Plasma cell cheilitis (PCC), also known as plasmocytosis circumorificialis and plasmocytosis mucosae,¹ is a poorly understood, uncommon inflammatory condition characterized by dense infiltration of mature plasma cells in the mucosal dermis of the lip.^2-5 The etiology of PCC is unknown but is thought to be a reactive immune process triggered by infection, mechanical friction, trauma, or solar damage.^1,5,6

The most common presentation of PCC is a slowly evolving, red-brown patch or plaque on the lower lip in older individuals.^2,3,5,7 Secondary changes with disease progression can include erosion, ulceration, fissures, edema, bleeding, or crusting.⁵ The diagnosis of PCC is challenging because it can mimic neoplastic, infectious, and inflammatory conditions.^8,9

Treatment strategies for PCC described in the literature vary, as does therapeutic response. Resolution of PCC has been documented after systemic steroids, intralesional steroids, systemic griseofulvin, and topical calcineurin inhibitors, among other agents.^6,7,10-16

We present the case of a patient with a lip lesion who ultimately was diagnosed with PCC after it progressed to an advanced necrotic stage.

Case Report

An 80-year-old male veteran of the Armed Services initially presented to our institution via teledermatology with redness and crusting of the lower lip (Figure 1). He had a history of myelodysplastic syndrome and anemia requiring iron transfusion. The process appeared to be consistent with actinic cheilitis vs squamous cell carcinoma. In-person dermatology consultation was recommended; however, the patient did not follow through with that appointment.

Five months later, additional photographs of the lesion were taken by the patient's primary care physician and sent through teledermatology, revealing progression to an erythematous, yellow-crusted erosion (Figure 2). The medical record indicated that a punch biopsy performed by the patient’s primary care physician showed hyperkeratosis and fungal organisms on periodic acid–Schiff staining. He subsequently applied ketoconazole and terbinafine cream to the lower lip without improvement. Prompt in-person evaluation by dermatology was again recommended.

Comment

The diagnosis and management of PCC is difficult because the condition is uncommon (though its true incidence is unknown) and the presentation is nonspecific, invoking a wide differential diagnosis. In the literature, PCC presents as a slowly progressive, red-brown patch or plaque on the lower lip in older individuals.^2,3,5,7 The lesion can progress to become eroded, ulcerated, fissured, or edematous.⁵

Differential Diagnosis
The clinical differential diagnosis of PCC is broad and includes inflammatory, infectious, and neoplastic causes, such as actinic cheilitis, allergic contact cheilitis, exfoliative cheilitis, granulomatous cheilitis, lichen planus, candidiasis, syphilis, and squamous cell carcinoma of the lip.^7,9 The histologic differential diagnosis includes allergic contact cheilitis, secondary syphilis, actinic cheilitis, squamous cell carcinoma, cheilitis granulomatosa, and plasmacytoma.^17-19

Histopathology
On biopsy, PCC usually is characterized by plasma cells in a bandlike pattern in the upper submucosa or even more diffusely throughout the submucosa.²⁰ In earlier studies, polyclonality of plasma cells with kappa and lambda light chains has been demonstrated⁵; in this case, such polyclonality militated against a plasma cell dyscrasia. There have been reports of a various number of eosinophils in PCC,^5,20 but eosinophils were not a prominent feature in our case.

Treatment
As reported in the literature, treatment of PCC has been attempted using a broad range of strategies; however, the optimal regimen has yet to be elucidated.¹⁵ Numerous therapies, including excision, radiation, electrocauterization, cryotherapy, steroids, systemic griseofulvin, topical fusidic acid, and topical calcineurin inhibitors, have yielded variable success.^6,7,10-16

The success of topical corticosteroids, as demonstrated in our case, has been unpredictable; the reported response has ranged from complete resolution to failure.⁹ This variability is thought to be related to epithelial width and the degree of acanthosis, with ulcerative lesions demonstrating a superior response to topical corticosteroids.⁹

Conclusion

Our case highlights the challenges of diagnosing and managing PCC, especially through teledermatology. Initial photographs of the lesion (Figure 1) that were submitted demonstrated a nonspecific erosion, which was concerning for any of several infectious, inflammatory, and malignant causes. Prompt in-person evaluation was warranted; regrettably, the patient’s condition worsened rapidly in the 10 days it took for him to be seen in-person by dermatology.

Furthermore, this case necessitated 3 separate biopsies because the pathology on the first 2 biopsies initially was equivocal, demonstrating ulceration and granulation tissue. The diagnosis was finally made after a third biopsy was recommended by a dermatopathologist, who eventually identified a bandlike distribution of polyclonal plasma cells in the upper submucosa, consistent with a diagnosis of PCC. Our patient’s final disease presentation (Figure 3) was exuberant and may represent the end point of untreated PCC.

Plasma cell cheilitis (PCC), also known as plasmocytosis circumorificialis and plasmocytosis mucosae,¹ is a poorly understood, uncommon inflammatory condition characterized by dense infiltration of mature plasma cells in the mucosal dermis of the lip.^2-5 The etiology of PCC is unknown but is thought to be a reactive immune process triggered by infection, mechanical friction, trauma, or solar damage.^1,5,6

The most common presentation of PCC is a slowly evolving, red-brown patch or plaque on the lower lip in older individuals.^2,3,5,7 Secondary changes with disease progression can include erosion, ulceration, fissures, edema, bleeding, or crusting.⁵ The diagnosis of PCC is challenging because it can mimic neoplastic, infectious, and inflammatory conditions.^8,9

Treatment strategies for PCC described in the literature vary, as does therapeutic response. Resolution of PCC has been documented after systemic steroids, intralesional steroids, systemic griseofulvin, and topical calcineurin inhibitors, among other agents.^6,7,10-16

We present the case of a patient with a lip lesion who ultimately was diagnosed with PCC after it progressed to an advanced necrotic stage.

Case Report

An 80-year-old male veteran of the Armed Services initially presented to our institution via teledermatology with redness and crusting of the lower lip (Figure 1). He had a history of myelodysplastic syndrome and anemia requiring iron transfusion. The process appeared to be consistent with actinic cheilitis vs squamous cell carcinoma. In-person dermatology consultation was recommended; however, the patient did not follow through with that appointment.

Five months later, additional photographs of the lesion were taken by the patient's primary care physician and sent through teledermatology, revealing progression to an erythematous, yellow-crusted erosion (Figure 2). The medical record indicated that a punch biopsy performed by the patient’s primary care physician showed hyperkeratosis and fungal organisms on periodic acid–Schiff staining. He subsequently applied ketoconazole and terbinafine cream to the lower lip without improvement. Prompt in-person evaluation by dermatology was again recommended.

Comment

The diagnosis and management of PCC is difficult because the condition is uncommon (though its true incidence is unknown) and the presentation is nonspecific, invoking a wide differential diagnosis. In the literature, PCC presents as a slowly progressive, red-brown patch or plaque on the lower lip in older individuals.^2,3,5,7 The lesion can progress to become eroded, ulcerated, fissured, or edematous.⁵

Differential Diagnosis
The clinical differential diagnosis of PCC is broad and includes inflammatory, infectious, and neoplastic causes, such as actinic cheilitis, allergic contact cheilitis, exfoliative cheilitis, granulomatous cheilitis, lichen planus, candidiasis, syphilis, and squamous cell carcinoma of the lip.^7,9 The histologic differential diagnosis includes allergic contact cheilitis, secondary syphilis, actinic cheilitis, squamous cell carcinoma, cheilitis granulomatosa, and plasmacytoma.^17-19

Histopathology
On biopsy, PCC usually is characterized by plasma cells in a bandlike pattern in the upper submucosa or even more diffusely throughout the submucosa.²⁰ In earlier studies, polyclonality of plasma cells with kappa and lambda light chains has been demonstrated⁵; in this case, such polyclonality militated against a plasma cell dyscrasia. There have been reports of a various number of eosinophils in PCC,^5,20 but eosinophils were not a prominent feature in our case.

Treatment
As reported in the literature, treatment of PCC has been attempted using a broad range of strategies; however, the optimal regimen has yet to be elucidated.¹⁵ Numerous therapies, including excision, radiation, electrocauterization, cryotherapy, steroids, systemic griseofulvin, topical fusidic acid, and topical calcineurin inhibitors, have yielded variable success.^6,7,10-16

The success of topical corticosteroids, as demonstrated in our case, has been unpredictable; the reported response has ranged from complete resolution to failure.⁹ This variability is thought to be related to epithelial width and the degree of acanthosis, with ulcerative lesions demonstrating a superior response to topical corticosteroids.⁹

Conclusion

Our case highlights the challenges of diagnosing and managing PCC, especially through teledermatology. Initial photographs of the lesion (Figure 1) that were submitted demonstrated a nonspecific erosion, which was concerning for any of several infectious, inflammatory, and malignant causes. Prompt in-person evaluation was warranted; regrettably, the patient’s condition worsened rapidly in the 10 days it took for him to be seen in-person by dermatology.

Furthermore, this case necessitated 3 separate biopsies because the pathology on the first 2 biopsies initially was equivocal, demonstrating ulceration and granulation tissue. The diagnosis was finally made after a third biopsy was recommended by a dermatopathologist, who eventually identified a bandlike distribution of polyclonal plasma cells in the upper submucosa, consistent with a diagnosis of PCC. Our patient’s final disease presentation (Figure 3) was exuberant and may represent the end point of untreated PCC.

Plasma cell cheilitis (PCC), also known as plasmocytosis circumorificialis and plasmocytosis mucosae,¹ is a poorly understood, uncommon inflammatory condition characterized by dense infiltration of mature plasma cells in the mucosal dermis of the lip.^2-5 The etiology of PCC is unknown but is thought to be a reactive immune process triggered by infection, mechanical friction, trauma, or solar damage.^1,5,6

The most common presentation of PCC is a slowly evolving, red-brown patch or plaque on the lower lip in older individuals.^2,3,5,7 Secondary changes with disease progression can include erosion, ulceration, fissures, edema, bleeding, or crusting.⁵ The diagnosis of PCC is challenging because it can mimic neoplastic, infectious, and inflammatory conditions.^8,9

Treatment strategies for PCC described in the literature vary, as does therapeutic response. Resolution of PCC has been documented after systemic steroids, intralesional steroids, systemic griseofulvin, and topical calcineurin inhibitors, among other agents.^6,7,10-16

We present the case of a patient with a lip lesion who ultimately was diagnosed with PCC after it progressed to an advanced necrotic stage.

Case Report

An 80-year-old male veteran of the Armed Services initially presented to our institution via teledermatology with redness and crusting of the lower lip (Figure 1). He had a history of myelodysplastic syndrome and anemia requiring iron transfusion. The process appeared to be consistent with actinic cheilitis vs squamous cell carcinoma. In-person dermatology consultation was recommended; however, the patient did not follow through with that appointment.

Five months later, additional photographs of the lesion were taken by the patient's primary care physician and sent through teledermatology, revealing progression to an erythematous, yellow-crusted erosion (Figure 2). The medical record indicated that a punch biopsy performed by the patient’s primary care physician showed hyperkeratosis and fungal organisms on periodic acid–Schiff staining. He subsequently applied ketoconazole and terbinafine cream to the lower lip without improvement. Prompt in-person evaluation by dermatology was again recommended.

Comment

The diagnosis and management of PCC is difficult because the condition is uncommon (though its true incidence is unknown) and the presentation is nonspecific, invoking a wide differential diagnosis. In the literature, PCC presents as a slowly progressive, red-brown patch or plaque on the lower lip in older individuals.^2,3,5,7 The lesion can progress to become eroded, ulcerated, fissured, or edematous.⁵

Differential Diagnosis
The clinical differential diagnosis of PCC is broad and includes inflammatory, infectious, and neoplastic causes, such as actinic cheilitis, allergic contact cheilitis, exfoliative cheilitis, granulomatous cheilitis, lichen planus, candidiasis, syphilis, and squamous cell carcinoma of the lip.^7,9 The histologic differential diagnosis includes allergic contact cheilitis, secondary syphilis, actinic cheilitis, squamous cell carcinoma, cheilitis granulomatosa, and plasmacytoma.^17-19

Histopathology
On biopsy, PCC usually is characterized by plasma cells in a bandlike pattern in the upper submucosa or even more diffusely throughout the submucosa.²⁰ In earlier studies, polyclonality of plasma cells with kappa and lambda light chains has been demonstrated⁵; in this case, such polyclonality militated against a plasma cell dyscrasia. There have been reports of a various number of eosinophils in PCC,^5,20 but eosinophils were not a prominent feature in our case.

Treatment
As reported in the literature, treatment of PCC has been attempted using a broad range of strategies; however, the optimal regimen has yet to be elucidated.¹⁵ Numerous therapies, including excision, radiation, electrocauterization, cryotherapy, steroids, systemic griseofulvin, topical fusidic acid, and topical calcineurin inhibitors, have yielded variable success.^6,7,10-16

The success of topical corticosteroids, as demonstrated in our case, has been unpredictable; the reported response has ranged from complete resolution to failure.⁹ This variability is thought to be related to epithelial width and the degree of acanthosis, with ulcerative lesions demonstrating a superior response to topical corticosteroids.⁹

Conclusion

Our case highlights the challenges of diagnosing and managing PCC, especially through teledermatology. Initial photographs of the lesion (Figure 1) that were submitted demonstrated a nonspecific erosion, which was concerning for any of several infectious, inflammatory, and malignant causes. Prompt in-person evaluation was warranted; regrettably, the patient’s condition worsened rapidly in the 10 days it took for him to be seen in-person by dermatology.

