2020 Feb;135(2):268-73; Guntupalli SR. Obstet Gynecol 2020 Feb;135(2):266-7.

The total number of hysterectomies performed during residency training has declined significantly since 2008, despite an increase in laparoscopic hysterectomies performed, according to a new analysis of data from graduating ob.gyn. residents that has implications for the structure of resident education.

U.S. Air Force photo by Staff Sgt. Ciara Gosier

The investigators abstracted case log data from the Accreditation Council for Graduate Medical Education (ACGME) database to assess trends in residents’ operative experience and found decreases in abdominal and vaginal cases but an increase in experience with laparoscopic hysterectomy.

The median number of abdominal hysterectomies performed per resident over 4 years of training decreased by 57% between 2002-2003 and 2017-2018 (from 85 cases to 37), and the median number of vaginal hysterectomies decreased by 36% (from 31 to 20 cases).

Laparoscopic hysterectomy increased by 115% from a median of 20 procedures in 2008-2009 to 43 in 2017-2018. Even so, the median total number of hysterectomies per resident decreased by 6%, from 112 to 105 procedures during those two time periods. (Data on total hysterectomy and laparoscopic hysterectomy were not collected by ACGME until 2008.)

While the absolute decrease in the total number of hysterectomies is “relatively small,” the trend “raises questions about what the appropriate number of hysterectomies per graduating resident should be,” Gregory M. Gressel, MD, MSc, of the Montefiore Medical Center, New York, and coauthors wrote in Obstetrics & Gynecology.

“These data point,” they wrote, “to the necessity of maximizing surgical exposure in the face of a declining availability of procedures and the importance of reflecting on which (and how many) procedures an obstetrics and gynecology resident needs to complete before entering clinical practice.”

The training numbers parallel an increased use of laparoscopic hysterectomy in the United States and other countries, as well as a well-documented decline in the total number of hysterectomies performed in the United States, the latter of which is driven largely by the availability and increasing use of alternatives to the procedure (such as hormone therapy, endometrial ablation, and uterine artery embolization).

Hysterectomy still is a “core procedure of gynecologic surgery,” however, and is “at the heart of surgical training in obstetrics and gynecology,” as surgical techniques developed from learning hysterectomy “are applied broadly in the pelvis,” Saketh R. Guntupalli, MD, wrote in an accompanying editorial.

Dr. Guntupalli, of the University of Colorado at Aurora, Denver, was involved in a survey of fellowship program directors, published in 2015, that found only 20% of first-year fellows were able to independently perform a vaginal hysterectomy and 46% to independently perform an abdominal hysterectomy (Obstet Gynecol. 2015;126:559-68).

This and other research suggest that fellowship training is “used to address deficiencies in residency training rather than to develop new, specialized surgical skills,” he wrote. Given a dearth of fellowship positions in ob.gyn., “it is impossible to adequately use those avenues to train the number of competent surgeons necessary to address the surgical needs of women’s health in the United States.”

To address such concerns, some residency programs have instituted resident tracking to direct more hysterectomy cases toward those residents who plan to pursue surgical subspecialties. The Cleveland Clinic, Dr. Guntupalli noted, has tried the latter approach “with success.”

An increase in the number of accredited training programs and a decrease in the number of residents per program also might help to improve surgical exposure for residents, Dr. Gressel and associates wrote. Over the 16-year study period, the number of graduating residents increased significantly (by 12 per year) and the number of residency programs decreased significantly (0.52 fewer programs per year).

Additionally, Dr. Guntupalli wrote, regulatory bodies may need to reevaluate how competencies are assessed, and whether minimal numbers of cases “continue to carry the same weight as they did in previous generations.”

In the study, one coauthor is a full-time employee of ACGME, and another receives funds as a director for the American Board of Obstetrics and Gynecology. The remaining authors had no relevant financial disclosures. There was no outside funding for the study. Dr. Guntupalli said he had no conflicts of interest.

SOURCES: Gressel GM et al. Obstet Gynecol. 2020 Feb;135(2):268-73; Guntupalli SR. Obstet Gynecol 2020 Feb;135(2):266-7.

The total number of hysterectomies performed during residency training has declined significantly since 2008, despite an increase in laparoscopic hysterectomies performed, according to a new analysis of data from graduating ob.gyn. residents that has implications for the structure of resident education.

U.S. Air Force photo by Staff Sgt. Ciara Gosier

The investigators abstracted case log data from the Accreditation Council for Graduate Medical Education (ACGME) database to assess trends in residents’ operative experience and found decreases in abdominal and vaginal cases but an increase in experience with laparoscopic hysterectomy.

The median number of abdominal hysterectomies performed per resident over 4 years of training decreased by 57% between 2002-2003 and 2017-2018 (from 85 cases to 37), and the median number of vaginal hysterectomies decreased by 36% (from 31 to 20 cases).

Laparoscopic hysterectomy increased by 115% from a median of 20 procedures in 2008-2009 to 43 in 2017-2018. Even so, the median total number of hysterectomies per resident decreased by 6%, from 112 to 105 procedures during those two time periods. (Data on total hysterectomy and laparoscopic hysterectomy were not collected by ACGME until 2008.)

While the absolute decrease in the total number of hysterectomies is “relatively small,” the trend “raises questions about what the appropriate number of hysterectomies per graduating resident should be,” Gregory M. Gressel, MD, MSc, of the Montefiore Medical Center, New York, and coauthors wrote in Obstetrics & Gynecology.

“These data point,” they wrote, “to the necessity of maximizing surgical exposure in the face of a declining availability of procedures and the importance of reflecting on which (and how many) procedures an obstetrics and gynecology resident needs to complete before entering clinical practice.”

The training numbers parallel an increased use of laparoscopic hysterectomy in the United States and other countries, as well as a well-documented decline in the total number of hysterectomies performed in the United States, the latter of which is driven largely by the availability and increasing use of alternatives to the procedure (such as hormone therapy, endometrial ablation, and uterine artery embolization).

Hysterectomy still is a “core procedure of gynecologic surgery,” however, and is “at the heart of surgical training in obstetrics and gynecology,” as surgical techniques developed from learning hysterectomy “are applied broadly in the pelvis,” Saketh R. Guntupalli, MD, wrote in an accompanying editorial.

Dr. Guntupalli, of the University of Colorado at Aurora, Denver, was involved in a survey of fellowship program directors, published in 2015, that found only 20% of first-year fellows were able to independently perform a vaginal hysterectomy and 46% to independently perform an abdominal hysterectomy (Obstet Gynecol. 2015;126:559-68).

This and other research suggest that fellowship training is “used to address deficiencies in residency training rather than to develop new, specialized surgical skills,” he wrote. Given a dearth of fellowship positions in ob.gyn., “it is impossible to adequately use those avenues to train the number of competent surgeons necessary to address the surgical needs of women’s health in the United States.”

To address such concerns, some residency programs have instituted resident tracking to direct more hysterectomy cases toward those residents who plan to pursue surgical subspecialties. The Cleveland Clinic, Dr. Guntupalli noted, has tried the latter approach “with success.”

An increase in the number of accredited training programs and a decrease in the number of residents per program also might help to improve surgical exposure for residents, Dr. Gressel and associates wrote. Over the 16-year study period, the number of graduating residents increased significantly (by 12 per year) and the number of residency programs decreased significantly (0.52 fewer programs per year).

Additionally, Dr. Guntupalli wrote, regulatory bodies may need to reevaluate how competencies are assessed, and whether minimal numbers of cases “continue to carry the same weight as they did in previous generations.”

In the study, one coauthor is a full-time employee of ACGME, and another receives funds as a director for the American Board of Obstetrics and Gynecology. The remaining authors had no relevant financial disclosures. There was no outside funding for the study. Dr. Guntupalli said he had no conflicts of interest.

SOURCES: Gressel GM et al. Obstet Gynecol. 2020 Feb;135(2):268-73; Guntupalli SR. Obstet Gynecol 2020 Feb;135(2):266-7.

Obesity during adolescence is associated with increased midlife cancer risk, according to findings from a large population-based cohort of Israeli teens examined between 1967 and 2010.

The association, which was stronger in individuals in the later period of the cohort than in those in the earlier years, suggests that the burden of obesity-related cancers might increase over time, given the increasing prevalence of adolescent obesity, wrote Ariel Furer, MD, of Israel Defense Forces Medical Corps, Ramat Gan, and colleagues. Their report is in The Lancet.

Obesity is a known causal factor for several types of cancer, but most studies have looked at middle-age or older individuals and had relatively short follow-up, and period effects are rarely assessed, the investigators said, noting that “the attributable burden of obesity-related cancer was previously calculated with an unverified assumption that the association remained unchanged over time.

“In contrast to this paucity of knowledge, the prevalence of youth obesity – particularly severe obesity – has increased worldwide, which parallels the rise in youth cancer incidence,” they wrote.

To address this paucity of data, the researchers reviewed medical and sociodemographic data for adolescents who were assessed at age 17 years for medical eligibility for mandatory military service, and linked that information with data from the National Cancer Registry to create a unified file. The primary study outcome was any cancer diagnosis between Jan. 1, 1967, and Dec. 31, 2012, and a secondary endpoint was all-cause mortality through Dec. 31, 2017, among those who developed cancer.

Among nearly 2.3 million participating adolescents who were evaluated for associations between body mass index at age 17 years and later cancer incidence, 1,370,020 were men with more than 29.5 million person-years of follow-up, and 928,110 were women with more than 18 million person-years of follow-up. The numbers of incident cancer cases in the men and women were 26,353 and 29,488, and the mean ages at diagnosis were 43.2 and 40.0 years, respectively, the investigators reported (Lancet. 2020 Feb 3. doi: 10.1016/S2213-8587(20)30019-X).

Adolescent obesity in men was significantly associated with midlife cancer incidence (hazard ratio, 1.26), but in women, no association was seen due to the previously reported inverse associations between obesity and cervical and breast cancers, they said.

However, when those cancers were excluded for women, the adjusted hazard ratio was similar to that for men (HR, 1.27).

Cancer incidence in both men and women increased gradually across BMI percentiles, and for both sexes, overweight BMI was associated with an increased cancer risk after 10 years of follow-up (HR, 1.14 for men, 1.22 for women after exclusion of cervical and breast cancer). Therefore, in some cases the increased cancer risk in those who were overweight as teens was evident before age 30 years, the authors noted.

Further, BMI was positively associated with greater mortality risk. For men, 5-year survival rates were 75.2% in those with adolescent BMI in the 5th-49th percentile, compared with 72.2% in those with BMI in the obesity range (95th percentile or greater), and the corresponding rates in women were 89.3% and 83.1% (HR, 1.33 and 1.89, respectively).

Of note, the investigators identified a period effect. That is, after stratification by enrollment period/cancer recording period (1967-1981/1982-1996 vs. 1982-1996/1997-2011), a stronger association was noted in individuals who entered the study during the later period, compared with those who entered in the early period (HR, 1.36 vs. 1.13; adjusted HR, 1.11 vs. 1.07 per 5 kg/m²). Possible mechanisms for this finding include environmental and nutritional factors, increased use of medical services, and changes in early cancer screening techniques, but further study is needed to verify the trend and “refine the exact nature of carcinogenic elements, compared with earlier periods,” they said.

Also of note, some cancers that were not associated with BMI in the early period, including stomach cancer, non-Hodgkin lymphoma, thyroid cancer, and colorectal and oral cavity cancers, became significantly associated with BMI in the late period.

“The projected population attributable risk percentage, using 2017 prevalence data of high BMI, was 5.1% for any cancer in men and 5.7% for cancers other than breast and cervical in women,” the researchers wrote, noting that this “is probably an underestimation, given the accentuation of the BMI-cancer association and the rapid increase in adolescent obesity prevalence within the past decade in Israel and worldwide.”

In an accompanying editorial, the journal editors noted that the findings by Dr. Furer and colleagues highlight the need to tackle obesity early in life and the need for obesity prevention strategies to reduce cancer incidence and mortality for those cancers that can be prevented by lifestyle modifications. They added, however, that care would be needed to avoid stigmatizing those with obesity, as obesity itself is a “multifactorial condition driven by social injustice and health inequalities” that most often affect those who are least able to implement lifestyle change (Lancet. 2020 Feb 3. doi: 10.106/S2213-8587(20)30031-0).

