Deep sedation during colonoscopies did not confer any improvement in the detection rate for adenomas or polyps among average-risk patients, based on results from a retrospective analysis at a single institution that switched from moderate to deep sedation.

There remains a question as to whether moderate sedation, such as benzodiazepine plus opioids, might affect adenoma detection rate (ADR). The issue is important in part because of the recent push to use propofol in outpatient colonoscopy clinics, according to Erica Turse, DO, MPH, of the University of Missouri–Columbia, and colleagues.

Previous studies looking at moderate versus deep sedation have yielded mixed results, possibly as a result of confounding variables arising from mixed patient populations and conditions.

The current study, published in Gastrointestinal Endoscopy, aimed to eliminate potential confounders by focusing only on average-risk index colonoscopies, with similar patient populations in both groups.

The researchers examined data from a tertiary care outpatient center at the University of Missouri, which switched from moderate to deep sedation in the spring of 2016. Moderate sedation was achieved using midazolam and fentanyl, and propofol was later used for deep sedation. The study included a total of 585 colonoscopies, with 338 patients in the moderate-sedation group and 247 in the deep-sedation group. The overall polyp detection rate (PDR) was 70.1%, and the ADR was 41.7%.

The two groups did not significantly differ in PDR (71.9% moderate vs. 67.6% deep, P = .27) or ADR (44.1% vs. 38.5%; P = .18). Among women, there was no difference in PDR (69.3% vs. 64.8%; P = .41) or ADR (42.2% vs. 32.4%; P = .09). Among men, the results were the same (PDR, 75.3% vs. 71.4%; P = .56; ADR, 46.6% vs. 46.7%; P = 1.0).

A strength of the study was that the populations in both the moderate- and deep-sedation groups were similar. A weakness is that the study was conducted at a single center. The authors called for a randomized, controlled trial to gain more insight into the benefits of moderate versus deep sedation.

The study had no external funding. The authors reported having no financial conflicts of interest.

SOURCE: Turse E et al. Gastrointest Endosc. 2019 May 15. doi: 10.1016/j.gie.2019.05.011.

Deep sedation during colonoscopies did not confer any improvement in the detection rate for adenomas or polyps among average-risk patients, based on results from a retrospective analysis at a single institution that switched from moderate to deep sedation.

There remains a question as to whether moderate sedation, such as benzodiazepine plus opioids, might affect adenoma detection rate (ADR). The issue is important in part because of the recent push to use propofol in outpatient colonoscopy clinics, according to Erica Turse, DO, MPH, of the University of Missouri–Columbia, and colleagues.

Previous studies looking at moderate versus deep sedation have yielded mixed results, possibly as a result of confounding variables arising from mixed patient populations and conditions.

The current study, published in Gastrointestinal Endoscopy, aimed to eliminate potential confounders by focusing only on average-risk index colonoscopies, with similar patient populations in both groups.

The researchers examined data from a tertiary care outpatient center at the University of Missouri, which switched from moderate to deep sedation in the spring of 2016. Moderate sedation was achieved using midazolam and fentanyl, and propofol was later used for deep sedation. The study included a total of 585 colonoscopies, with 338 patients in the moderate-sedation group and 247 in the deep-sedation group. The overall polyp detection rate (PDR) was 70.1%, and the ADR was 41.7%.

The two groups did not significantly differ in PDR (71.9% moderate vs. 67.6% deep, P = .27) or ADR (44.1% vs. 38.5%; P = .18). Among women, there was no difference in PDR (69.3% vs. 64.8%; P = .41) or ADR (42.2% vs. 32.4%; P = .09). Among men, the results were the same (PDR, 75.3% vs. 71.4%; P = .56; ADR, 46.6% vs. 46.7%; P = 1.0).

A strength of the study was that the populations in both the moderate- and deep-sedation groups were similar. A weakness is that the study was conducted at a single center. The authors called for a randomized, controlled trial to gain more insight into the benefits of moderate versus deep sedation.

The study had no external funding. The authors reported having no financial conflicts of interest.

SOURCE: Turse E et al. Gastrointest Endosc. 2019 May 15. doi: 10.1016/j.gie.2019.05.011.

Deep sedation during colonoscopies did not confer any improvement in the detection rate for adenomas or polyps among average-risk patients, based on results from a retrospective analysis at a single institution that switched from moderate to deep sedation.

There remains a question as to whether moderate sedation, such as benzodiazepine plus opioids, might affect adenoma detection rate (ADR). The issue is important in part because of the recent push to use propofol in outpatient colonoscopy clinics, according to Erica Turse, DO, MPH, of the University of Missouri–Columbia, and colleagues.

Previous studies looking at moderate versus deep sedation have yielded mixed results, possibly as a result of confounding variables arising from mixed patient populations and conditions.

The current study, published in Gastrointestinal Endoscopy, aimed to eliminate potential confounders by focusing only on average-risk index colonoscopies, with similar patient populations in both groups.

The researchers examined data from a tertiary care outpatient center at the University of Missouri, which switched from moderate to deep sedation in the spring of 2016. Moderate sedation was achieved using midazolam and fentanyl, and propofol was later used for deep sedation. The study included a total of 585 colonoscopies, with 338 patients in the moderate-sedation group and 247 in the deep-sedation group. The overall polyp detection rate (PDR) was 70.1%, and the ADR was 41.7%.

The two groups did not significantly differ in PDR (71.9% moderate vs. 67.6% deep, P = .27) or ADR (44.1% vs. 38.5%; P = .18). Among women, there was no difference in PDR (69.3% vs. 64.8%; P = .41) or ADR (42.2% vs. 32.4%; P = .09). Among men, the results were the same (PDR, 75.3% vs. 71.4%; P = .56; ADR, 46.6% vs. 46.7%; P = 1.0).

A strength of the study was that the populations in both the moderate- and deep-sedation groups were similar. A weakness is that the study was conducted at a single center. The authors called for a randomized, controlled trial to gain more insight into the benefits of moderate versus deep sedation.

The study had no external funding. The authors reported having no financial conflicts of interest.

SOURCE: Turse E et al. Gastrointest Endosc. 2019 May 15. doi: 10.1016/j.gie.2019.05.011.

The new National Coverage Determination by Medicare for transcatheter aortic valve replacement should produce a bump in the number of U.S. programs offering the procedure, especially with the Food and Drug Administration on the cusp of approving the procedure for low-risk patients.

Mitchel L. Zoler/MDedge News

In the revised National Coverage Determination (NCD) by the Centers for Medicare & Medicaid Services that went into effect on June 21, 2019, the agency allowed for Medicare coverage of transcatheter aortic valve (TAVR) procedures at hospitals that perform at least 20 of these procedures annually or at least 40 every 2 years, the same volume minimums that CMS first applied to TAVR in its prior 2012 NCD. Retention of this minimum ran against the 2018 proposal of the American College of Cardiology, the Society of Thoracic Surgeons, and two other collaborating societies that called for an annual TAVR volume minimum at a hospital program of 50 procedures annually or 100 every 2 years (J Am Coll Cardiol. 2019 Jan 29;73[3]:340-74).

That change, coupled with a cut in the minimum number of annual percutaneous coronary interventions a TAVR program needs to perform – newly revised to a minimum of 300 cases/year – will likely mean more U.S. sites performing TAVR, predicted James Vavricek, director of regulatory affairs for the ACC in Washington. TAVR volume is seen as a reasonable, approximate surrogate for a more rigorous, statistically adjusted assessment of program quality. The ACC and representatives from the other societies that collaborated on the 2018 statement used a 50 case/year minimum for a TAVR program because volume at that level generates enough outcomes data to allow for a meaningful, risk-adjusted measure of performance.

The ACC does not consider the minimum of 20 TAVR cases/year the “right decision,” Mr. Vavricek said in an interview, but the ACC sees it as a compromise that accommodated the interests of multiple TAVR stakeholders. “It will be interesting to see where new TAVR programs locate,” whether they will expand access in underserved regions or mostly cluster in regions already fairly replete with TAVR access, he added. Currently, over 600 U.S. TAVR programs are in operation.

In April 2019, the president of the ACC along with the presidents of three other U.S. societies with an interest in TAVR told the CMS in a comment letter that “we are extremely concerned that the proposed volume requirements will translate into a proliferation of low-volume TAVR programs at increased risk for having suboptimal outcomes.”

Another change to procedure volume requirements in the new NCD was setting a minimum of 100 total TAVR plus surgical aortic valve replacements in a 2-year period or 50 total procedures/year for each TAVR program. Setting a minimum that bundles TAVR plus surgical valve replacements is a “forward-looking” approach as wider application of TAVR gradually erodes the volume of surgical procedures, Mr. Vavricek said.

An additional notable change in the revised NCD was elimination of the “two-surgeon” rule, which the CMS had made mandatory for TAVR decisions until now, stipulating that a patient considered for TAVR needed independent assessment by two cardiac surgeons. The final 2019 NCD calls for the TAVR decision to come from one cardiac surgeon and one interventional cardiologist working together on a care team.

“The ACC is pleased to see CMS issue updated TAVR coverage criteria that emphasizes care by an interdisciplinary heart team for these complex patients, as well as continues to mandate the collection of TAVR patient data. With the new lowered minimum yearly volume criteria set by CMS in their efforts to improve patient access, the value of the STS/ACC TVT Registry, along with ACC’s Transcatheter Valve Certification, will be critical in assuring quality of care for our patients particularly in low-volume centers,” commented Richard J. Kovacs, MD, ACC’s president.

[email protected]

The new National Coverage Determination by Medicare for transcatheter aortic valve replacement should produce a bump in the number of U.S. programs offering the procedure, especially with the Food and Drug Administration on the cusp of approving the procedure for low-risk patients.

Mitchel L. Zoler/MDedge News

In the revised National Coverage Determination (NCD) by the Centers for Medicare & Medicaid Services that went into effect on June 21, 2019, the agency allowed for Medicare coverage of transcatheter aortic valve (TAVR) procedures at hospitals that perform at least 20 of these procedures annually or at least 40 every 2 years, the same volume minimums that CMS first applied to TAVR in its prior 2012 NCD. Retention of this minimum ran against the 2018 proposal of the American College of Cardiology, the Society of Thoracic Surgeons, and two other collaborating societies that called for an annual TAVR volume minimum at a hospital program of 50 procedures annually or 100 every 2 years (J Am Coll Cardiol. 2019 Jan 29;73[3]:340-74).

