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Optimal management of dysplastic nevi continues to evolve
San Diego – The way Benjamin Kelley, MD, sees it,
“There’s a confusion in the terminology, a term the late A. Bernard Ackerman, MD, called ‘patho-babel,’ ” Dr. Kelley, a Mohs micrographic surgeon and dermatopathologist in La Jolla, Calif., said at the annual Cutaneous Malignancy Update. “The idea of DN was originally used to describe a clinical melanoma syndrome. Now we use it for individual lesions, not just clinically but histologically. Some dermatologists refer to DN as ‘pre-melanoma,’ which is a negative framing,” he noted.
“We also refer to common nevi as ‘benign,’ which implies that DN are not benign,” he added. “The good news is that regardless of what they are called, the histologic criteria is generally agreed upon. The names can be used interchangeably.”
The bad news, he continued, is that there is less-than-perfect interobserver variability for grading DN lesions and significant variability in the treatment recommendations that pathologists give to clinicians. In one study, a group of pathology experts was asked to review 48 photomicrographs of melanocytic lesions and provide their diagnosis and treatment recommendations based on the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis scheme. For one, which showed a broad lesion with irregular epidermal thinning and thickening, the diagnoses ranged from solar lentigo to melanoma in situ. Treatment recommendations ranged from no treatment to re-excise with appropriate margins.
“This is an extreme example, but it shows you how difficult [establishing a diagnosis] can be,” Dr. Kelley said.
In a more recent study, researchers analyzed interobserver reproducibility in grading 179 DN cases among three observers who applied the 2018 World Health Organization grading criteria. The observers showed moderate to good agreement for most of the architectural features, except for criteria regarding focal continuous basal proliferation of melanocytes, density of non-nested junctional melanocytes, and presence of dyscohesive nests of intraepidermal melanocytes, whereas fair agreement was achieved for the cytological criteria. “So, it sounds to me like there was not a whole lot of agreement,” Dr. Kelley said.
An earlier single-center study titled “Clinicians Are From Mars and Pathologists Are From Venus” found that surgeons misunderstood the pathologist’s report 30% of the time.
In Dr. Kelly’s opinion, management of DNs will be successful if clinicians have a good working relationship with their dermatopathologists, if they biopsy to ensure an adequate, representative specimen, and if that they know what the terminology on the pathology report means and what actions to take. “The biopsy method matters,” he emphasized.
In a 14-year follow-up survey, investigators assessed DN management trends among 703 U.S. dermatologists. One key finding was that 69% of dermatologists in 2015 performed total removals when biopsying DN to achieve clear margins, compared with 86% in 2001.
A subsequent survey of 213 New England–based dermatologists found that the degree of clinical suspicion for melanoma was important in DN biopsy technique, with more respondents favoring shave biopsies for lesions with low suspicion and full-thickness biopsies for highly suspicious lesions.
“Misdiagnosis is more common for melanomas that have been assessed with punch and shave biopsies than with an excisional biopsy,” Dr. Kelley said. “I’m not too much of a stickler. I don’t require everyone to send me a giant excision, but I do want a representative sample.”
What about re-excision of DN considered to be mild or moderate? In 2015, members of the Pigmented Lesion Subcommittee of the Melanoma Prevention Working Group published a consensus statement on DN management recommendations for clinically atypical nevi/DN based on a review of published evidence. The subcommittee members concluded that mildly and moderately DN with clear margins do not need to be re-excised, and that mildly DN biopsied with positive histologic margins without clinical residual pigmentation may be safely observed rather than re-excised.
For moderately DN with positive histologic margins without clinically apparent residual pigmentation, the subcommittee members concluded that observation may be reasonable.
In his own informal analysis, Dr. Kelley compiled data from published studies he could find on DN management and divided them into two groups: the observation group, in which researchers from eight studies biopsied the DN lesion and watched the patients over time to see what happened, and the re-excision group, in which researchers from seven studies biopsied the DN lesion and subsequently re-excised it. There were about 1,500 patients in both groups. No deaths occurred in either group, he said, but 15 patients in the re-excision group developed a melanoma at the site of the original biopsy (1%), compared with 7 in the observation group (0.5%).
Six of seven melanomas in the observation group came from one article conducted at a VA clinic. In the study, 6 of 304 observed DN subsequently developed melanoma at the site of the lesion. “However, five of six that developed melanoma had an original biopsy that was a partial biopsy with grossly positive margins; I think that’s where the problem lies,” Dr. Kelley said at the meeting, which was hosted by Scripps MD Anderson Cancer Center. “All five grew lentigo maligna type melanoma, which we know can extend multiple millimeters beyond the clinically apparent lesion.”
The findings support mounting evidence that re-excising mild and moderate DN, regardless of border involvement, may not be necessary. “Currently, most clinicians still re-excise moderate and severe DN involving margins, especially if there is residual pigment,” Dr. Kelley said. “Most re-excise severe DN regardless of margin involvement, but beware if your biopsy was a partial sample of a larger lesion.”
He acknowledged limitations to pathologic studies of DN, including the potential for diagnostic uncertainty. “That doesn’t necessarily mean that the pathologist got the diagnosis wrong. It could be, what is the risk that the portion of tissue not visualized contains melanoma? If you give me a 5 mm sample of a DN, and I cut it into 4-micrometer sections, I’m only looking at less than 1% of the actual nevus. That’s compounded if the pathologist only receives a partial sample.”
Dr. Kelley reported having no relevant disclosures.
San Diego – The way Benjamin Kelley, MD, sees it,
“There’s a confusion in the terminology, a term the late A. Bernard Ackerman, MD, called ‘patho-babel,’ ” Dr. Kelley, a Mohs micrographic surgeon and dermatopathologist in La Jolla, Calif., said at the annual Cutaneous Malignancy Update. “The idea of DN was originally used to describe a clinical melanoma syndrome. Now we use it for individual lesions, not just clinically but histologically. Some dermatologists refer to DN as ‘pre-melanoma,’ which is a negative framing,” he noted.
“We also refer to common nevi as ‘benign,’ which implies that DN are not benign,” he added. “The good news is that regardless of what they are called, the histologic criteria is generally agreed upon. The names can be used interchangeably.”