Furthermore, this case necessitated 3 separate biopsies because the pathology on the first 2 biopsies initially was equivocal, demonstrating ulceration and granulation tissue. The diagnosis was finally made after a third biopsy was recommended by a dermatopathologist, who eventually identified a bandlike distribution of polyclonal plasma cells in the upper submucosa, consistent with a diagnosis of PCC. Our patient’s final disease presentation (Figure 3) was exuberant and may represent the end point of untreated PCC.

To the Editor:

The art of tattooing continues to gain popularity in the 21st century, albeit with accompanying hazards.¹ Reported adverse reactions to tattoos include infections, tumors, and hypersensitivity and granulomatous reactions.² Various infectious agents may involve tattoos, including human papillomavirus (HPV), molluscum contagiosum, herpes simplex virus, hepatitis C virus, tuberculoid and nontuberculoid mycobacteria, and Staphylococcus aureus.² Verruca vulgaris infrequently has been reported to develop in tattoos.^3,4 Previously reported cases of verruca in tattoos suggest a predilection for blue or black pigment.^1-5 We report a case of verruca vulgaris occurring within the red-inked areas of a tattoo that first appeared approximately 18 years after the initial tattoo placement.

A 44-year-old woman presented with erythema, induration, and irritation of a tattoo on the left leg of 2 years’ duration. The tattoo initially was inscribed more than 20 years prior. The patient had a history of type 2 diabetes mellitus and chronic obstructive pulmonary disease. She reported no prior trauma to the area, prior rash or irritation, or similar changes to her other tattoos, including those with red ink. The affected tattoo was inscribed at a separate time from the other tattoos. Physical examination of the irritated tattoo revealed hyperkeratotic papules with firm scaling in the zone of dermal red pigment (Figure 1). Notable nodularity or deep induration was not present. The clinical differential diagnosis included a hypersensitivity reaction to red tattoo ink, sarcoidosis, and an infectious process, such as an atypical mycobacterial infection. A punch biopsy demonstrated papillomatous epidermal hyperplasia with hyperkeratosis, focal parakeratosis, and frequent vacuolization of keratinocytes with enlarged keratohyalin granules, diagnostic of verruca vulgaris (Figure 2). Of note, the patient did not have clinically apparent viral warts elsewhere on physical examination. The patient was successfully managedwith a combination of 2 treatments of intralesional Candida antigen and 3 treatments of cryotherapy with resolution of most lesions over the course of 8 months. Over the following several months, the patient applied topical salicylic acid, which led to the resolution of the remaining lesions. The verrucae had not recurred 19 months after the initial presentation.

The development of verruca vulgaris within a tattoo may occur secondary to various mechanisms of HPV inoculation, including introduction of the virus through contaminated ink, the tattoo artist’s saliva, autoinoculation, or koebnerization of a pre-existing verruca vulgaris.⁴ Local immune system dysregulation secondary to tattoo ink also has been proposed as a mechanism for HPV infection in this setting.^1,5 The contents of darker tattoo pigments may promote formation of reactive oxygen species inducing local immunocompromise.⁵

The pathogenic mechanism was elusive in our patient. Although the localization of verruca vulgaris to the zones of red pigment may be merely coincidental, this phenomenon raised suspicion for direct inoculation via contaminated red ink. The patient’s other red ink–containing tattoos that were inscribed separately were spared, compatible with contamination of the red ink used for the affected tattoo. However, the delayed onset of nearly 2 decades was exceptional, given the shorter previously reported latencies ranging from months to 10 years.⁴ Autoinoculation or koebnerization is plausible, though greater involvement of nonred pigments would be expected as well as a briefer latency. Finally, the possibility of local immune dysregulation seemed feasible, given the slow evolution of the lesions largely restricted to one pigment type.

We report a case of verruca vulgaris within the red area of a multicolored tattoo that occurred approximately 18 years after tattoo placement. This case highlights a rare presentation of an infectious agent that may complicate tattoos. Both predilection for red pigment rather than black or blue pigment and the long latency period raised interesting questions regarding pathogenesis. Confirmatory biopsy enables effective management of this tattoo complication.

To the Editor:

The art of tattooing continues to gain popularity in the 21st century, albeit with accompanying hazards.¹ Reported adverse reactions to tattoos include infections, tumors, and hypersensitivity and granulomatous reactions.² Various infectious agents may involve tattoos, including human papillomavirus (HPV), molluscum contagiosum, herpes simplex virus, hepatitis C virus, tuberculoid and nontuberculoid mycobacteria, and Staphylococcus aureus.² Verruca vulgaris infrequently has been reported to develop in tattoos.^3,4 Previously reported cases of verruca in tattoos suggest a predilection for blue or black pigment.^1-5 We report a case of verruca vulgaris occurring within the red-inked areas of a tattoo that first appeared approximately 18 years after the initial tattoo placement.

A 44-year-old woman presented with erythema, induration, and irritation of a tattoo on the left leg of 2 years’ duration. The tattoo initially was inscribed more than 20 years prior. The patient had a history of type 2 diabetes mellitus and chronic obstructive pulmonary disease. She reported no prior trauma to the area, prior rash or irritation, or similar changes to her other tattoos, including those with red ink. The affected tattoo was inscribed at a separate time from the other tattoos. Physical examination of the irritated tattoo revealed hyperkeratotic papules with firm scaling in the zone of dermal red pigment (Figure 1). Notable nodularity or deep induration was not present. The clinical differential diagnosis included a hypersensitivity reaction to red tattoo ink, sarcoidosis, and an infectious process, such as an atypical mycobacterial infection. A punch biopsy demonstrated papillomatous epidermal hyperplasia with hyperkeratosis, focal parakeratosis, and frequent vacuolization of keratinocytes with enlarged keratohyalin granules, diagnostic of verruca vulgaris (Figure 2). Of note, the patient did not have clinically apparent viral warts elsewhere on physical examination. The patient was successfully managedwith a combination of 2 treatments of intralesional Candida antigen and 3 treatments of cryotherapy with resolution of most lesions over the course of 8 months. Over the following several months, the patient applied topical salicylic acid, which led to the resolution of the remaining lesions. The verrucae had not recurred 19 months after the initial presentation.

The development of verruca vulgaris within a tattoo may occur secondary to various mechanisms of HPV inoculation, including introduction of the virus through contaminated ink, the tattoo artist’s saliva, autoinoculation, or koebnerization of a pre-existing verruca vulgaris.⁴ Local immune system dysregulation secondary to tattoo ink also has been proposed as a mechanism for HPV infection in this setting.^1,5 The contents of darker tattoo pigments may promote formation of reactive oxygen species inducing local immunocompromise.⁵

The pathogenic mechanism was elusive in our patient. Although the localization of verruca vulgaris to the zones of red pigment may be merely coincidental, this phenomenon raised suspicion for direct inoculation via contaminated red ink. The patient’s other red ink–containing tattoos that were inscribed separately were spared, compatible with contamination of the red ink used for the affected tattoo. However, the delayed onset of nearly 2 decades was exceptional, given the shorter previously reported latencies ranging from months to 10 years.⁴ Autoinoculation or koebnerization is plausible, though greater involvement of nonred pigments would be expected as well as a briefer latency. Finally, the possibility of local immune dysregulation seemed feasible, given the slow evolution of the lesions largely restricted to one pigment type.

We report a case of verruca vulgaris within the red area of a multicolored tattoo that occurred approximately 18 years after tattoo placement. This case highlights a rare presentation of an infectious agent that may complicate tattoos. Both predilection for red pigment rather than black or blue pigment and the long latency period raised interesting questions regarding pathogenesis. Confirmatory biopsy enables effective management of this tattoo complication.

To the Editor:

The art of tattooing continues to gain popularity in the 21st century, albeit with accompanying hazards.¹ Reported adverse reactions to tattoos include infections, tumors, and hypersensitivity and granulomatous reactions.² Various infectious agents may involve tattoos, including human papillomavirus (HPV), molluscum contagiosum, herpes simplex virus, hepatitis C virus, tuberculoid and nontuberculoid mycobacteria, and Staphylococcus aureus.² Verruca vulgaris infrequently has been reported to develop in tattoos.^3,4 Previously reported cases of verruca in tattoos suggest a predilection for blue or black pigment.^1-5 We report a case of verruca vulgaris occurring within the red-inked areas of a tattoo that first appeared approximately 18 years after the initial tattoo placement.

A 44-year-old woman presented with erythema, induration, and irritation of a tattoo on the left leg of 2 years’ duration. The tattoo initially was inscribed more than 20 years prior. The patient had a history of type 2 diabetes mellitus and chronic obstructive pulmonary disease. She reported no prior trauma to the area, prior rash or irritation, or similar changes to her other tattoos, including those with red ink. The affected tattoo was inscribed at a separate time from the other tattoos. Physical examination of the irritated tattoo revealed hyperkeratotic papules with firm scaling in the zone of dermal red pigment (Figure 1). Notable nodularity or deep induration was not present. The clinical differential diagnosis included a hypersensitivity reaction to red tattoo ink, sarcoidosis, and an infectious process, such as an atypical mycobacterial infection. A punch biopsy demonstrated papillomatous epidermal hyperplasia with hyperkeratosis, focal parakeratosis, and frequent vacuolization of keratinocytes with enlarged keratohyalin granules, diagnostic of verruca vulgaris (Figure 2). Of note, the patient did not have clinically apparent viral warts elsewhere on physical examination. The patient was successfully managedwith a combination of 2 treatments of intralesional Candida antigen and 3 treatments of cryotherapy with resolution of most lesions over the course of 8 months. Over the following several months, the patient applied topical salicylic acid, which led to the resolution of the remaining lesions. The verrucae had not recurred 19 months after the initial presentation.

The development of verruca vulgaris within a tattoo may occur secondary to various mechanisms of HPV inoculation, including introduction of the virus through contaminated ink, the tattoo artist’s saliva, autoinoculation, or koebnerization of a pre-existing verruca vulgaris.⁴ Local immune system dysregulation secondary to tattoo ink also has been proposed as a mechanism for HPV infection in this setting.^1,5 The contents of darker tattoo pigments may promote formation of reactive oxygen species inducing local immunocompromise.⁵

The pathogenic mechanism was elusive in our patient. Although the localization of verruca vulgaris to the zones of red pigment may be merely coincidental, this phenomenon raised suspicion for direct inoculation via contaminated red ink. The patient’s other red ink–containing tattoos that were inscribed separately were spared, compatible with contamination of the red ink used for the affected tattoo. However, the delayed onset of nearly 2 decades was exceptional, given the shorter previously reported latencies ranging from months to 10 years.⁴ Autoinoculation or koebnerization is plausible, though greater involvement of nonred pigments would be expected as well as a briefer latency. Finally, the possibility of local immune dysregulation seemed feasible, given the slow evolution of the lesions largely restricted to one pigment type.

We report a case of verruca vulgaris within the red area of a multicolored tattoo that occurred approximately 18 years after tattoo placement. This case highlights a rare presentation of an infectious agent that may complicate tattoos. Both predilection for red pigment rather than black or blue pigment and the long latency period raised interesting questions regarding pathogenesis. Confirmatory biopsy enables effective management of this tattoo complication.

Insurance companies pay National Cancer Institute–designated cancer centers more for common cancer surgeries, but there’s no improvement in length of stay, subsequent ED use, or 90-day hospital readmission, compared with community hospitals, according to a recent report in JAMA Network Open.

“While acceptable to pay higher prices for care that is expected to be of higher quality, we found no differences in short-term postsurgical outcomes,” said authors led by Samuel Takvorian, MD, a medical oncologist at the University of Pennsylvania, Philadelphia.

The team looked at what insurance companies paid for incident breast, colon, and lung cancer surgeries, which together account for most cancer surgeries, among 66,878 patients treated from 2011 to 2014 at almost 3,000 U.S. hospitals.

Three-quarters had surgery at a community hospital, and 8.3% were treated at one of the nation’s 71 NCI centers, which are recognized by the NCI as meeting rigorous standards in cancer care. The remaining patients were treated at non-NCI academic hospitals.

The mean surgery-specific insurer prices paid at NCI centers was $18,526 versus $14,772 at community hospitals, a difference of $3,755 (P < .001) that was driven primarily by higher facility payments at NCI centers, a mean of $17,704 versus $14,120 at community hospitals.

Mean 90-day postdischarge payments were also $5,744 higher at NCI centers, $47,035 versus $41,291 at community hospitals (P = .006).

The team used postsurgical acute care utilization as a marker of quality but found no differences between the two settings. Mean length of stay was 5.1 days and the probability of ED utilization just over 13% in both, and both had a 90-day readmission rate of just over 10%.
 

Who should be treated at an NCI center?