That change, coupled with a cut in the minimum number of annual percutaneous coronary interventions a TAVR program needs to perform – newly revised to a minimum of 300 cases/year – will likely mean more U.S. sites performing TAVR, predicted James Vavricek, director of regulatory affairs for the ACC in Washington. TAVR volume is seen as a reasonable, approximate surrogate for a more rigorous, statistically adjusted assessment of program quality. The ACC and representatives from the other societies that collaborated on the 2018 statement used a 50 case/year minimum for a TAVR program because volume at that level generates enough outcomes data to allow for a meaningful, risk-adjusted measure of performance.

The ACC does not consider the minimum of 20 TAVR cases/year the “right decision,” Mr. Vavricek said in an interview, but the ACC sees it as a compromise that accommodated the interests of multiple TAVR stakeholders. “It will be interesting to see where new TAVR programs locate,” whether they will expand access in underserved regions or mostly cluster in regions already fairly replete with TAVR access, he added. Currently, over 600 U.S. TAVR programs are in operation.

In April 2019, the president of the ACC along with the presidents of three other U.S. societies with an interest in TAVR told the CMS in a comment letter that “we are extremely concerned that the proposed volume requirements will translate into a proliferation of low-volume TAVR programs at increased risk for having suboptimal outcomes.”

Another change to procedure volume requirements in the new NCD was setting a minimum of 100 total TAVR plus surgical aortic valve replacements in a 2-year period or 50 total procedures/year for each TAVR program. Setting a minimum that bundles TAVR plus surgical valve replacements is a “forward-looking” approach as wider application of TAVR gradually erodes the volume of surgical procedures, Mr. Vavricek said.

An additional notable change in the revised NCD was elimination of the “two-surgeon” rule, which the CMS had made mandatory for TAVR decisions until now, stipulating that a patient considered for TAVR needed independent assessment by two cardiac surgeons. The final 2019 NCD calls for the TAVR decision to come from one cardiac surgeon and one interventional cardiologist working together on a care team.

“The ACC is pleased to see CMS issue updated TAVR coverage criteria that emphasizes care by an interdisciplinary heart team for these complex patients, as well as continues to mandate the collection of TAVR patient data. With the new lowered minimum yearly volume criteria set by CMS in their efforts to improve patient access, the value of the STS/ACC TVT Registry, along with ACC’s Transcatheter Valve Certification, will be critical in assuring quality of care for our patients particularly in low-volume centers,” commented Richard J. Kovacs, MD, ACC’s president.

[email protected]

The new National Coverage Determination by Medicare for transcatheter aortic valve replacement should produce a bump in the number of U.S. programs offering the procedure, especially with the Food and Drug Administration on the cusp of approving the procedure for low-risk patients.

Mitchel L. Zoler/MDedge News

In the revised National Coverage Determination (NCD) by the Centers for Medicare & Medicaid Services that went into effect on June 21, 2019, the agency allowed for Medicare coverage of transcatheter aortic valve (TAVR) procedures at hospitals that perform at least 20 of these procedures annually or at least 40 every 2 years, the same volume minimums that CMS first applied to TAVR in its prior 2012 NCD. Retention of this minimum ran against the 2018 proposal of the American College of Cardiology, the Society of Thoracic Surgeons, and two other collaborating societies that called for an annual TAVR volume minimum at a hospital program of 50 procedures annually or 100 every 2 years (J Am Coll Cardiol. 2019 Jan 29;73[3]:340-74).

That change, coupled with a cut in the minimum number of annual percutaneous coronary interventions a TAVR program needs to perform – newly revised to a minimum of 300 cases/year – will likely mean more U.S. sites performing TAVR, predicted James Vavricek, director of regulatory affairs for the ACC in Washington. TAVR volume is seen as a reasonable, approximate surrogate for a more rigorous, statistically adjusted assessment of program quality. The ACC and representatives from the other societies that collaborated on the 2018 statement used a 50 case/year minimum for a TAVR program because volume at that level generates enough outcomes data to allow for a meaningful, risk-adjusted measure of performance.

The ACC does not consider the minimum of 20 TAVR cases/year the “right decision,” Mr. Vavricek said in an interview, but the ACC sees it as a compromise that accommodated the interests of multiple TAVR stakeholders. “It will be interesting to see where new TAVR programs locate,” whether they will expand access in underserved regions or mostly cluster in regions already fairly replete with TAVR access, he added. Currently, over 600 U.S. TAVR programs are in operation.

In April 2019, the president of the ACC along with the presidents of three other U.S. societies with an interest in TAVR told the CMS in a comment letter that “we are extremely concerned that the proposed volume requirements will translate into a proliferation of low-volume TAVR programs at increased risk for having suboptimal outcomes.”

Another change to procedure volume requirements in the new NCD was setting a minimum of 100 total TAVR plus surgical aortic valve replacements in a 2-year period or 50 total procedures/year for each TAVR program. Setting a minimum that bundles TAVR plus surgical valve replacements is a “forward-looking” approach as wider application of TAVR gradually erodes the volume of surgical procedures, Mr. Vavricek said.

An additional notable change in the revised NCD was elimination of the “two-surgeon” rule, which the CMS had made mandatory for TAVR decisions until now, stipulating that a patient considered for TAVR needed independent assessment by two cardiac surgeons. The final 2019 NCD calls for the TAVR decision to come from one cardiac surgeon and one interventional cardiologist working together on a care team.

“The ACC is pleased to see CMS issue updated TAVR coverage criteria that emphasizes care by an interdisciplinary heart team for these complex patients, as well as continues to mandate the collection of TAVR patient data. With the new lowered minimum yearly volume criteria set by CMS in their efforts to improve patient access, the value of the STS/ACC TVT Registry, along with ACC’s Transcatheter Valve Certification, will be critical in assuring quality of care for our patients particularly in low-volume centers,” commented Richard J. Kovacs, MD, ACC’s president.

[email protected]

The Diagnosis: Wells Syndrome 

Histopathologic examination of the biopsy demonstrated overlying acanthosis, focal spongiosis, and exocytosis. There also was proliferation and thickening of superficial capillaries and papillary fibrosis (Figure, A). There was a mixed interstitial and perivascular inflammatory infiltrate consisting of lymphocytes, histiocytes, plasma cells, and eosinophils (Figure, A and B). Occasional flame figures were identified (Figure, C). 

Wells syndrome, also known as eosinophilic cellulitis, was first described in 1971 by Wells¹ as a recurrent granulomatous dermatitis with eosinophilia. Rarely reported worldwide, this chronic relapsing condition is characterized by a pronounced eosinophilic infiltrate of the dermis resembling urticaria or cellulitis.² The exact etiology has not been elucidated; however, links to certain medications, vaccines, exaggerated arthropod reactions, infections, and malignancies have been documented.³  

Wells syndrome is a diagnosis of exclusion and lacks a predictable dermatologic presentation, thereby mandating focused clinical follow-up as well as correlation with histopathology findings. Although the classic histologic hallmark of Wells syndrome is scattered flame figures, this finding is not specific and can be found in other hypereosinophilic conditions.² Clinical manifestations most often consist of 2 distinct phases: an initial painful burning or pruritic sensation, followed by the development of erythematous and edematous dermal plaques that may heal with slight hyperpigmentation over 4 to 8 weeks. A case series of 19 patients demonstrated variants of Wells syndrome, with an annular granuloma-like appearance found primarily in adults and the signature plaque-type appearance predominating in children.⁴  

Acute urticaria is characterized by pruritic erythematous wheals secondary to a histamine-mediated response brought on by a variety of triggers, typically allergic and self-resolving within 24 hours. When such lesions last longer than 24 hours, biopsy should be performed to exclude urticarial vasculitis, which is characterized by a burning or painful sensation rather than pruritis, in addition to dermal neutrophilia and perivascular infiltrate on histology. Erythema migrans of Lyme disease begins at the site of a tick bite, evolving from a red macule to an expanding targetoid lesion and typically is not pruritic. Infectious cellulitis presents with warm, tender, and poorly defined erythematous patches; can progress rapidly; and is accompanied by systemic symptoms such as fevers, malaise, and lymphadenopathy.  

Best evidence favors the use of moderate- to high-dose corticosteroids as first-line treatment.⁵ The use of tumor necrosis factor blockers, various immunomodulating agents, and combination therapy with levocetirizine and hydroxyzine have demonstrated variable levels of efficacy, albeit often followed by high rates of relapse with drug discontinuation.⁶  

The Diagnosis: Wells Syndrome 

Histopathologic examination of the biopsy demonstrated overlying acanthosis, focal spongiosis, and exocytosis. There also was proliferation and thickening of superficial capillaries and papillary fibrosis (Figure, A). There was a mixed interstitial and perivascular inflammatory infiltrate consisting of lymphocytes, histiocytes, plasma cells, and eosinophils (Figure, A and B). Occasional flame figures were identified (Figure, C). 

Wells syndrome, also known as eosinophilic cellulitis, was first described in 1971 by Wells¹ as a recurrent granulomatous dermatitis with eosinophilia. Rarely reported worldwide, this chronic relapsing condition is characterized by a pronounced eosinophilic infiltrate of the dermis resembling urticaria or cellulitis.² The exact etiology has not been elucidated; however, links to certain medications, vaccines, exaggerated arthropod reactions, infections, and malignancies have been documented.³  

Wells syndrome is a diagnosis of exclusion and lacks a predictable dermatologic presentation, thereby mandating focused clinical follow-up as well as correlation with histopathology findings. Although the classic histologic hallmark of Wells syndrome is scattered flame figures, this finding is not specific and can be found in other hypereosinophilic conditions.² Clinical manifestations most often consist of 2 distinct phases: an initial painful burning or pruritic sensation, followed by the development of erythematous and edematous dermal plaques that may heal with slight hyperpigmentation over 4 to 8 weeks. A case series of 19 patients demonstrated variants of Wells syndrome, with an annular granuloma-like appearance found primarily in adults and the signature plaque-type appearance predominating in children.⁴  

Acute urticaria is characterized by pruritic erythematous wheals secondary to a histamine-mediated response brought on by a variety of triggers, typically allergic and self-resolving within 24 hours. When such lesions last longer than 24 hours, biopsy should be performed to exclude urticarial vasculitis, which is characterized by a burning or painful sensation rather than pruritis, in addition to dermal neutrophilia and perivascular infiltrate on histology. Erythema migrans of Lyme disease begins at the site of a tick bite, evolving from a red macule to an expanding targetoid lesion and typically is not pruritic. Infectious cellulitis presents with warm, tender, and poorly defined erythematous patches; can progress rapidly; and is accompanied by systemic symptoms such as fevers, malaise, and lymphadenopathy.  