The bad news, he continued, is that there is less-than-perfect interobserver variability for grading DN lesions and significant variability in the treatment recommendations that pathologists give to clinicians. In one study, a group of pathology experts was asked to review 48 photomicrographs of melanocytic lesions and provide their diagnosis and treatment recommendations based on the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis scheme. For one, which showed a broad lesion with irregular epidermal thinning and thickening, the diagnoses ranged from solar lentigo to melanoma in situ. Treatment recommendations ranged from no treatment to re-excise with appropriate margins.
“This is an extreme example, but it shows you how difficult [establishing a diagnosis] can be,” Dr. Kelley said.
In a more recent study, researchers analyzed interobserver reproducibility in grading 179 DN cases among three observers who applied the 2018 World Health Organization grading criteria. The observers showed moderate to good agreement for most of the architectural features, except for criteria regarding focal continuous basal proliferation of melanocytes, density of non-nested junctional melanocytes, and presence of dyscohesive nests of intraepidermal melanocytes, whereas fair agreement was achieved for the cytological criteria. “So, it sounds to me like there was not a whole lot of agreement,” Dr. Kelley said.
An earlier single-center study titled “Clinicians Are From Mars and Pathologists Are From Venus” found that surgeons misunderstood the pathologist’s report 30% of the time.
In Dr. Kelly’s opinion, management of DNs will be successful if clinicians have a good working relationship with their dermatopathologists, if they biopsy to ensure an adequate, representative specimen, and if that they know what the terminology on the pathology report means and what actions to take. “The biopsy method matters,” he emphasized.
In a 14-year follow-up survey, investigators assessed DN management trends among 703 U.S. dermatologists. One key finding was that 69% of dermatologists in 2015 performed total removals when biopsying DN to achieve clear margins, compared with 86% in 2001.
A subsequent survey of 213 New England–based dermatologists found that the degree of clinical suspicion for melanoma was important in DN biopsy technique, with more respondents favoring shave biopsies for lesions with low suspicion and full-thickness biopsies for highly suspicious lesions.
“Misdiagnosis is more common for melanomas that have been assessed with punch and shave biopsies than with an excisional biopsy,” Dr. Kelley said. “I’m not too much of a stickler. I don’t require everyone to send me a giant excision, but I do want a representative sample.”
What about re-excision of DN considered to be mild or moderate? In 2015, members of the Pigmented Lesion Subcommittee of the Melanoma Prevention Working Group published a consensus statement on DN management recommendations for clinically atypical nevi/DN based on a review of published evidence. The subcommittee members concluded that mildly and moderately DN with clear margins do not need to be re-excised, and that mildly DN biopsied with positive histologic margins without clinical residual pigmentation may be safely observed rather than re-excised.
For moderately DN with positive histologic margins without clinically apparent residual pigmentation, the subcommittee members concluded that observation may be reasonable.
In his own informal analysis, Dr. Kelley compiled data from published studies he could find on DN management and divided them into two groups: the observation group, in which researchers from eight studies biopsied the DN lesion and watched the patients over time to see what happened, and the re-excision group, in which researchers from seven studies biopsied the DN lesion and subsequently re-excised it. There were about 1,500 patients in both groups. No deaths occurred in either group, he said, but 15 patients in the re-excision group developed a melanoma at the site of the original biopsy (1%), compared with 7 in the observation group (0.5%).
Six of seven melanomas in the observation group came from one article conducted at a VA clinic. In the study, 6 of 304 observed DN subsequently developed melanoma at the site of the lesion. “However, five of six that developed melanoma had an original biopsy that was a partial biopsy with grossly positive margins; I think that’s where the problem lies,” Dr. Kelley said at the meeting, which was hosted by Scripps MD Anderson Cancer Center. “All five grew lentigo maligna type melanoma, which we know can extend multiple millimeters beyond the clinically apparent lesion.”
The findings support mounting evidence that re-excising mild and moderate DN, regardless of border involvement, may not be necessary. “Currently, most clinicians still re-excise moderate and severe DN involving margins, especially if there is residual pigment,” Dr. Kelley said. “Most re-excise severe DN regardless of margin involvement, but beware if your biopsy was a partial sample of a larger lesion.”
He acknowledged limitations to pathologic studies of DN, including the potential for diagnostic uncertainty. “That doesn’t necessarily mean that the pathologist got the diagnosis wrong. It could be, what is the risk that the portion of tissue not visualized contains melanoma? If you give me a 5 mm sample of a DN, and I cut it into 4-micrometer sections, I’m only looking at less than 1% of the actual nevus. That’s compounded if the pathologist only receives a partial sample.”
Dr. Kelley reported having no relevant disclosures.
San Diego – The way Benjamin Kelley, MD, sees it,
“There’s a confusion in the terminology, a term the late A. Bernard Ackerman, MD, called ‘patho-babel,’ ” Dr. Kelley, a Mohs micrographic surgeon and dermatopathologist in La Jolla, Calif., said at the annual Cutaneous Malignancy Update. “The idea of DN was originally used to describe a clinical melanoma syndrome. Now we use it for individual lesions, not just clinically but histologically. Some dermatologists refer to DN as ‘pre-melanoma,’ which is a negative framing,” he noted.
“We also refer to common nevi as ‘benign,’ which implies that DN are not benign,” he added. “The good news is that regardless of what they are called, the histologic criteria is generally agreed upon. The names can be used interchangeably.”
The bad news, he continued, is that there is less-than-perfect interobserver variability for grading DN lesions and significant variability in the treatment recommendations that pathologists give to clinicians. In one study, a group of pathology experts was asked to review 48 photomicrographs of melanocytic lesions and provide their diagnosis and treatment recommendations based on the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis scheme. For one, which showed a broad lesion with irregular epidermal thinning and thickening, the diagnoses ranged from solar lentigo to melanoma in situ. Treatment recommendations ranged from no treatment to re-excise with appropriate margins.
“This is an extreme example, but it shows you how difficult [establishing a diagnosis] can be,” Dr. Kelley said.
In a more recent study, researchers analyzed interobserver reproducibility in grading 179 DN cases among three observers who applied the 2018 World Health Organization grading criteria. The observers showed moderate to good agreement for most of the architectural features, except for criteria regarding focal continuous basal proliferation of melanocytes, density of non-nested junctional melanocytes, and presence of dyscohesive nests of intraepidermal melanocytes, whereas fair agreement was achieved for the cytological criteria. “So, it sounds to me like there was not a whole lot of agreement,” Dr. Kelley said.