The data didn’t allow for direct comparison of surgical quality, such as margin status, number of lymph nodes assessed, or postoperative complications, but the postsurgery utilization outcomes “suggest that quality may have been similar,” said Nancy Keating, MD, a health care policy and medicine professor at Harvard Medical School, Boston, in an invited commentary.

The price differences are probably because NCI centers, with their comprehensive offerings, market share, and prestige, can negotiate higher reimbursement rates from insurers, the researchers said.

There is also evidence of better outcomes at NCI centers, particularly for more advanced and complex cases. However, “this study focused on common cancer surgical procedures ... revealing that there is a premium associated with receipt of surgical cancer care at NCI centers.” Further research “is necessary to judge whether and under what circumstances the premium price of NCI centers is justified,” the investigators said.

Dr. Keating noted that “it is likely that some patients benefit from the highly specialized care available at NCI-designated cancer centers ... but it is also likely that many other patients will do equally well regardless of where they receive their care.”

Amid ever-increasing cancer care costs and the need to strategically allocate financial resources, more research is needed to “identify subgroups of patients for whom highly specialized care is particularly necessary to achieve better outcomes. Such data could also be used by payers considering tiered networks and by physician organizations participating in risk contracts for decisions about where to refer patients with cancer for treatment,” she said.
 

Rectifying a ‘misalignment’

The researchers also said the findings reveal competing incentives, with commercial payers wanting to steer patients away from high-cost hospitals but health systems hoping to maximize surgical volume at lucrative referral centers.

“Value-based or bundled payment reimbursement for surgical episodes, particularly when paired with mandatory reporting on surgical outcomes, could help to rectify this misalignment,” they said.

Out-of-pocket spending wasn’t analyzed in the study, so it’s unknown how the higher prices at NCI centers hit patients in the pocketbook.

Meanwhile, non-NCI academic hospitals also had higher insurer prices paid than community hospitals, but the differences were not statistically significant, nor were differences in the study’s utilization outcomes.

Over half the patients had breast cancer, about one-third had colon cancer, and the rest had lung tumors. Patients treated at NCI centers tended to be younger than those treated at community hospitals and more likely to be women, but comorbidity scores were similar between the groups.

NCI centers, compared with community hospitals, were larger with higher surgical volumes and in more populated areas. They also had higher rates of laparoscopic partial colectomies and pneumonectomies.

Data came from the Health Care Cost Institute’s national commercial claims data set, which includes claims from three of the country’s five largest commercial insurers: Aetna, Humana, and UnitedHealthcare.

The work was funded by the Commonwealth of Pennsylvania and the National Cancer Institute. Dr. Takvorian and Dr. Keating didn’t have any disclosures. One of Dr. Takvorian’s coauthors reported grants and/or personal fees from several sources, including Pfizer, UnitedHealthcare, and Blue Cross Blue Shield of North Carolina.

[email protected]

Insurance companies pay National Cancer Institute–designated cancer centers more for common cancer surgeries, but there’s no improvement in length of stay, subsequent ED use, or 90-day hospital readmission, compared with community hospitals, according to a recent report in JAMA Network Open.

“While acceptable to pay higher prices for care that is expected to be of higher quality, we found no differences in short-term postsurgical outcomes,” said authors led by Samuel Takvorian, MD, a medical oncologist at the University of Pennsylvania, Philadelphia.

The team looked at what insurance companies paid for incident breast, colon, and lung cancer surgeries, which together account for most cancer surgeries, among 66,878 patients treated from 2011 to 2014 at almost 3,000 U.S. hospitals.

Three-quarters had surgery at a community hospital, and 8.3% were treated at one of the nation’s 71 NCI centers, which are recognized by the NCI as meeting rigorous standards in cancer care. The remaining patients were treated at non-NCI academic hospitals.

The mean surgery-specific insurer prices paid at NCI centers was $18,526 versus $14,772 at community hospitals, a difference of $3,755 (P < .001) that was driven primarily by higher facility payments at NCI centers, a mean of $17,704 versus $14,120 at community hospitals.

Mean 90-day postdischarge payments were also $5,744 higher at NCI centers, $47,035 versus $41,291 at community hospitals (P = .006).

The team used postsurgical acute care utilization as a marker of quality but found no differences between the two settings. Mean length of stay was 5.1 days and the probability of ED utilization just over 13% in both, and both had a 90-day readmission rate of just over 10%.
 

Who should be treated at an NCI center?

The data didn’t allow for direct comparison of surgical quality, such as margin status, number of lymph nodes assessed, or postoperative complications, but the postsurgery utilization outcomes “suggest that quality may have been similar,” said Nancy Keating, MD, a health care policy and medicine professor at Harvard Medical School, Boston, in an invited commentary.

The price differences are probably because NCI centers, with their comprehensive offerings, market share, and prestige, can negotiate higher reimbursement rates from insurers, the researchers said.

There is also evidence of better outcomes at NCI centers, particularly for more advanced and complex cases. However, “this study focused on common cancer surgical procedures ... revealing that there is a premium associated with receipt of surgical cancer care at NCI centers.” Further research “is necessary to judge whether and under what circumstances the premium price of NCI centers is justified,” the investigators said.

Dr. Keating noted that “it is likely that some patients benefit from the highly specialized care available at NCI-designated cancer centers ... but it is also likely that many other patients will do equally well regardless of where they receive their care.”

Amid ever-increasing cancer care costs and the need to strategically allocate financial resources, more research is needed to “identify subgroups of patients for whom highly specialized care is particularly necessary to achieve better outcomes. Such data could also be used by payers considering tiered networks and by physician organizations participating in risk contracts for decisions about where to refer patients with cancer for treatment,” she said.
 

Rectifying a ‘misalignment’

The researchers also said the findings reveal competing incentives, with commercial payers wanting to steer patients away from high-cost hospitals but health systems hoping to maximize surgical volume at lucrative referral centers.

“Value-based or bundled payment reimbursement for surgical episodes, particularly when paired with mandatory reporting on surgical outcomes, could help to rectify this misalignment,” they said.

Out-of-pocket spending wasn’t analyzed in the study, so it’s unknown how the higher prices at NCI centers hit patients in the pocketbook.

Meanwhile, non-NCI academic hospitals also had higher insurer prices paid than community hospitals, but the differences were not statistically significant, nor were differences in the study’s utilization outcomes.

Over half the patients had breast cancer, about one-third had colon cancer, and the rest had lung tumors. Patients treated at NCI centers tended to be younger than those treated at community hospitals and more likely to be women, but comorbidity scores were similar between the groups.

NCI centers, compared with community hospitals, were larger with higher surgical volumes and in more populated areas. They also had higher rates of laparoscopic partial colectomies and pneumonectomies.

Data came from the Health Care Cost Institute’s national commercial claims data set, which includes claims from three of the country’s five largest commercial insurers: Aetna, Humana, and UnitedHealthcare.

The work was funded by the Commonwealth of Pennsylvania and the National Cancer Institute. Dr. Takvorian and Dr. Keating didn’t have any disclosures. One of Dr. Takvorian’s coauthors reported grants and/or personal fees from several sources, including Pfizer, UnitedHealthcare, and Blue Cross Blue Shield of North Carolina.

[email protected]

Insurance companies pay National Cancer Institute–designated cancer centers more for common cancer surgeries, but there’s no improvement in length of stay, subsequent ED use, or 90-day hospital readmission, compared with community hospitals, according to a recent report in JAMA Network Open.

“While acceptable to pay higher prices for care that is expected to be of higher quality, we found no differences in short-term postsurgical outcomes,” said authors led by Samuel Takvorian, MD, a medical oncologist at the University of Pennsylvania, Philadelphia.

The team looked at what insurance companies paid for incident breast, colon, and lung cancer surgeries, which together account for most cancer surgeries, among 66,878 patients treated from 2011 to 2014 at almost 3,000 U.S. hospitals.

Three-quarters had surgery at a community hospital, and 8.3% were treated at one of the nation’s 71 NCI centers, which are recognized by the NCI as meeting rigorous standards in cancer care. The remaining patients were treated at non-NCI academic hospitals.

The mean surgery-specific insurer prices paid at NCI centers was $18,526 versus $14,772 at community hospitals, a difference of $3,755 (P < .001) that was driven primarily by higher facility payments at NCI centers, a mean of $17,704 versus $14,120 at community hospitals.

Mean 90-day postdischarge payments were also $5,744 higher at NCI centers, $47,035 versus $41,291 at community hospitals (P = .006).

The team used postsurgical acute care utilization as a marker of quality but found no differences between the two settings. Mean length of stay was 5.1 days and the probability of ED utilization just over 13% in both, and both had a 90-day readmission rate of just over 10%.
 

Who should be treated at an NCI center?

The data didn’t allow for direct comparison of surgical quality, such as margin status, number of lymph nodes assessed, or postoperative complications, but the postsurgery utilization outcomes “suggest that quality may have been similar,” said Nancy Keating, MD, a health care policy and medicine professor at Harvard Medical School, Boston, in an invited commentary.

The price differences are probably because NCI centers, with their comprehensive offerings, market share, and prestige, can negotiate higher reimbursement rates from insurers, the researchers said.

There is also evidence of better outcomes at NCI centers, particularly for more advanced and complex cases. However, “this study focused on common cancer surgical procedures ... revealing that there is a premium associated with receipt of surgical cancer care at NCI centers.” Further research “is necessary to judge whether and under what circumstances the premium price of NCI centers is justified,” the investigators said.

Dr. Keating noted that “it is likely that some patients benefit from the highly specialized care available at NCI-designated cancer centers ... but it is also likely that many other patients will do equally well regardless of where they receive their care.”

Amid ever-increasing cancer care costs and the need to strategically allocate financial resources, more research is needed to “identify subgroups of patients for whom highly specialized care is particularly necessary to achieve better outcomes. Such data could also be used by payers considering tiered networks and by physician organizations participating in risk contracts for decisions about where to refer patients with cancer for treatment,” she said.
 

Rectifying a ‘misalignment’

The researchers also said the findings reveal competing incentives, with commercial payers wanting to steer patients away from high-cost hospitals but health systems hoping to maximize surgical volume at lucrative referral centers.

“Value-based or bundled payment reimbursement for surgical episodes, particularly when paired with mandatory reporting on surgical outcomes, could help to rectify this misalignment,” they said.

Out-of-pocket spending wasn’t analyzed in the study, so it’s unknown how the higher prices at NCI centers hit patients in the pocketbook.

Meanwhile, non-NCI academic hospitals also had higher insurer prices paid than community hospitals, but the differences were not statistically significant, nor were differences in the study’s utilization outcomes.

Over half the patients had breast cancer, about one-third had colon cancer, and the rest had lung tumors. Patients treated at NCI centers tended to be younger than those treated at community hospitals and more likely to be women, but comorbidity scores were similar between the groups.

NCI centers, compared with community hospitals, were larger with higher surgical volumes and in more populated areas. They also had higher rates of laparoscopic partial colectomies and pneumonectomies.

Data came from the Health Care Cost Institute’s national commercial claims data set, which includes claims from three of the country’s five largest commercial insurers: Aetna, Humana, and UnitedHealthcare.

The work was funded by the Commonwealth of Pennsylvania and the National Cancer Institute. Dr. Takvorian and Dr. Keating didn’t have any disclosures. One of Dr. Takvorian’s coauthors reported grants and/or personal fees from several sources, including Pfizer, UnitedHealthcare, and Blue Cross Blue Shield of North Carolina.

[email protected]

To the Editor:

Lupus erythematosus panniculitis (LEP) is rare in the pediatric population. It can be difficult to manage, as patients may not respond to conventional treatments including hydroxychloroquine and prednisone. We report the use of rituximab in the treatment of a 20-year-old woman with LEP of the face, legs, and arms that was refractory to standard treatments. She also had a history of hemophagocytic lymphohistiocytosis (HLH). Further studies are warranted to determine the role of rituximab in the treatment of pediatric patients with LEP.

A 20-year-old woman with history of LEP and HLH initially presented with migratory violaceous nodules on the face 16 years prior to the current presentation. A skin biopsy 3 years after that initial presentation suggested a diagnosis of cutaneous lupus erythematosus. Six years later, numerous asymptomatic lesions appeared on the legs, predominantly on the calves; she was successfully treated with hydroxychloroquine and high-dose prednisone. Four years prior to the current presentation, a febrile illness prompted discontinuation of hydroxychloroquine and hospitalization, where she was first was diagnosed with HLH; she achieved remission with cyclosporine. At the current presentation, she continued to have persistent violaceous lesions on the face, lower arms, and legs with underlying nodularity (Figure 1). Skin biopsies revealed LEP and were less suggestive of HLH. She was restarted on hydroxychloroquine, which did not adequately control the disease. Rheumatologic workup was only notable for an antinuclear antibody titer of 1:80 (reference range, <1:80) in a speckled pattern.

Rituximab, a chimeric monoclonal antibody targeting B-cell surface marker CD20, results in depletion of mature B cells. Use of rituximab for LEP has been described in multiple case reports involving an 8-year-old boy, 22-year-old girl, and 2 middle-aged women.^2-4 In addition, a recently published case series of 4 patients with childhood-onset refractory LEP described improvement of disease activity with rituximab.⁵ It is important to rule out subcutaneous T-cell lymphoma before treatment with rituximab, as its histopathology can closely resemble that seen in LEP and HLH-associated cytophagic histiocytic panniculitis.^1,6

Rituximab may be an effective treatment option in pediatric patients with refractory LEP. Larger studies on the use of rituximab in the pediatric population are necessary.