They also emphasized that the links between obesity and cancer, like those between obesity and other diseases such as diabetes, underscore the fact that noncommunicable diseases do not exist in isolation, and that tackling them requires bold action, a consolidated approach, and elimination of the environmental and social factors driving the epidemic.

The study was limited by a number of factors, including the lack of data on lifestyle factors, underrepresentation of some ethnicities, and lack of data on BMI and medical comorbidities at the time of cancer diagnosis. However, strengths of the study include the systematic data collection, narrow range of age at study entry, strict control of coexisting conditions, and high statistical power, which strengthen the generalizability of the results, the investigators said, concluding, therefore, that “[c]urrent trends of rising BMI among adolescents could constitute an important intervention target for cancer prevention.”

The authors reported having no disclosures.

sworcester@mdedge.com

SOURCE: Furer A et al. Lancet Diabetes Endocrinol. 2020 Feb 3. doi: 10.1016/S2213-8587(20)30019-X.

Obesity during adolescence is associated with increased midlife cancer risk, according to findings from a large population-based cohort of Israeli teens examined between 1967 and 2010.

The association, which was stronger in individuals in the later period of the cohort than in those in the earlier years, suggests that the burden of obesity-related cancers might increase over time, given the increasing prevalence of adolescent obesity, wrote Ariel Furer, MD, of Israel Defense Forces Medical Corps, Ramat Gan, and colleagues. Their report is in The Lancet.

Obesity is a known causal factor for several types of cancer, but most studies have looked at middle-age or older individuals and had relatively short follow-up, and period effects are rarely assessed, the investigators said, noting that “the attributable burden of obesity-related cancer was previously calculated with an unverified assumption that the association remained unchanged over time.

“In contrast to this paucity of knowledge, the prevalence of youth obesity – particularly severe obesity – has increased worldwide, which parallels the rise in youth cancer incidence,” they wrote.

To address this paucity of data, the researchers reviewed medical and sociodemographic data for adolescents who were assessed at age 17 years for medical eligibility for mandatory military service, and linked that information with data from the National Cancer Registry to create a unified file. The primary study outcome was any cancer diagnosis between Jan. 1, 1967, and Dec. 31, 2012, and a secondary endpoint was all-cause mortality through Dec. 31, 2017, among those who developed cancer.

Among nearly 2.3 million participating adolescents who were evaluated for associations between body mass index at age 17 years and later cancer incidence, 1,370,020 were men with more than 29.5 million person-years of follow-up, and 928,110 were women with more than 18 million person-years of follow-up. The numbers of incident cancer cases in the men and women were 26,353 and 29,488, and the mean ages at diagnosis were 43.2 and 40.0 years, respectively, the investigators reported (Lancet. 2020 Feb 3. doi: 10.1016/S2213-8587(20)30019-X).

Adolescent obesity in men was significantly associated with midlife cancer incidence (hazard ratio, 1.26), but in women, no association was seen due to the previously reported inverse associations between obesity and cervical and breast cancers, they said.

However, when those cancers were excluded for women, the adjusted hazard ratio was similar to that for men (HR, 1.27).

Cancer incidence in both men and women increased gradually across BMI percentiles, and for both sexes, overweight BMI was associated with an increased cancer risk after 10 years of follow-up (HR, 1.14 for men, 1.22 for women after exclusion of cervical and breast cancer). Therefore, in some cases the increased cancer risk in those who were overweight as teens was evident before age 30 years, the authors noted.

Further, BMI was positively associated with greater mortality risk. For men, 5-year survival rates were 75.2% in those with adolescent BMI in the 5th-49th percentile, compared with 72.2% in those with BMI in the obesity range (95th percentile or greater), and the corresponding rates in women were 89.3% and 83.1% (HR, 1.33 and 1.89, respectively).

Of note, the investigators identified a period effect. That is, after stratification by enrollment period/cancer recording period (1967-1981/1982-1996 vs. 1982-1996/1997-2011), a stronger association was noted in individuals who entered the study during the later period, compared with those who entered in the early period (HR, 1.36 vs. 1.13; adjusted HR, 1.11 vs. 1.07 per 5 kg/m²). Possible mechanisms for this finding include environmental and nutritional factors, increased use of medical services, and changes in early cancer screening techniques, but further study is needed to verify the trend and “refine the exact nature of carcinogenic elements, compared with earlier periods,” they said.

Also of note, some cancers that were not associated with BMI in the early period, including stomach cancer, non-Hodgkin lymphoma, thyroid cancer, and colorectal and oral cavity cancers, became significantly associated with BMI in the late period.

“The projected population attributable risk percentage, using 2017 prevalence data of high BMI, was 5.1% for any cancer in men and 5.7% for cancers other than breast and cervical in women,” the researchers wrote, noting that this “is probably an underestimation, given the accentuation of the BMI-cancer association and the rapid increase in adolescent obesity prevalence within the past decade in Israel and worldwide.”

In an accompanying editorial, the journal editors noted that the findings by Dr. Furer and colleagues highlight the need to tackle obesity early in life and the need for obesity prevention strategies to reduce cancer incidence and mortality for those cancers that can be prevented by lifestyle modifications. They added, however, that care would be needed to avoid stigmatizing those with obesity, as obesity itself is a “multifactorial condition driven by social injustice and health inequalities” that most often affect those who are least able to implement lifestyle change (Lancet. 2020 Feb 3. doi: 10.106/S2213-8587(20)30031-0).

They also emphasized that the links between obesity and cancer, like those between obesity and other diseases such as diabetes, underscore the fact that noncommunicable diseases do not exist in isolation, and that tackling them requires bold action, a consolidated approach, and elimination of the environmental and social factors driving the epidemic.

The study was limited by a number of factors, including the lack of data on lifestyle factors, underrepresentation of some ethnicities, and lack of data on BMI and medical comorbidities at the time of cancer diagnosis. However, strengths of the study include the systematic data collection, narrow range of age at study entry, strict control of coexisting conditions, and high statistical power, which strengthen the generalizability of the results, the investigators said, concluding, therefore, that “[c]urrent trends of rising BMI among adolescents could constitute an important intervention target for cancer prevention.”

The authors reported having no disclosures.

sworcester@mdedge.com

SOURCE: Furer A et al. Lancet Diabetes Endocrinol. 2020 Feb 3. doi: 10.1016/S2213-8587(20)30019-X.

Obesity during adolescence is associated with increased midlife cancer risk, according to findings from a large population-based cohort of Israeli teens examined between 1967 and 2010.

The association, which was stronger in individuals in the later period of the cohort than in those in the earlier years, suggests that the burden of obesity-related cancers might increase over time, given the increasing prevalence of adolescent obesity, wrote Ariel Furer, MD, of Israel Defense Forces Medical Corps, Ramat Gan, and colleagues. Their report is in The Lancet.

Obesity is a known causal factor for several types of cancer, but most studies have looked at middle-age or older individuals and had relatively short follow-up, and period effects are rarely assessed, the investigators said, noting that “the attributable burden of obesity-related cancer was previously calculated with an unverified assumption that the association remained unchanged over time.

“In contrast to this paucity of knowledge, the prevalence of youth obesity – particularly severe obesity – has increased worldwide, which parallels the rise in youth cancer incidence,” they wrote.

To address this paucity of data, the researchers reviewed medical and sociodemographic data for adolescents who were assessed at age 17 years for medical eligibility for mandatory military service, and linked that information with data from the National Cancer Registry to create a unified file. The primary study outcome was any cancer diagnosis between Jan. 1, 1967, and Dec. 31, 2012, and a secondary endpoint was all-cause mortality through Dec. 31, 2017, among those who developed cancer.

Among nearly 2.3 million participating adolescents who were evaluated for associations between body mass index at age 17 years and later cancer incidence, 1,370,020 were men with more than 29.5 million person-years of follow-up, and 928,110 were women with more than 18 million person-years of follow-up. The numbers of incident cancer cases in the men and women were 26,353 and 29,488, and the mean ages at diagnosis were 43.2 and 40.0 years, respectively, the investigators reported (Lancet. 2020 Feb 3. doi: 10.1016/S2213-8587(20)30019-X).

Adolescent obesity in men was significantly associated with midlife cancer incidence (hazard ratio, 1.26), but in women, no association was seen due to the previously reported inverse associations between obesity and cervical and breast cancers, they said.

However, when those cancers were excluded for women, the adjusted hazard ratio was similar to that for men (HR, 1.27).

Cancer incidence in both men and women increased gradually across BMI percentiles, and for both sexes, overweight BMI was associated with an increased cancer risk after 10 years of follow-up (HR, 1.14 for men, 1.22 for women after exclusion of cervical and breast cancer). Therefore, in some cases the increased cancer risk in those who were overweight as teens was evident before age 30 years, the authors noted.

Further, BMI was positively associated with greater mortality risk. For men, 5-year survival rates were 75.2% in those with adolescent BMI in the 5th-49th percentile, compared with 72.2% in those with BMI in the obesity range (95th percentile or greater), and the corresponding rates in women were 89.3% and 83.1% (HR, 1.33 and 1.89, respectively).

Of note, the investigators identified a period effect. That is, after stratification by enrollment period/cancer recording period (1967-1981/1982-1996 vs. 1982-1996/1997-2011), a stronger association was noted in individuals who entered the study during the later period, compared with those who entered in the early period (HR, 1.36 vs. 1.13; adjusted HR, 1.11 vs. 1.07 per 5 kg/m²). Possible mechanisms for this finding include environmental and nutritional factors, increased use of medical services, and changes in early cancer screening techniques, but further study is needed to verify the trend and “refine the exact nature of carcinogenic elements, compared with earlier periods,” they said.

Also of note, some cancers that were not associated with BMI in the early period, including stomach cancer, non-Hodgkin lymphoma, thyroid cancer, and colorectal and oral cavity cancers, became significantly associated with BMI in the late period.

“The projected population attributable risk percentage, using 2017 prevalence data of high BMI, was 5.1% for any cancer in men and 5.7% for cancers other than breast and cervical in women,” the researchers wrote, noting that this “is probably an underestimation, given the accentuation of the BMI-cancer association and the rapid increase in adolescent obesity prevalence within the past decade in Israel and worldwide.”

In an accompanying editorial, the journal editors noted that the findings by Dr. Furer and colleagues highlight the need to tackle obesity early in life and the need for obesity prevention strategies to reduce cancer incidence and mortality for those cancers that can be prevented by lifestyle modifications. They added, however, that care would be needed to avoid stigmatizing those with obesity, as obesity itself is a “multifactorial condition driven by social injustice and health inequalities” that most often affect those who are least able to implement lifestyle change (Lancet. 2020 Feb 3. doi: 10.106/S2213-8587(20)30031-0).

They also emphasized that the links between obesity and cancer, like those between obesity and other diseases such as diabetes, underscore the fact that noncommunicable diseases do not exist in isolation, and that tackling them requires bold action, a consolidated approach, and elimination of the environmental and social factors driving the epidemic.

The study was limited by a number of factors, including the lack of data on lifestyle factors, underrepresentation of some ethnicities, and lack of data on BMI and medical comorbidities at the time of cancer diagnosis. However, strengths of the study include the systematic data collection, narrow range of age at study entry, strict control of coexisting conditions, and high statistical power, which strengthen the generalizability of the results, the investigators said, concluding, therefore, that “[c]urrent trends of rising BMI among adolescents could constitute an important intervention target for cancer prevention.”

The authors reported having no disclosures.

sworcester@mdedge.com

SOURCE: Furer A et al. Lancet Diabetes Endocrinol. 2020 Feb 3. doi: 10.1016/S2213-8587(20)30019-X.

The dermMentors™ Resident of Distinction Award™ recognizes top residents in dermatology. DermMentors.org and the dermMentors™ Resident of Distinction Award™ are sponsored by Beiersdorf Inc and administered by DermEd, Inc. The 2020 dermMentors™ Residents of Distinction™ presented new scientific research during the general sessions of the 19th Annual Caribbean Dermatology Symposium on January 25, 2020.