An earlier single-center study titled “Clinicians Are From Mars and Pathologists Are From Venus” found that surgeons misunderstood the pathologist’s report 30% of the time.
In Dr. Kelly’s opinion, management of DNs will be successful if clinicians have a good working relationship with their dermatopathologists, if they biopsy to ensure an adequate, representative specimen, and if that they know what the terminology on the pathology report means and what actions to take. “The biopsy method matters,” he emphasized.
In a 14-year follow-up survey, investigators assessed DN management trends among 703 U.S. dermatologists. One key finding was that 69% of dermatologists in 2015 performed total removals when biopsying DN to achieve clear margins, compared with 86% in 2001.
A subsequent survey of 213 New England–based dermatologists found that the degree of clinical suspicion for melanoma was important in DN biopsy technique, with more respondents favoring shave biopsies for lesions with low suspicion and full-thickness biopsies for highly suspicious lesions.
“Misdiagnosis is more common for melanomas that have been assessed with punch and shave biopsies than with an excisional biopsy,” Dr. Kelley said. “I’m not too much of a stickler. I don’t require everyone to send me a giant excision, but I do want a representative sample.”
What about re-excision of DN considered to be mild or moderate? In 2015, members of the Pigmented Lesion Subcommittee of the Melanoma Prevention Working Group published a consensus statement on DN management recommendations for clinically atypical nevi/DN based on a review of published evidence. The subcommittee members concluded that mildly and moderately DN with clear margins do not need to be re-excised, and that mildly DN biopsied with positive histologic margins without clinical residual pigmentation may be safely observed rather than re-excised.
For moderately DN with positive histologic margins without clinically apparent residual pigmentation, the subcommittee members concluded that observation may be reasonable.
In his own informal analysis, Dr. Kelley compiled data from published studies he could find on DN management and divided them into two groups: the observation group, in which researchers from eight studies biopsied the DN lesion and watched the patients over time to see what happened, and the re-excision group, in which researchers from seven studies biopsied the DN lesion and subsequently re-excised it. There were about 1,500 patients in both groups. No deaths occurred in either group, he said, but 15 patients in the re-excision group developed a melanoma at the site of the original biopsy (1%), compared with 7 in the observation group (0.5%).
Six of seven melanomas in the observation group came from one article conducted at a VA clinic. In the study, 6 of 304 observed DN subsequently developed melanoma at the site of the lesion. “However, five of six that developed melanoma had an original biopsy that was a partial biopsy with grossly positive margins; I think that’s where the problem lies,” Dr. Kelley said at the meeting, which was hosted by Scripps MD Anderson Cancer Center. “All five grew lentigo maligna type melanoma, which we know can extend multiple millimeters beyond the clinically apparent lesion.”
The findings support mounting evidence that re-excising mild and moderate DN, regardless of border involvement, may not be necessary. “Currently, most clinicians still re-excise moderate and severe DN involving margins, especially if there is residual pigment,” Dr. Kelley said. “Most re-excise severe DN regardless of margin involvement, but beware if your biopsy was a partial sample of a larger lesion.”
He acknowledged limitations to pathologic studies of DN, including the potential for diagnostic uncertainty. “That doesn’t necessarily mean that the pathologist got the diagnosis wrong. It could be, what is the risk that the portion of tissue not visualized contains melanoma? If you give me a 5 mm sample of a DN, and I cut it into 4-micrometer sections, I’m only looking at less than 1% of the actual nevus. That’s compounded if the pathologist only receives a partial sample.”
Dr. Kelley reported having no relevant disclosures.
AT MELANOMA 2023
More than 97K new cutaneous melanoma diagnoses expected in 2023
SAN DIEGO – , following cancer of the colorectal area, lung and bronchus, prostate, and breast.
“The incidence of melanoma seems to have continued to go up since the early 1990s,” David E. Kent, MD, a dermatologist who practices in Macon, Ga., said at the annual Cutaneous Malignancy Update. “The death rates have been flat and may have slightly decreased.”
In 2023, the ACS estimates that about 97,610 new melanomas will be diagnosed in the United States (58,120 men and 39,490 women), and about 7,990 people are expected to die of melanoma (5,420 men and 2,570 women). In addition, ACS data from 2017-2019 project that about 2.1% of men and women will be diagnosed with cutaneous melanoma in their lifetime. To date, more than 1.3 million people in the United States live with cutaneous melanoma, and the overall 5-year survival is 93.7%.
Epidemiologic studies show an increase in melanoma incidence, primarily among White populations. “This is believed to be due primarily to sun exposure and to changing recreational behaviors and tanning bed exposures,” said Dr. Kent, who holds a faculty position in the department of dermatology at the Medical College of Georgia, Augusta. Increased surveillance and diagnosis also play a role. In the medical literature, annual increases in melanoma incidence vary from 3% to 7% per year, “which translates into a doubling of rates every 10-20 years,” he said, noting that annual melanoma costs are approximately $3.3 billion.
While incidence rates are lower in non-White, non-Hispanic populations, poor outcomes are disproportionately higher in persons of color. Blacks present at diagnosis with more advanced stage disease and are 1.5 times more likely to die from melanoma, he said, while Hispanics are 2.4 times more likely to present with stage III disease and 3.6 times more likely to have distant metastases. Persons of color also have higher rates of mucosal, acral lentiginous, and subungual melanoma.
Known genetic risk factors for melanoma include having skin types I and II, particularly those with light hair, light eyes, and freckling, and those with a family history have a twofold increased risk. Also, up to 40% of genetic cases are from inherited mutations in CDKN2A, CDK4, BAP1, and MCR1. Other genetic-related risk factors include the number and size of nevi, having atypical nevus syndrome, DNA repair defects, large congenital nevi, and a personal history of melanoma.
The main environmental risk factor for melanoma is exposure to ultraviolet radiation. “You can break it down in terms of whether this exposure is lifetime, intermittent intense UV exposure, from the use of tanning beds, or due to sunburns during childhood,” Dr. Kent said at the meeting, which was hosted by Scripps MD Anderson Cancer Center. Other environmental risk factors include distance from the equator, having a high socioeconomic status, being immunosuppressed, and exposure to heavy metals, insecticides, or hormones.