To the Editor:

Lupus erythematosus panniculitis (LEP) is rare in the pediatric population. It can be difficult to manage, as patients may not respond to conventional treatments including hydroxychloroquine and prednisone. We report the use of rituximab in the treatment of a 20-year-old woman with LEP of the face, legs, and arms that was refractory to standard treatments. She also had a history of hemophagocytic lymphohistiocytosis (HLH). Further studies are warranted to determine the role of rituximab in the treatment of pediatric patients with LEP.

A 20-year-old woman with history of LEP and HLH initially presented with migratory violaceous nodules on the face 16 years prior to the current presentation. A skin biopsy 3 years after that initial presentation suggested a diagnosis of cutaneous lupus erythematosus. Six years later, numerous asymptomatic lesions appeared on the legs, predominantly on the calves; she was successfully treated with hydroxychloroquine and high-dose prednisone. Four years prior to the current presentation, a febrile illness prompted discontinuation of hydroxychloroquine and hospitalization, where she was first was diagnosed with HLH; she achieved remission with cyclosporine. At the current presentation, she continued to have persistent violaceous lesions on the face, lower arms, and legs with underlying nodularity (Figure 1). Skin biopsies revealed LEP and were less suggestive of HLH. She was restarted on hydroxychloroquine, which did not adequately control the disease. Rheumatologic workup was only notable for an antinuclear antibody titer of 1:80 (reference range, <1:80) in a speckled pattern.

Rituximab, a chimeric monoclonal antibody targeting B-cell surface marker CD20, results in depletion of mature B cells. Use of rituximab for LEP has been described in multiple case reports involving an 8-year-old boy, 22-year-old girl, and 2 middle-aged women.^2-4 In addition, a recently published case series of 4 patients with childhood-onset refractory LEP described improvement of disease activity with rituximab.⁵ It is important to rule out subcutaneous T-cell lymphoma before treatment with rituximab, as its histopathology can closely resemble that seen in LEP and HLH-associated cytophagic histiocytic panniculitis.^1,6

Rituximab may be an effective treatment option in pediatric patients with refractory LEP. Larger studies on the use of rituximab in the pediatric population are necessary.

To the Editor:

Lupus erythematosus panniculitis (LEP) is rare in the pediatric population. It can be difficult to manage, as patients may not respond to conventional treatments including hydroxychloroquine and prednisone. We report the use of rituximab in the treatment of a 20-year-old woman with LEP of the face, legs, and arms that was refractory to standard treatments. She also had a history of hemophagocytic lymphohistiocytosis (HLH). Further studies are warranted to determine the role of rituximab in the treatment of pediatric patients with LEP.

A 20-year-old woman with history of LEP and HLH initially presented with migratory violaceous nodules on the face 16 years prior to the current presentation. A skin biopsy 3 years after that initial presentation suggested a diagnosis of cutaneous lupus erythematosus. Six years later, numerous asymptomatic lesions appeared on the legs, predominantly on the calves; she was successfully treated with hydroxychloroquine and high-dose prednisone. Four years prior to the current presentation, a febrile illness prompted discontinuation of hydroxychloroquine and hospitalization, where she was first was diagnosed with HLH; she achieved remission with cyclosporine. At the current presentation, she continued to have persistent violaceous lesions on the face, lower arms, and legs with underlying nodularity (Figure 1). Skin biopsies revealed LEP and were less suggestive of HLH. She was restarted on hydroxychloroquine, which did not adequately control the disease. Rheumatologic workup was only notable for an antinuclear antibody titer of 1:80 (reference range, <1:80) in a speckled pattern.

Rituximab, a chimeric monoclonal antibody targeting B-cell surface marker CD20, results in depletion of mature B cells. Use of rituximab for LEP has been described in multiple case reports involving an 8-year-old boy, 22-year-old girl, and 2 middle-aged women.^2-4 In addition, a recently published case series of 4 patients with childhood-onset refractory LEP described improvement of disease activity with rituximab.⁵ It is important to rule out subcutaneous T-cell lymphoma before treatment with rituximab, as its histopathology can closely resemble that seen in LEP and HLH-associated cytophagic histiocytic panniculitis.^1,6

Rituximab may be an effective treatment option in pediatric patients with refractory LEP. Larger studies on the use of rituximab in the pediatric population are necessary.

A new joint statement by the American Thyroid Association (ATA), European Thyroid Association, and Society of Nuclear Medicine and Molecular Imaging tackles the rapidly evolving role of molecular markers in the diagnosis and treatment of thyroid cancer with radioactive iodine (RAI), supporting their increased implementation, particularly for risk stratification. 

The statement was issued as ever more data on molecular markers help launch a “new paradigm” in the approach to thyroid cancer, while driving ongoing debate over how they will feed into the use of RAI, first author Seza A. Gulec, MD, of Herbert Wertheim College of Medicine, Florida International University, Miami, said in an interview.

“The controversy over the appropriate use of RAI in thyroid cancer goes back 70 years, as we’ve been long using it based on the assumption that the majority of high-risk tumors respond to RAI,” he explained. 

“But the new paradigm calls for identifying, through molecular analysis, the cancers that have the ability to respond to RAI and/or those that could have the response to RAI enhanced through pretreatment.”

In the statement, published in Thyroid, the working group for the three societies describes their agreement on key issues in three broad areas of RAI use: RAI in perioperative risk stratification, the role of RAI imaging in initial staging, and the need to refine understanding of markers of response to RAI therapy.
 

Avoid unnecessary treatment 

The working group underscores the value of the traditional risk stratification and staging models for thyroid cancer – the American Joint Committee on Cancer eighth edition staging rules and ATA risk stratification system – in the immediate perioperative period, which is well established.

The group supports the inclusion of secondary prognostic factors, specifically molecular markers, in risk stratification in the perioperative period, citing their therapeutic and diagnostic (or theranostic) value in improving individualized treatment decisions.

Molecular theranostics comprise molecular cytology, molecular pathology, and molecular imaging.

“Traditional risk stratification systems can be further refined by ... judicious incorporation of molecular theranostics in the primary framework to guide initial patient management decisions,” the authors wrote.

Dr. Gulec said the inclusion of molecular analysis in risk stratification in particular offers the potential to avoid unnecessary treatment in people who can be identified as likely nonresponders.

“The bottom line is that we need to know more about the cancer before we make decisions on how to tackle it,” he said in an interview.

“For the thyroid cancer to respond to RAI, it has to have an intact system to handle the treatment, and the fact is that most high-risk patients have a molecular profile that does not allow them to respond to RAI or to benefit from total thyroidectomy,” Dr. Gulec explained.

However, the ability to perform a complete genomic analysis with advanced molecular sequencing and identify those patients is radically changing things, he concluded.

Dr. Gulec has  reported no relevant financial relationships.

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

A new joint statement by the American Thyroid Association (ATA), European Thyroid Association, and Society of Nuclear Medicine and Molecular Imaging tackles the rapidly evolving role of molecular markers in the diagnosis and treatment of thyroid cancer with radioactive iodine (RAI), supporting their increased implementation, particularly for risk stratification. 

The statement was issued as ever more data on molecular markers help launch a “new paradigm” in the approach to thyroid cancer, while driving ongoing debate over how they will feed into the use of RAI, first author Seza A. Gulec, MD, of Herbert Wertheim College of Medicine, Florida International University, Miami, said in an interview.

“The controversy over the appropriate use of RAI in thyroid cancer goes back 70 years, as we’ve been long using it based on the assumption that the majority of high-risk tumors respond to RAI,” he explained. 

“But the new paradigm calls for identifying, through molecular analysis, the cancers that have the ability to respond to RAI and/or those that could have the response to RAI enhanced through pretreatment.”

In the statement, published in Thyroid, the working group for the three societies describes their agreement on key issues in three broad areas of RAI use: RAI in perioperative risk stratification, the role of RAI imaging in initial staging, and the need to refine understanding of markers of response to RAI therapy.
 

Avoid unnecessary treatment 

The working group underscores the value of the traditional risk stratification and staging models for thyroid cancer – the American Joint Committee on Cancer eighth edition staging rules and ATA risk stratification system – in the immediate perioperative period, which is well established.

The group supports the inclusion of secondary prognostic factors, specifically molecular markers, in risk stratification in the perioperative period, citing their therapeutic and diagnostic (or theranostic) value in improving individualized treatment decisions.

Molecular theranostics comprise molecular cytology, molecular pathology, and molecular imaging.

“Traditional risk stratification systems can be further refined by ... judicious incorporation of molecular theranostics in the primary framework to guide initial patient management decisions,” the authors wrote.

Dr. Gulec said the inclusion of molecular analysis in risk stratification in particular offers the potential to avoid unnecessary treatment in people who can be identified as likely nonresponders.

“The bottom line is that we need to know more about the cancer before we make decisions on how to tackle it,” he said in an interview.

“For the thyroid cancer to respond to RAI, it has to have an intact system to handle the treatment, and the fact is that most high-risk patients have a molecular profile that does not allow them to respond to RAI or to benefit from total thyroidectomy,” Dr. Gulec explained.

However, the ability to perform a complete genomic analysis with advanced molecular sequencing and identify those patients is radically changing things, he concluded.

Dr. Gulec has  reported no relevant financial relationships.

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

A new joint statement by the American Thyroid Association (ATA), European Thyroid Association, and Society of Nuclear Medicine and Molecular Imaging tackles the rapidly evolving role of molecular markers in the diagnosis and treatment of thyroid cancer with radioactive iodine (RAI), supporting their increased implementation, particularly for risk stratification. 

The statement was issued as ever more data on molecular markers help launch a “new paradigm” in the approach to thyroid cancer, while driving ongoing debate over how they will feed into the use of RAI, first author Seza A. Gulec, MD, of Herbert Wertheim College of Medicine, Florida International University, Miami, said in an interview.

“The controversy over the appropriate use of RAI in thyroid cancer goes back 70 years, as we’ve been long using it based on the assumption that the majority of high-risk tumors respond to RAI,” he explained. 

“But the new paradigm calls for identifying, through molecular analysis, the cancers that have the ability to respond to RAI and/or those that could have the response to RAI enhanced through pretreatment.”

In the statement, published in Thyroid, the working group for the three societies describes their agreement on key issues in three broad areas of RAI use: RAI in perioperative risk stratification, the role of RAI imaging in initial staging, and the need to refine understanding of markers of response to RAI therapy.
 

Avoid unnecessary treatment 

The working group underscores the value of the traditional risk stratification and staging models for thyroid cancer – the American Joint Committee on Cancer eighth edition staging rules and ATA risk stratification system – in the immediate perioperative period, which is well established.

The group supports the inclusion of secondary prognostic factors, specifically molecular markers, in risk stratification in the perioperative period, citing their therapeutic and diagnostic (or theranostic) value in improving individualized treatment decisions.

Molecular theranostics comprise molecular cytology, molecular pathology, and molecular imaging.

“Traditional risk stratification systems can be further refined by ... judicious incorporation of molecular theranostics in the primary framework to guide initial patient management decisions,” the authors wrote.

Dr. Gulec said the inclusion of molecular analysis in risk stratification in particular offers the potential to avoid unnecessary treatment in people who can be identified as likely nonresponders.

“The bottom line is that we need to know more about the cancer before we make decisions on how to tackle it,” he said in an interview.

“For the thyroid cancer to respond to RAI, it has to have an intact system to handle the treatment, and the fact is that most high-risk patients have a molecular profile that does not allow them to respond to RAI or to benefit from total thyroidectomy,” Dr. Gulec explained.

However, the ability to perform a complete genomic analysis with advanced molecular sequencing and identify those patients is radically changing things, he concluded.

Dr. Gulec has  reported no relevant financial relationships.

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

The Food and Drug Administration on Aug. 20 issued a new safety communication about the use of robotically assisted mastectomy, warning patients and physicians that the safety and effectiveness of such devices have not been established in the prevention or treatment of breast cancer.

The agency also called out robotically assisted surgical (RAS) device use in the United States that lacks proper federal oversight.

“The FDA is aware of allegations that clinical studies are being conducted” with RAS devices in breast cancer “without the FDA oversight required for such significant risk studies,” the agency said.

The new advisory comes 4 weeks after a Medscape Medical News exclusive story on a set of clinical trials recently underway using RAS devices for nipple-sparing mastectomy, both prophylactically and as a breast cancer treatment.

The report found that investigators are either not collecting cancer outcomes or not doing so as a primary measure – despite a stiff warning in 2019 from the FDA that those outcomes are important. 

“Congratulations to the press on doing its job well and informing government. I think this [safety communication] is a direct result of Medscape following up on this issue,” said Hooman Noorchashm, MD, PhD, a patient advocate from Philadelphia. He is a former surgeon and faculty member at the University of Pennsylvania.

In reviewing the FDA’s new warning, Dr. Noorchashm pointed out that the agency also stated unequivocally – after previously hinting – that any study of robotic mastectomy “must include monitoring of long-term clinical outcomes” such as cancer recurrence, disease-free survival, and overall survival.