Best evidence favors the use of moderate- to high-dose corticosteroids as first-line treatment.⁵ The use of tumor necrosis factor blockers, various immunomodulating agents, and combination therapy with levocetirizine and hydroxyzine have demonstrated variable levels of efficacy, albeit often followed by high rates of relapse with drug discontinuation.⁶  

The Diagnosis: Wells Syndrome 

Histopathologic examination of the biopsy demonstrated overlying acanthosis, focal spongiosis, and exocytosis. There also was proliferation and thickening of superficial capillaries and papillary fibrosis (Figure, A). There was a mixed interstitial and perivascular inflammatory infiltrate consisting of lymphocytes, histiocytes, plasma cells, and eosinophils (Figure, A and B). Occasional flame figures were identified (Figure, C). 

Wells syndrome, also known as eosinophilic cellulitis, was first described in 1971 by Wells¹ as a recurrent granulomatous dermatitis with eosinophilia. Rarely reported worldwide, this chronic relapsing condition is characterized by a pronounced eosinophilic infiltrate of the dermis resembling urticaria or cellulitis.² The exact etiology has not been elucidated; however, links to certain medications, vaccines, exaggerated arthropod reactions, infections, and malignancies have been documented.³  

Wells syndrome is a diagnosis of exclusion and lacks a predictable dermatologic presentation, thereby mandating focused clinical follow-up as well as correlation with histopathology findings. Although the classic histologic hallmark of Wells syndrome is scattered flame figures, this finding is not specific and can be found in other hypereosinophilic conditions.² Clinical manifestations most often consist of 2 distinct phases: an initial painful burning or pruritic sensation, followed by the development of erythematous and edematous dermal plaques that may heal with slight hyperpigmentation over 4 to 8 weeks. A case series of 19 patients demonstrated variants of Wells syndrome, with an annular granuloma-like appearance found primarily in adults and the signature plaque-type appearance predominating in children.⁴  

Acute urticaria is characterized by pruritic erythematous wheals secondary to a histamine-mediated response brought on by a variety of triggers, typically allergic and self-resolving within 24 hours. When such lesions last longer than 24 hours, biopsy should be performed to exclude urticarial vasculitis, which is characterized by a burning or painful sensation rather than pruritis, in addition to dermal neutrophilia and perivascular infiltrate on histology. Erythema migrans of Lyme disease begins at the site of a tick bite, evolving from a red macule to an expanding targetoid lesion and typically is not pruritic. Infectious cellulitis presents with warm, tender, and poorly defined erythematous patches; can progress rapidly; and is accompanied by systemic symptoms such as fevers, malaise, and lymphadenopathy.  

Best evidence favors the use of moderate- to high-dose corticosteroids as first-line treatment.⁵ The use of tumor necrosis factor blockers, various immunomodulating agents, and combination therapy with levocetirizine and hydroxyzine have demonstrated variable levels of efficacy, albeit often followed by high rates of relapse with drug discontinuation.⁶  

AMSTERDAM – Rozanolixizumab, a subcutaneous antibody for the human neonatal Fc receptor, provides clinically meaningful improvements in platelet count for patients with primary immune thrombocytopenia, according to results from a recent phase 2 trial.

Rozanolixizumab was well tolerated across all dose groups, with higher doses delivering faster responses, reported lead author Tadeusz Robak, MD, PhD, of the Medical University of Lodz (Poland).

Targeting the Fc receptor interrupts recirculation of IgG, a key autoantibody in immune thrombocytopenia (ITP) pathogenesis, Dr. Robak explained during a presentation at the annual congress of the European Hematology Association. This approach represents an emerging treatment paradigm, he said, noting that rozanolixizumab is also being studied for the treatment of other IgG-driven autoimmune diseases, such as myasthenia gravis and chronic inflammatory demyelinating polyneuropathy.

The present open-label, dose-escalation study involved 54 adult patients with primary ITP of at least 3 months duration and platelet counts of less than 30 x 10⁹/L at screening and 35 x 10⁹/L at baseline. Eligibility required a previous response to ITP therapy. Enrolled patients were randomized into four dose groups: 4 mg/kg (five doses), 7 mg/kg (three doses), 10 mg/kg (two doses), or 15 mg/kg (one dose). After dosing, patients were followed for 8 weeks. Clinically relevant efficacy was defined as a platelet count of at least 50 x 10⁹/L. Decreases in IgG were also reported.

A safety analysis showed that the regimen was well tolerated across all dose groups. In total, 20.4% of patients experienced at least one treatment-related adverse event. The most common adverse events were headache (31.5%), diarrhea (11.1%), and vomiting (3.7%); all of which were mild or moderate. Headache appeared to be dose related, as 42% of patients in the 15-mg/kg group reported headache, compared with 8% in the 10-mg/kg group, 7% in the 7-mg/kg group, and none in the 4-mg/kg group. Out of four reported serious adverse events, none were considered treatment related.

Concerning efficacy, higher doses were associated with higher response rates and faster response times. In the 4-mg/kg group, 33% of patients achieved a platelet count of at least 50 x 10⁹/L, compared with 33% of the 7-mg/kg group, 50% of the 10-mg/kg group, and 67% of the 15-mg/kg group. Of the patients that achieved clinically meaningful responses, 20% of the 4-mg/kg group did so within 8 days, compared with 40% of 7-mg/kg responders, 50% of 10-mg/kg responders, and 87.5% of 15-mg/kg responders. Additional observations included dose-dependent decreases in IgG titer and longer response durations after multiple lower doses.

“Data from this study indicate that we can achieve effective increases in platelet levels, we can observe decreasing IgG levels, and the treatment was safe for the patients,” Dr. Robak said.

When asked about the intended clinical application of rozanolixizumab, Dr. Robak suggested that the agent may have a role in the postacute care setting. “We should develop a method of prolonged administration of [rozanolixizumab], as we saw that lower, multiple doses gave longer response durations.”

Still, he noted that more research is needed, since responses in diverse patient populations remain unknown. “We do not know how the drug will be active in truly refractory patients and we need this response before we establish the indication for the drug.”

The investigators reported financial relationships with Celgene, Roche, GlaxoSmithKline, Amgen, AbbVie, and other companies.

SOURCE: Robak T et al. EHA Congress, Abstract S850.

AMSTERDAM – Rozanolixizumab, a subcutaneous antibody for the human neonatal Fc receptor, provides clinically meaningful improvements in platelet count for patients with primary immune thrombocytopenia, according to results from a recent phase 2 trial.

Rozanolixizumab was well tolerated across all dose groups, with higher doses delivering faster responses, reported lead author Tadeusz Robak, MD, PhD, of the Medical University of Lodz (Poland).

Targeting the Fc receptor interrupts recirculation of IgG, a key autoantibody in immune thrombocytopenia (ITP) pathogenesis, Dr. Robak explained during a presentation at the annual congress of the European Hematology Association. This approach represents an emerging treatment paradigm, he said, noting that rozanolixizumab is also being studied for the treatment of other IgG-driven autoimmune diseases, such as myasthenia gravis and chronic inflammatory demyelinating polyneuropathy.

The present open-label, dose-escalation study involved 54 adult patients with primary ITP of at least 3 months duration and platelet counts of less than 30 x 10⁹/L at screening and 35 x 10⁹/L at baseline. Eligibility required a previous response to ITP therapy. Enrolled patients were randomized into four dose groups: 4 mg/kg (five doses), 7 mg/kg (three doses), 10 mg/kg (two doses), or 15 mg/kg (one dose). After dosing, patients were followed for 8 weeks. Clinically relevant efficacy was defined as a platelet count of at least 50 x 10⁹/L. Decreases in IgG were also reported.

A safety analysis showed that the regimen was well tolerated across all dose groups. In total, 20.4% of patients experienced at least one treatment-related adverse event. The most common adverse events were headache (31.5%), diarrhea (11.1%), and vomiting (3.7%); all of which were mild or moderate. Headache appeared to be dose related, as 42% of patients in the 15-mg/kg group reported headache, compared with 8% in the 10-mg/kg group, 7% in the 7-mg/kg group, and none in the 4-mg/kg group. Out of four reported serious adverse events, none were considered treatment related.

Concerning efficacy, higher doses were associated with higher response rates and faster response times. In the 4-mg/kg group, 33% of patients achieved a platelet count of at least 50 x 10⁹/L, compared with 33% of the 7-mg/kg group, 50% of the 10-mg/kg group, and 67% of the 15-mg/kg group. Of the patients that achieved clinically meaningful responses, 20% of the 4-mg/kg group did so within 8 days, compared with 40% of 7-mg/kg responders, 50% of 10-mg/kg responders, and 87.5% of 15-mg/kg responders. Additional observations included dose-dependent decreases in IgG titer and longer response durations after multiple lower doses.

“Data from this study indicate that we can achieve effective increases in platelet levels, we can observe decreasing IgG levels, and the treatment was safe for the patients,” Dr. Robak said.

When asked about the intended clinical application of rozanolixizumab, Dr. Robak suggested that the agent may have a role in the postacute care setting. “We should develop a method of prolonged administration of [rozanolixizumab], as we saw that lower, multiple doses gave longer response durations.”

Still, he noted that more research is needed, since responses in diverse patient populations remain unknown. “We do not know how the drug will be active in truly refractory patients and we need this response before we establish the indication for the drug.”

The investigators reported financial relationships with Celgene, Roche, GlaxoSmithKline, Amgen, AbbVie, and other companies.

SOURCE: Robak T et al. EHA Congress, Abstract S850.

AMSTERDAM – Rozanolixizumab, a subcutaneous antibody for the human neonatal Fc receptor, provides clinically meaningful improvements in platelet count for patients with primary immune thrombocytopenia, according to results from a recent phase 2 trial.

Rozanolixizumab was well tolerated across all dose groups, with higher doses delivering faster responses, reported lead author Tadeusz Robak, MD, PhD, of the Medical University of Lodz (Poland).

Targeting the Fc receptor interrupts recirculation of IgG, a key autoantibody in immune thrombocytopenia (ITP) pathogenesis, Dr. Robak explained during a presentation at the annual congress of the European Hematology Association. This approach represents an emerging treatment paradigm, he said, noting that rozanolixizumab is also being studied for the treatment of other IgG-driven autoimmune diseases, such as myasthenia gravis and chronic inflammatory demyelinating polyneuropathy.

The present open-label, dose-escalation study involved 54 adult patients with primary ITP of at least 3 months duration and platelet counts of less than 30 x 10⁹/L at screening and 35 x 10⁹/L at baseline. Eligibility required a previous response to ITP therapy. Enrolled patients were randomized into four dose groups: 4 mg/kg (five doses), 7 mg/kg (three doses), 10 mg/kg (two doses), or 15 mg/kg (one dose). After dosing, patients were followed for 8 weeks. Clinically relevant efficacy was defined as a platelet count of at least 50 x 10⁹/L. Decreases in IgG were also reported.