In a recently published study, researchers investigated the risk factors associated with first and second primary melanomas in 38,845 patients who were followed in Australia between 2011 and 2018. During a median follow-up of 7.4 years, 1,212 patients (3.1%) had a single primary melanoma diagnosis and 245 (0.6%) had a secondary primary melanoma diagnosis. The researchers found that second melanomas were more likely than were first melanomas to be in situ; for invasive tumors, second melanomas were more likely to be thin (defined as 1 mm or less) than were first melanomas.
In addition, having many self-reported moles at age 21 years was more strongly associated with second melanomas compared with first melanomas (hazard ratio [HR], 6.36 vs. 3.46, respectively; P = .01), as was having a high genetic predisposition (HR, 3.28 vs. 2.06; P = .03).
Second melanomas were also more strongly associated with a history of multiple skin cancer excisions than were first melanomas (HR, 2.63 vs. 1.86; P = .05). “Interestingly, there were no differences in UV exposure between the first primary and second primary melanoma groups,” said Dr. Kent, who was not involved with the study.
He noted that while sunscreen use protects against melanoma, a National Ambulatory Medical Care Survey (NAMCS) found that internists and pediatricians mentioned sunscreen at fewer than 0.1% of visits – even those with patients who have a diagnosis of skin disease. “Physicians need to do better,” he said. “We as dermatologists have work to do to help educate them.”
Dr. Kent reported having no relevant disclosures.
SAN DIEGO – , following cancer of the colorectal area, lung and bronchus, prostate, and breast.
“The incidence of melanoma seems to have continued to go up since the early 1990s,” David E. Kent, MD, a dermatologist who practices in Macon, Ga., said at the annual Cutaneous Malignancy Update. “The death rates have been flat and may have slightly decreased.”
In 2023, the ACS estimates that about 97,610 new melanomas will be diagnosed in the United States (58,120 men and 39,490 women), and about 7,990 people are expected to die of melanoma (5,420 men and 2,570 women). In addition, ACS data from 2017-2019 project that about 2.1% of men and women will be diagnosed with cutaneous melanoma in their lifetime. To date, more than 1.3 million people in the United States live with cutaneous melanoma, and the overall 5-year survival is 93.7%.
Epidemiologic studies show an increase in melanoma incidence, primarily among White populations. “This is believed to be due primarily to sun exposure and to changing recreational behaviors and tanning bed exposures,” said Dr. Kent, who holds a faculty position in the department of dermatology at the Medical College of Georgia, Augusta. Increased surveillance and diagnosis also play a role. In the medical literature, annual increases in melanoma incidence vary from 3% to 7% per year, “which translates into a doubling of rates every 10-20 years,” he said, noting that annual melanoma costs are approximately $3.3 billion.
While incidence rates are lower in non-White, non-Hispanic populations, poor outcomes are disproportionately higher in persons of color. Blacks present at diagnosis with more advanced stage disease and are 1.5 times more likely to die from melanoma, he said, while Hispanics are 2.4 times more likely to present with stage III disease and 3.6 times more likely to have distant metastases. Persons of color also have higher rates of mucosal, acral lentiginous, and subungual melanoma.
Known genetic risk factors for melanoma include having skin types I and II, particularly those with light hair, light eyes, and freckling, and those with a family history have a twofold increased risk. Also, up to 40% of genetic cases are from inherited mutations in CDKN2A, CDK4, BAP1, and MCR1. Other genetic-related risk factors include the number and size of nevi, having atypical nevus syndrome, DNA repair defects, large congenital nevi, and a personal history of melanoma.
The main environmental risk factor for melanoma is exposure to ultraviolet radiation. “You can break it down in terms of whether this exposure is lifetime, intermittent intense UV exposure, from the use of tanning beds, or due to sunburns during childhood,” Dr. Kent said at the meeting, which was hosted by Scripps MD Anderson Cancer Center. Other environmental risk factors include distance from the equator, having a high socioeconomic status, being immunosuppressed, and exposure to heavy metals, insecticides, or hormones.
In a recently published study, researchers investigated the risk factors associated with first and second primary melanomas in 38,845 patients who were followed in Australia between 2011 and 2018. During a median follow-up of 7.4 years, 1,212 patients (3.1%) had a single primary melanoma diagnosis and 245 (0.6%) had a secondary primary melanoma diagnosis. The researchers found that second melanomas were more likely than were first melanomas to be in situ; for invasive tumors, second melanomas were more likely to be thin (defined as 1 mm or less) than were first melanomas.
In addition, having many self-reported moles at age 21 years was more strongly associated with second melanomas compared with first melanomas (hazard ratio [HR], 6.36 vs. 3.46, respectively; P = .01), as was having a high genetic predisposition (HR, 3.28 vs. 2.06; P = .03).
Second melanomas were also more strongly associated with a history of multiple skin cancer excisions than were first melanomas (HR, 2.63 vs. 1.86; P = .05). “Interestingly, there were no differences in UV exposure between the first primary and second primary melanoma groups,” said Dr. Kent, who was not involved with the study.
He noted that while sunscreen use protects against melanoma, a National Ambulatory Medical Care Survey (NAMCS) found that internists and pediatricians mentioned sunscreen at fewer than 0.1% of visits – even those with patients who have a diagnosis of skin disease. “Physicians need to do better,” he said. “We as dermatologists have work to do to help educate them.”
Dr. Kent reported having no relevant disclosures.
SAN DIEGO – , following cancer of the colorectal area, lung and bronchus, prostate, and breast.
“The incidence of melanoma seems to have continued to go up since the early 1990s,” David E. Kent, MD, a dermatologist who practices in Macon, Ga., said at the annual Cutaneous Malignancy Update. “The death rates have been flat and may have slightly decreased.”
In 2023, the ACS estimates that about 97,610 new melanomas will be diagnosed in the United States (58,120 men and 39,490 women), and about 7,990 people are expected to die of melanoma (5,420 men and 2,570 women). In addition, ACS data from 2017-2019 project that about 2.1% of men and women will be diagnosed with cutaneous melanoma in their lifetime. To date, more than 1.3 million people in the United States live with cutaneous melanoma, and the overall 5-year survival is 93.7%.