Overall Grand Prize
Topical Imiquimod in Combination With Brachytherapy for Unresectable Cutaneous Melanoma Metastases

Jennifer E. Yeh, MD, PhD, Department of Dermatology, Brigham and Women’s Hospital, Boston, Massachusetts; Marilyn T. Wan, MBChB, Department of Dermatology, Brigham and Women’s Hospital, Boston, Massachusetts; Allireza Alloo, MD, Department of Dermatology, Northwell Health, Lake Success, New York; Nageatte Ibrahim, MD, Dana-Farber Cancer Institute, Melanoma Program, Boston, Massachusetts; Phillip M. Devlin, MD, Dana-Farber Cancer Institute, Melanoma Program, Boston, Massachusetts; Patrick A. Ott, MD, PhD, Dana-Farber Cancer Institute, Melanoma Program, Boston, Massachusetts; Jennifer Y. Lin MD, Department of Dermatology, Brigham and Women’s Hospital, Boston, Massachusetts, and Dana-Farber Cancer Institute, Melanoma Program, Boston, Massachusetts 
Disclosures: None. 

Background

Case Presentation
Three patients with scalp melanoma initially treated with wide local excision and found to have negative sentinel lymph node biopsy presented with scalp lesions adjacent to the initial melanoma consistent with in-transit metastases. Given the presence of multiple metastatic lesions including 1 patient with numerous cutaneous metastases on reconstructed skin, each patient was treated with brachytherapy (5 fractions of 600 cGy over 2 to 3 weeks), followed by imiquimod cream 5% for 12 weeks. One patient’s excision showed residual melanoma as close as 1.4 mm to the nearest margin. All 3 patients achieved complete response and have been disease free for more than 2 years. Adverse effects were limited to pruritus and low-grade dermatitis. Of note, 2 patients later developed distant metastases that subsequently resolved with systemic immunotherapy. 

Conclusions
While surgical excision is the first-line treatment of single, discrete cutaneous metastases, it may not be practical in patients with multiple foci of disease distributed over large areas, as seen in the 3 patients presented here who achieved complete resolution of their cutaneous metastatic burden with concurrent topical imiquimod and brachytherapy. Brachytherapy may be especially beneficial for cutaneous metastases on complex surfaces such as the scalp, reducing excessive brain irradiation by using moldable applicators that allow precise targeting. Moreover, one of the cases presented here suggests that brachytherapy may have utility for close-margin excisions. Although further investigations using larger patient cohorts are needed to determine the reproducibility of our findings, concomitant use of topical imiquimod and brachytherapy may represent a promising strategy for control of cutaneous melanoma metastases.

Up next: Burden of Common Skin Diseases in the Caribbean

Burden of Common Skin Diseases in the Caribbean and Potential Correlation With Socioeconomics

Rachel Giesey, DO, Case Western Reserve University, Cleveland, Ohio, and University Hospitals Cleveland Medical Center, Cleveland, Ohio
Disclosures: None. 

Objective
This observational study aims to measure the burden of common skin diseases in the Caribbean and the potential relationship with a country’s socioeconomic status.
 
Methods
For this study, we selected Global Burden of Disease Study (GBD) data sets analyzing the most recent DALYs of the most common dermatoses in 2017 among 18 Caribbean countries, along with the Caribbean as a region, and the United States for comparison. Three categories of dermatoses were analyzed by country: neoplastic, infectious, and inflammatory. Each country was assigned a ranking from 1 (highest DALYs) to 20 (lowest DALYs) for each disease. The principal country-level economic factor used to measure socioeconomic status was gross domestic product (GDP) per capita in 2017 from the International Monetary Fund and the World Bank. Statistical analysis of correlations between country wealth and disease was performed using a 2-tailed linear regression. Level of significance was set at P<.05.

Results
Countries were ordered by column from left (least wealthy) to right (most wealthy). To generate a heat table, the countries were ranked by DALYs (ranging from 1 [highest disease burden] to 20 [lowest burden]) for each skin disease. There was a statistically significant inverse relationship between country wealth and cutaneous neoplasms (melanoma, nonmelanoma skin cancers, and lip/oral cancers), as well as some inflammatory dermatoses (contact dermatitis, psoriasis, and pruritus). In contrast, there was a statistically significant positive correlation between country wealth and dermatology-related infectious diseases (scabies, viral skin infections, syphilis, human immunodeficiency virus/AIDS, and tuberculosis) and some other inflammatory dermatoses (urticaria, asthma, and atopic dermatitis). 

Conclusion
Dermatologists interested in a particular disease may elect to focus time and resources in a Caribbean country with the highest respective DALYs, or dermatologists interested in traveling to a particular country may find the most impactful and sustainable interventions by focusing on the dermatoses with highest DALYs in that country. The relationship between GDP and health expenditure on dermatologic disease is complex, and the influence of income levels on this causal relationship is unclear. Further work is necessary to more consistently assess the impact of income on common dermatoses in low- and middle-income countries across the globe.

Up next: Doxycycline for LPP and FFA

The Use of Doxycycline in Lichen Planopilaris and Frontal Fibrosing Alopecia: A Retrospective Study of 138 Patients at a Tertiary Referral Clinic

Janice Tiao, MD; Lynne J. Goldberg, MD, Department of Dermatology, Boston University Medical Center, Boston, Massachusetts 
Disclosures: None. 

Methods
After obtaining institutional review board approval, the authors reviewed the medical records of 138 patients with LPP and FFA who presented to the outpatient specialty hair clinic at Boston University Medical Center from 2015-2017. 

Results
Of 138 subjects, 1 was excluded because there was no electronic medical record on file. Thirty-one subjects had a diagnosis of LPP, 103 had a diagnosis of FFA, and 3 were diagnosed with both LPP and FFA. Of the 31 LPP-only subjects, 16 had been prescribed doxycycline for their condition. Of these subjects, 9 (56.3%) reported or were observed to improve or stabilize, 2 (12.5%) did not improve, and 5 (31.3%) had unclear response or were lost to follow-up. Of the 106 subjects with FFA, 40 had been prescribed doxycycline for their condition. Of these 40 subjects, 17 (42.5%) were felt to improve or stabilize, 7 (17.5%) did not improve, and 15 (37.5%) had unclear response or were lost to follow-up. The average duration of use was 8 months. Of note, 14 of 56 (25%) subjects who took doxycycline discontinued the medication secondary to side effects, most commonly gastrointestinal.

Conclusion
Although a number of subjects did not tolerate the medication, the data confirm that doxycycline may be helpful in the treatment of LPP and FFA.

References

1. Bolduc C, Sperling LC, Shapiro J. Primary cicatricial alopecia. J Am Acad Dermatol. 2016;75:1081-1099.
2. Ochoa BE, King LE, Price VH. Lichen planopilaris: annual incidence in four hair referral centers in the United States. J Am Acad Dermatol. 2008;58:352-353.
3. Errichetti E, Figini M, Croatto M, et al. Therapeutic management of classic lichen planopilaris: a systematic review. Clin Cosmet Investig Dermatol. 2018;11:91-102.
4. Spencer LA, Hawryluk EB, English JC. Lichen planopilaris: Retrospective study and stepwise therapeutic approach. Arch Dermatol. 2009;45:333-334.
5. Lyakhovitsky A, Amichai B, Sizopoulou C, et al. A case series of 46 patients with lichen planopilaris: demographics, clinical evaluation, and treatment experience. J Dermatolog Treat. 2015;26:275-279.
6. Samrao A, Chew A-I, Price V. Frontal fibrosing alopecia: a clinical review of 36 patients. Br J Dermatol. 2010;163:1296-1300.

Up next: Counterfeits and Medical Spas

Counterfeits and Medical Spas in Dermatology: A Call for Patient Safety 

Jordan V. Wang, MD, MBE, MBA, Thomas Jefferson University, Philadelphia, Pennsylvania 
Disclosures: None. 

Medical Spas 
Medical spas have experienced a recent rise in popularity by consumers. They can offer various aesthetic procedures, including neurotoxins, fillers, and lasers and light devices. Oftentimes their prices are marketed as lower than those directly from physician-based practices. Rules and regulations, especially concerning their oversight and credentialing processes, vary from state to state. Unfortunately, many patients have experienced various complications from medical spas. Shedding more light on the current state of medical spas and their complications in dermatology can help to increase awareness and lead to improved patient safety. Our recent survey of aesthetic practitioners demonstrated that patients who have experienced complications from medical spas are frequently encountered. For example, of all cosmetic complications encountered in the past 2 years, the majority reported that the percentage of complications seen in their practice attributable to medical spas ranged from 61% to 100%. The most commonly cited complications from medical spas were burns, discoloration, and misuse of product, while the most commonly cited treatments resulting in complications were fillers, intense pulsed light, and laser hair removal. For safety and outcomes, medical spas were rated as inferior to physician-based practices. Practitioners believed medical spas to be endangering patients, desired stricter rules and regulations, and requested more support from medical societies.

Up next: Online Reviews of Minimally and Noninvasive Cosmetic Procedures

Lessons From Unfavorable Online Reviews of Minimally and Noninvasive Cosmetic Procedures

Jacqueline D. Watchmaker, MD, Boston University School of Medicine, Boston, Massachusetts 
Disclosures: None. 

Methods
Between June 2019 and July 2019, the authors extracted patient-reported outcome data from RealSelf.com for the following treatments: Coolsculpting, Ultherapy, Kybella injections, miraDry, Thermage, Cellfina, Emsculpt, and thread-lifts. On the RealSelf website, patients are able to rate their aesthetic procedure as “worth it”, “not sure” or “not worth it”; only data from “not worth it” reviews were extracted for this study. In total, there were 1359 reviews. Reviews from outside the United States were excluded. If a patient listed 2 reasons for dissatisfaction (eg, complication and ineffective treatment) both reasons were recorded. Specific complications and postoperative time frame of review, when listed, were recorded. 
 
Results
In total, 1204 reviews were included in the analysis. The most frequent reason for patient dissatisfaction was ineffectiveness for Coolsculpting (n=427, 82.9%), Ultherapy (n=120, 67.8%), Kybella (n=55, 75.3%), miraDry (n=40, 85.1%), Thermage (n=81, 61.4%), Cellfina (n=18, 78.3%), and Emsculpt (n=5, 100%), with complications listed as the second most common reason for discontent. For thread-lifts, however, the most common reason for a “not worth it” rating was a complication (n=43, 70.5%) followed by perceived ineffectiveness (n=36, 59%). Severe pain during and/or after the procedure was the most common patient-reported complication for Coolsculpting (n=62, 37.3%) and thread-lifts (n=10, 23.3%). Perceived fat loss was the most common side effect for Ultherapy (n=32, 38.6%) and Thermage (n=26, 40%), with swelling, numbness, new-onset “lumps,” and flatter buttock muscles as the most common patient-reported complications for Kybella (n=9, 40.9%), miraDry (n=6, 27.3%), Cellfina (n=6, 46.2%), and Emsculpt (n=1, 100%). 

Discussion
Our study shows that perceived ineffectiveness and complications were the most common reasons for dissatisfaction of the minimally and noninvasive cosmetic procedures analyzed. Knowing the most common patient-reported complaints of a given procedure can help physicians counsel and educate patients prior to a procedure. Many of the patient-reported complications found in this study are known and unfortunate true potential complications; it is important to note, however, that many dissatisfied patients listed an expected side effect such as pain, bruising, or swelling, rather than a true complication as their reason for discontent. More thorough preprocedure education may help patients differentiate between a true complication and a transient and expected side effect that in turn may improve patient satisfaction. In the modern era of social media and online reviews, a positive patient perspective on an aesthetic treatment is increasingly important. Patient dissatisfaction due to true complications and ineffective treatment cannot be completely prevented; however, by learning from the negative patient-reported outcomes as detailed in this study, physicians can work toward improving the patient experience. 

The dermMentors™ Resident of Distinction Award™ recognizes top residents in dermatology. DermMentors.org and the dermMentors™ Resident of Distinction Award™ are sponsored by Beiersdorf Inc and administered by DermEd, Inc. The 2020 dermMentors™ Residents of Distinction™ presented new scientific research during the general sessions of the 19th Annual Caribbean Dermatology Symposium on January 25, 2020.