That’s a change in approach – previously the FDA has typically approved/cleared RAS devices for use in cancer surgery based on 30-day complication rates (compared with standards of care) and had no requirement for cancer-related outcomes data.

“This [new] advisory reiterates the need for a clear focus on primary oncologic outcomes to, at the very least, demonstrate the noninferiority of robotic assisted surgical devices for performing mastectomy procedures,” said Dr. Noorchashm.

In a 2019 warning about robotic mastectomy, the FDA suggested that it would require oncologic measures moving forward, saying that it “anticipates” that any evaluation of new use of robotic devices in women’s cancer “would be supported” by long-term cancer outcomes. But it stopped short of publicly saying so. The new advisory changes that.
 

Direct comparison with traditional mastectomy needed

There are safety concerns with robotic mastectomy. Experts question whether a surgeon can easily remove a breast tumor in one piece through the small incision (a selling point of the robot). If the tissue cannot be removed in one piece, cancer fragments may be left behind.

As a result, a randomized trial with traditional open mastectomy as a comparator is needed, Dr. Noorchashm stressed. The current batch of clinical trials in the United States are all single-arm studies and as such are “totally inappropriate,” he said.

Julie Margenthaler, MD, a breast surgeon at Washington University in St Louis, also noted the importance of a randomized trial.

“I feel strongly that robotic-assisted mastectomy should only be performed in the setting of a well-designed clinical trial and that oncologic outcomes should be a primary or secondary endpoint analysis as part of that trial,” she said in an email.

Intuitive Surgical, a California-based manufacturer of robotic devices in health care and a pioneer in robot-assisted surgery, is funding one of the current clinical trials of robotic mastectomy in the United States – a single-arm, five-center trial examining use in the prophylactic setting. The two primary outcomes are conversions to open mastectomy (efficacy measure) and the incidence of adverse events during surgery to 42 days after surgery (safety measure).

This news organization previously asked the company, which manufactures the market leader da Vinci robotic surgical equipment, if it planned to conduct a randomized trial.

“Any plans for use of da Vinci Xi surgical system in nipple-sparing mastectomy will be based on these [single-arm] study results as well as other data and evidence,” said a spokesperson, who did not confirm use of a randomized trial.

The new FDA requirement for long-term oncologic outcomes also in part arises from “diminished long-term survival” that was associated with robotic surgery and other minimally invasive surgery for hysterectomy related to cervical cancer.

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

The Food and Drug Administration on Aug. 20 issued a new safety communication about the use of robotically assisted mastectomy, warning patients and physicians that the safety and effectiveness of such devices have not been established in the prevention or treatment of breast cancer.

The agency also called out robotically assisted surgical (RAS) device use in the United States that lacks proper federal oversight.

“The FDA is aware of allegations that clinical studies are being conducted” with RAS devices in breast cancer “without the FDA oversight required for such significant risk studies,” the agency said.

The new advisory comes 4 weeks after a Medscape Medical News exclusive story on a set of clinical trials recently underway using RAS devices for nipple-sparing mastectomy, both prophylactically and as a breast cancer treatment.

The report found that investigators are either not collecting cancer outcomes or not doing so as a primary measure – despite a stiff warning in 2019 from the FDA that those outcomes are important. 

“Congratulations to the press on doing its job well and informing government. I think this [safety communication] is a direct result of Medscape following up on this issue,” said Hooman Noorchashm, MD, PhD, a patient advocate from Philadelphia. He is a former surgeon and faculty member at the University of Pennsylvania.

In reviewing the FDA’s new warning, Dr. Noorchashm pointed out that the agency also stated unequivocally – after previously hinting – that any study of robotic mastectomy “must include monitoring of long-term clinical outcomes” such as cancer recurrence, disease-free survival, and overall survival.

That’s a change in approach – previously the FDA has typically approved/cleared RAS devices for use in cancer surgery based on 30-day complication rates (compared with standards of care) and had no requirement for cancer-related outcomes data.

“This [new] advisory reiterates the need for a clear focus on primary oncologic outcomes to, at the very least, demonstrate the noninferiority of robotic assisted surgical devices for performing mastectomy procedures,” said Dr. Noorchashm.

In a 2019 warning about robotic mastectomy, the FDA suggested that it would require oncologic measures moving forward, saying that it “anticipates” that any evaluation of new use of robotic devices in women’s cancer “would be supported” by long-term cancer outcomes. But it stopped short of publicly saying so. The new advisory changes that.
 

Direct comparison with traditional mastectomy needed

There are safety concerns with robotic mastectomy. Experts question whether a surgeon can easily remove a breast tumor in one piece through the small incision (a selling point of the robot). If the tissue cannot be removed in one piece, cancer fragments may be left behind.

As a result, a randomized trial with traditional open mastectomy as a comparator is needed, Dr. Noorchashm stressed. The current batch of clinical trials in the United States are all single-arm studies and as such are “totally inappropriate,” he said.

Julie Margenthaler, MD, a breast surgeon at Washington University in St Louis, also noted the importance of a randomized trial.

“I feel strongly that robotic-assisted mastectomy should only be performed in the setting of a well-designed clinical trial and that oncologic outcomes should be a primary or secondary endpoint analysis as part of that trial,” she said in an email.

Intuitive Surgical, a California-based manufacturer of robotic devices in health care and a pioneer in robot-assisted surgery, is funding one of the current clinical trials of robotic mastectomy in the United States – a single-arm, five-center trial examining use in the prophylactic setting. The two primary outcomes are conversions to open mastectomy (efficacy measure) and the incidence of adverse events during surgery to 42 days after surgery (safety measure).

This news organization previously asked the company, which manufactures the market leader da Vinci robotic surgical equipment, if it planned to conduct a randomized trial.

“Any plans for use of da Vinci Xi surgical system in nipple-sparing mastectomy will be based on these [single-arm] study results as well as other data and evidence,” said a spokesperson, who did not confirm use of a randomized trial.

The new FDA requirement for long-term oncologic outcomes also in part arises from “diminished long-term survival” that was associated with robotic surgery and other minimally invasive surgery for hysterectomy related to cervical cancer.

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

The Food and Drug Administration on Aug. 20 issued a new safety communication about the use of robotically assisted mastectomy, warning patients and physicians that the safety and effectiveness of such devices have not been established in the prevention or treatment of breast cancer.

The agency also called out robotically assisted surgical (RAS) device use in the United States that lacks proper federal oversight.

“The FDA is aware of allegations that clinical studies are being conducted” with RAS devices in breast cancer “without the FDA oversight required for such significant risk studies,” the agency said.

The new advisory comes 4 weeks after a Medscape Medical News exclusive story on a set of clinical trials recently underway using RAS devices for nipple-sparing mastectomy, both prophylactically and as a breast cancer treatment.

The report found that investigators are either not collecting cancer outcomes or not doing so as a primary measure – despite a stiff warning in 2019 from the FDA that those outcomes are important. 

“Congratulations to the press on doing its job well and informing government. I think this [safety communication] is a direct result of Medscape following up on this issue,” said Hooman Noorchashm, MD, PhD, a patient advocate from Philadelphia. He is a former surgeon and faculty member at the University of Pennsylvania.

In reviewing the FDA’s new warning, Dr. Noorchashm pointed out that the agency also stated unequivocally – after previously hinting – that any study of robotic mastectomy “must include monitoring of long-term clinical outcomes” such as cancer recurrence, disease-free survival, and overall survival.

That’s a change in approach – previously the FDA has typically approved/cleared RAS devices for use in cancer surgery based on 30-day complication rates (compared with standards of care) and had no requirement for cancer-related outcomes data.

“This [new] advisory reiterates the need for a clear focus on primary oncologic outcomes to, at the very least, demonstrate the noninferiority of robotic assisted surgical devices for performing mastectomy procedures,” said Dr. Noorchashm.

In a 2019 warning about robotic mastectomy, the FDA suggested that it would require oncologic measures moving forward, saying that it “anticipates” that any evaluation of new use of robotic devices in women’s cancer “would be supported” by long-term cancer outcomes. But it stopped short of publicly saying so. The new advisory changes that.
 

Direct comparison with traditional mastectomy needed

There are safety concerns with robotic mastectomy. Experts question whether a surgeon can easily remove a breast tumor in one piece through the small incision (a selling point of the robot). If the tissue cannot be removed in one piece, cancer fragments may be left behind.

As a result, a randomized trial with traditional open mastectomy as a comparator is needed, Dr. Noorchashm stressed. The current batch of clinical trials in the United States are all single-arm studies and as such are “totally inappropriate,” he said.

Julie Margenthaler, MD, a breast surgeon at Washington University in St Louis, also noted the importance of a randomized trial.

“I feel strongly that robotic-assisted mastectomy should only be performed in the setting of a well-designed clinical trial and that oncologic outcomes should be a primary or secondary endpoint analysis as part of that trial,” she said in an email.

Intuitive Surgical, a California-based manufacturer of robotic devices in health care and a pioneer in robot-assisted surgery, is funding one of the current clinical trials of robotic mastectomy in the United States – a single-arm, five-center trial examining use in the prophylactic setting. The two primary outcomes are conversions to open mastectomy (efficacy measure) and the incidence of adverse events during surgery to 42 days after surgery (safety measure).

This news organization previously asked the company, which manufactures the market leader da Vinci robotic surgical equipment, if it planned to conduct a randomized trial.

“Any plans for use of da Vinci Xi surgical system in nipple-sparing mastectomy will be based on these [single-arm] study results as well as other data and evidence,” said a spokesperson, who did not confirm use of a randomized trial.

The new FDA requirement for long-term oncologic outcomes also in part arises from “diminished long-term survival” that was associated with robotic surgery and other minimally invasive surgery for hysterectomy related to cervical cancer.

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

A team of researchers from the Cleveland Clinic, the Moffitt Cancer Center in Tampa, and Case Western Reserve University in Cleveland is zeroing in on a way to personalize radiation therapy for cancer patients based on genomic profile, much as genomics is used to tailor oncologic drug therapy.

It’s called “genomic-adjusted radiation dose” (GARD), a dose tailored to a person’s radiosensitivity as determined by the expression of 10 genes, known as the radiosensitivity index (RSI), combined with a linear quadratic model to yield GARD, a prediction of risk and benefit at various radiation doses for a particular patient.

A recent report in The Lancet Oncology validated GARD in 1,615 patients with seven cancer types from 11 study cohorts. If it holds up in clinical trials set to start later this year, GARD should “allow us to predict the benefit of radiation for an individual patient and adjust their treatment strategy,” wrote the authors of an editorial that accompanied the study. “The efforts need to be applauded worldwide, because radiotherapy is considerably lagging, compared with the enormous progress done in the field of personalized medicine,” Orit Kaidar-Person, MD, a radiation oncologist at Sheba Medical Center in Ramat Gan, Israel, and colleagues wrote.

GARD was associated with time to first recurrence and overall survival for patients receiving radiotherapy and predicted radiotherapy benefit, while physical dose did not. The team found a relative 2% reduction in risk of first recurrence for each unit increase of GARD (P = .0017) and a relative 3% increase in overall survival for each unit increase in GARD (P = .0007), among those who got radiotherapy. Values of GARD run from 0 to over 100, with higher scores meaning more radiation benefit.

The radiosensitivity index, which was derived from genomic studies of cancer cell lines exposed to radiation, was previously validated by the team and other groups across several tumor types.

Currently, radiation dosing is generally uniform for a given disease site and stage, based on the assumption that a given dose of radiation results in the same clinical effect across patients. In fact, the biological effect of a given dose varies widely between individual patients. “Patients we treat uniformly do not have a uniform response” which is why a more personalized approach would help, said lead investigator and Cleveland Clinic radiation oncologist Jacob Scott, MD, DPhil.

One patient with a given tumor might benefit from 2 extra fractions, while the next might need an extra 15 for the same benefit. “You need to know about [a patient’s] tumor genomics to know how hard you have to work,” he said.

Dr. Scott and colleagues are working with a genomics company to commercialize the approach. The vision for now is that physicians would ship in biopsy samples to be analyzed; RSI and GARD would be calculated, and then a decision support report would be sent back to the treatment team outlining the risks and benefits of various doses for the patient.

Dr. Scott, who holds proprietary rights on the approach, is bullish. When asked if he anticipates GARD dosing to be standard of care in 10 years, he said that “I can’t imagine another world. Everything else in cancer is personalized. Why aren’t we? It just makes sense. I know there’s a better way” to prescribe radiation, “and I’m excited for the future when I can use it.”

When asked for comment, Brian Marples, PhD, a radiation oncology professor at the University of Rochester (N.Y.), said the data so far for GARD “seem very solid. I’m very excited by the concept.”

It’s been “the holy grail” of radiation researchers to find a biologic marker that predicts what dosages patients need and what can be given safely. “This strategy is a good way of doing that. Other groups are proposing similar strategies, but I think this group is ahead. I can see [GARD] being readily applied to the clinic because patients are [already] getting their tumors genomically characterized as part of care,” Dr. Marples said.

But many questions remain. For instance, the editorial writers questioned how GARD is “affected by tumor heterogeneity, response to systemic therapy, and changes in the tumor microenvironment.” Also, the approach is based on conventional 2 Gy fractions, but other fractionation regimens are becoming more common.