A safety analysis showed that the regimen was well tolerated across all dose groups. In total, 20.4% of patients experienced at least one treatment-related adverse event. The most common adverse events were headache (31.5%), diarrhea (11.1%), and vomiting (3.7%); all of which were mild or moderate. Headache appeared to be dose related, as 42% of patients in the 15-mg/kg group reported headache, compared with 8% in the 10-mg/kg group, 7% in the 7-mg/kg group, and none in the 4-mg/kg group. Out of four reported serious adverse events, none were considered treatment related.

Concerning efficacy, higher doses were associated with higher response rates and faster response times. In the 4-mg/kg group, 33% of patients achieved a platelet count of at least 50 x 10⁹/L, compared with 33% of the 7-mg/kg group, 50% of the 10-mg/kg group, and 67% of the 15-mg/kg group. Of the patients that achieved clinically meaningful responses, 20% of the 4-mg/kg group did so within 8 days, compared with 40% of 7-mg/kg responders, 50% of 10-mg/kg responders, and 87.5% of 15-mg/kg responders. Additional observations included dose-dependent decreases in IgG titer and longer response durations after multiple lower doses.

“Data from this study indicate that we can achieve effective increases in platelet levels, we can observe decreasing IgG levels, and the treatment was safe for the patients,” Dr. Robak said.

When asked about the intended clinical application of rozanolixizumab, Dr. Robak suggested that the agent may have a role in the postacute care setting. “We should develop a method of prolonged administration of [rozanolixizumab], as we saw that lower, multiple doses gave longer response durations.”

Still, he noted that more research is needed, since responses in diverse patient populations remain unknown. “We do not know how the drug will be active in truly refractory patients and we need this response before we establish the indication for the drug.”

The investigators reported financial relationships with Celgene, Roche, GlaxoSmithKline, Amgen, AbbVie, and other companies.

SOURCE: Robak T et al. EHA Congress, Abstract S850.

Budesonide orodispersible tablets (BOTs) are highly effective in inducing disease remission in adults with active eosinophilic esophagitis (EOE), according to a study of the tablets versus placebo in European patients.

“A 6-week treatment with 1 mg budesonide twice daily was highly superior over placebo with regard to all predefined primary and secondary outcomes,” wrote Alfredo J. Lucendo, MD, of Hospital General de Tomelloso in Real, Spain, and his coauthors. The study was published in Gastroenterology.

To assess the effectiveness and tolerability of BOT in adults with EOE, Dr. Lucendo and his fellow researchers launched a randomized, placebo-controlled trial made up of 88 European adults with active EoE. Patients were assigned to either a group that received BOT twice daily (n = 59) or a group that received placebo (n = 29). The primary endpoint was complete remission.

After 6 weeks, 34 of 59 patients (58%) receiving BOT had achieved complete remission, compared with 0 patients receiving placebo (P less than .0001). After 12 weeks, 50 of 59 patients (85%) in the BOT group had achieved complete remission. BOT was also well tolerated; no serious adverse event was reported, and no differences were observed between groups with regard to commonly reported adverse events.

The coauthors acknowledged their study’s limitations, including the fact that it was designed to demonstrate budesonide’s superiority to placebo at 6 weeks, not to identify the time of its maximal effect. In addition, the researchers did not identify a minimally effective dose; they did, however, note their belief that a lower dose could still achieve similar rates of remission and “a higher dose would not achieve a higher clinico-remission rate.”

The study was funded by Dr. Falk Pharma. The authors reported numerous conflicts of interest, including receiving research funding and speaker fees from various pharmaceutical companies and foundations.

SOURCE: Lucendo AJ et al. Gastroenterology. 2019 Mar 25. doi: 10.1053/j.gastro.2019.03.025.

Budesonide orodispersible tablets (BOTs) are highly effective in inducing disease remission in adults with active eosinophilic esophagitis (EOE), according to a study of the tablets versus placebo in European patients.

“A 6-week treatment with 1 mg budesonide twice daily was highly superior over placebo with regard to all predefined primary and secondary outcomes,” wrote Alfredo J. Lucendo, MD, of Hospital General de Tomelloso in Real, Spain, and his coauthors. The study was published in Gastroenterology.

To assess the effectiveness and tolerability of BOT in adults with EOE, Dr. Lucendo and his fellow researchers launched a randomized, placebo-controlled trial made up of 88 European adults with active EoE. Patients were assigned to either a group that received BOT twice daily (n = 59) or a group that received placebo (n = 29). The primary endpoint was complete remission.

After 6 weeks, 34 of 59 patients (58%) receiving BOT had achieved complete remission, compared with 0 patients receiving placebo (P less than .0001). After 12 weeks, 50 of 59 patients (85%) in the BOT group had achieved complete remission. BOT was also well tolerated; no serious adverse event was reported, and no differences were observed between groups with regard to commonly reported adverse events.

The coauthors acknowledged their study’s limitations, including the fact that it was designed to demonstrate budesonide’s superiority to placebo at 6 weeks, not to identify the time of its maximal effect. In addition, the researchers did not identify a minimally effective dose; they did, however, note their belief that a lower dose could still achieve similar rates of remission and “a higher dose would not achieve a higher clinico-remission rate.”

The study was funded by Dr. Falk Pharma. The authors reported numerous conflicts of interest, including receiving research funding and speaker fees from various pharmaceutical companies and foundations.

SOURCE: Lucendo AJ et al. Gastroenterology. 2019 Mar 25. doi: 10.1053/j.gastro.2019.03.025.

Budesonide orodispersible tablets (BOTs) are highly effective in inducing disease remission in adults with active eosinophilic esophagitis (EOE), according to a study of the tablets versus placebo in European patients.

“A 6-week treatment with 1 mg budesonide twice daily was highly superior over placebo with regard to all predefined primary and secondary outcomes,” wrote Alfredo J. Lucendo, MD, of Hospital General de Tomelloso in Real, Spain, and his coauthors. The study was published in Gastroenterology.

To assess the effectiveness and tolerability of BOT in adults with EOE, Dr. Lucendo and his fellow researchers launched a randomized, placebo-controlled trial made up of 88 European adults with active EoE. Patients were assigned to either a group that received BOT twice daily (n = 59) or a group that received placebo (n = 29). The primary endpoint was complete remission.

After 6 weeks, 34 of 59 patients (58%) receiving BOT had achieved complete remission, compared with 0 patients receiving placebo (P less than .0001). After 12 weeks, 50 of 59 patients (85%) in the BOT group had achieved complete remission. BOT was also well tolerated; no serious adverse event was reported, and no differences were observed between groups with regard to commonly reported adverse events.

The coauthors acknowledged their study’s limitations, including the fact that it was designed to demonstrate budesonide’s superiority to placebo at 6 weeks, not to identify the time of its maximal effect. In addition, the researchers did not identify a minimally effective dose; they did, however, note their belief that a lower dose could still achieve similar rates of remission and “a higher dose would not achieve a higher clinico-remission rate.”

The study was funded by Dr. Falk Pharma. The authors reported numerous conflicts of interest, including receiving research funding and speaker fees from various pharmaceutical companies and foundations.

SOURCE: Lucendo AJ et al. Gastroenterology. 2019 Mar 25. doi: 10.1053/j.gastro.2019.03.025.

Click here to read the supplement

Key Points

• The Global Initiative for Chronic Obstructive Lung Disease (GOLD) program releases consensus reports to provide evidence-based recommendations about the management and prevention of chronic obstructive pulmonary disease (COPD);
• The most recent major update occurred in November 2018.
• The 2019 GOLD strategy for COPD assessment now separates lung function measures from respiratory symptom scores because lung function is only weakly correlated to symptoms and health status impairment.
• The updated strategy now provides recommendations for initiation and maintenance of pharmacologic therapy in patients based on exacerbation risk and symptom scores, with consideration of blood eosinophil counts.
• Management of exacerbations now includes the prevention of future exacerbations, which may require adding another medication to the patient's maintenance regimen.

Click here to read more

About the Authors:

Jennifer Banfield, APRN, FNP
Clinical Research Coordinator
Boys Town National Research Hospital
Boys Town, Nebraska

Kevin R. Murphy, MD
Director of Allergy, Asthma, and Pulmonary Research
Boys Town National Research Hospital
Boys Town, Nebraska
University of Nebraska Medical Center
Creighton University School of Medicine
Omaha, Nebraska

Click here to read the supplement

Key Points

• The Global Initiative for Chronic Obstructive Lung Disease (GOLD) program releases consensus reports to provide evidence-based recommendations about the management and prevention of chronic obstructive pulmonary disease (COPD);
• The most recent major update occurred in November 2018.
• The 2019 GOLD strategy for COPD assessment now separates lung function measures from respiratory symptom scores because lung function is only weakly correlated to symptoms and health status impairment.
• The updated strategy now provides recommendations for initiation and maintenance of pharmacologic therapy in patients based on exacerbation risk and symptom scores, with consideration of blood eosinophil counts.
• Management of exacerbations now includes the prevention of future exacerbations, which may require adding another medication to the patient's maintenance regimen.

Click here to read more

About the Authors:

Jennifer Banfield, APRN, FNP
Clinical Research Coordinator
Boys Town National Research Hospital
Boys Town, Nebraska

Kevin R. Murphy, MD
Director of Allergy, Asthma, and Pulmonary Research
Boys Town National Research Hospital
Boys Town, Nebraska
University of Nebraska Medical Center
Creighton University School of Medicine
Omaha, Nebraska

Click here to read the supplement

Key Points

• The Global Initiative for Chronic Obstructive Lung Disease (GOLD) program releases consensus reports to provide evidence-based recommendations about the management and prevention of chronic obstructive pulmonary disease (COPD);
• The most recent major update occurred in November 2018.
• The 2019 GOLD strategy for COPD assessment now separates lung function measures from respiratory symptom scores because lung function is only weakly correlated to symptoms and health status impairment.
• The updated strategy now provides recommendations for initiation and maintenance of pharmacologic therapy in patients based on exacerbation risk and symptom scores, with consideration of blood eosinophil counts.
• Management of exacerbations now includes the prevention of future exacerbations, which may require adding another medication to the patient's maintenance regimen.