Overall Grand Prize
Topical Imiquimod in Combination With Brachytherapy for Unresectable Cutaneous Melanoma Metastases

Jennifer E. Yeh, MD, PhD, Department of Dermatology, Brigham and Women’s Hospital, Boston, Massachusetts; Marilyn T. Wan, MBChB, Department of Dermatology, Brigham and Women’s Hospital, Boston, Massachusetts; Allireza Alloo, MD, Department of Dermatology, Northwell Health, Lake Success, New York; Nageatte Ibrahim, MD, Dana-Farber Cancer Institute, Melanoma Program, Boston, Massachusetts; Phillip M. Devlin, MD, Dana-Farber Cancer Institute, Melanoma Program, Boston, Massachusetts; Patrick A. Ott, MD, PhD, Dana-Farber Cancer Institute, Melanoma Program, Boston, Massachusetts; Jennifer Y. Lin MD, Department of Dermatology, Brigham and Women’s Hospital, Boston, Massachusetts, and Dana-Farber Cancer Institute, Melanoma Program, Boston, Massachusetts 
Disclosures: None. 

Background

Case Presentation
Three patients with scalp melanoma initially treated with wide local excision and found to have negative sentinel lymph node biopsy presented with scalp lesions adjacent to the initial melanoma consistent with in-transit metastases. Given the presence of multiple metastatic lesions including 1 patient with numerous cutaneous metastases on reconstructed skin, each patient was treated with brachytherapy (5 fractions of 600 cGy over 2 to 3 weeks), followed by imiquimod cream 5% for 12 weeks. One patient’s excision showed residual melanoma as close as 1.4 mm to the nearest margin. All 3 patients achieved complete response and have been disease free for more than 2 years. Adverse effects were limited to pruritus and low-grade dermatitis. Of note, 2 patients later developed distant metastases that subsequently resolved with systemic immunotherapy. 

Conclusions
While surgical excision is the first-line treatment of single, discrete cutaneous metastases, it may not be practical in patients with multiple foci of disease distributed over large areas, as seen in the 3 patients presented here who achieved complete resolution of their cutaneous metastatic burden with concurrent topical imiquimod and brachytherapy. Brachytherapy may be especially beneficial for cutaneous metastases on complex surfaces such as the scalp, reducing excessive brain irradiation by using moldable applicators that allow precise targeting. Moreover, one of the cases presented here suggests that brachytherapy may have utility for close-margin excisions. Although further investigations using larger patient cohorts are needed to determine the reproducibility of our findings, concomitant use of topical imiquimod and brachytherapy may represent a promising strategy for control of cutaneous melanoma metastases.

Up next: Burden of Common Skin Diseases in the Caribbean

Burden of Common Skin Diseases in the Caribbean and Potential Correlation With Socioeconomics

Rachel Giesey, DO, Case Western Reserve University, Cleveland, Ohio, and University Hospitals Cleveland Medical Center, Cleveland, Ohio
Disclosures: None. 

Objective
This observational study aims to measure the burden of common skin diseases in the Caribbean and the potential relationship with a country’s socioeconomic status.
 
Methods
For this study, we selected Global Burden of Disease Study (GBD) data sets analyzing the most recent DALYs of the most common dermatoses in 2017 among 18 Caribbean countries, along with the Caribbean as a region, and the United States for comparison. Three categories of dermatoses were analyzed by country: neoplastic, infectious, and inflammatory. Each country was assigned a ranking from 1 (highest DALYs) to 20 (lowest DALYs) for each disease. The principal country-level economic factor used to measure socioeconomic status was gross domestic product (GDP) per capita in 2017 from the International Monetary Fund and the World Bank. Statistical analysis of correlations between country wealth and disease was performed using a 2-tailed linear regression. Level of significance was set at P<.05.

Results
Countries were ordered by column from left (least wealthy) to right (most wealthy). To generate a heat table, the countries were ranked by DALYs (ranging from 1 [highest disease burden] to 20 [lowest burden]) for each skin disease. There was a statistically significant inverse relationship between country wealth and cutaneous neoplasms (melanoma, nonmelanoma skin cancers, and lip/oral cancers), as well as some inflammatory dermatoses (contact dermatitis, psoriasis, and pruritus). In contrast, there was a statistically significant positive correlation between country wealth and dermatology-related infectious diseases (scabies, viral skin infections, syphilis, human immunodeficiency virus/AIDS, and tuberculosis) and some other inflammatory dermatoses (urticaria, asthma, and atopic dermatitis). 

Conclusion
Dermatologists interested in a particular disease may elect to focus time and resources in a Caribbean country with the highest respective DALYs, or dermatologists interested in traveling to a particular country may find the most impactful and sustainable interventions by focusing on the dermatoses with highest DALYs in that country. The relationship between GDP and health expenditure on dermatologic disease is complex, and the influence of income levels on this causal relationship is unclear. Further work is necessary to more consistently assess the impact of income on common dermatoses in low- and middle-income countries across the globe.

Up next: Doxycycline for LPP and FFA

The Use of Doxycycline in Lichen Planopilaris and Frontal Fibrosing Alopecia: A Retrospective Study of 138 Patients at a Tertiary Referral Clinic

Janice Tiao, MD; Lynne J. Goldberg, MD, Department of Dermatology, Boston University Medical Center, Boston, Massachusetts 
Disclosures: None. 

Methods
After obtaining institutional review board approval, the authors reviewed the medical records of 138 patients with LPP and FFA who presented to the outpatient specialty hair clinic at Boston University Medical Center from 2015-2017. 

Results
Of 138 subjects, 1 was excluded because there was no electronic medical record on file. Thirty-one subjects had a diagnosis of LPP, 103 had a diagnosis of FFA, and 3 were diagnosed with both LPP and FFA. Of the 31 LPP-only subjects, 16 had been prescribed doxycycline for their condition. Of these subjects, 9 (56.3%) reported or were observed to improve or stabilize, 2 (12.5%) did not improve, and 5 (31.3%) had unclear response or were lost to follow-up. Of the 106 subjects with FFA, 40 had been prescribed doxycycline for their condition. Of these 40 subjects, 17 (42.5%) were felt to improve or stabilize, 7 (17.5%) did not improve, and 15 (37.5%) had unclear response or were lost to follow-up. The average duration of use was 8 months. Of note, 14 of 56 (25%) subjects who took doxycycline discontinued the medication secondary to side effects, most commonly gastrointestinal.

Conclusion
Although a number of subjects did not tolerate the medication, the data confirm that doxycycline may be helpful in the treatment of LPP and FFA.

References

1. Bolduc C, Sperling LC, Shapiro J. Primary cicatricial alopecia. J Am Acad Dermatol. 2016;75:1081-1099.
2. Ochoa BE, King LE, Price VH. Lichen planopilaris: annual incidence in four hair referral centers in the United States. J Am Acad Dermatol. 2008;58:352-353.
3. Errichetti E, Figini M, Croatto M, et al. Therapeutic management of classic lichen planopilaris: a systematic review. Clin Cosmet Investig Dermatol. 2018;11:91-102.
4. Spencer LA, Hawryluk EB, English JC. Lichen planopilaris: Retrospective study and stepwise therapeutic approach. Arch Dermatol. 2009;45:333-334.
5. Lyakhovitsky A, Amichai B, Sizopoulou C, et al. A case series of 46 patients with lichen planopilaris: demographics, clinical evaluation, and treatment experience. J Dermatolog Treat. 2015;26:275-279.
6. Samrao A, Chew A-I, Price V. Frontal fibrosing alopecia: a clinical review of 36 patients. Br J Dermatol. 2010;163:1296-1300.

Up next: Counterfeits and Medical Spas

Counterfeits and Medical Spas in Dermatology: A Call for Patient Safety 

Jordan V. Wang, MD, MBE, MBA, Thomas Jefferson University, Philadelphia, Pennsylvania 
Disclosures: None. 

Medical Spas 
Medical spas have experienced a recent rise in popularity by consumers. They can offer various aesthetic procedures, including neurotoxins, fillers, and lasers and light devices. Oftentimes their prices are marketed as lower than those directly from physician-based practices. Rules and regulations, especially concerning their oversight and credentialing processes, vary from state to state. Unfortunately, many patients have experienced various complications from medical spas. Shedding more light on the current state of medical spas and their complications in dermatology can help to increase awareness and lead to improved patient safety. Our recent survey of aesthetic practitioners demonstrated that patients who have experienced complications from medical spas are frequently encountered. For example, of all cosmetic complications encountered in the past 2 years, the majority reported that the percentage of complications seen in their practice attributable to medical spas ranged from 61% to 100%. The most commonly cited complications from medical spas were burns, discoloration, and misuse of product, while the most commonly cited treatments resulting in complications were fillers, intense pulsed light, and laser hair removal. For safety and outcomes, medical spas were rated as inferior to physician-based practices. Practitioners believed medical spas to be endangering patients, desired stricter rules and regulations, and requested more support from medical societies.

Up next: Online Reviews of Minimally and Noninvasive Cosmetic Procedures

Lessons From Unfavorable Online Reviews of Minimally and Noninvasive Cosmetic Procedures

Jacqueline D. Watchmaker, MD, Boston University School of Medicine, Boston, Massachusetts 
Disclosures: None. 

Methods
Between June 2019 and July 2019, the authors extracted patient-reported outcome data from RealSelf.com for the following treatments: Coolsculpting, Ultherapy, Kybella injections, miraDry, Thermage, Cellfina, Emsculpt, and thread-lifts. On the RealSelf website, patients are able to rate their aesthetic procedure as “worth it”, “not sure” or “not worth it”; only data from “not worth it” reviews were extracted for this study. In total, there were 1359 reviews. Reviews from outside the United States were excluded. If a patient listed 2 reasons for dissatisfaction (eg, complication and ineffective treatment) both reasons were recorded. Specific complications and postoperative time frame of review, when listed, were recorded. 
 
Results
In total, 1204 reviews were included in the analysis. The most frequent reason for patient dissatisfaction was ineffectiveness for Coolsculpting (n=427, 82.9%), Ultherapy (n=120, 67.8%), Kybella (n=55, 75.3%), miraDry (n=40, 85.1%), Thermage (n=81, 61.4%), Cellfina (n=18, 78.3%), and Emsculpt (n=5, 100%), with complications listed as the second most common reason for discontent. For thread-lifts, however, the most common reason for a “not worth it” rating was a complication (n=43, 70.5%) followed by perceived ineffectiveness (n=36, 59%). Severe pain during and/or after the procedure was the most common patient-reported complication for Coolsculpting (n=62, 37.3%) and thread-lifts (n=10, 23.3%). Perceived fat loss was the most common side effect for Ultherapy (n=32, 38.6%) and Thermage (n=26, 40%), with swelling, numbness, new-onset “lumps,” and flatter buttock muscles as the most common patient-reported complications for Kybella (n=9, 40.9%), miraDry (n=6, 27.3%), Cellfina (n=6, 46.2%), and Emsculpt (n=1, 100%). 

Discussion
Our study shows that perceived ineffectiveness and complications were the most common reasons for dissatisfaction of the minimally and noninvasive cosmetic procedures analyzed. Knowing the most common patient-reported complaints of a given procedure can help physicians counsel and educate patients prior to a procedure. Many of the patient-reported complications found in this study are known and unfortunate true potential complications; it is important to note, however, that many dissatisfied patients listed an expected side effect such as pain, bruising, or swelling, rather than a true complication as their reason for discontent. More thorough preprocedure education may help patients differentiate between a true complication and a transient and expected side effect that in turn may improve patient satisfaction. In the modern era of social media and online reviews, a positive patient perspective on an aesthetic treatment is increasingly important. Patient dissatisfaction due to true complications and ineffective treatment cannot be completely prevented; however, by learning from the negative patient-reported outcomes as detailed in this study, physicians can work toward improving the patient experience. 

The dermMentors™ Resident of Distinction Award™ recognizes top residents in dermatology. DermMentors.org and the dermMentors™ Resident of Distinction Award™ are sponsored by Beiersdorf Inc and administered by DermEd, Inc. The 2020 dermMentors™ Residents of Distinction™ presented new scientific research during the general sessions of the 19th Annual Caribbean Dermatology Symposium on January 25, 2020.