For Dr. Marples, the big caveat is that most cancer patients are treated with both radiation and chemotherapy. He said he would like to see GARD validated in patients who receive both.

They seven tumor types in the study included breast cancer, head and neck cancer, non–small cell lung cancer, pancreatic cancer, endometrial cancer, melanoma, and glioma. The majority of the subjects were treated with radiation, and each had the genomic data needed to calculate GARD.

Dr. Scott, senior author and Moffitt Center radiation oncologist Javier Torres-Roca, MD, and a third author hold intellectual property rights on RSI, GARD, and prescription dose base on RSI, plus equity in Cvergenx, a company that seeks to commercialize the approach. Dr. Torres-Roca and another author are cofounders. The editorial writers and Dr. Marples did not have any relevant disclosures.
 

[email protected]

A team of researchers from the Cleveland Clinic, the Moffitt Cancer Center in Tampa, and Case Western Reserve University in Cleveland is zeroing in on a way to personalize radiation therapy for cancer patients based on genomic profile, much as genomics is used to tailor oncologic drug therapy.

It’s called “genomic-adjusted radiation dose” (GARD), a dose tailored to a person’s radiosensitivity as determined by the expression of 10 genes, known as the radiosensitivity index (RSI), combined with a linear quadratic model to yield GARD, a prediction of risk and benefit at various radiation doses for a particular patient.

A recent report in The Lancet Oncology validated GARD in 1,615 patients with seven cancer types from 11 study cohorts. If it holds up in clinical trials set to start later this year, GARD should “allow us to predict the benefit of radiation for an individual patient and adjust their treatment strategy,” wrote the authors of an editorial that accompanied the study. “The efforts need to be applauded worldwide, because radiotherapy is considerably lagging, compared with the enormous progress done in the field of personalized medicine,” Orit Kaidar-Person, MD, a radiation oncologist at Sheba Medical Center in Ramat Gan, Israel, and colleagues wrote.

GARD was associated with time to first recurrence and overall survival for patients receiving radiotherapy and predicted radiotherapy benefit, while physical dose did not. The team found a relative 2% reduction in risk of first recurrence for each unit increase of GARD (P = .0017) and a relative 3% increase in overall survival for each unit increase in GARD (P = .0007), among those who got radiotherapy. Values of GARD run from 0 to over 100, with higher scores meaning more radiation benefit.

The radiosensitivity index, which was derived from genomic studies of cancer cell lines exposed to radiation, was previously validated by the team and other groups across several tumor types.

Currently, radiation dosing is generally uniform for a given disease site and stage, based on the assumption that a given dose of radiation results in the same clinical effect across patients. In fact, the biological effect of a given dose varies widely between individual patients. “Patients we treat uniformly do not have a uniform response” which is why a more personalized approach would help, said lead investigator and Cleveland Clinic radiation oncologist Jacob Scott, MD, DPhil.

One patient with a given tumor might benefit from 2 extra fractions, while the next might need an extra 15 for the same benefit. “You need to know about [a patient’s] tumor genomics to know how hard you have to work,” he said.

Dr. Scott and colleagues are working with a genomics company to commercialize the approach. The vision for now is that physicians would ship in biopsy samples to be analyzed; RSI and GARD would be calculated, and then a decision support report would be sent back to the treatment team outlining the risks and benefits of various doses for the patient.

Dr. Scott, who holds proprietary rights on the approach, is bullish. When asked if he anticipates GARD dosing to be standard of care in 10 years, he said that “I can’t imagine another world. Everything else in cancer is personalized. Why aren’t we? It just makes sense. I know there’s a better way” to prescribe radiation, “and I’m excited for the future when I can use it.”

When asked for comment, Brian Marples, PhD, a radiation oncology professor at the University of Rochester (N.Y.), said the data so far for GARD “seem very solid. I’m very excited by the concept.”

It’s been “the holy grail” of radiation researchers to find a biologic marker that predicts what dosages patients need and what can be given safely. “This strategy is a good way of doing that. Other groups are proposing similar strategies, but I think this group is ahead. I can see [GARD] being readily applied to the clinic because patients are [already] getting their tumors genomically characterized as part of care,” Dr. Marples said.

But many questions remain. For instance, the editorial writers questioned how GARD is “affected by tumor heterogeneity, response to systemic therapy, and changes in the tumor microenvironment.” Also, the approach is based on conventional 2 Gy fractions, but other fractionation regimens are becoming more common.

For Dr. Marples, the big caveat is that most cancer patients are treated with both radiation and chemotherapy. He said he would like to see GARD validated in patients who receive both.

They seven tumor types in the study included breast cancer, head and neck cancer, non–small cell lung cancer, pancreatic cancer, endometrial cancer, melanoma, and glioma. The majority of the subjects were treated with radiation, and each had the genomic data needed to calculate GARD.

Dr. Scott, senior author and Moffitt Center radiation oncologist Javier Torres-Roca, MD, and a third author hold intellectual property rights on RSI, GARD, and prescription dose base on RSI, plus equity in Cvergenx, a company that seeks to commercialize the approach. Dr. Torres-Roca and another author are cofounders. The editorial writers and Dr. Marples did not have any relevant disclosures.
 

[email protected]

A team of researchers from the Cleveland Clinic, the Moffitt Cancer Center in Tampa, and Case Western Reserve University in Cleveland is zeroing in on a way to personalize radiation therapy for cancer patients based on genomic profile, much as genomics is used to tailor oncologic drug therapy.

It’s called “genomic-adjusted radiation dose” (GARD), a dose tailored to a person’s radiosensitivity as determined by the expression of 10 genes, known as the radiosensitivity index (RSI), combined with a linear quadratic model to yield GARD, a prediction of risk and benefit at various radiation doses for a particular patient.

A recent report in The Lancet Oncology validated GARD in 1,615 patients with seven cancer types from 11 study cohorts. If it holds up in clinical trials set to start later this year, GARD should “allow us to predict the benefit of radiation for an individual patient and adjust their treatment strategy,” wrote the authors of an editorial that accompanied the study. “The efforts need to be applauded worldwide, because radiotherapy is considerably lagging, compared with the enormous progress done in the field of personalized medicine,” Orit Kaidar-Person, MD, a radiation oncologist at Sheba Medical Center in Ramat Gan, Israel, and colleagues wrote.

GARD was associated with time to first recurrence and overall survival for patients receiving radiotherapy and predicted radiotherapy benefit, while physical dose did not. The team found a relative 2% reduction in risk of first recurrence for each unit increase of GARD (P = .0017) and a relative 3% increase in overall survival for each unit increase in GARD (P = .0007), among those who got radiotherapy. Values of GARD run from 0 to over 100, with higher scores meaning more radiation benefit.

The radiosensitivity index, which was derived from genomic studies of cancer cell lines exposed to radiation, was previously validated by the team and other groups across several tumor types.

Currently, radiation dosing is generally uniform for a given disease site and stage, based on the assumption that a given dose of radiation results in the same clinical effect across patients. In fact, the biological effect of a given dose varies widely between individual patients. “Patients we treat uniformly do not have a uniform response” which is why a more personalized approach would help, said lead investigator and Cleveland Clinic radiation oncologist Jacob Scott, MD, DPhil.

One patient with a given tumor might benefit from 2 extra fractions, while the next might need an extra 15 for the same benefit. “You need to know about [a patient’s] tumor genomics to know how hard you have to work,” he said.

Dr. Scott and colleagues are working with a genomics company to commercialize the approach. The vision for now is that physicians would ship in biopsy samples to be analyzed; RSI and GARD would be calculated, and then a decision support report would be sent back to the treatment team outlining the risks and benefits of various doses for the patient.

Dr. Scott, who holds proprietary rights on the approach, is bullish. When asked if he anticipates GARD dosing to be standard of care in 10 years, he said that “I can’t imagine another world. Everything else in cancer is personalized. Why aren’t we? It just makes sense. I know there’s a better way” to prescribe radiation, “and I’m excited for the future when I can use it.”

When asked for comment, Brian Marples, PhD, a radiation oncology professor at the University of Rochester (N.Y.), said the data so far for GARD “seem very solid. I’m very excited by the concept.”

It’s been “the holy grail” of radiation researchers to find a biologic marker that predicts what dosages patients need and what can be given safely. “This strategy is a good way of doing that. Other groups are proposing similar strategies, but I think this group is ahead. I can see [GARD] being readily applied to the clinic because patients are [already] getting their tumors genomically characterized as part of care,” Dr. Marples said.

But many questions remain. For instance, the editorial writers questioned how GARD is “affected by tumor heterogeneity, response to systemic therapy, and changes in the tumor microenvironment.” Also, the approach is based on conventional 2 Gy fractions, but other fractionation regimens are becoming more common.

For Dr. Marples, the big caveat is that most cancer patients are treated with both radiation and chemotherapy. He said he would like to see GARD validated in patients who receive both.

They seven tumor types in the study included breast cancer, head and neck cancer, non–small cell lung cancer, pancreatic cancer, endometrial cancer, melanoma, and glioma. The majority of the subjects were treated with radiation, and each had the genomic data needed to calculate GARD.

Dr. Scott, senior author and Moffitt Center radiation oncologist Javier Torres-Roca, MD, and a third author hold intellectual property rights on RSI, GARD, and prescription dose base on RSI, plus equity in Cvergenx, a company that seeks to commercialize the approach. Dr. Torres-Roca and another author are cofounders. The editorial writers and Dr. Marples did not have any relevant disclosures.
 

[email protected]

Background: Despite advances in perioperative care, postoperative pulmonary complications represent a leading cause of morbidity and mortality that are associated with increased risk of admission to critical care and prolonged length of hospital stay. There are multiple interventions that are used, despite there being no consensus guidelines aimed at reducing the risk of PPCs.

Unfortunately, only a minority of the trials reviewed were large, multi-center studies with a low risk of bias. The studies were also heterogeneous, posing a challenge for meta-analysis.

Bottom line: There is limited evidence supporting the efficacy of any intervention preventing postoperative pulmonary complications, with moderate-quality evidence supporting intraoperative lung protective ventilation and goal-directed hemodynamic strategies reducing PPCs.

Citation: Odor PM et al. Perioperative interventions for prevention of postoperative pulmonary complication: Systemic review and meta-analysis. BMJ. 2020 Mar 11. doi: 10.1136/bmj.m540.

Dr. Weaver is a hospitalist and assistant professor of medicine at UK HealthCare, Lexington, Ky.

Background: Despite advances in perioperative care, postoperative pulmonary complications represent a leading cause of morbidity and mortality that are associated with increased risk of admission to critical care and prolonged length of hospital stay. There are multiple interventions that are used, despite there being no consensus guidelines aimed at reducing the risk of PPCs.

Unfortunately, only a minority of the trials reviewed were large, multi-center studies with a low risk of bias. The studies were also heterogeneous, posing a challenge for meta-analysis.

Bottom line: There is limited evidence supporting the efficacy of any intervention preventing postoperative pulmonary complications, with moderate-quality evidence supporting intraoperative lung protective ventilation and goal-directed hemodynamic strategies reducing PPCs.

Citation: Odor PM et al. Perioperative interventions for prevention of postoperative pulmonary complication: Systemic review and meta-analysis. BMJ. 2020 Mar 11. doi: 10.1136/bmj.m540.

Dr. Weaver is a hospitalist and assistant professor of medicine at UK HealthCare, Lexington, Ky.

Background: Despite advances in perioperative care, postoperative pulmonary complications represent a leading cause of morbidity and mortality that are associated with increased risk of admission to critical care and prolonged length of hospital stay. There are multiple interventions that are used, despite there being no consensus guidelines aimed at reducing the risk of PPCs.

Unfortunately, only a minority of the trials reviewed were large, multi-center studies with a low risk of bias. The studies were also heterogeneous, posing a challenge for meta-analysis.

Bottom line: There is limited evidence supporting the efficacy of any intervention preventing postoperative pulmonary complications, with moderate-quality evidence supporting intraoperative lung protective ventilation and goal-directed hemodynamic strategies reducing PPCs.

Citation: Odor PM et al. Perioperative interventions for prevention of postoperative pulmonary complication: Systemic review and meta-analysis. BMJ. 2020 Mar 11. doi: 10.1136/bmj.m540.

Dr. Weaver is a hospitalist and assistant professor of medicine at UK HealthCare, Lexington, Ky.

A new joint consensus statement by four major diabetes organizations aims to standardize the terminology, definition, and assessment to the phenomenon of diabetes “remission.”

The statement was jointly issued by the American Diabetes Association, the Endocrine Society, the European Association for the Study of Diabetes, and Diabetes UK.

The 12-member international writing panel proposed use of the term “remission,” as opposed to others such as “reversal,” “resolution,” or “cure,” to describe the phenomenon of prolonged normoglycemia without the use of glucose-lowering medication in a person previously diagnosed with type 2 diabetes.

“Diabetes remission may be occurring more often due to advances in treatment,” writing group member Amy Rothberg, MD, of the University of Michigan, Ann Arbor, said in a statement.