Click here to read more

About the Authors:

Jennifer Banfield, APRN, FNP
Clinical Research Coordinator
Boys Town National Research Hospital
Boys Town, Nebraska

Kevin R. Murphy, MD
Director of Allergy, Asthma, and Pulmonary Research
Boys Town National Research Hospital
Boys Town, Nebraska
University of Nebraska Medical Center
Creighton University School of Medicine
Omaha, Nebraska

Atypical vascular lesions (AVLs) are rare flesh-colored, erythematous, or violaceous macules, patches, papules, or plaques that may occur following adjuvant radiation in breast cancer patients who have undergone conservative lumpectomy.^1,2 They range in size from 1 mm to 6 cm and are most often confined to the radiation field. Presentation occurs 1 to 20 years following radiation, though the lesions most often present within 5 years.^1,2 Although generally considered benign, 2 of 29 cases of AVLs progressed to angiosarcoma over a 5-year follow-up period in a retrospective clinicopathologic study.¹

Atypical vascular lesions show considerable histologic and clinical overlap with radiation-induced angiosarcomas (RIAs), making differentiation between the two challenging.^3,4 Mentzel et al⁵ compared benign, atypical, and malignant postradiation vascular lesions with nonradiation-associated angiosarcomas and found that RIAs were highly variable histopathologically, ranging from well differentiated to poorly differentiated, with atypia ranging from mild to severe. Radiation-induced angiosarcomas could be distinguished from AVLs and nonradiation-associated angiosarcomas by their oncogene amplification and protein expression profiles. Most strikingly, they found amplification of the MYC oncogene by fluorescence in situ hybridization in the nucleus of almost all the RIA cells, which was not seen in AVLs or nonradiation-associated angiosarcomas. Similarly, they found positive nuclear staining for MYC protein by immunohistochemistry in the nucleus of almost all cases of RIA but not in AVL or nonradiation-associated angiosarcomas, making MYC staining a useful diagnostic marker.⁵ In contrast, a study by Patton et al¹ concluded that AVLs demonstrate morphologic patterns and clinical outcomes that suggest they are precursors of angiosarcoma rather than just markers of risk.

Atypical vascular lesions and RIAs usually follow a total radiation dose of 40 to 50 Gy, but RIAs typically are diagnosed later (approximately 10 years following exposure).^6,7 Although RIAs are rare, they are known to be aggressive and often high grade, with a median survival of less than 5 years.^6,7 Survival is poor even with radical surgical treatment.⁸ We present a patient with at least 29 AVLs following breast-conserving surgery and radiation and suggest the need for increased awareness of the elevated risk for RIA in patients with numerous benign AVLs.

Case Report

A 43-year-old woman with a history of breast cancer who underwent breast-conserving lumpectomy and adjuvant radiation presented to dermatology upon referral from surgical oncology for multiple lesions on the right breast (Figure 1). Seven years prior to presentation she was diagnosed with grade 3 poorly differentiated invasive ductal carcinoma with lobular features in the right breast that was positive for human epidermal growth factor receptor 2 but negative for estrogen or progesterone receptors. She was given neoadjuvant treatment with trastuzumab, docetaxel, and carboplatin prior to conservation lumpectomy with adjuvant radiation. She received a total dose of 50.4 Gy in 28 fractions of 1.8 Gy each over 1 month, with a final boost of 10 Gy in 5 fractions of 2 Gy, each with local skin irritation as the only concern posttreatment.

She initially presented to dermatology approximately 3 years after radiotherapy (5 years prior to current presentation) with lesions on the breast that had been present for 6 to 9 months. Physical examination showed 2 firm, painless, 4- to 5-mm papules on the right upper breast. The patient was reassured that the lesions were not suspicious for malignancy; however, 3 years later she presented to surgical oncology with 8 bluish papules or macules (all approximately 4 mm in diameter) on the right breast. These lesions were biopsied and examined by 2 institutions. Pathology of the initial punch biopsy favored a diagnosis of AVLs, though the possibility of RIA could not be ruled out without a complete excisional biopsy. Two excisional biopsies a month later were again consistent with AVLs. In all cases, the lesions were negative for MYC protein. The patient was again reassured but referred to dermatology for a second opinion.

At the current presentation, physical examination showed at least 29 subcutaneous nodules on the right breast ranging in color from pink to deep blue to flesh colored with others more superficially hyperpigmented, possibly secondary to prior biopsy, and measuring 2 to 8 mm in diameter. Histopathologic examination of the biopsy specimens showed a vascular proliferation extending from the dermis into the subcutaneous tissue comprised of dilated and cavernous vascular channels lined by a single layer of endothelial cells with minimal cytologic atypia (Figure 2). There were focal areas of anastomosing slitlike vascular spaces dissecting dermal collagen. No features of malignancy, such as nuclear crowding, multilayering, or increased mitotic activity, were evident. Immunohistochemical studies for MYC protein were negative. The overall morphologic features and immunoprofile were felt to be most consistent with postradiation AVLs.

Comment

Conservative breast cancer surgery and radiotherapy are becoming more prevalent for breast cancer treatment, thus the number of patients likely to present with AVLs has increased. These patients are at risk for transformation to RIAs.⁶ It is important for clinicians to be aware of the diagnosis of both AVLs and RIAs and their management given their more frequent presentation. In most cases, one or a few AVLs are present, and excision is the treatment of choice. In a retrospective study by Brenn and Fletcher³ examining 16 patients with AVLs and 26 patients with RIA, the majority of cases of AVL had a single lesion and the maximum number of AVLs was 4. One patient in their study had 30 AVLs (each 3–4 mm in diameter), and she was diagnosed with RIA.³ Our patient—with at least 29 identifiable AVL lesions—was felt to be at considerable risk for developing RIA, as the only other case reported with this many AVLs developed RIA.¹ Given the large number of lesions, it was neither feasible to excise each one individually nor monitor all of them for malignant transformation.

Our case demonstrates the important role dermatologists may play in orchestrating care by a multispecialty team including oncology, radiation oncology, surgery, and plastic surgery. In our patient, a close examination of the literature by the dermatology team led to recognition of the potentially elevated risk for malignant transformation. The dermatology team also brought the case for review at the tumor board.

Although future studies are required to determine the relationship between AVL burden and the risk for progression to RIA, it is clear that a multidisciplinary approach and careful consideration of the current literature can prevent unnecessary morbidity and mortality for patients with this increasingly common problem.

Atypical vascular lesions (AVLs) are rare flesh-colored, erythematous, or violaceous macules, patches, papules, or plaques that may occur following adjuvant radiation in breast cancer patients who have undergone conservative lumpectomy.^1,2 They range in size from 1 mm to 6 cm and are most often confined to the radiation field. Presentation occurs 1 to 20 years following radiation, though the lesions most often present within 5 years.^1,2 Although generally considered benign, 2 of 29 cases of AVLs progressed to angiosarcoma over a 5-year follow-up period in a retrospective clinicopathologic study.¹

Atypical vascular lesions show considerable histologic and clinical overlap with radiation-induced angiosarcomas (RIAs), making differentiation between the two challenging.^3,4 Mentzel et al⁵ compared benign, atypical, and malignant postradiation vascular lesions with nonradiation-associated angiosarcomas and found that RIAs were highly variable histopathologically, ranging from well differentiated to poorly differentiated, with atypia ranging from mild to severe. Radiation-induced angiosarcomas could be distinguished from AVLs and nonradiation-associated angiosarcomas by their oncogene amplification and protein expression profiles. Most strikingly, they found amplification of the MYC oncogene by fluorescence in situ hybridization in the nucleus of almost all the RIA cells, which was not seen in AVLs or nonradiation-associated angiosarcomas. Similarly, they found positive nuclear staining for MYC protein by immunohistochemistry in the nucleus of almost all cases of RIA but not in AVL or nonradiation-associated angiosarcomas, making MYC staining a useful diagnostic marker.⁵ In contrast, a study by Patton et al¹ concluded that AVLs demonstrate morphologic patterns and clinical outcomes that suggest they are precursors of angiosarcoma rather than just markers of risk.

Atypical vascular lesions and RIAs usually follow a total radiation dose of 40 to 50 Gy, but RIAs typically are diagnosed later (approximately 10 years following exposure).^6,7 Although RIAs are rare, they are known to be aggressive and often high grade, with a median survival of less than 5 years.^6,7 Survival is poor even with radical surgical treatment.⁸ We present a patient with at least 29 AVLs following breast-conserving surgery and radiation and suggest the need for increased awareness of the elevated risk for RIA in patients with numerous benign AVLs.

Case Report

A 43-year-old woman with a history of breast cancer who underwent breast-conserving lumpectomy and adjuvant radiation presented to dermatology upon referral from surgical oncology for multiple lesions on the right breast (Figure 1). Seven years prior to presentation she was diagnosed with grade 3 poorly differentiated invasive ductal carcinoma with lobular features in the right breast that was positive for human epidermal growth factor receptor 2 but negative for estrogen or progesterone receptors. She was given neoadjuvant treatment with trastuzumab, docetaxel, and carboplatin prior to conservation lumpectomy with adjuvant radiation. She received a total dose of 50.4 Gy in 28 fractions of 1.8 Gy each over 1 month, with a final boost of 10 Gy in 5 fractions of 2 Gy, each with local skin irritation as the only concern posttreatment.

She initially presented to dermatology approximately 3 years after radiotherapy (5 years prior to current presentation) with lesions on the breast that had been present for 6 to 9 months. Physical examination showed 2 firm, painless, 4- to 5-mm papules on the right upper breast. The patient was reassured that the lesions were not suspicious for malignancy; however, 3 years later she presented to surgical oncology with 8 bluish papules or macules (all approximately 4 mm in diameter) on the right breast. These lesions were biopsied and examined by 2 institutions. Pathology of the initial punch biopsy favored a diagnosis of AVLs, though the possibility of RIA could not be ruled out without a complete excisional biopsy. Two excisional biopsies a month later were again consistent with AVLs. In all cases, the lesions were negative for MYC protein. The patient was again reassured but referred to dermatology for a second opinion.

At the current presentation, physical examination showed at least 29 subcutaneous nodules on the right breast ranging in color from pink to deep blue to flesh colored with others more superficially hyperpigmented, possibly secondary to prior biopsy, and measuring 2 to 8 mm in diameter. Histopathologic examination of the biopsy specimens showed a vascular proliferation extending from the dermis into the subcutaneous tissue comprised of dilated and cavernous vascular channels lined by a single layer of endothelial cells with minimal cytologic atypia (Figure 2). There were focal areas of anastomosing slitlike vascular spaces dissecting dermal collagen. No features of malignancy, such as nuclear crowding, multilayering, or increased mitotic activity, were evident. Immunohistochemical studies for MYC protein were negative. The overall morphologic features and immunoprofile were felt to be most consistent with postradiation AVLs.