Overall Grand Prize
Topical Imiquimod in Combination With Brachytherapy for Unresectable Cutaneous Melanoma Metastases

Jennifer E. Yeh, MD, PhD, Department of Dermatology, Brigham and Women’s Hospital, Boston, Massachusetts; Marilyn T. Wan, MBChB, Department of Dermatology, Brigham and Women’s Hospital, Boston, Massachusetts; Allireza Alloo, MD, Department of Dermatology, Northwell Health, Lake Success, New York; Nageatte Ibrahim, MD, Dana-Farber Cancer Institute, Melanoma Program, Boston, Massachusetts; Phillip M. Devlin, MD, Dana-Farber Cancer Institute, Melanoma Program, Boston, Massachusetts; Patrick A. Ott, MD, PhD, Dana-Farber Cancer Institute, Melanoma Program, Boston, Massachusetts; Jennifer Y. Lin MD, Department of Dermatology, Brigham and Women’s Hospital, Boston, Massachusetts, and Dana-Farber Cancer Institute, Melanoma Program, Boston, Massachusetts 
Disclosures: None. 

Background

Case Presentation
Three patients with scalp melanoma initially treated with wide local excision and found to have negative sentinel lymph node biopsy presented with scalp lesions adjacent to the initial melanoma consistent with in-transit metastases. Given the presence of multiple metastatic lesions including 1 patient with numerous cutaneous metastases on reconstructed skin, each patient was treated with brachytherapy (5 fractions of 600 cGy over 2 to 3 weeks), followed by imiquimod cream 5% for 12 weeks. One patient’s excision showed residual melanoma as close as 1.4 mm to the nearest margin. All 3 patients achieved complete response and have been disease free for more than 2 years. Adverse effects were limited to pruritus and low-grade dermatitis. Of note, 2 patients later developed distant metastases that subsequently resolved with systemic immunotherapy. 

Conclusions
While surgical excision is the first-line treatment of single, discrete cutaneous metastases, it may not be practical in patients with multiple foci of disease distributed over large areas, as seen in the 3 patients presented here who achieved complete resolution of their cutaneous metastatic burden with concurrent topical imiquimod and brachytherapy. Brachytherapy may be especially beneficial for cutaneous metastases on complex surfaces such as the scalp, reducing excessive brain irradiation by using moldable applicators that allow precise targeting. Moreover, one of the cases presented here suggests that brachytherapy may have utility for close-margin excisions. Although further investigations using larger patient cohorts are needed to determine the reproducibility of our findings, concomitant use of topical imiquimod and brachytherapy may represent a promising strategy for control of cutaneous melanoma metastases.

Up next: Burden of Common Skin Diseases in the Caribbean

Burden of Common Skin Diseases in the Caribbean and Potential Correlation With Socioeconomics

Rachel Giesey, DO, Case Western Reserve University, Cleveland, Ohio, and University Hospitals Cleveland Medical Center, Cleveland, Ohio
Disclosures: None. 

Objective
This observational study aims to measure the burden of common skin diseases in the Caribbean and the potential relationship with a country’s socioeconomic status.
 
Methods
For this study, we selected Global Burden of Disease Study (GBD) data sets analyzing the most recent DALYs of the most common dermatoses in 2017 among 18 Caribbean countries, along with the Caribbean as a region, and the United States for comparison. Three categories of dermatoses were analyzed by country: neoplastic, infectious, and inflammatory. Each country was assigned a ranking from 1 (highest DALYs) to 20 (lowest DALYs) for each disease. The principal country-level economic factor used to measure socioeconomic status was gross domestic product (GDP) per capita in 2017 from the International Monetary Fund and the World Bank. Statistical analysis of correlations between country wealth and disease was performed using a 2-tailed linear regression. Level of significance was set at P<.05.

Results
Countries were ordered by column from left (least wealthy) to right (most wealthy). To generate a heat table, the countries were ranked by DALYs (ranging from 1 [highest disease burden] to 20 [lowest burden]) for each skin disease. There was a statistically significant inverse relationship between country wealth and cutaneous neoplasms (melanoma, nonmelanoma skin cancers, and lip/oral cancers), as well as some inflammatory dermatoses (contact dermatitis, psoriasis, and pruritus). In contrast, there was a statistically significant positive correlation between country wealth and dermatology-related infectious diseases (scabies, viral skin infections, syphilis, human immunodeficiency virus/AIDS, and tuberculosis) and some other inflammatory dermatoses (urticaria, asthma, and atopic dermatitis). 

Conclusion
Dermatologists interested in a particular disease may elect to focus time and resources in a Caribbean country with the highest respective DALYs, or dermatologists interested in traveling to a particular country may find the most impactful and sustainable interventions by focusing on the dermatoses with highest DALYs in that country. The relationship between GDP and health expenditure on dermatologic disease is complex, and the influence of income levels on this causal relationship is unclear. Further work is necessary to more consistently assess the impact of income on common dermatoses in low- and middle-income countries across the globe.

Up next: Doxycycline for LPP and FFA

The Use of Doxycycline in Lichen Planopilaris and Frontal Fibrosing Alopecia: A Retrospective Study of 138 Patients at a Tertiary Referral Clinic

Janice Tiao, MD; Lynne J. Goldberg, MD, Department of Dermatology, Boston University Medical Center, Boston, Massachusetts 
Disclosures: None. 

Methods
After obtaining institutional review board approval, the authors reviewed the medical records of 138 patients with LPP and FFA who presented to the outpatient specialty hair clinic at Boston University Medical Center from 2015-2017. 

Results
Of 138 subjects, 1 was excluded because there was no electronic medical record on file. Thirty-one subjects had a diagnosis of LPP, 103 had a diagnosis of FFA, and 3 were diagnosed with both LPP and FFA. Of the 31 LPP-only subjects, 16 had been prescribed doxycycline for their condition. Of these subjects, 9 (56.3%) reported or were observed to improve or stabilize, 2 (12.5%) did not improve, and 5 (31.3%) had unclear response or were lost to follow-up. Of the 106 subjects with FFA, 40 had been prescribed doxycycline for their condition. Of these 40 subjects, 17 (42.5%) were felt to improve or stabilize, 7 (17.5%) did not improve, and 15 (37.5%) had unclear response or were lost to follow-up. The average duration of use was 8 months. Of note, 14 of 56 (25%) subjects who took doxycycline discontinued the medication secondary to side effects, most commonly gastrointestinal.

Conclusion
Although a number of subjects did not tolerate the medication, the data confirm that doxycycline may be helpful in the treatment of LPP and FFA.

References

1. Bolduc C, Sperling LC, Shapiro J. Primary cicatricial alopecia. J Am Acad Dermatol. 2016;75:1081-1099.
2. Ochoa BE, King LE, Price VH. Lichen planopilaris: annual incidence in four hair referral centers in the United States. J Am Acad Dermatol. 2008;58:352-353.
3. Errichetti E, Figini M, Croatto M, et al. Therapeutic management of classic lichen planopilaris: a systematic review. Clin Cosmet Investig Dermatol. 2018;11:91-102.
4. Spencer LA, Hawryluk EB, English JC. Lichen planopilaris: Retrospective study and stepwise therapeutic approach. Arch Dermatol. 2009;45:333-334.
5. Lyakhovitsky A, Amichai B, Sizopoulou C, et al. A case series of 46 patients with lichen planopilaris: demographics, clinical evaluation, and treatment experience. J Dermatolog Treat. 2015;26:275-279.
6. Samrao A, Chew A-I, Price V. Frontal fibrosing alopecia: a clinical review of 36 patients. Br J Dermatol. 2010;163:1296-1300.

Up next: Counterfeits and Medical Spas

Counterfeits and Medical Spas in Dermatology: A Call for Patient Safety 

Jordan V. Wang, MD, MBE, MBA, Thomas Jefferson University, Philadelphia, Pennsylvania 
Disclosures: None. 

Medical Spas 
Medical spas have experienced a recent rise in popularity by consumers. They can offer various aesthetic procedures, including neurotoxins, fillers, and lasers and light devices. Oftentimes their prices are marketed as lower than those directly from physician-based practices. Rules and regulations, especially concerning their oversight and credentialing processes, vary from state to state. Unfortunately, many patients have experienced various complications from medical spas. Shedding more light on the current state of medical spas and their complications in dermatology can help to increase awareness and lead to improved patient safety. Our recent survey of aesthetic practitioners demonstrated that patients who have experienced complications from medical spas are frequently encountered. For example, of all cosmetic complications encountered in the past 2 years, the majority reported that the percentage of complications seen in their practice attributable to medical spas ranged from 61% to 100%. The most commonly cited complications from medical spas were burns, discoloration, and misuse of product, while the most commonly cited treatments resulting in complications were fillers, intense pulsed light, and laser hair removal. For safety and outcomes, medical spas were rated as inferior to physician-based practices. Practitioners believed medical spas to be endangering patients, desired stricter rules and regulations, and requested more support from medical societies.

Up next: Online Reviews of Minimally and Noninvasive Cosmetic Procedures

Lessons From Unfavorable Online Reviews of Minimally and Noninvasive Cosmetic Procedures

Jacqueline D. Watchmaker, MD, Boston University School of Medicine, Boston, Massachusetts 
Disclosures: None. 

Methods
Between June 2019 and July 2019, the authors extracted patient-reported outcome data from RealSelf.com for the following treatments: Coolsculpting, Ultherapy, Kybella injections, miraDry, Thermage, Cellfina, Emsculpt, and thread-lifts. On the RealSelf website, patients are able to rate their aesthetic procedure as “worth it”, “not sure” or “not worth it”; only data from “not worth it” reviews were extracted for this study. In total, there were 1359 reviews. Reviews from outside the United States were excluded. If a patient listed 2 reasons for dissatisfaction (eg, complication and ineffective treatment) both reasons were recorded. Specific complications and postoperative time frame of review, when listed, were recorded. 
 
Results
In total, 1204 reviews were included in the analysis. The most frequent reason for patient dissatisfaction was ineffectiveness for Coolsculpting (n=427, 82.9%), Ultherapy (n=120, 67.8%), Kybella (n=55, 75.3%), miraDry (n=40, 85.1%), Thermage (n=81, 61.4%), Cellfina (n=18, 78.3%), and Emsculpt (n=5, 100%), with complications listed as the second most common reason for discontent. For thread-lifts, however, the most common reason for a “not worth it” rating was a complication (n=43, 70.5%) followed by perceived ineffectiveness (n=36, 59%). Severe pain during and/or after the procedure was the most common patient-reported complication for Coolsculpting (n=62, 37.3%) and thread-lifts (n=10, 23.3%). Perceived fat loss was the most common side effect for Ultherapy (n=32, 38.6%) and Thermage (n=26, 40%), with swelling, numbness, new-onset “lumps,” and flatter buttock muscles as the most common patient-reported complications for Kybella (n=9, 40.9%), miraDry (n=6, 27.3%), Cellfina (n=6, 46.2%), and Emsculpt (n=1, 100%). 

Discussion
Our study shows that perceived ineffectiveness and complications were the most common reasons for dissatisfaction of the minimally and noninvasive cosmetic procedures analyzed. Knowing the most common patient-reported complaints of a given procedure can help physicians counsel and educate patients prior to a procedure. Many of the patient-reported complications found in this study are known and unfortunate true potential complications; it is important to note, however, that many dissatisfied patients listed an expected side effect such as pain, bruising, or swelling, rather than a true complication as their reason for discontent. More thorough preprocedure education may help patients differentiate between a true complication and a transient and expected side effect that in turn may improve patient satisfaction. In the modern era of social media and online reviews, a positive patient perspective on an aesthetic treatment is increasingly important. Patient dissatisfaction due to true complications and ineffective treatment cannot be completely prevented; however, by learning from the negative patient-reported outcomes as detailed in this study, physicians can work toward improving the patient experience. 

LAHAINA, HAWAII – It’s important to counsel patients about the degree of improvement to expect with noninvasive skin tightening procedures, Nazanin Saedi, MD, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

Many devices are available that can be used for facial skin tightening, “but there are definitely limitations to what we can do noninvasively, and we really need to educate our patients about what we can do so that they have realistic expectations,” said Dr. Saedi, director of laser surgery and cosmetic dermatology at Sidney Kimmel Medical College, Philadelphia.

Treatment with these devices improve skin laxity, and some improve skin texture as well, she said. These devices are not an option for patients who want to have several inches of excess skin removed.