Epidemiologic studies show an increase in melanoma incidence, primarily among White populations. “This is believed to be due primarily to sun exposure and to changing recreational behaviors and tanning bed exposures,” said Dr. Kent, who holds a faculty position in the department of dermatology at the Medical College of Georgia, Augusta. Increased surveillance and diagnosis also play a role. In the medical literature, annual increases in melanoma incidence vary from 3% to 7% per year, “which translates into a doubling of rates every 10-20 years,” he said, noting that annual melanoma costs are approximately $3.3 billion.
While incidence rates are lower in non-White, non-Hispanic populations, poor outcomes are disproportionately higher in persons of color. Blacks present at diagnosis with more advanced stage disease and are 1.5 times more likely to die from melanoma, he said, while Hispanics are 2.4 times more likely to present with stage III disease and 3.6 times more likely to have distant metastases. Persons of color also have higher rates of mucosal, acral lentiginous, and subungual melanoma.
Known genetic risk factors for melanoma include having skin types I and II, particularly those with light hair, light eyes, and freckling, and those with a family history have a twofold increased risk. Also, up to 40% of genetic cases are from inherited mutations in CDKN2A, CDK4, BAP1, and MCR1. Other genetic-related risk factors include the number and size of nevi, having atypical nevus syndrome, DNA repair defects, large congenital nevi, and a personal history of melanoma.
The main environmental risk factor for melanoma is exposure to ultraviolet radiation. “You can break it down in terms of whether this exposure is lifetime, intermittent intense UV exposure, from the use of tanning beds, or due to sunburns during childhood,” Dr. Kent said at the meeting, which was hosted by Scripps MD Anderson Cancer Center. Other environmental risk factors include distance from the equator, having a high socioeconomic status, being immunosuppressed, and exposure to heavy metals, insecticides, or hormones.
In a recently published study, researchers investigated the risk factors associated with first and second primary melanomas in 38,845 patients who were followed in Australia between 2011 and 2018. During a median follow-up of 7.4 years, 1,212 patients (3.1%) had a single primary melanoma diagnosis and 245 (0.6%) had a secondary primary melanoma diagnosis. The researchers found that second melanomas were more likely than were first melanomas to be in situ; for invasive tumors, second melanomas were more likely to be thin (defined as 1 mm or less) than were first melanomas.
In addition, having many self-reported moles at age 21 years was more strongly associated with second melanomas compared with first melanomas (hazard ratio [HR], 6.36 vs. 3.46, respectively; P = .01), as was having a high genetic predisposition (HR, 3.28 vs. 2.06; P = .03).
Second melanomas were also more strongly associated with a history of multiple skin cancer excisions than were first melanomas (HR, 2.63 vs. 1.86; P = .05). “Interestingly, there were no differences in UV exposure between the first primary and second primary melanoma groups,” said Dr. Kent, who was not involved with the study.
He noted that while sunscreen use protects against melanoma, a National Ambulatory Medical Care Survey (NAMCS) found that internists and pediatricians mentioned sunscreen at fewer than 0.1% of visits – even those with patients who have a diagnosis of skin disease. “Physicians need to do better,” he said. “We as dermatologists have work to do to help educate them.”
Dr. Kent reported having no relevant disclosures.
AT MELANOMA 2023
Dermoscopy, other modalities for improving melanoma diagnoses reviewed
San Diego – .
“I don’t think that’s going to change in the short term,” Travis W. Blalock, MD, director of dermatologic surgery, Mohs micrographic surgery, and cutaneous oncology at Emory University, Atlanta, said at the annual Cutaneous Malignancy Update. “But I do think we can supplement that with other modalities that will improve the clinical examination and help dermatopathologists as they assess and evaluate these lesions,” he said, adding: “The reality is, histopathology, while it may be the gold standard, is not necessarily a consistently reproducible evaluation. That raises the question: What can we do better?”
According to Dr. Blalock, the future may include more routine use of noninvasive genetic molecular assays to assist with the diagnostics challenges linked to the visual image and pattern recognition approach of detecting cutaneous melanoma. For example, a two-gene classification method based on LINC00518 and preferentially expressed antigen in melanoma (PRAME) gene expression was evaluated and validated in 555 pigmented lesions obtained noninvasively via adhesive patch biopsy.
“Today, you can pick up a kit from your local pharmacy that can tell you a bit about broad genetic susceptibilities,” he said at the meeting, which was hosted by Scripps MD Anderson Cancer Center. He predicted that using adhesive patch biopsies to assess suspicious melanocytic lesions “is likely the wave of the future.” This may increase patient understanding “as to the types of risks they have, the different lesions they have, and minimize invasive disease, but it also will pose different challenges for us when it comes to deploying patient-centered health care. For example, in a patient with multiple different lesions, how are you going to keep track of them all?”
Dermoscopy
In Dr. Blalock’s clinical opinion, dermoscopy improves the sensitivity of human visual detection of melanoma and may allow detection before a lesion displays classical features described with the “ABCDE rule.” However, the learning curve for dermoscopy is steep, he added, and whether the technique should be considered a first-line tool or as a supplement to other methods of examining cutaneous lesions remains a matter of debate.
“Dermoscopy is our version of the stethoscope,” he said. “We need to figure out when we’re going to use it. Should we be using it all of the time or only some of the time? Based on the clinical setting, maybe it’s a personal choice, but this can be a helpful skill and art in your practice if you’re willing to take the time to learn.”
In 2007, the International Dermoscopy Society (IDS) established a proposal for the standardization and recommended criteria necessary to effectively convey dermoscopic findings to consulting physicians and colleagues. The document includes 10 points categorized as either recommended or optional for a standardized dermoscopy report.
“The first step is to assess the lesion to determine whether or not it’s melanocytic in the first place,” said Dr. Blalock. “There are many different features – the mile-high [global features] evaluation of the lesions – then more specific local features that may clue you in to specific diagnoses,” he noted. “Once we get past that first step of determining that a lesion is melanocytic, it’s not enough to stop there, because we don’t want to biopsy every single lesion that’s melanocytic,” so there is a need to determine which ones require intervention, which is where dermoscopy “gets trickier and a little more challenging.”