Comment

Conservative breast cancer surgery and radiotherapy are becoming more prevalent for breast cancer treatment, thus the number of patients likely to present with AVLs has increased. These patients are at risk for transformation to RIAs.⁶ It is important for clinicians to be aware of the diagnosis of both AVLs and RIAs and their management given their more frequent presentation. In most cases, one or a few AVLs are present, and excision is the treatment of choice. In a retrospective study by Brenn and Fletcher³ examining 16 patients with AVLs and 26 patients with RIA, the majority of cases of AVL had a single lesion and the maximum number of AVLs was 4. One patient in their study had 30 AVLs (each 3–4 mm in diameter), and she was diagnosed with RIA.³ Our patient—with at least 29 identifiable AVL lesions—was felt to be at considerable risk for developing RIA, as the only other case reported with this many AVLs developed RIA.¹ Given the large number of lesions, it was neither feasible to excise each one individually nor monitor all of them for malignant transformation.

Our case demonstrates the important role dermatologists may play in orchestrating care by a multispecialty team including oncology, radiation oncology, surgery, and plastic surgery. In our patient, a close examination of the literature by the dermatology team led to recognition of the potentially elevated risk for malignant transformation. The dermatology team also brought the case for review at the tumor board.

Although future studies are required to determine the relationship between AVL burden and the risk for progression to RIA, it is clear that a multidisciplinary approach and careful consideration of the current literature can prevent unnecessary morbidity and mortality for patients with this increasingly common problem.

Atypical vascular lesions (AVLs) are rare flesh-colored, erythematous, or violaceous macules, patches, papules, or plaques that may occur following adjuvant radiation in breast cancer patients who have undergone conservative lumpectomy.^1,2 They range in size from 1 mm to 6 cm and are most often confined to the radiation field. Presentation occurs 1 to 20 years following radiation, though the lesions most often present within 5 years.^1,2 Although generally considered benign, 2 of 29 cases of AVLs progressed to angiosarcoma over a 5-year follow-up period in a retrospective clinicopathologic study.¹

Atypical vascular lesions show considerable histologic and clinical overlap with radiation-induced angiosarcomas (RIAs), making differentiation between the two challenging.^3,4 Mentzel et al⁵ compared benign, atypical, and malignant postradiation vascular lesions with nonradiation-associated angiosarcomas and found that RIAs were highly variable histopathologically, ranging from well differentiated to poorly differentiated, with atypia ranging from mild to severe. Radiation-induced angiosarcomas could be distinguished from AVLs and nonradiation-associated angiosarcomas by their oncogene amplification and protein expression profiles. Most strikingly, they found amplification of the MYC oncogene by fluorescence in situ hybridization in the nucleus of almost all the RIA cells, which was not seen in AVLs or nonradiation-associated angiosarcomas. Similarly, they found positive nuclear staining for MYC protein by immunohistochemistry in the nucleus of almost all cases of RIA but not in AVL or nonradiation-associated angiosarcomas, making MYC staining a useful diagnostic marker.⁵ In contrast, a study by Patton et al¹ concluded that AVLs demonstrate morphologic patterns and clinical outcomes that suggest they are precursors of angiosarcoma rather than just markers of risk.

Atypical vascular lesions and RIAs usually follow a total radiation dose of 40 to 50 Gy, but RIAs typically are diagnosed later (approximately 10 years following exposure).^6,7 Although RIAs are rare, they are known to be aggressive and often high grade, with a median survival of less than 5 years.^6,7 Survival is poor even with radical surgical treatment.⁸ We present a patient with at least 29 AVLs following breast-conserving surgery and radiation and suggest the need for increased awareness of the elevated risk for RIA in patients with numerous benign AVLs.

Case Report

A 43-year-old woman with a history of breast cancer who underwent breast-conserving lumpectomy and adjuvant radiation presented to dermatology upon referral from surgical oncology for multiple lesions on the right breast (Figure 1). Seven years prior to presentation she was diagnosed with grade 3 poorly differentiated invasive ductal carcinoma with lobular features in the right breast that was positive for human epidermal growth factor receptor 2 but negative for estrogen or progesterone receptors. She was given neoadjuvant treatment with trastuzumab, docetaxel, and carboplatin prior to conservation lumpectomy with adjuvant radiation. She received a total dose of 50.4 Gy in 28 fractions of 1.8 Gy each over 1 month, with a final boost of 10 Gy in 5 fractions of 2 Gy, each with local skin irritation as the only concern posttreatment.

She initially presented to dermatology approximately 3 years after radiotherapy (5 years prior to current presentation) with lesions on the breast that had been present for 6 to 9 months. Physical examination showed 2 firm, painless, 4- to 5-mm papules on the right upper breast. The patient was reassured that the lesions were not suspicious for malignancy; however, 3 years later she presented to surgical oncology with 8 bluish papules or macules (all approximately 4 mm in diameter) on the right breast. These lesions were biopsied and examined by 2 institutions. Pathology of the initial punch biopsy favored a diagnosis of AVLs, though the possibility of RIA could not be ruled out without a complete excisional biopsy. Two excisional biopsies a month later were again consistent with AVLs. In all cases, the lesions were negative for MYC protein. The patient was again reassured but referred to dermatology for a second opinion.

At the current presentation, physical examination showed at least 29 subcutaneous nodules on the right breast ranging in color from pink to deep blue to flesh colored with others more superficially hyperpigmented, possibly secondary to prior biopsy, and measuring 2 to 8 mm in diameter. Histopathologic examination of the biopsy specimens showed a vascular proliferation extending from the dermis into the subcutaneous tissue comprised of dilated and cavernous vascular channels lined by a single layer of endothelial cells with minimal cytologic atypia (Figure 2). There were focal areas of anastomosing slitlike vascular spaces dissecting dermal collagen. No features of malignancy, such as nuclear crowding, multilayering, or increased mitotic activity, were evident. Immunohistochemical studies for MYC protein were negative. The overall morphologic features and immunoprofile were felt to be most consistent with postradiation AVLs.

Comment

Conservative breast cancer surgery and radiotherapy are becoming more prevalent for breast cancer treatment, thus the number of patients likely to present with AVLs has increased. These patients are at risk for transformation to RIAs.⁶ It is important for clinicians to be aware of the diagnosis of both AVLs and RIAs and their management given their more frequent presentation. In most cases, one or a few AVLs are present, and excision is the treatment of choice. In a retrospective study by Brenn and Fletcher³ examining 16 patients with AVLs and 26 patients with RIA, the majority of cases of AVL had a single lesion and the maximum number of AVLs was 4. One patient in their study had 30 AVLs (each 3–4 mm in diameter), and she was diagnosed with RIA.³ Our patient—with at least 29 identifiable AVL lesions—was felt to be at considerable risk for developing RIA, as the only other case reported with this many AVLs developed RIA.¹ Given the large number of lesions, it was neither feasible to excise each one individually nor monitor all of them for malignant transformation.

Our case demonstrates the important role dermatologists may play in orchestrating care by a multispecialty team including oncology, radiation oncology, surgery, and plastic surgery. In our patient, a close examination of the literature by the dermatology team led to recognition of the potentially elevated risk for malignant transformation. The dermatology team also brought the case for review at the tumor board.

Although future studies are required to determine the relationship between AVL burden and the risk for progression to RIA, it is clear that a multidisciplinary approach and careful consideration of the current literature can prevent unnecessary morbidity and mortality for patients with this increasingly common problem.

A study found that only 2% of children hospitalized with community-acquired pneumonia (CAP) actually had any causative pathogen in their blood culture results, despite national guidelines that recommend blood cultures for all children hospitalized with moderate to severe CAP.

CDC/Dr. Mike Miller

The guidelines are the 2011 guidelines for managing CAP published by the Pediatric Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA) (Clin Infect Dis. 2011 Oct;53[7]:617-30).

Cristin O. Fritz, MD, of the Children’s Hospital of Colorado, Aurora, and associates conducted a data analysis of the EPIC (Etiology of Pneumonia in the Community) study to estimate prevalence, risk factors, and clinical outcomes in children hospitalized with bacteremic CAP and to evaluate the relationship between positive blood culture results, empirical antibiotics, and changes in antibiotic treatment regimens.

Data were collected at two Tennessee hospitals and one Utah hospital during Jan. 1, 2010–June 30, 2012. Of the 2,358 children with CAP enrolled in the study, 2,143 (91%) with blood cultures were included in Dr. Fritz’s analysis. Of the 53 patients presenting with positive blood culture results, 46 (2%; 95% confidence interval: 1.6%-2.9%) were identified as having bacteremia. Half of all cases observed were caused by Streptococcus pneumoniae, with Staphylococcus aureus and Streptococcus pyogenes noted less frequently, according to the study published in Pediatrics.

A previous meta-analysis of smaller studies also found that children with CAP rarely had positive blood culture results, a pooled prevalence of 5% (Pediatr Infect Dis J. 2013;32[7]:736-40). Although it is believed that positive blood culture results are key to narrowing the choice of antibiotic and predicting treatment outcomes, the literature – to date – reveals a paucity of data supporting this assumption.

Overall, children in the study presenting with bacteremia experienced more severe clinical outcomes, including longer length of stay, greater likelihood of ICU admission, and invasive mechanical ventilation and/or shock. The authors also observed that bacteremia was less likely to be detected in children given antibiotics after admission but before cultures were obtained (0.8% vs 3%; P = .021). Pleural effusion detected with chest radiograph also consistently indicated bacteremic pneumonia, an observation made within this and other similar studies.

Also of note in detection is the biomarker procalcitonin, which is typically present with bacterial disease. Dr. Fritz and colleagues stressed that because the procalcitonin rate was higher in patients presenting with bacteremia, “this information could influence decisions around culturing if results are rapidly available.” Risk-stratification tools also might serve a valuable purpose in ferreting out those patients presenting with moderate to severe pneumonia most at increased risk for bacterial CAP.

Compared with other studies reporting prevalence ranges of 1%-7%, the prevalence of bacteremia in this study is lower at 2%. The authors attributed the difference to a possible potential limitation with the other studies, for which culture data was only available for a median 47% of enrollees. Dr. Fritz and her colleagues caution that “because cultures were obtained at the discretion of the treating clinician in a majority of studies, blood cultures were likely obtained more often in those with more severe illness or who had not already received antibiotics.” In this scenario, the likelihood that prevalence of bacteremia was overestimated is noteworthy.

The authors observed that penicillin-susceptible S. pneumonia was the most common cause of bacteremic CAP. They further acknowledged that their study and findings by Neuman et al. in 2017 give credence to the joint 2011 PIDS/IDSA guideline recommending narrow-spectrum aminopenicillins specifically to treat children hospitalized due to suspected bacterial CAP.