“You have to tell patients that this isn’t a replacement for a face-lift or a mini face-lift,” but patients can expect to see mild and modest improvement, and they’ll continue to see improvement for 3-6 months.

Patient selection is also important. Patients with mild to moderate laxity who do not want to undergo surgery and anesthesia are good candidates, as opposed to those who are older and have thin, sagging skin, Dr. Saedi said, noting that there still is no standard method of defining laxity.

She referred to a recent study illustrating the importance of counseling patients about what to expect. Of the 83 patients in a practice who had undergone microfocused ultrasound treatments and responded to an anonymous survey about the results of treatment, almost 80% reported at least mild improvement (14.5% said the improvement was significant, almost 28% said it was moderate, 37.3% said it was mild, and 20.5% said there was no improvement).

However, although about half (53.1%) reported being satisfied with their results, almost 45% said that the results did not meet their expectations (Lasers Surg Med. 2019;51[6]:495-9).

In an interview at the meeting, Dr. Saedi commented on these results and the importance of counseling.

Listen to the interview by clicking the play button at the end of this story.

During the presentation, Dr. Saedi, who is also codirector of cutaneous surgery in the department of dermatology and cutaneous biology at Sidney Kimmel Medical College, reviewed different technologies used for noninvasive skin tightening, including ablative and fractional laser resurfacing, radiofrequency, and microfocused ultrasound with visualization.

She disclosed serving on the advisory board and/or as a consultant for Aerolase, Alastin, Alma, Cartessa Aesthetics, Cynosure, and Vivo Capital, and that she has equipment from these companies, except for Vivo Capital and Alastin.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

To listen to the interview, click the play button below.
 

emechcatie@mdedge.com

LAHAINA, HAWAII – It’s important to counsel patients about the degree of improvement to expect with noninvasive skin tightening procedures, Nazanin Saedi, MD, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

Many devices are available that can be used for facial skin tightening, “but there are definitely limitations to what we can do noninvasively, and we really need to educate our patients about what we can do so that they have realistic expectations,” said Dr. Saedi, director of laser surgery and cosmetic dermatology at Sidney Kimmel Medical College, Philadelphia.

Treatment with these devices improve skin laxity, and some improve skin texture as well, she said. These devices are not an option for patients who want to have several inches of excess skin removed.

“You have to tell patients that this isn’t a replacement for a face-lift or a mini face-lift,” but patients can expect to see mild and modest improvement, and they’ll continue to see improvement for 3-6 months.

Patient selection is also important. Patients with mild to moderate laxity who do not want to undergo surgery and anesthesia are good candidates, as opposed to those who are older and have thin, sagging skin, Dr. Saedi said, noting that there still is no standard method of defining laxity.

She referred to a recent study illustrating the importance of counseling patients about what to expect. Of the 83 patients in a practice who had undergone microfocused ultrasound treatments and responded to an anonymous survey about the results of treatment, almost 80% reported at least mild improvement (14.5% said the improvement was significant, almost 28% said it was moderate, 37.3% said it was mild, and 20.5% said there was no improvement).

However, although about half (53.1%) reported being satisfied with their results, almost 45% said that the results did not meet their expectations (Lasers Surg Med. 2019;51[6]:495-9).

In an interview at the meeting, Dr. Saedi commented on these results and the importance of counseling.

Listen to the interview by clicking the play button at the end of this story.

During the presentation, Dr. Saedi, who is also codirector of cutaneous surgery in the department of dermatology and cutaneous biology at Sidney Kimmel Medical College, reviewed different technologies used for noninvasive skin tightening, including ablative and fractional laser resurfacing, radiofrequency, and microfocused ultrasound with visualization.

She disclosed serving on the advisory board and/or as a consultant for Aerolase, Alastin, Alma, Cartessa Aesthetics, Cynosure, and Vivo Capital, and that she has equipment from these companies, except for Vivo Capital and Alastin.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

To listen to the interview, click the play button below.
 

emechcatie@mdedge.com

LAHAINA, HAWAII – It’s important to counsel patients about the degree of improvement to expect with noninvasive skin tightening procedures, Nazanin Saedi, MD, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

Many devices are available that can be used for facial skin tightening, “but there are definitely limitations to what we can do noninvasively, and we really need to educate our patients about what we can do so that they have realistic expectations,” said Dr. Saedi, director of laser surgery and cosmetic dermatology at Sidney Kimmel Medical College, Philadelphia.

Treatment with these devices improve skin laxity, and some improve skin texture as well, she said. These devices are not an option for patients who want to have several inches of excess skin removed.

“You have to tell patients that this isn’t a replacement for a face-lift or a mini face-lift,” but patients can expect to see mild and modest improvement, and they’ll continue to see improvement for 3-6 months.

Patient selection is also important. Patients with mild to moderate laxity who do not want to undergo surgery and anesthesia are good candidates, as opposed to those who are older and have thin, sagging skin, Dr. Saedi said, noting that there still is no standard method of defining laxity.

She referred to a recent study illustrating the importance of counseling patients about what to expect. Of the 83 patients in a practice who had undergone microfocused ultrasound treatments and responded to an anonymous survey about the results of treatment, almost 80% reported at least mild improvement (14.5% said the improvement was significant, almost 28% said it was moderate, 37.3% said it was mild, and 20.5% said there was no improvement).

However, although about half (53.1%) reported being satisfied with their results, almost 45% said that the results did not meet their expectations (Lasers Surg Med. 2019;51[6]:495-9).

In an interview at the meeting, Dr. Saedi commented on these results and the importance of counseling.

Listen to the interview by clicking the play button at the end of this story.

During the presentation, Dr. Saedi, who is also codirector of cutaneous surgery in the department of dermatology and cutaneous biology at Sidney Kimmel Medical College, reviewed different technologies used for noninvasive skin tightening, including ablative and fractional laser resurfacing, radiofrequency, and microfocused ultrasound with visualization.

She disclosed serving on the advisory board and/or as a consultant for Aerolase, Alastin, Alma, Cartessa Aesthetics, Cynosure, and Vivo Capital, and that she has equipment from these companies, except for Vivo Capital and Alastin.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

To listen to the interview, click the play button below.
 

emechcatie@mdedge.com

SAN FRANCISCO – Using stereotactic body radiation therapy (SBRT) to stimulate the immune response may boost the efficacy of immunotherapy in metastatic renal cell carcinoma (RCC), results of the RADVAX RCC trial suggest.

Susan London/MDedge News

More than half of patients (56%) who received SBRT plus nivolumab and ipilimumab achieved a response in nonirradiated lesions, but the prespecified threshold for efficacy was not met (70%). Still, the combination was active and well tolerated, and it warrants further investigation, according to Hans J. Hammers, MD, PhD, of the University of Texas, Dallas.

Dr. Hammers presented results from the RADVAX RCC trial at the 2020 Genitourinary Cancers Symposium sponsored by the American Society for Clinical Oncology, ASTRO, and the Society of Urologic Oncology.
 

Study details

The phase 2 trial enrolled 25 patients with metastatic clear-cell RCC. They had at least two metastatic sites, one of which was measurable for response. Forty percent had received at least one prior line of systemic therapy, and 30% had tumors positive for programmed death–ligand 1 expression. Almost a third had not undergone nephrectomy and therefore still had their primary tumor.

Patients received SBRT (50 Gy in five fractions) at one or two sites while also receiving nivolumab and ipilimumab. SBRT was given right after the first of four nivolumab-ipilimumab treatments and was delivered to lesions in the lung (56% of patients), lymph nodes (20%), bone or soft tissue (12%), and kidney (12%). Patients went on to receive maintenance nivolumab monotherapy.

At a median follow-up of 24 months, 56% of patients achieved a response in nonirradiated lesions. All were partial responses.

The 56% response rate fell short of the trial’s predefined efficacy endpoint of 70%. However, “we felt that an increase to around 60% [with the addition of SBRT] would probably be a reasonable signal for this small signal-finding study,” Dr. Hammers said, noting that this would be in line with the increase seen with intratumoral injections of immune stimulators.

“I would say we are not that far off if the numbers are real,” he added. “That certainly needs to be confirmed and expanded. And I’m sure we can make it more intelligent by choosing which tumors we go after because, right now, we are doing it completely blindly.”

The lack of any complete responses is likely explained, in part, by the large share of patients still having their primary tumor, Dr. Hammers said.

The median duration of response was not reached. The median progression-free survival was 8.21 months, and the median overall survival was not reached.

Thirty-six percent of patients experienced grade 3-4 adverse events, all gastrointestinal. Of the two patients (8%) experiencing grade 2 radiation pneumonitis, one was a case of radiation recall. Some patients needed high-dose corticosteroids (40%) and additional immune suppression (28%) for side effect management.

Should SBRT move forward in RCC?

“We feel that the combination of SBRT with dual immune checkpoint inhibition is feasible and associated with an acceptable safety profile,” Dr. Hammers said. “We do see an encouraging antitumor activity that we believe warrants further investigation.”

A proposed RADVAX II trial would assess programmed death–ligand 1 expression across tumor sites using PET. “We would then direct the radiation to the cold [noninflamed] tumors to derive potentially the maximum benefit in the sense of in situ vaccination,” Dr. Hammers explained.

Susan London/MDedge News

Invited discussant Thomas Powles, MD, PhD, of the Barts Cancer Institute in London, questioned whether SBRT plus immunotherapy should move forward in RCC patients. He noted that the abscopal effect was first described in the 1950s, but evidence of its clinical efficacy remains limited and inconsistent.

“We are in an era where we are keen to believe that this [phenomenon] exists,” Dr. Powles said. “But just because we can do SBRT in our hospitals doesn’t mean we should be doing it without robust data. The robustness of this data in renal cancer is not there at the moment.”

The 56% response rate seen in the RADVAX RCC trial was somewhat better than the 42% response rate seen in the CheckMate 214 trial with nivolumab and ipilimumab alone among patients with metastatic RCC treated in the first-line setting (Lancet Oncol. 2019;20:1370-85), Dr. Powles noted, while acknowledging the limitations of a cross-trial comparison.

“[However,] there were no complete responses, and this is therefore not a home run, in my opinion,” he said. “Progression-free survival was modest. Clearly, tolerability was okay.”

“In this work, the null hypothesis has not been rejected,” he added. “That’s an English way of saying it didn’t work very well. The question I put to you is, if [SBRT and immunotherapy] were a drug combination, would we be taking it further in randomized trials? And I suspect the answer to that is probably no.”

This trial was funded by KidneyCAN. Dr. Hammers and Dr. Powles disclosed relationships with Bristol-Myers Squibb, which markets nivolumab and ipilimumab, as well as other companies.

SOURCE: Hammers HJ et al. GUCS 2020, Abstract 614.

SAN FRANCISCO – Using stereotactic body radiation therapy (SBRT) to stimulate the immune response may boost the efficacy of immunotherapy in metastatic renal cell carcinoma (RCC), results of the RADVAX RCC trial suggest.

Susan London/MDedge News

More than half of patients (56%) who received SBRT plus nivolumab and ipilimumab achieved a response in nonirradiated lesions, but the prespecified threshold for efficacy was not met (70%). Still, the combination was active and well tolerated, and it warrants further investigation, according to Hans J. Hammers, MD, PhD, of the University of Texas, Dallas.

Dr. Hammers presented results from the RADVAX RCC trial at the 2020 Genitourinary Cancers Symposium sponsored by the American Society for Clinical Oncology, ASTRO, and the Society of Urologic Oncology.
 

Study details

The phase 2 trial enrolled 25 patients with metastatic clear-cell RCC. They had at least two metastatic sites, one of which was measurable for response. Forty percent had received at least one prior line of systemic therapy, and 30% had tumors positive for programmed death–ligand 1 expression. Almost a third had not undergone nephrectomy and therefore still had their primary tumor.

Patients received SBRT (50 Gy in five fractions) at one or two sites while also receiving nivolumab and ipilimumab. SBRT was given right after the first of four nivolumab-ipilimumab treatments and was delivered to lesions in the lung (56% of patients), lymph nodes (20%), bone or soft tissue (12%), and kidney (12%). Patients went on to receive maintenance nivolumab monotherapy.