The group defined “remission” – whether attained via lifestyle, bariatric surgery, or other means – as an A1c < 6.5% (< 48 mmol/mol) at least 3 months after cessation of glucose-lowering pharmacotherapy. The panel also suggested monitoring individuals experiencing diabetes remission and raised questions that need further attention and study.

But it’s not a guideline, panel chair Matthew C. Riddle, MD, said in an interview. Rather, the “main purpose of the statement was to provide definitions, terminology, cut-points, and timing recommendations to allow data collection that will eventually lead to clinical guidelines,” he said.

A great deal of epidemiological research is conducted by analyzing data from medical records, he noted. “If clinicians are more consistent in entering data into the records and in doing measurements, it will be a better database.”
 

Remission reality: Advice needed for deprescribing, talking to patients

“Increasingly our treatments are getting glucose levels into the normal range, and in many cases, even after withdrawal of drug therapy. That’s not an anomaly or a fiction, it’s reality. Clinicians need to know how to talk to their patients about it,” noted Dr. Riddle, of the division of endocrinology, diabetes, and clinical nutrition at Oregon Health & Science University, Portland.

There is a need for data on the effects of deprescribing once normoglycemia is achieved, he said. “It really goes a long way to have strong epidemiological and interventional evidence. That’s what we need here, and that’s what the group is really hoping for.”

The statement recommends the following:

• The term “remission” should be used to describe a sustained metabolic improvement in type 2 diabetes to near normal levels. The panel agreed the word strikes the best balance, given that insulin resistance and beta-cell dysfunction may still be present despite normoglycemia. “Diabetes doesn’t get cured. The underlying abnormalities are still there. Remission is defined by glucose,” Dr. Riddle said. The panel also decided to do away with ADA’s former terms “partial,” “complete,” and “prolonged” remission because they are ambiguous and unhelpful. 
• Remission should be defined as a return to an A1c of < 6.5% (< 48 mmol/mol) – the threshold used to diagnose diabetes – spontaneously or following an intervention and that persists for at least 3 months in the absence of usual glucose-lowering medication.
• When A1c may be unreliable, such as conditions involving variant hemoglobin or erythrocyte survival alterations, acceptable alternatives are a fasting blood glucose < 126 mg/dL (< 7.0 mmol/L) or an estimated A1c < 6.5% calculated from continuous glucose monitoring data.
• A1c testing to document a remission should be performed just prior to an intervention and no sooner than 3 months after initiation of the intervention and withdrawal of any glucose-lowering medication.
• Subsequent ongoing A1c testing should be done at least yearly thereafter, along with routine monitoring for diabetes-related complications, including retinal screening, renal function assessment, foot exams, and cardiovascular risk factor testing. “At present, there is no long-term evidence indicating that any of the usually recommended assessments for complications can safely be discontinued,” the authors wrote.
• Research based on the terminology and definitions in the present statement is needed to determine the frequency, duration, and effects on short- and long-term medical outcomes of type 2 diabetes remissions using available interventions.

Dr. Riddle said in an interview: “We thought that the clinical community needed to understand where this issue stands right now. The feasibility of a remission is greater than it used to be.

“We’re going to see more patients who have what we can now call a remission according to a standardized definition. In the future, there are likely to be guidelines regarding the kind of patients and the kind of tactics appropriate for seeking a remission,” he said.

The statement was simultaneously published online in each of the organizations’ respective journals: Diabetes Care, Journal of Clinical Endocrinology & Metabolism, Diabetologia, and Diabetic Medicine.

Dr. Riddle has reported receiving research grant support through Oregon Health & Science University from Eli Lilly, Novo Nordisk, and AstraZeneca and honoraria for consulting from Adocia, Intercept, and Theracos.

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

A new joint consensus statement by four major diabetes organizations aims to standardize the terminology, definition, and assessment to the phenomenon of diabetes “remission.”

The statement was jointly issued by the American Diabetes Association, the Endocrine Society, the European Association for the Study of Diabetes, and Diabetes UK.

The 12-member international writing panel proposed use of the term “remission,” as opposed to others such as “reversal,” “resolution,” or “cure,” to describe the phenomenon of prolonged normoglycemia without the use of glucose-lowering medication in a person previously diagnosed with type 2 diabetes.

“Diabetes remission may be occurring more often due to advances in treatment,” writing group member Amy Rothberg, MD, of the University of Michigan, Ann Arbor, said in a statement.

The group defined “remission” – whether attained via lifestyle, bariatric surgery, or other means – as an A1c < 6.5% (< 48 mmol/mol) at least 3 months after cessation of glucose-lowering pharmacotherapy. The panel also suggested monitoring individuals experiencing diabetes remission and raised questions that need further attention and study.

But it’s not a guideline, panel chair Matthew C. Riddle, MD, said in an interview. Rather, the “main purpose of the statement was to provide definitions, terminology, cut-points, and timing recommendations to allow data collection that will eventually lead to clinical guidelines,” he said.

A great deal of epidemiological research is conducted by analyzing data from medical records, he noted. “If clinicians are more consistent in entering data into the records and in doing measurements, it will be a better database.”
 

Remission reality: Advice needed for deprescribing, talking to patients

“Increasingly our treatments are getting glucose levels into the normal range, and in many cases, even after withdrawal of drug therapy. That’s not an anomaly or a fiction, it’s reality. Clinicians need to know how to talk to their patients about it,” noted Dr. Riddle, of the division of endocrinology, diabetes, and clinical nutrition at Oregon Health & Science University, Portland.

There is a need for data on the effects of deprescribing once normoglycemia is achieved, he said. “It really goes a long way to have strong epidemiological and interventional evidence. That’s what we need here, and that’s what the group is really hoping for.”

The statement recommends the following:

• The term “remission” should be used to describe a sustained metabolic improvement in type 2 diabetes to near normal levels. The panel agreed the word strikes the best balance, given that insulin resistance and beta-cell dysfunction may still be present despite normoglycemia. “Diabetes doesn’t get cured. The underlying abnormalities are still there. Remission is defined by glucose,” Dr. Riddle said. The panel also decided to do away with ADA’s former terms “partial,” “complete,” and “prolonged” remission because they are ambiguous and unhelpful. 
• Remission should be defined as a return to an A1c of < 6.5% (< 48 mmol/mol) – the threshold used to diagnose diabetes – spontaneously or following an intervention and that persists for at least 3 months in the absence of usual glucose-lowering medication.
• When A1c may be unreliable, such as conditions involving variant hemoglobin or erythrocyte survival alterations, acceptable alternatives are a fasting blood glucose < 126 mg/dL (< 7.0 mmol/L) or an estimated A1c < 6.5% calculated from continuous glucose monitoring data.
• A1c testing to document a remission should be performed just prior to an intervention and no sooner than 3 months after initiation of the intervention and withdrawal of any glucose-lowering medication.
• Subsequent ongoing A1c testing should be done at least yearly thereafter, along with routine monitoring for diabetes-related complications, including retinal screening, renal function assessment, foot exams, and cardiovascular risk factor testing. “At present, there is no long-term evidence indicating that any of the usually recommended assessments for complications can safely be discontinued,” the authors wrote.
• Research based on the terminology and definitions in the present statement is needed to determine the frequency, duration, and effects on short- and long-term medical outcomes of type 2 diabetes remissions using available interventions.

Dr. Riddle said in an interview: “We thought that the clinical community needed to understand where this issue stands right now. The feasibility of a remission is greater than it used to be.

“We’re going to see more patients who have what we can now call a remission according to a standardized definition. In the future, there are likely to be guidelines regarding the kind of patients and the kind of tactics appropriate for seeking a remission,” he said.

The statement was simultaneously published online in each of the organizations’ respective journals: Diabetes Care, Journal of Clinical Endocrinology & Metabolism, Diabetologia, and Diabetic Medicine.

Dr. Riddle has reported receiving research grant support through Oregon Health & Science University from Eli Lilly, Novo Nordisk, and AstraZeneca and honoraria for consulting from Adocia, Intercept, and Theracos.

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

A new joint consensus statement by four major diabetes organizations aims to standardize the terminology, definition, and assessment to the phenomenon of diabetes “remission.”

The statement was jointly issued by the American Diabetes Association, the Endocrine Society, the European Association for the Study of Diabetes, and Diabetes UK.

The 12-member international writing panel proposed use of the term “remission,” as opposed to others such as “reversal,” “resolution,” or “cure,” to describe the phenomenon of prolonged normoglycemia without the use of glucose-lowering medication in a person previously diagnosed with type 2 diabetes.

“Diabetes remission may be occurring more often due to advances in treatment,” writing group member Amy Rothberg, MD, of the University of Michigan, Ann Arbor, said in a statement.

The group defined “remission” – whether attained via lifestyle, bariatric surgery, or other means – as an A1c < 6.5% (< 48 mmol/mol) at least 3 months after cessation of glucose-lowering pharmacotherapy. The panel also suggested monitoring individuals experiencing diabetes remission and raised questions that need further attention and study.

But it’s not a guideline, panel chair Matthew C. Riddle, MD, said in an interview. Rather, the “main purpose of the statement was to provide definitions, terminology, cut-points, and timing recommendations to allow data collection that will eventually lead to clinical guidelines,” he said.

A great deal of epidemiological research is conducted by analyzing data from medical records, he noted. “If clinicians are more consistent in entering data into the records and in doing measurements, it will be a better database.”
 

Remission reality: Advice needed for deprescribing, talking to patients

“Increasingly our treatments are getting glucose levels into the normal range, and in many cases, even after withdrawal of drug therapy. That’s not an anomaly or a fiction, it’s reality. Clinicians need to know how to talk to their patients about it,” noted Dr. Riddle, of the division of endocrinology, diabetes, and clinical nutrition at Oregon Health & Science University, Portland.

There is a need for data on the effects of deprescribing once normoglycemia is achieved, he said. “It really goes a long way to have strong epidemiological and interventional evidence. That’s what we need here, and that’s what the group is really hoping for.”

The statement recommends the following:

• The term “remission” should be used to describe a sustained metabolic improvement in type 2 diabetes to near normal levels. The panel agreed the word strikes the best balance, given that insulin resistance and beta-cell dysfunction may still be present despite normoglycemia. “Diabetes doesn’t get cured. The underlying abnormalities are still there. Remission is defined by glucose,” Dr. Riddle said. The panel also decided to do away with ADA’s former terms “partial,” “complete,” and “prolonged” remission because they are ambiguous and unhelpful. 
• Remission should be defined as a return to an A1c of < 6.5% (< 48 mmol/mol) – the threshold used to diagnose diabetes – spontaneously or following an intervention and that persists for at least 3 months in the absence of usual glucose-lowering medication.
• When A1c may be unreliable, such as conditions involving variant hemoglobin or erythrocyte survival alterations, acceptable alternatives are a fasting blood glucose < 126 mg/dL (< 7.0 mmol/L) or an estimated A1c < 6.5% calculated from continuous glucose monitoring data.
• A1c testing to document a remission should be performed just prior to an intervention and no sooner than 3 months after initiation of the intervention and withdrawal of any glucose-lowering medication.
• Subsequent ongoing A1c testing should be done at least yearly thereafter, along with routine monitoring for diabetes-related complications, including retinal screening, renal function assessment, foot exams, and cardiovascular risk factor testing. “At present, there is no long-term evidence indicating that any of the usually recommended assessments for complications can safely be discontinued,” the authors wrote.
• Research based on the terminology and definitions in the present statement is needed to determine the frequency, duration, and effects on short- and long-term medical outcomes of type 2 diabetes remissions using available interventions.

Dr. Riddle said in an interview: “We thought that the clinical community needed to understand where this issue stands right now. The feasibility of a remission is greater than it used to be.

“We’re going to see more patients who have what we can now call a remission according to a standardized definition. In the future, there are likely to be guidelines regarding the kind of patients and the kind of tactics appropriate for seeking a remission,” he said.

The statement was simultaneously published online in each of the organizations’ respective journals: Diabetes Care, Journal of Clinical Endocrinology & Metabolism, Diabetologia, and Diabetic Medicine.

Dr. Riddle has reported receiving research grant support through Oregon Health & Science University from Eli Lilly, Novo Nordisk, and AstraZeneca and honoraria for consulting from Adocia, Intercept, and Theracos.

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

The anti-inflammatory agents colchicine and icosapent ethyl (Vascepa; Amarin) failed to provide substantial benefits in separate randomized COVID-19 trials.

Both were reported at the European Society of Cardiology (ESC) Congress 2021.

The open-label ECLA PHRI COLCOVID trial randomized 1,277 hospitalized adults (mean age 62 years) to usual care alone or with colchicine at a loading dose of 1.5 mg for 2 hours followed by 0.5 mg on day 1 and then 0.5 mg twice daily for 14 days or until discharge.

The investigators hypothesized that colchicine, which is widely used to treat gout and other inflammatory conditions, might modulate the hyperinflammatory syndrome, or cytokine storm, associated with COVID-19.

Results showed that the need for mechanical ventilation or death occurred in 25.0% of patients receiving colchicine and 28.8% with usual care (P = .08).

The coprimary endpoint of death at 28 days was also not significantly different between groups (20.5% vs. 22.2%), principal investigator Rafael Diaz, MD, said in a late-breaking COVID-19 trials session at the congress.