Despite its small sample size, the results of this study clearly demonstrate that children with bacteremia because of S. pyogenes or S. aureus experience increased morbidity, compared with children with S. pneumoniae, they said

While this is acknowledged to be one of the largest studies of its kind to date, a key limitation was the small number of observable patients with bacteremia, which prevented the researchers from conducting a more in-depth analysis of risk factors and pathogen-specific differences. That one-fourth of patients received in-patient antibiotics before cultures could be collected also likely led to an underestimation of risk factors and misclassification bias. Lastly, the use of blood culture instead of whole-blood polymerase chain reaction, which is known to be more sensitive, also may have led to underestimation of overall bacteremia prevalence.

“In an era with widespread pneumococcal vaccination and low prevalence of bacteremia in the United States, children admitted with CAP that have pleural effusion or require ICU admission may represent a high-yield population for identifying bacteremia,” noted Dr. Fritz and associates.

Dr. Fritz had no conflicts of interest to report. Some coauthors cited multiple sources of potential conflict of interest related to consulting fees, grant support, and research support from various pharmaceutical companies and agencies. The study was funded by the National Institutes of Health and in part by a grant from the National Institute of Allergy and Infectious Diseases.

SOURCE: Fritz C et al. Pediatrics. 2019;144(1):e20183090.

A study found that only 2% of children hospitalized with community-acquired pneumonia (CAP) actually had any causative pathogen in their blood culture results, despite national guidelines that recommend blood cultures for all children hospitalized with moderate to severe CAP.

CDC/Dr. Mike Miller

The guidelines are the 2011 guidelines for managing CAP published by the Pediatric Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA) (Clin Infect Dis. 2011 Oct;53[7]:617-30).

Cristin O. Fritz, MD, of the Children’s Hospital of Colorado, Aurora, and associates conducted a data analysis of the EPIC (Etiology of Pneumonia in the Community) study to estimate prevalence, risk factors, and clinical outcomes in children hospitalized with bacteremic CAP and to evaluate the relationship between positive blood culture results, empirical antibiotics, and changes in antibiotic treatment regimens.

Data were collected at two Tennessee hospitals and one Utah hospital during Jan. 1, 2010–June 30, 2012. Of the 2,358 children with CAP enrolled in the study, 2,143 (91%) with blood cultures were included in Dr. Fritz’s analysis. Of the 53 patients presenting with positive blood culture results, 46 (2%; 95% confidence interval: 1.6%-2.9%) were identified as having bacteremia. Half of all cases observed were caused by Streptococcus pneumoniae, with Staphylococcus aureus and Streptococcus pyogenes noted less frequently, according to the study published in Pediatrics.

A previous meta-analysis of smaller studies also found that children with CAP rarely had positive blood culture results, a pooled prevalence of 5% (Pediatr Infect Dis J. 2013;32[7]:736-40). Although it is believed that positive blood culture results are key to narrowing the choice of antibiotic and predicting treatment outcomes, the literature – to date – reveals a paucity of data supporting this assumption.

Overall, children in the study presenting with bacteremia experienced more severe clinical outcomes, including longer length of stay, greater likelihood of ICU admission, and invasive mechanical ventilation and/or shock. The authors also observed that bacteremia was less likely to be detected in children given antibiotics after admission but before cultures were obtained (0.8% vs 3%; P = .021). Pleural effusion detected with chest radiograph also consistently indicated bacteremic pneumonia, an observation made within this and other similar studies.

Also of note in detection is the biomarker procalcitonin, which is typically present with bacterial disease. Dr. Fritz and colleagues stressed that because the procalcitonin rate was higher in patients presenting with bacteremia, “this information could influence decisions around culturing if results are rapidly available.” Risk-stratification tools also might serve a valuable purpose in ferreting out those patients presenting with moderate to severe pneumonia most at increased risk for bacterial CAP.

Compared with other studies reporting prevalence ranges of 1%-7%, the prevalence of bacteremia in this study is lower at 2%. The authors attributed the difference to a possible potential limitation with the other studies, for which culture data was only available for a median 47% of enrollees. Dr. Fritz and her colleagues caution that “because cultures were obtained at the discretion of the treating clinician in a majority of studies, blood cultures were likely obtained more often in those with more severe illness or who had not already received antibiotics.” In this scenario, the likelihood that prevalence of bacteremia was overestimated is noteworthy.

The authors observed that penicillin-susceptible S. pneumonia was the most common cause of bacteremic CAP. They further acknowledged that their study and findings by Neuman et al. in 2017 give credence to the joint 2011 PIDS/IDSA guideline recommending narrow-spectrum aminopenicillins specifically to treat children hospitalized due to suspected bacterial CAP.

Despite its small sample size, the results of this study clearly demonstrate that children with bacteremia because of S. pyogenes or S. aureus experience increased morbidity, compared with children with S. pneumoniae, they said

While this is acknowledged to be one of the largest studies of its kind to date, a key limitation was the small number of observable patients with bacteremia, which prevented the researchers from conducting a more in-depth analysis of risk factors and pathogen-specific differences. That one-fourth of patients received in-patient antibiotics before cultures could be collected also likely led to an underestimation of risk factors and misclassification bias. Lastly, the use of blood culture instead of whole-blood polymerase chain reaction, which is known to be more sensitive, also may have led to underestimation of overall bacteremia prevalence.

“In an era with widespread pneumococcal vaccination and low prevalence of bacteremia in the United States, children admitted with CAP that have pleural effusion or require ICU admission may represent a high-yield population for identifying bacteremia,” noted Dr. Fritz and associates.

Dr. Fritz had no conflicts of interest to report. Some coauthors cited multiple sources of potential conflict of interest related to consulting fees, grant support, and research support from various pharmaceutical companies and agencies. The study was funded by the National Institutes of Health and in part by a grant from the National Institute of Allergy and Infectious Diseases.

SOURCE: Fritz C et al. Pediatrics. 2019;144(1):e20183090.

A study found that only 2% of children hospitalized with community-acquired pneumonia (CAP) actually had any causative pathogen in their blood culture results, despite national guidelines that recommend blood cultures for all children hospitalized with moderate to severe CAP.

CDC/Dr. Mike Miller

The guidelines are the 2011 guidelines for managing CAP published by the Pediatric Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA) (Clin Infect Dis. 2011 Oct;53[7]:617-30).

Cristin O. Fritz, MD, of the Children’s Hospital of Colorado, Aurora, and associates conducted a data analysis of the EPIC (Etiology of Pneumonia in the Community) study to estimate prevalence, risk factors, and clinical outcomes in children hospitalized with bacteremic CAP and to evaluate the relationship between positive blood culture results, empirical antibiotics, and changes in antibiotic treatment regimens.

Data were collected at two Tennessee hospitals and one Utah hospital during Jan. 1, 2010–June 30, 2012. Of the 2,358 children with CAP enrolled in the study, 2,143 (91%) with blood cultures were included in Dr. Fritz’s analysis. Of the 53 patients presenting with positive blood culture results, 46 (2%; 95% confidence interval: 1.6%-2.9%) were identified as having bacteremia. Half of all cases observed were caused by Streptococcus pneumoniae, with Staphylococcus aureus and Streptococcus pyogenes noted less frequently, according to the study published in Pediatrics.

A previous meta-analysis of smaller studies also found that children with CAP rarely had positive blood culture results, a pooled prevalence of 5% (Pediatr Infect Dis J. 2013;32[7]:736-40). Although it is believed that positive blood culture results are key to narrowing the choice of antibiotic and predicting treatment outcomes, the literature – to date – reveals a paucity of data supporting this assumption.

Overall, children in the study presenting with bacteremia experienced more severe clinical outcomes, including longer length of stay, greater likelihood of ICU admission, and invasive mechanical ventilation and/or shock. The authors also observed that bacteremia was less likely to be detected in children given antibiotics after admission but before cultures were obtained (0.8% vs 3%; P = .021). Pleural effusion detected with chest radiograph also consistently indicated bacteremic pneumonia, an observation made within this and other similar studies.

Also of note in detection is the biomarker procalcitonin, which is typically present with bacterial disease. Dr. Fritz and colleagues stressed that because the procalcitonin rate was higher in patients presenting with bacteremia, “this information could influence decisions around culturing if results are rapidly available.” Risk-stratification tools also might serve a valuable purpose in ferreting out those patients presenting with moderate to severe pneumonia most at increased risk for bacterial CAP.

Compared with other studies reporting prevalence ranges of 1%-7%, the prevalence of bacteremia in this study is lower at 2%. The authors attributed the difference to a possible potential limitation with the other studies, for which culture data was only available for a median 47% of enrollees. Dr. Fritz and her colleagues caution that “because cultures were obtained at the discretion of the treating clinician in a majority of studies, blood cultures were likely obtained more often in those with more severe illness or who had not already received antibiotics.” In this scenario, the likelihood that prevalence of bacteremia was overestimated is noteworthy.

The authors observed that penicillin-susceptible S. pneumonia was the most common cause of bacteremic CAP. They further acknowledged that their study and findings by Neuman et al. in 2017 give credence to the joint 2011 PIDS/IDSA guideline recommending narrow-spectrum aminopenicillins specifically to treat children hospitalized due to suspected bacterial CAP.

Despite its small sample size, the results of this study clearly demonstrate that children with bacteremia because of S. pyogenes or S. aureus experience increased morbidity, compared with children with S. pneumoniae, they said

While this is acknowledged to be one of the largest studies of its kind to date, a key limitation was the small number of observable patients with bacteremia, which prevented the researchers from conducting a more in-depth analysis of risk factors and pathogen-specific differences. That one-fourth of patients received in-patient antibiotics before cultures could be collected also likely led to an underestimation of risk factors and misclassification bias. Lastly, the use of blood culture instead of whole-blood polymerase chain reaction, which is known to be more sensitive, also may have led to underestimation of overall bacteremia prevalence.

“In an era with widespread pneumococcal vaccination and low prevalence of bacteremia in the United States, children admitted with CAP that have pleural effusion or require ICU admission may represent a high-yield population for identifying bacteremia,” noted Dr. Fritz and associates.

Dr. Fritz had no conflicts of interest to report. Some coauthors cited multiple sources of potential conflict of interest related to consulting fees, grant support, and research support from various pharmaceutical companies and agencies. The study was funded by the National Institutes of Health and in part by a grant from the National Institute of Allergy and Infectious Diseases.

SOURCE: Fritz C et al. Pediatrics. 2019;144(1):e20183090.