At a median follow-up of 24 months, 56% of patients achieved a response in nonirradiated lesions. All were partial responses.

The 56% response rate fell short of the trial’s predefined efficacy endpoint of 70%. However, “we felt that an increase to around 60% [with the addition of SBRT] would probably be a reasonable signal for this small signal-finding study,” Dr. Hammers said, noting that this would be in line with the increase seen with intratumoral injections of immune stimulators.

“I would say we are not that far off if the numbers are real,” he added. “That certainly needs to be confirmed and expanded. And I’m sure we can make it more intelligent by choosing which tumors we go after because, right now, we are doing it completely blindly.”

The lack of any complete responses is likely explained, in part, by the large share of patients still having their primary tumor, Dr. Hammers said.

The median duration of response was not reached. The median progression-free survival was 8.21 months, and the median overall survival was not reached.

Thirty-six percent of patients experienced grade 3-4 adverse events, all gastrointestinal. Of the two patients (8%) experiencing grade 2 radiation pneumonitis, one was a case of radiation recall. Some patients needed high-dose corticosteroids (40%) and additional immune suppression (28%) for side effect management.

Should SBRT move forward in RCC?

“We feel that the combination of SBRT with dual immune checkpoint inhibition is feasible and associated with an acceptable safety profile,” Dr. Hammers said. “We do see an encouraging antitumor activity that we believe warrants further investigation.”

A proposed RADVAX II trial would assess programmed death–ligand 1 expression across tumor sites using PET. “We would then direct the radiation to the cold [noninflamed] tumors to derive potentially the maximum benefit in the sense of in situ vaccination,” Dr. Hammers explained.

Susan London/MDedge News

Invited discussant Thomas Powles, MD, PhD, of the Barts Cancer Institute in London, questioned whether SBRT plus immunotherapy should move forward in RCC patients. He noted that the abscopal effect was first described in the 1950s, but evidence of its clinical efficacy remains limited and inconsistent.

“We are in an era where we are keen to believe that this [phenomenon] exists,” Dr. Powles said. “But just because we can do SBRT in our hospitals doesn’t mean we should be doing it without robust data. The robustness of this data in renal cancer is not there at the moment.”

The 56% response rate seen in the RADVAX RCC trial was somewhat better than the 42% response rate seen in the CheckMate 214 trial with nivolumab and ipilimumab alone among patients with metastatic RCC treated in the first-line setting (Lancet Oncol. 2019;20:1370-85), Dr. Powles noted, while acknowledging the limitations of a cross-trial comparison.

“[However,] there were no complete responses, and this is therefore not a home run, in my opinion,” he said. “Progression-free survival was modest. Clearly, tolerability was okay.”

“In this work, the null hypothesis has not been rejected,” he added. “That’s an English way of saying it didn’t work very well. The question I put to you is, if [SBRT and immunotherapy] were a drug combination, would we be taking it further in randomized trials? And I suspect the answer to that is probably no.”

This trial was funded by KidneyCAN. Dr. Hammers and Dr. Powles disclosed relationships with Bristol-Myers Squibb, which markets nivolumab and ipilimumab, as well as other companies.

SOURCE: Hammers HJ et al. GUCS 2020, Abstract 614.

SAN FRANCISCO – Using stereotactic body radiation therapy (SBRT) to stimulate the immune response may boost the efficacy of immunotherapy in metastatic renal cell carcinoma (RCC), results of the RADVAX RCC trial suggest.

Susan London/MDedge News

More than half of patients (56%) who received SBRT plus nivolumab and ipilimumab achieved a response in nonirradiated lesions, but the prespecified threshold for efficacy was not met (70%). Still, the combination was active and well tolerated, and it warrants further investigation, according to Hans J. Hammers, MD, PhD, of the University of Texas, Dallas.

Dr. Hammers presented results from the RADVAX RCC trial at the 2020 Genitourinary Cancers Symposium sponsored by the American Society for Clinical Oncology, ASTRO, and the Society of Urologic Oncology.
 

Study details

The phase 2 trial enrolled 25 patients with metastatic clear-cell RCC. They had at least two metastatic sites, one of which was measurable for response. Forty percent had received at least one prior line of systemic therapy, and 30% had tumors positive for programmed death–ligand 1 expression. Almost a third had not undergone nephrectomy and therefore still had their primary tumor.

Patients received SBRT (50 Gy in five fractions) at one or two sites while also receiving nivolumab and ipilimumab. SBRT was given right after the first of four nivolumab-ipilimumab treatments and was delivered to lesions in the lung (56% of patients), lymph nodes (20%), bone or soft tissue (12%), and kidney (12%). Patients went on to receive maintenance nivolumab monotherapy.

At a median follow-up of 24 months, 56% of patients achieved a response in nonirradiated lesions. All were partial responses.

The 56% response rate fell short of the trial’s predefined efficacy endpoint of 70%. However, “we felt that an increase to around 60% [with the addition of SBRT] would probably be a reasonable signal for this small signal-finding study,” Dr. Hammers said, noting that this would be in line with the increase seen with intratumoral injections of immune stimulators.

“I would say we are not that far off if the numbers are real,” he added. “That certainly needs to be confirmed and expanded. And I’m sure we can make it more intelligent by choosing which tumors we go after because, right now, we are doing it completely blindly.”

The lack of any complete responses is likely explained, in part, by the large share of patients still having their primary tumor, Dr. Hammers said.

The median duration of response was not reached. The median progression-free survival was 8.21 months, and the median overall survival was not reached.

Thirty-six percent of patients experienced grade 3-4 adverse events, all gastrointestinal. Of the two patients (8%) experiencing grade 2 radiation pneumonitis, one was a case of radiation recall. Some patients needed high-dose corticosteroids (40%) and additional immune suppression (28%) for side effect management.

Should SBRT move forward in RCC?

“We feel that the combination of SBRT with dual immune checkpoint inhibition is feasible and associated with an acceptable safety profile,” Dr. Hammers said. “We do see an encouraging antitumor activity that we believe warrants further investigation.”

A proposed RADVAX II trial would assess programmed death–ligand 1 expression across tumor sites using PET. “We would then direct the radiation to the cold [noninflamed] tumors to derive potentially the maximum benefit in the sense of in situ vaccination,” Dr. Hammers explained.

Susan London/MDedge News

Invited discussant Thomas Powles, MD, PhD, of the Barts Cancer Institute in London, questioned whether SBRT plus immunotherapy should move forward in RCC patients. He noted that the abscopal effect was first described in the 1950s, but evidence of its clinical efficacy remains limited and inconsistent.

“We are in an era where we are keen to believe that this [phenomenon] exists,” Dr. Powles said. “But just because we can do SBRT in our hospitals doesn’t mean we should be doing it without robust data. The robustness of this data in renal cancer is not there at the moment.”

The 56% response rate seen in the RADVAX RCC trial was somewhat better than the 42% response rate seen in the CheckMate 214 trial with nivolumab and ipilimumab alone among patients with metastatic RCC treated in the first-line setting (Lancet Oncol. 2019;20:1370-85), Dr. Powles noted, while acknowledging the limitations of a cross-trial comparison.

“[However,] there were no complete responses, and this is therefore not a home run, in my opinion,” he said. “Progression-free survival was modest. Clearly, tolerability was okay.”

“In this work, the null hypothesis has not been rejected,” he added. “That’s an English way of saying it didn’t work very well. The question I put to you is, if [SBRT and immunotherapy] were a drug combination, would we be taking it further in randomized trials? And I suspect the answer to that is probably no.”

This trial was funded by KidneyCAN. Dr. Hammers and Dr. Powles disclosed relationships with Bristol-Myers Squibb, which markets nivolumab and ipilimumab, as well as other companies.

SOURCE: Hammers HJ et al. GUCS 2020, Abstract 614.

Higher out-of-pocket costs for prescription drugs are associated with poorer adherence across common neurologic conditions, a new study has found, suggesting that physicians should take patient costs into consideration when choosing which drugs to prescribe.

For their study, published online Feb. 19 in Neurology, Brian C. Callaghan, MD, of the University of Michigan, Ann Arbor, and colleagues looked at claims records from a large national private insurer to identify new cases of dementia, Parkinson’s disease, and neuropathy between 2001 and 2016, along with pharmacy records following diagnoses.

The researchers identified more than 52,000 patients with neuropathy on gabapentinoids and another 5,000 treated with serotonin-norepinephrine reuptake inhibitors for the same. They also identified some 20,000 patients with dementia taking cholinesterase inhibitors, and 3,000 with Parkinson’s disease taking dopamine agonists. Dr. Callaghan and colleagues compared patient adherence over 6 months for pairs of drugs in the same class with similar or equal efficacy, but with different costs to the patient.

Such cost differences can be stark: The researchers noted that the average 2016 out-of-pocket cost for 30 days of pregabalin, a drug used in the treatment of peripheral neuropathy, was $65.70, compared with $8.40 for gabapentin. With two common dementia drugs the difference was even more pronounced: $79.30 for rivastigmine compared with $3.10 for donepezil, both cholinesterase inhibitors with similar efficacy and tolerability.

Dr. Callaghan and colleagues found that such cost differences bore significantly on patient adherence. An increase of $50 in patient costs was seen decreasing adherence by 9% for neuropathy patients on gabapentinoids (adjusted incidence rate ratio [IRR] 0.91, 0.89-0.93) and by 12% for dementia patients on cholinesterase inhibitors (adjusted IRR 0.88, 0.86-0.91, P less than .05 for both). Similar price-linked decreases were seen for neuropathy patients on SNRIs and Parkinson’s patients on dopamine agonists, but the differences did not reach statistical significance.

Black, Asian, and Hispanic patients saw greater drops in adherence than did white patients associated with the same out-of-pocket cost differences, leading the researchers to note that special care should be taken in prescribing decisions for these populations.

“When choosing among medications with differential [out-of-pocket] costs, prescribing the medication with lower [out-of-pocket] expense will likely improve medication adherence while reducing overall costs,” Dr. Callaghan and colleagues wrote in their analysis. “For example, prescribing gabapentin or venlafaxine to patients with newly diagnosed neuropathy is likely to lead to higher adherence compared with pregabalin or duloxetine, and therefore, there is a higher likelihood of relief from neuropathic pain.” The researchers noted that while combination pills and extended-release formulations may be marketed as a way to increase adherence, the higher out-of-pocket costs of such medicines could offset any adherence benefit.

Dr. Callaghan and his colleagues described as strengths of their study its large sample and statistical approach that “allowed us to best estimate the causal relationship between [out-of-pocket] costs and medication adherence by limiting selection bias, residual confounding, and the confounding inherent to medication choice.” Nonadherence – patients who never filled a prescription after diagnosis – was not captured in the study.

The American Academy of Neurology funded the study. Two of its authors reported financial conflicts of interest in the form of compensation from pharmaceutical or device companies. Its lead author, Dr. Callaghan, reported funding for a device maker and performing medical legal consultations.

SOURCE: Reynolds EL et al. Neurology. 2020 Feb 19. doi/10.1212/WNL.0000000000009039.

Higher out-of-pocket costs for prescription drugs are associated with poorer adherence across common neurologic conditions, a new study has found, suggesting that physicians should take patient costs into consideration when choosing which drugs to prescribe.

For their study, published online Feb. 19 in Neurology, Brian C. Callaghan, MD, of the University of Michigan, Ann Arbor, and colleagues looked at claims records from a large national private insurer to identify new cases of dementia, Parkinson’s disease, and neuropathy between 2001 and 2016, along with pharmacy records following diagnoses.

The researchers identified more than 52,000 patients with neuropathy on gabapentinoids and another 5,000 treated with serotonin-norepinephrine reuptake inhibitors for the same. They also identified some 20,000 patients with dementia taking cholinesterase inhibitors, and 3,000 with Parkinson’s disease taking dopamine agonists. Dr. Callaghan and colleagues compared patient adherence over 6 months for pairs of drugs in the same class with similar or equal efficacy, but with different costs to the patient.

Such cost differences can be stark: The researchers noted that the average 2016 out-of-pocket cost for 30 days of pregabalin, a drug used in the treatment of peripheral neuropathy, was $65.70, compared with $8.40 for gabapentin. With two common dementia drugs the difference was even more pronounced: $79.30 for rivastigmine compared with $3.10 for donepezil, both cholinesterase inhibitors with similar efficacy and tolerability.