According to the IDS, a standard dermoscopy report should include the patient’s age, relevant history pertaining to the lesion, pertinent personal and family history (recommended); clinical description of the lesion (recommended); the two-step method of dermoscopy differentiating melanocytic from nonmelanocytic tumors (recommended); and the use of standardized terms to describe structures as defined by the Dermoscopy Consensus Report published in 2003.
For new terms, the document states, “it would be helpful” for the physician to provide a working definition (recommended); the dermoscopic algorithm used should be mentioned (optional); information on the imaging equipment and magnification (recommended); clinical and dermoscopic images of the tumor (recommended); a diagnosis or differential diagnosis (recommended); decision concerning management (recommended), and specific comments for the pathologist when excision and histopathologic examination are recommended (optional).
The 2007 IDS document also includes a proposed seven-point checklist to differentiate between benign and melanocytic lesions on dermoscopy. Three major criteria are worth two points each: The presence of an atypical pigment network, gray-blue areas (commonly known as the veil), and an atypical vascular pattern. Four minor criteria are worth one point each: Irregular streaks, irregular dots/globules, irregular pigmentation, and regression structures. A minimum total score of 3 is required to establish a diagnosis of melanoma.
Another diagnostic technique, digital mole mapping, involves the use of photography to detect new or changing lesions. Dr. Blalock described this approach as rife with limitations, including variations in quality, challenges of storing and maintaining records, cost, time required to evaluate them, and determining which patients are appropriate candidates.
Other techniques being evaluated include computer algorithms to help dermatologists determine the diagnosis of melanoma from dermoscopic images, electrical impedance spectroscopy for noninvasive evaluation of atypical pigmented lesions, and ultrasound for staging of cutaneous malignant tumors.
Ultimately, “I think we’ll have multiple tools in our belt,” Dr. Blalock said, adding, “How do we pull them out at the right time to improve the lives of our patients? Are we going to use ultrasound? Dermoscopy? Integrate them with some of the genetic findings?”
Dr. Blalock disclosed that he has served as a principal investigator for Castle Biosciences.
San Diego – .
“I don’t think that’s going to change in the short term,” Travis W. Blalock, MD, director of dermatologic surgery, Mohs micrographic surgery, and cutaneous oncology at Emory University, Atlanta, said at the annual Cutaneous Malignancy Update. “But I do think we can supplement that with other modalities that will improve the clinical examination and help dermatopathologists as they assess and evaluate these lesions,” he said, adding: “The reality is, histopathology, while it may be the gold standard, is not necessarily a consistently reproducible evaluation. That raises the question: What can we do better?”
According to Dr. Blalock, the future may include more routine use of noninvasive genetic molecular assays to assist with the diagnostics challenges linked to the visual image and pattern recognition approach of detecting cutaneous melanoma. For example, a two-gene classification method based on LINC00518 and preferentially expressed antigen in melanoma (PRAME) gene expression was evaluated and validated in 555 pigmented lesions obtained noninvasively via adhesive patch biopsy.
“Today, you can pick up a kit from your local pharmacy that can tell you a bit about broad genetic susceptibilities,” he said at the meeting, which was hosted by Scripps MD Anderson Cancer Center. He predicted that using adhesive patch biopsies to assess suspicious melanocytic lesions “is likely the wave of the future.” This may increase patient understanding “as to the types of risks they have, the different lesions they have, and minimize invasive disease, but it also will pose different challenges for us when it comes to deploying patient-centered health care. For example, in a patient with multiple different lesions, how are you going to keep track of them all?”
Dermoscopy
In Dr. Blalock’s clinical opinion, dermoscopy improves the sensitivity of human visual detection of melanoma and may allow detection before a lesion displays classical features described with the “ABCDE rule.” However, the learning curve for dermoscopy is steep, he added, and whether the technique should be considered a first-line tool or as a supplement to other methods of examining cutaneous lesions remains a matter of debate.
“Dermoscopy is our version of the stethoscope,” he said. “We need to figure out when we’re going to use it. Should we be using it all of the time or only some of the time? Based on the clinical setting, maybe it’s a personal choice, but this can be a helpful skill and art in your practice if you’re willing to take the time to learn.”
In 2007, the International Dermoscopy Society (IDS) established a proposal for the standardization and recommended criteria necessary to effectively convey dermoscopic findings to consulting physicians and colleagues. The document includes 10 points categorized as either recommended or optional for a standardized dermoscopy report.
“The first step is to assess the lesion to determine whether or not it’s melanocytic in the first place,” said Dr. Blalock. “There are many different features – the mile-high [global features] evaluation of the lesions – then more specific local features that may clue you in to specific diagnoses,” he noted. “Once we get past that first step of determining that a lesion is melanocytic, it’s not enough to stop there, because we don’t want to biopsy every single lesion that’s melanocytic,” so there is a need to determine which ones require intervention, which is where dermoscopy “gets trickier and a little more challenging.”
According to the IDS, a standard dermoscopy report should include the patient’s age, relevant history pertaining to the lesion, pertinent personal and family history (recommended); clinical description of the lesion (recommended); the two-step method of dermoscopy differentiating melanocytic from nonmelanocytic tumors (recommended); and the use of standardized terms to describe structures as defined by the Dermoscopy Consensus Report published in 2003.
For new terms, the document states, “it would be helpful” for the physician to provide a working definition (recommended); the dermoscopic algorithm used should be mentioned (optional); information on the imaging equipment and magnification (recommended); clinical and dermoscopic images of the tumor (recommended); a diagnosis or differential diagnosis (recommended); decision concerning management (recommended), and specific comments for the pathologist when excision and histopathologic examination are recommended (optional).
The 2007 IDS document also includes a proposed seven-point checklist to differentiate between benign and melanocytic lesions on dermoscopy. Three major criteria are worth two points each: The presence of an atypical pigment network, gray-blue areas (commonly known as the veil), and an atypical vascular pattern. Four minor criteria are worth one point each: Irregular streaks, irregular dots/globules, irregular pigmentation, and regression structures. A minimum total score of 3 is required to establish a diagnosis of melanoma.