There were 33 new measles cases reported last week, bringing the U.S. total to 1,077 for the year through June 20, according to the Centers for Disease Control and Prevention.

The number of new cases is an increase from the 22 reported the week before, but weekly incidence has been trending downward since hitting a high of 90 in mid-April, CDC data show.

The two continuing outbreaks in New York State made up more than half of the new cases, as Rockland County reported nine cases and New York City reported eight (seven in Brooklyn and one in Queens). Only one new case was reported in California as of the CDC’s June 20 cutoff, but the Los Angeles County Department of Public Health said on June 22 that it was assessing two possible cases, with potential public exposures occurring in a theater and a restaurant.

In a survey conducted in April, a majority of physicians with experience treating measles said that summer travel would lead to increased measles outbreaks and deaths.

[email protected]

There were 33 new measles cases reported last week, bringing the U.S. total to 1,077 for the year through June 20, according to the Centers for Disease Control and Prevention.

The number of new cases is an increase from the 22 reported the week before, but weekly incidence has been trending downward since hitting a high of 90 in mid-April, CDC data show.

The two continuing outbreaks in New York State made up more than half of the new cases, as Rockland County reported nine cases and New York City reported eight (seven in Brooklyn and one in Queens). Only one new case was reported in California as of the CDC’s June 20 cutoff, but the Los Angeles County Department of Public Health said on June 22 that it was assessing two possible cases, with potential public exposures occurring in a theater and a restaurant.

In a survey conducted in April, a majority of physicians with experience treating measles said that summer travel would lead to increased measles outbreaks and deaths.

[email protected]

There were 33 new measles cases reported last week, bringing the U.S. total to 1,077 for the year through June 20, according to the Centers for Disease Control and Prevention.

The number of new cases is an increase from the 22 reported the week before, but weekly incidence has been trending downward since hitting a high of 90 in mid-April, CDC data show.

The two continuing outbreaks in New York State made up more than half of the new cases, as Rockland County reported nine cases and New York City reported eight (seven in Brooklyn and one in Queens). Only one new case was reported in California as of the CDC’s June 20 cutoff, but the Los Angeles County Department of Public Health said on June 22 that it was assessing two possible cases, with potential public exposures occurring in a theater and a restaurant.

In a survey conducted in April, a majority of physicians with experience treating measles said that summer travel would lead to increased measles outbreaks and deaths.

[email protected]

Two liquid biopsy assays show generally good concordance with the gold standard of next-generation sequencing (NGS) performed on tissue for detecting epidermal growth factor receptor (EGFR) mutations in non–small cell lung (NSCLC), finds a retrospective cohort study.

Availability of targeted therapies for EGFR-mutated NSCLC underscores the importance of detecting these molecular aberrations, note lead investigator Christi M.J. Steendam, MD, department of pulmonary diseases, Erasmus MC Rotterdam, and Amphia Hospital, Breda, the Netherlands, and coinvestigators. In addition, assessing and monitoring mutational status can provide information about resistance and better inform treatment decisions.

The investigators studied 36 patients with EGFR-mutated NSCLC who had experienced progression on their current therapy and had both tissue and plasma available. They first compared results of droplet digital polymerase chain reaction (ddPCR) and NGS for detecting primary activating EGFR mutations and the resistance p.T790M EGFR mutation (the most common resistance mechanism to first- and second-generation tyrosine kinase inhibitors in this population) in plasma-derived cell-free DNA. They then compared each assay against NGS performed on conventional tissue.

Study results showed high agreement between ddPCR and NGS, at 86% for detection of the primary activating mutation and at 94% for detection of the p.T790M mutation. Findings were similar for the quantified allele ratio (mutant alleles divided by total alleles).

Overall, 15 patients (41.7%) had some degree of discrepant results. Six had no detectable mutations in cell-free DNA, three had detectable p.T790M in plasma but not in tissue, and three others had detectable p.T790M in tissue but not in plasma.

Finally, there was generally good concordance of the cell-free DNA results and the results obtained in tissue for detection of the primary activating mutation (69% for ddPCR, 83% for NGS) and for detection of p.T790M (75% for ddPCR, 75% for NGS). Patients with discordant results tended to have intrathoracic and/or CNS progression.

“ddPCR and NGS yield comparable results, with similar sensitivity for the mutations that can be detected by both methods, and the concordance with tissue-based results is high,” Dr. Steendam and coinvestigators summarize in JCO Precision Oncology. “When searching for a resistance mechanism, NGS analysis of cell-free DNA in plasma offers a more comprehensive view than ddPCR, with comparable precision at a single mutation level. When no mutations are detected in plasma, tissue-based investigation remains desirable.”

“Our results confirm the ability to detect targetable aberrations in blood, which provides possibilities for new lines of targeted treatments in daily practice without the necessity of tissue procurement in many patients,” they conclude.

Dr. Steendam disclosed that she receives research funding from AstraZeneca (institutional) and travel, accommodations, and/or expenses from Roche, Boehringer Ingelheim, and Eli Lilly. The study did not receive any specific funding.

SOURCE: Steendam CMJ et al. JCO Precis Oncol. 2019 June 20. doi: 10.1200/PO.18.00401.

Two liquid biopsy assays show generally good concordance with the gold standard of next-generation sequencing (NGS) performed on tissue for detecting epidermal growth factor receptor (EGFR) mutations in non–small cell lung (NSCLC), finds a retrospective cohort study.

Availability of targeted therapies for EGFR-mutated NSCLC underscores the importance of detecting these molecular aberrations, note lead investigator Christi M.J. Steendam, MD, department of pulmonary diseases, Erasmus MC Rotterdam, and Amphia Hospital, Breda, the Netherlands, and coinvestigators. In addition, assessing and monitoring mutational status can provide information about resistance and better inform treatment decisions.

The investigators studied 36 patients with EGFR-mutated NSCLC who had experienced progression on their current therapy and had both tissue and plasma available. They first compared results of droplet digital polymerase chain reaction (ddPCR) and NGS for detecting primary activating EGFR mutations and the resistance p.T790M EGFR mutation (the most common resistance mechanism to first- and second-generation tyrosine kinase inhibitors in this population) in plasma-derived cell-free DNA. They then compared each assay against NGS performed on conventional tissue.

Study results showed high agreement between ddPCR and NGS, at 86% for detection of the primary activating mutation and at 94% for detection of the p.T790M mutation. Findings were similar for the quantified allele ratio (mutant alleles divided by total alleles).

Overall, 15 patients (41.7%) had some degree of discrepant results. Six had no detectable mutations in cell-free DNA, three had detectable p.T790M in plasma but not in tissue, and three others had detectable p.T790M in tissue but not in plasma.

Finally, there was generally good concordance of the cell-free DNA results and the results obtained in tissue for detection of the primary activating mutation (69% for ddPCR, 83% for NGS) and for detection of p.T790M (75% for ddPCR, 75% for NGS). Patients with discordant results tended to have intrathoracic and/or CNS progression.

“ddPCR and NGS yield comparable results, with similar sensitivity for the mutations that can be detected by both methods, and the concordance with tissue-based results is high,” Dr. Steendam and coinvestigators summarize in JCO Precision Oncology. “When searching for a resistance mechanism, NGS analysis of cell-free DNA in plasma offers a more comprehensive view than ddPCR, with comparable precision at a single mutation level. When no mutations are detected in plasma, tissue-based investigation remains desirable.”

“Our results confirm the ability to detect targetable aberrations in blood, which provides possibilities for new lines of targeted treatments in daily practice without the necessity of tissue procurement in many patients,” they conclude.

Dr. Steendam disclosed that she receives research funding from AstraZeneca (institutional) and travel, accommodations, and/or expenses from Roche, Boehringer Ingelheim, and Eli Lilly. The study did not receive any specific funding.

SOURCE: Steendam CMJ et al. JCO Precis Oncol. 2019 June 20. doi: 10.1200/PO.18.00401.

Two liquid biopsy assays show generally good concordance with the gold standard of next-generation sequencing (NGS) performed on tissue for detecting epidermal growth factor receptor (EGFR) mutations in non–small cell lung (NSCLC), finds a retrospective cohort study.

Availability of targeted therapies for EGFR-mutated NSCLC underscores the importance of detecting these molecular aberrations, note lead investigator Christi M.J. Steendam, MD, department of pulmonary diseases, Erasmus MC Rotterdam, and Amphia Hospital, Breda, the Netherlands, and coinvestigators. In addition, assessing and monitoring mutational status can provide information about resistance and better inform treatment decisions.

The investigators studied 36 patients with EGFR-mutated NSCLC who had experienced progression on their current therapy and had both tissue and plasma available. They first compared results of droplet digital polymerase chain reaction (ddPCR) and NGS for detecting primary activating EGFR mutations and the resistance p.T790M EGFR mutation (the most common resistance mechanism to first- and second-generation tyrosine kinase inhibitors in this population) in plasma-derived cell-free DNA. They then compared each assay against NGS performed on conventional tissue.

Study results showed high agreement between ddPCR and NGS, at 86% for detection of the primary activating mutation and at 94% for detection of the p.T790M mutation. Findings were similar for the quantified allele ratio (mutant alleles divided by total alleles).

Overall, 15 patients (41.7%) had some degree of discrepant results. Six had no detectable mutations in cell-free DNA, three had detectable p.T790M in plasma but not in tissue, and three others had detectable p.T790M in tissue but not in plasma.

Finally, there was generally good concordance of the cell-free DNA results and the results obtained in tissue for detection of the primary activating mutation (69% for ddPCR, 83% for NGS) and for detection of p.T790M (75% for ddPCR, 75% for NGS). Patients with discordant results tended to have intrathoracic and/or CNS progression.

“ddPCR and NGS yield comparable results, with similar sensitivity for the mutations that can be detected by both methods, and the concordance with tissue-based results is high,” Dr. Steendam and coinvestigators summarize in JCO Precision Oncology. “When searching for a resistance mechanism, NGS analysis of cell-free DNA in plasma offers a more comprehensive view than ddPCR, with comparable precision at a single mutation level. When no mutations are detected in plasma, tissue-based investigation remains desirable.”

“Our results confirm the ability to detect targetable aberrations in blood, which provides possibilities for new lines of targeted treatments in daily practice without the necessity of tissue procurement in many patients,” they conclude.

Dr. Steendam disclosed that she receives research funding from AstraZeneca (institutional) and travel, accommodations, and/or expenses from Roche, Boehringer Ingelheim, and Eli Lilly. The study did not receive any specific funding.

SOURCE: Steendam CMJ et al. JCO Precis Oncol. 2019 June 20. doi: 10.1200/PO.18.00401.