Dr. Callaghan and colleagues found that such cost differences bore significantly on patient adherence. An increase of $50 in patient costs was seen decreasing adherence by 9% for neuropathy patients on gabapentinoids (adjusted incidence rate ratio [IRR] 0.91, 0.89-0.93) and by 12% for dementia patients on cholinesterase inhibitors (adjusted IRR 0.88, 0.86-0.91, P less than .05 for both). Similar price-linked decreases were seen for neuropathy patients on SNRIs and Parkinson’s patients on dopamine agonists, but the differences did not reach statistical significance.

Black, Asian, and Hispanic patients saw greater drops in adherence than did white patients associated with the same out-of-pocket cost differences, leading the researchers to note that special care should be taken in prescribing decisions for these populations.

“When choosing among medications with differential [out-of-pocket] costs, prescribing the medication with lower [out-of-pocket] expense will likely improve medication adherence while reducing overall costs,” Dr. Callaghan and colleagues wrote in their analysis. “For example, prescribing gabapentin or venlafaxine to patients with newly diagnosed neuropathy is likely to lead to higher adherence compared with pregabalin or duloxetine, and therefore, there is a higher likelihood of relief from neuropathic pain.” The researchers noted that while combination pills and extended-release formulations may be marketed as a way to increase adherence, the higher out-of-pocket costs of such medicines could offset any adherence benefit.

Dr. Callaghan and his colleagues described as strengths of their study its large sample and statistical approach that “allowed us to best estimate the causal relationship between [out-of-pocket] costs and medication adherence by limiting selection bias, residual confounding, and the confounding inherent to medication choice.” Nonadherence – patients who never filled a prescription after diagnosis – was not captured in the study.

The American Academy of Neurology funded the study. Two of its authors reported financial conflicts of interest in the form of compensation from pharmaceutical or device companies. Its lead author, Dr. Callaghan, reported funding for a device maker and performing medical legal consultations.

SOURCE: Reynolds EL et al. Neurology. 2020 Feb 19. doi/10.1212/WNL.0000000000009039.

Higher out-of-pocket costs for prescription drugs are associated with poorer adherence across common neurologic conditions, a new study has found, suggesting that physicians should take patient costs into consideration when choosing which drugs to prescribe.

For their study, published online Feb. 19 in Neurology, Brian C. Callaghan, MD, of the University of Michigan, Ann Arbor, and colleagues looked at claims records from a large national private insurer to identify new cases of dementia, Parkinson’s disease, and neuropathy between 2001 and 2016, along with pharmacy records following diagnoses.

The researchers identified more than 52,000 patients with neuropathy on gabapentinoids and another 5,000 treated with serotonin-norepinephrine reuptake inhibitors for the same. They also identified some 20,000 patients with dementia taking cholinesterase inhibitors, and 3,000 with Parkinson’s disease taking dopamine agonists. Dr. Callaghan and colleagues compared patient adherence over 6 months for pairs of drugs in the same class with similar or equal efficacy, but with different costs to the patient.

Such cost differences can be stark: The researchers noted that the average 2016 out-of-pocket cost for 30 days of pregabalin, a drug used in the treatment of peripheral neuropathy, was $65.70, compared with $8.40 for gabapentin. With two common dementia drugs the difference was even more pronounced: $79.30 for rivastigmine compared with $3.10 for donepezil, both cholinesterase inhibitors with similar efficacy and tolerability.

Dr. Callaghan and colleagues found that such cost differences bore significantly on patient adherence. An increase of $50 in patient costs was seen decreasing adherence by 9% for neuropathy patients on gabapentinoids (adjusted incidence rate ratio [IRR] 0.91, 0.89-0.93) and by 12% for dementia patients on cholinesterase inhibitors (adjusted IRR 0.88, 0.86-0.91, P less than .05 for both). Similar price-linked decreases were seen for neuropathy patients on SNRIs and Parkinson’s patients on dopamine agonists, but the differences did not reach statistical significance.

Black, Asian, and Hispanic patients saw greater drops in adherence than did white patients associated with the same out-of-pocket cost differences, leading the researchers to note that special care should be taken in prescribing decisions for these populations.

“When choosing among medications with differential [out-of-pocket] costs, prescribing the medication with lower [out-of-pocket] expense will likely improve medication adherence while reducing overall costs,” Dr. Callaghan and colleagues wrote in their analysis. “For example, prescribing gabapentin or venlafaxine to patients with newly diagnosed neuropathy is likely to lead to higher adherence compared with pregabalin or duloxetine, and therefore, there is a higher likelihood of relief from neuropathic pain.” The researchers noted that while combination pills and extended-release formulations may be marketed as a way to increase adherence, the higher out-of-pocket costs of such medicines could offset any adherence benefit.

Dr. Callaghan and his colleagues described as strengths of their study its large sample and statistical approach that “allowed us to best estimate the causal relationship between [out-of-pocket] costs and medication adherence by limiting selection bias, residual confounding, and the confounding inherent to medication choice.” Nonadherence – patients who never filled a prescription after diagnosis – was not captured in the study.

The American Academy of Neurology funded the study. Two of its authors reported financial conflicts of interest in the form of compensation from pharmaceutical or device companies. Its lead author, Dr. Callaghan, reported funding for a device maker and performing medical legal consultations.

SOURCE: Reynolds EL et al. Neurology. 2020 Feb 19. doi/10.1212/WNL.0000000000009039.

As many as 24% of individuals with schizophrenia spectrum disorder who underwent a comprehensive neurocognitive battery performed above the mean healthy score for some neurocognitive domains, compared with a group of controls, results from a novel study show.

“Based on these findings, we recommend that neurocognitive assessment should be performed as early as possible after illness onset,” researchers led by Lars Helldin, MD, PhD, of the department of psychiatry at NU Health-Care Hospital, Region Västra Götaland, Sweden, wrote in a study published in Schizophrenia Research: Cognition (2020 Jun doi: 10.1016/j.scog.2020.100172). “Early identification of cognitive risk factors for poor real-life functional outcome is necessary in order to alert the clinical and rehabilitation services about patients in need of extra care.”

For the study, 291 men and women suffering from schizophrenia spectrum disorder (SSD) and 302 controls underwent assessment with a series of comprehensive neurocognitive tests, including the Global Assessment of Functioning (GAF), the Positive and Negative Syndrome Scale (PANSS), the Specific Level of Functioning Scale (SLOF), the Rey Auditory Verbal Learning Test (RAVLT), and the Wisconsin Card Sorting Test (WCST). The researchers found that the neurocognitive function of the SSD patients was significantly lower than that of the healthy controls on all assessments, with very large effect sizes. “There was considerable diversity within each group, as subgroups of patients scored higher than the control mean and subgroups of controls scored lower than the patient mean, particularly on tests of working memory, verbal learning and memory, and executive function,” wrote Dr. Helldin and associates.

As for the WSCT score, the cognitively intact group had a significantly lower PANSS negative symptom level (P less than .01), a lower PANSS general pathology level (P less than .05), and a lower PANSS total symptom level (P less than .01). As for the WAIS Vocabulary score, the patient group with a higher score than the controls had a significantly lower PANSS negative symptom level (P less than .05).

“Here, we have linked neurocognitive heterogeneity to functional outcome differences, and suggest that personalized treatment with emphasis on practical daily skills may be of great significance especially for those with large baseline cognitive deficits,” the researchers concluded. “Such efforts are imperative not only in order to reduce personal suffering and increase quality of life for the patients, but also to reduce the enormous society level economic costs of functional deficits.”

The study was funded by the Regional Health Authority, VG Region, Sweden. The authors reported having no financial disclosures.

dbrunk@mdedge.com

As many as 24% of individuals with schizophrenia spectrum disorder who underwent a comprehensive neurocognitive battery performed above the mean healthy score for some neurocognitive domains, compared with a group of controls, results from a novel study show.

“Based on these findings, we recommend that neurocognitive assessment should be performed as early as possible after illness onset,” researchers led by Lars Helldin, MD, PhD, of the department of psychiatry at NU Health-Care Hospital, Region Västra Götaland, Sweden, wrote in a study published in Schizophrenia Research: Cognition (2020 Jun doi: 10.1016/j.scog.2020.100172). “Early identification of cognitive risk factors for poor real-life functional outcome is necessary in order to alert the clinical and rehabilitation services about patients in need of extra care.”

For the study, 291 men and women suffering from schizophrenia spectrum disorder (SSD) and 302 controls underwent assessment with a series of comprehensive neurocognitive tests, including the Global Assessment of Functioning (GAF), the Positive and Negative Syndrome Scale (PANSS), the Specific Level of Functioning Scale (SLOF), the Rey Auditory Verbal Learning Test (RAVLT), and the Wisconsin Card Sorting Test (WCST). The researchers found that the neurocognitive function of the SSD patients was significantly lower than that of the healthy controls on all assessments, with very large effect sizes. “There was considerable diversity within each group, as subgroups of patients scored higher than the control mean and subgroups of controls scored lower than the patient mean, particularly on tests of working memory, verbal learning and memory, and executive function,” wrote Dr. Helldin and associates.

As for the WSCT score, the cognitively intact group had a significantly lower PANSS negative symptom level (P less than .01), a lower PANSS general pathology level (P less than .05), and a lower PANSS total symptom level (P less than .01). As for the WAIS Vocabulary score, the patient group with a higher score than the controls had a significantly lower PANSS negative symptom level (P less than .05).

“Here, we have linked neurocognitive heterogeneity to functional outcome differences, and suggest that personalized treatment with emphasis on practical daily skills may be of great significance especially for those with large baseline cognitive deficits,” the researchers concluded. “Such efforts are imperative not only in order to reduce personal suffering and increase quality of life for the patients, but also to reduce the enormous society level economic costs of functional deficits.”

The study was funded by the Regional Health Authority, VG Region, Sweden. The authors reported having no financial disclosures.

dbrunk@mdedge.com

As many as 24% of individuals with schizophrenia spectrum disorder who underwent a comprehensive neurocognitive battery performed above the mean healthy score for some neurocognitive domains, compared with a group of controls, results from a novel study show.

“Based on these findings, we recommend that neurocognitive assessment should be performed as early as possible after illness onset,” researchers led by Lars Helldin, MD, PhD, of the department of psychiatry at NU Health-Care Hospital, Region Västra Götaland, Sweden, wrote in a study published in Schizophrenia Research: Cognition (2020 Jun doi: 10.1016/j.scog.2020.100172). “Early identification of cognitive risk factors for poor real-life functional outcome is necessary in order to alert the clinical and rehabilitation services about patients in need of extra care.”

For the study, 291 men and women suffering from schizophrenia spectrum disorder (SSD) and 302 controls underwent assessment with a series of comprehensive neurocognitive tests, including the Global Assessment of Functioning (GAF), the Positive and Negative Syndrome Scale (PANSS), the Specific Level of Functioning Scale (SLOF), the Rey Auditory Verbal Learning Test (RAVLT), and the Wisconsin Card Sorting Test (WCST). The researchers found that the neurocognitive function of the SSD patients was significantly lower than that of the healthy controls on all assessments, with very large effect sizes. “There was considerable diversity within each group, as subgroups of patients scored higher than the control mean and subgroups of controls scored lower than the patient mean, particularly on tests of working memory, verbal learning and memory, and executive function,” wrote Dr. Helldin and associates.

As for the WSCT score, the cognitively intact group had a significantly lower PANSS negative symptom level (P less than .01), a lower PANSS general pathology level (P less than .05), and a lower PANSS total symptom level (P less than .01). As for the WAIS Vocabulary score, the patient group with a higher score than the controls had a significantly lower PANSS negative symptom level (P less than .05).

“Here, we have linked neurocognitive heterogeneity to functional outcome differences, and suggest that personalized treatment with emphasis on practical daily skills may be of great significance especially for those with large baseline cognitive deficits,” the researchers concluded. “Such efforts are imperative not only in order to reduce personal suffering and increase quality of life for the patients, but also to reduce the enormous society level economic costs of functional deficits.”

The study was funded by the Regional Health Authority, VG Region, Sweden. The authors reported having no financial disclosures.

dbrunk@mdedge.com