Another diagnostic technique, digital mole mapping, involves the use of photography to detect new or changing lesions. Dr. Blalock described this approach as rife with limitations, including variations in quality, challenges of storing and maintaining records, cost, time required to evaluate them, and determining which patients are appropriate candidates.
Other techniques being evaluated include computer algorithms to help dermatologists determine the diagnosis of melanoma from dermoscopic images, electrical impedance spectroscopy for noninvasive evaluation of atypical pigmented lesions, and ultrasound for staging of cutaneous malignant tumors.
Ultimately, “I think we’ll have multiple tools in our belt,” Dr. Blalock said, adding, “How do we pull them out at the right time to improve the lives of our patients? Are we going to use ultrasound? Dermoscopy? Integrate them with some of the genetic findings?”
Dr. Blalock disclosed that he has served as a principal investigator for Castle Biosciences.
San Diego – .
“I don’t think that’s going to change in the short term,” Travis W. Blalock, MD, director of dermatologic surgery, Mohs micrographic surgery, and cutaneous oncology at Emory University, Atlanta, said at the annual Cutaneous Malignancy Update. “But I do think we can supplement that with other modalities that will improve the clinical examination and help dermatopathologists as they assess and evaluate these lesions,” he said, adding: “The reality is, histopathology, while it may be the gold standard, is not necessarily a consistently reproducible evaluation. That raises the question: What can we do better?”
According to Dr. Blalock, the future may include more routine use of noninvasive genetic molecular assays to assist with the diagnostics challenges linked to the visual image and pattern recognition approach of detecting cutaneous melanoma. For example, a two-gene classification method based on LINC00518 and preferentially expressed antigen in melanoma (PRAME) gene expression was evaluated and validated in 555 pigmented lesions obtained noninvasively via adhesive patch biopsy.
“Today, you can pick up a kit from your local pharmacy that can tell you a bit about broad genetic susceptibilities,” he said at the meeting, which was hosted by Scripps MD Anderson Cancer Center. He predicted that using adhesive patch biopsies to assess suspicious melanocytic lesions “is likely the wave of the future.” This may increase patient understanding “as to the types of risks they have, the different lesions they have, and minimize invasive disease, but it also will pose different challenges for us when it comes to deploying patient-centered health care. For example, in a patient with multiple different lesions, how are you going to keep track of them all?”
Dermoscopy
In Dr. Blalock’s clinical opinion, dermoscopy improves the sensitivity of human visual detection of melanoma and may allow detection before a lesion displays classical features described with the “ABCDE rule.” However, the learning curve for dermoscopy is steep, he added, and whether the technique should be considered a first-line tool or as a supplement to other methods of examining cutaneous lesions remains a matter of debate.
“Dermoscopy is our version of the stethoscope,” he said. “We need to figure out when we’re going to use it. Should we be using it all of the time or only some of the time? Based on the clinical setting, maybe it’s a personal choice, but this can be a helpful skill and art in your practice if you’re willing to take the time to learn.”
In 2007, the International Dermoscopy Society (IDS) established a proposal for the standardization and recommended criteria necessary to effectively convey dermoscopic findings to consulting physicians and colleagues. The document includes 10 points categorized as either recommended or optional for a standardized dermoscopy report.
“The first step is to assess the lesion to determine whether or not it’s melanocytic in the first place,” said Dr. Blalock. “There are many different features – the mile-high [global features] evaluation of the lesions – then more specific local features that may clue you in to specific diagnoses,” he noted. “Once we get past that first step of determining that a lesion is melanocytic, it’s not enough to stop there, because we don’t want to biopsy every single lesion that’s melanocytic,” so there is a need to determine which ones require intervention, which is where dermoscopy “gets trickier and a little more challenging.”
According to the IDS, a standard dermoscopy report should include the patient’s age, relevant history pertaining to the lesion, pertinent personal and family history (recommended); clinical description of the lesion (recommended); the two-step method of dermoscopy differentiating melanocytic from nonmelanocytic tumors (recommended); and the use of standardized terms to describe structures as defined by the Dermoscopy Consensus Report published in 2003.
For new terms, the document states, “it would be helpful” for the physician to provide a working definition (recommended); the dermoscopic algorithm used should be mentioned (optional); information on the imaging equipment and magnification (recommended); clinical and dermoscopic images of the tumor (recommended); a diagnosis or differential diagnosis (recommended); decision concerning management (recommended), and specific comments for the pathologist when excision and histopathologic examination are recommended (optional).
The 2007 IDS document also includes a proposed seven-point checklist to differentiate between benign and melanocytic lesions on dermoscopy. Three major criteria are worth two points each: The presence of an atypical pigment network, gray-blue areas (commonly known as the veil), and an atypical vascular pattern. Four minor criteria are worth one point each: Irregular streaks, irregular dots/globules, irregular pigmentation, and regression structures. A minimum total score of 3 is required to establish a diagnosis of melanoma.
Another diagnostic technique, digital mole mapping, involves the use of photography to detect new or changing lesions. Dr. Blalock described this approach as rife with limitations, including variations in quality, challenges of storing and maintaining records, cost, time required to evaluate them, and determining which patients are appropriate candidates.
Other techniques being evaluated include computer algorithms to help dermatologists determine the diagnosis of melanoma from dermoscopic images, electrical impedance spectroscopy for noninvasive evaluation of atypical pigmented lesions, and ultrasound for staging of cutaneous malignant tumors.
Ultimately, “I think we’ll have multiple tools in our belt,” Dr. Blalock said, adding, “How do we pull them out at the right time to improve the lives of our patients? Are we going to use ultrasound? Dermoscopy? Integrate them with some of the genetic findings?”
Dr. Blalock disclosed that he has served as a principal investigator for Castle Biosciences.
AT MELANOMA 2023
Spectrum of dermatologic adverse events associated with amivantamab use
associated with EGFR inhibitors and atypical presentations. Toxic effects, however, were mitigated by dose interruptions, dAE management, and amivantamab dose reductions, allowing for cancer therapy continuation in all cases. Amivantamab doses were reduced in 5 out of 6 cases, according to a research letter published in JAMA Dermatology.