Among the secondary outcomes at 28 days, colchicine significantly reduced the incidence of new intubation or death from respiratory failure from 27.0% to 22.3% (hazard ratio, 0.79; 95% confidence interval, 0.63-0.99) but not mortality from respiratory failure (19.5% vs. 16.8%).

The only important adverse effect was severe diarrhea, which was reported in 11.3% of the colchicine group vs. 4.5% in the control group, said Dr. Diaz, director of Estudios Clínicos Latinoamérica (ECLA), Rosario, Argentina.

The results are consistent with those from the massive RECOVERY trial, which earlier this year stopped enrollment in the colchicine arm for lack of efficacy in patients hospitalized with COVID-19, and COLCORONA, which missed its primary endpoint using colchicine among nonhospitalized adults with COVID-19.

Session chair and COLCORONA principal investigator Jean-Claude Tardif, MD, pointed out that, as clinicians, it’s fairly uncommon to combine systemic steroids with colchicine, which was the case in 92% of patients in ECLA PHRI COLCOVID.

“I think it is an inherent limitation of testing colchicine on top of steroids,” said Dr. Tardif, of the Montreal Heart Institute.
 

Icosapent ethyl in PREPARE-IT

Dr. Diaz returned in the ESC session to present the results of the PREPARE-IT trial, which tested whether icosapent ethyl – at a loading dose of 8 grams (4 capsules) for the first 3 days and 4 g/d on days 4-60 – could reduce the risk for SARS-CoV-2 infection in 2,041 health care and other public workers in Argentina at high risk for infection (mean age 40.5 years).

Vascepa was approved by the Food and Drug Administration in 2012 for the reduction of elevated triglyceride levels, with an added indication in 2019 to reduce cardiovascular (CV) events in people with elevated triglycerides and established CV disease or diabetes with other CV risk factors.

The rationale for using the high-dose prescription eicosapentaenoic acid (EPA) preparation includes its anti-inflammatory and antithrombotic effects, and that unsaturated fatty acids, especially EPA, might inactivate the enveloped virus, he explained.

Among 1,712 participants followed for up to 60 days, however, the SARS-CoV-2 infection rate was 7.9% with icosapent ethyl vs. 7.1% with a mineral oil placebo (P = .58).

There were also no significant changes from baseline in the icosapent ethyl and placebo groups for the secondary outcomes of high-sensitivity C-reactive protein (0 vs. 0), triglycerides (median –2 mg/dL vs. 7 mg/dL), or Influenza Patient-Reported Outcome (FLU-PRO) questionnaire scores (median 0.01 vs. 0.03).

The use of a mineral oil placebo has been the subject of controversy in previous fish oil trials, but, Dr. Diaz noted, it did not have a significant proinflammatory effect or cause any excess adverse events.

Overall, adverse events were similar between the active and placebo groups, including atrial fibrillation (none), major bleeding (none), minor bleeding (7 events vs. 10 events), gastrointestinal symptoms (6.8% vs. 7.0%), and diarrhea (8.6% vs. 7.7%).

Although it missed the primary endpoint, Dr. Diaz said, “this is the first large, randomized blinded trial to demonstrate excellent safety and tolerability of an 8-gram-per-day loading dose of icosapent ethyl, opening up the potential for acute use in randomized trials of myocardial infarction, acute coronary syndromes, strokes, and revascularization.”

During a discussion of the results, Dr. Diaz said the Delta variant was not present at the time of the analysis and that the second half of the trial will report on whether icosapent ethyl can reduce the risk for hospitalization or death in participants diagnosed with COVID-19.

ECLA PHRI COLCOVID was supported by the Estudios Clínicos Latinoamérica Population Health Research Institute. PREPARE-IT was supported by Estudios Clínicos Latinoamérica with collaboration from Amarin. Dr. Diaz reports no relevant financial relationships.

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

The anti-inflammatory agents colchicine and icosapent ethyl (Vascepa; Amarin) failed to provide substantial benefits in separate randomized COVID-19 trials.

Both were reported at the European Society of Cardiology (ESC) Congress 2021.

The open-label ECLA PHRI COLCOVID trial randomized 1,277 hospitalized adults (mean age 62 years) to usual care alone or with colchicine at a loading dose of 1.5 mg for 2 hours followed by 0.5 mg on day 1 and then 0.5 mg twice daily for 14 days or until discharge.

The investigators hypothesized that colchicine, which is widely used to treat gout and other inflammatory conditions, might modulate the hyperinflammatory syndrome, or cytokine storm, associated with COVID-19.

Results showed that the need for mechanical ventilation or death occurred in 25.0% of patients receiving colchicine and 28.8% with usual care (P = .08).

The coprimary endpoint of death at 28 days was also not significantly different between groups (20.5% vs. 22.2%), principal investigator Rafael Diaz, MD, said in a late-breaking COVID-19 trials session at the congress.

Among the secondary outcomes at 28 days, colchicine significantly reduced the incidence of new intubation or death from respiratory failure from 27.0% to 22.3% (hazard ratio, 0.79; 95% confidence interval, 0.63-0.99) but not mortality from respiratory failure (19.5% vs. 16.8%).

The only important adverse effect was severe diarrhea, which was reported in 11.3% of the colchicine group vs. 4.5% in the control group, said Dr. Diaz, director of Estudios Clínicos Latinoamérica (ECLA), Rosario, Argentina.

The results are consistent with those from the massive RECOVERY trial, which earlier this year stopped enrollment in the colchicine arm for lack of efficacy in patients hospitalized with COVID-19, and COLCORONA, which missed its primary endpoint using colchicine among nonhospitalized adults with COVID-19.

Session chair and COLCORONA principal investigator Jean-Claude Tardif, MD, pointed out that, as clinicians, it’s fairly uncommon to combine systemic steroids with colchicine, which was the case in 92% of patients in ECLA PHRI COLCOVID.

“I think it is an inherent limitation of testing colchicine on top of steroids,” said Dr. Tardif, of the Montreal Heart Institute.
 

Icosapent ethyl in PREPARE-IT

Dr. Diaz returned in the ESC session to present the results of the PREPARE-IT trial, which tested whether icosapent ethyl – at a loading dose of 8 grams (4 capsules) for the first 3 days and 4 g/d on days 4-60 – could reduce the risk for SARS-CoV-2 infection in 2,041 health care and other public workers in Argentina at high risk for infection (mean age 40.5 years).

Vascepa was approved by the Food and Drug Administration in 2012 for the reduction of elevated triglyceride levels, with an added indication in 2019 to reduce cardiovascular (CV) events in people with elevated triglycerides and established CV disease or diabetes with other CV risk factors.

The rationale for using the high-dose prescription eicosapentaenoic acid (EPA) preparation includes its anti-inflammatory and antithrombotic effects, and that unsaturated fatty acids, especially EPA, might inactivate the enveloped virus, he explained.

Among 1,712 participants followed for up to 60 days, however, the SARS-CoV-2 infection rate was 7.9% with icosapent ethyl vs. 7.1% with a mineral oil placebo (P = .58).

There were also no significant changes from baseline in the icosapent ethyl and placebo groups for the secondary outcomes of high-sensitivity C-reactive protein (0 vs. 0), triglycerides (median –2 mg/dL vs. 7 mg/dL), or Influenza Patient-Reported Outcome (FLU-PRO) questionnaire scores (median 0.01 vs. 0.03).

The use of a mineral oil placebo has been the subject of controversy in previous fish oil trials, but, Dr. Diaz noted, it did not have a significant proinflammatory effect or cause any excess adverse events.

Overall, adverse events were similar between the active and placebo groups, including atrial fibrillation (none), major bleeding (none), minor bleeding (7 events vs. 10 events), gastrointestinal symptoms (6.8% vs. 7.0%), and diarrhea (8.6% vs. 7.7%).

Although it missed the primary endpoint, Dr. Diaz said, “this is the first large, randomized blinded trial to demonstrate excellent safety and tolerability of an 8-gram-per-day loading dose of icosapent ethyl, opening up the potential for acute use in randomized trials of myocardial infarction, acute coronary syndromes, strokes, and revascularization.”

During a discussion of the results, Dr. Diaz said the Delta variant was not present at the time of the analysis and that the second half of the trial will report on whether icosapent ethyl can reduce the risk for hospitalization or death in participants diagnosed with COVID-19.

ECLA PHRI COLCOVID was supported by the Estudios Clínicos Latinoamérica Population Health Research Institute. PREPARE-IT was supported by Estudios Clínicos Latinoamérica with collaboration from Amarin. Dr. Diaz reports no relevant financial relationships.

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

The anti-inflammatory agents colchicine and icosapent ethyl (Vascepa; Amarin) failed to provide substantial benefits in separate randomized COVID-19 trials.

Both were reported at the European Society of Cardiology (ESC) Congress 2021.

The open-label ECLA PHRI COLCOVID trial randomized 1,277 hospitalized adults (mean age 62 years) to usual care alone or with colchicine at a loading dose of 1.5 mg for 2 hours followed by 0.5 mg on day 1 and then 0.5 mg twice daily for 14 days or until discharge.

The investigators hypothesized that colchicine, which is widely used to treat gout and other inflammatory conditions, might modulate the hyperinflammatory syndrome, or cytokine storm, associated with COVID-19.

Results showed that the need for mechanical ventilation or death occurred in 25.0% of patients receiving colchicine and 28.8% with usual care (P = .08).

The coprimary endpoint of death at 28 days was also not significantly different between groups (20.5% vs. 22.2%), principal investigator Rafael Diaz, MD, said in a late-breaking COVID-19 trials session at the congress.

Among the secondary outcomes at 28 days, colchicine significantly reduced the incidence of new intubation or death from respiratory failure from 27.0% to 22.3% (hazard ratio, 0.79; 95% confidence interval, 0.63-0.99) but not mortality from respiratory failure (19.5% vs. 16.8%).

The only important adverse effect was severe diarrhea, which was reported in 11.3% of the colchicine group vs. 4.5% in the control group, said Dr. Diaz, director of Estudios Clínicos Latinoamérica (ECLA), Rosario, Argentina.

The results are consistent with those from the massive RECOVERY trial, which earlier this year stopped enrollment in the colchicine arm for lack of efficacy in patients hospitalized with COVID-19, and COLCORONA, which missed its primary endpoint using colchicine among nonhospitalized adults with COVID-19.

Session chair and COLCORONA principal investigator Jean-Claude Tardif, MD, pointed out that, as clinicians, it’s fairly uncommon to combine systemic steroids with colchicine, which was the case in 92% of patients in ECLA PHRI COLCOVID.

“I think it is an inherent limitation of testing colchicine on top of steroids,” said Dr. Tardif, of the Montreal Heart Institute.
 

Icosapent ethyl in PREPARE-IT

Dr. Diaz returned in the ESC session to present the results of the PREPARE-IT trial, which tested whether icosapent ethyl – at a loading dose of 8 grams (4 capsules) for the first 3 days and 4 g/d on days 4-60 – could reduce the risk for SARS-CoV-2 infection in 2,041 health care and other public workers in Argentina at high risk for infection (mean age 40.5 years).

Vascepa was approved by the Food and Drug Administration in 2012 for the reduction of elevated triglyceride levels, with an added indication in 2019 to reduce cardiovascular (CV) events in people with elevated triglycerides and established CV disease or diabetes with other CV risk factors.

The rationale for using the high-dose prescription eicosapentaenoic acid (EPA) preparation includes its anti-inflammatory and antithrombotic effects, and that unsaturated fatty acids, especially EPA, might inactivate the enveloped virus, he explained.

Among 1,712 participants followed for up to 60 days, however, the SARS-CoV-2 infection rate was 7.9% with icosapent ethyl vs. 7.1% with a mineral oil placebo (P = .58).

There were also no significant changes from baseline in the icosapent ethyl and placebo groups for the secondary outcomes of high-sensitivity C-reactive protein (0 vs. 0), triglycerides (median –2 mg/dL vs. 7 mg/dL), or Influenza Patient-Reported Outcome (FLU-PRO) questionnaire scores (median 0.01 vs. 0.03).

The use of a mineral oil placebo has been the subject of controversy in previous fish oil trials, but, Dr. Diaz noted, it did not have a significant proinflammatory effect or cause any excess adverse events.

Overall, adverse events were similar between the active and placebo groups, including atrial fibrillation (none), major bleeding (none), minor bleeding (7 events vs. 10 events), gastrointestinal symptoms (6.8% vs. 7.0%), and diarrhea (8.6% vs. 7.7%).

Although it missed the primary endpoint, Dr. Diaz said, “this is the first large, randomized blinded trial to demonstrate excellent safety and tolerability of an 8-gram-per-day loading dose of icosapent ethyl, opening up the potential for acute use in randomized trials of myocardial infarction, acute coronary syndromes, strokes, and revascularization.”

During a discussion of the results, Dr. Diaz said the Delta variant was not present at the time of the analysis and that the second half of the trial will report on whether icosapent ethyl can reduce the risk for hospitalization or death in participants diagnosed with COVID-19.

ECLA PHRI COLCOVID was supported by the Estudios Clínicos Latinoamérica Population Health Research Institute. PREPARE-IT was supported by Estudios Clínicos Latinoamérica with collaboration from Amarin. Dr. Diaz reports no relevant financial relationships.

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