The EGFR exon 20 insertion–mutation portends insensitivity to EGFR tyrosine kinase inhibitors and poor prognosis. Amivantamab, a bispecific monoclonal antibody targeting EGFR and mesenchymal epithelial transition factor (MET) is Food and Drug Administration approved for this population. Acneiform eruptions and pruritus are the most common dAEs associated with EGFR inhibitors, with xerosis, fissures, and nail and hair changes occurring additionally. While no FDA-approved monoclonal antibody targets MET exclusively, capmatinib and tepotinib (both tyrosine kinase inhibitors) inhibit MET. They have been associated with photosensitivity, acneiform rash, paronychia, xerosis, pruritus, and mucositis.
The Belzer et al. letter reviewed six consecutive cases (mean age, 58) of dAEs associated with amivantamab at two academic health centers (treated June 2021 to August 2022) in order to describe dAEs associated with amivantamab use. “I suspect the rate of dAEs with amivantamab is similar to the rate of dAEs associated with first- and second-generation EGFR inhibitors, where the majority of patients, actually 75%-90%, develop cutaneous toxicity,” said Jonathan Leventhal, MD, Yale University, New Haven, Conn., corresponding author for the Belzer et al. letter.
Time from treatment initiation with amivantamab to dAE ranged from less than 1 month to 4 months. All dAEs were grade 2 or 3 and all included acneiform eruptions. These were widespread in four cases and in another case complicated by impetiginization (culture results positive for methicillin-susceptible Staphylococcus aureus), and a further case was limited to the scalp, face, upper back, and upper chest. Others with widespread acneiform eruption included the face with hyperkeratotic crust of the scalp and dermatitis of the posterior neck. Fissuring of the palms and soles was noted in two cases with widespread acneiform eruptions. Paronychia with pyogenic granulomas was reported in four cases. Another case included onycholysis with suppurative paronychia.
In five cases amivantamab was stopped but successfully reinitiated at 67%-75% of the original dose. In one case amivantamab was continued at the original dose.
Doxycycline at 100 mg twice daily was included among all of the treatments for cutaneous dAEs. Silver nitrate cautery was applied for pyogenic granulomas in clinic. The case of grade 3 acneiform eruption of the scalp and face was treated with hydrogen peroxide soaks with debridement in clinic, doxycycline, aluminum acetate soaks, and triamcinolone ointment. All dermatologic cases resolved fully without scarring.
“It is very likely that this series highlights the more severe and unusual presentations of dAEs which were referred to oncodermatology. I suspect milder presentations were likely managed by oncologists,” Dr. Leventhal said in the interview.
“It is important for dermatologists and oncologists to be aware of the more severe and atypical dAEs associated with this novel FDA-approved targeted therapy.” Dr. Belzer said. “As amivantamab use increases, oncologists and dermatologists need to collaborate to ensure swift diagnosis and management of dAEs.”
One trial, the authors stated, revealed more than half of patients receiving EGFR inhibitors taking preemptive treatment with moisturizers, sunscreen, topical corticosteroids, and an oral tetracycline to have more than a 50% reduction in grade 2 or higher dAEs. Belzer et al. concluded that prophylactic treatment, including sun protection, should be considered before initiating treatment with amivantamab.
A limitation of the study, Belzer et al. acknowledged, was the small sample size.
Dr. Leventhal reported receiving personal fees from the advisory boards of Sanofi, Regeneron, and La Roche-Posay as well as clinical trial funding from Azitra and OnQuality Pharmaceuticals outside the submitted work.
associated with EGFR inhibitors and atypical presentations. Toxic effects, however, were mitigated by dose interruptions, dAE management, and amivantamab dose reductions, allowing for cancer therapy continuation in all cases. Amivantamab doses were reduced in 5 out of 6 cases, according to a research letter published in JAMA Dermatology.
The EGFR exon 20 insertion–mutation portends insensitivity to EGFR tyrosine kinase inhibitors and poor prognosis. Amivantamab, a bispecific monoclonal antibody targeting EGFR and mesenchymal epithelial transition factor (MET) is Food and Drug Administration approved for this population. Acneiform eruptions and pruritus are the most common dAEs associated with EGFR inhibitors, with xerosis, fissures, and nail and hair changes occurring additionally. While no FDA-approved monoclonal antibody targets MET exclusively, capmatinib and tepotinib (both tyrosine kinase inhibitors) inhibit MET. They have been associated with photosensitivity, acneiform rash, paronychia, xerosis, pruritus, and mucositis.
The Belzer et al. letter reviewed six consecutive cases (mean age, 58) of dAEs associated with amivantamab at two academic health centers (treated June 2021 to August 2022) in order to describe dAEs associated with amivantamab use. “I suspect the rate of dAEs with amivantamab is similar to the rate of dAEs associated with first- and second-generation EGFR inhibitors, where the majority of patients, actually 75%-90%, develop cutaneous toxicity,” said Jonathan Leventhal, MD, Yale University, New Haven, Conn., corresponding author for the Belzer et al. letter.
Time from treatment initiation with amivantamab to dAE ranged from less than 1 month to 4 months. All dAEs were grade 2 or 3 and all included acneiform eruptions. These were widespread in four cases and in another case complicated by impetiginization (culture results positive for methicillin-susceptible Staphylococcus aureus), and a further case was limited to the scalp, face, upper back, and upper chest. Others with widespread acneiform eruption included the face with hyperkeratotic crust of the scalp and dermatitis of the posterior neck. Fissuring of the palms and soles was noted in two cases with widespread acneiform eruptions. Paronychia with pyogenic granulomas was reported in four cases. Another case included onycholysis with suppurative paronychia.
In five cases amivantamab was stopped but successfully reinitiated at 67%-75% of the original dose. In one case amivantamab was continued at the original dose.
Doxycycline at 100 mg twice daily was included among all of the treatments for cutaneous dAEs. Silver nitrate cautery was applied for pyogenic granulomas in clinic. The case of grade 3 acneiform eruption of the scalp and face was treated with hydrogen peroxide soaks with debridement in clinic, doxycycline, aluminum acetate soaks, and triamcinolone ointment. All dermatologic cases resolved fully without scarring.
“It is very likely that this series highlights the more severe and unusual presentations of dAEs which were referred to oncodermatology. I suspect milder presentations were likely managed by oncologists,” Dr. Leventhal said in the interview.
“It is important for dermatologists and oncologists to be aware of the more severe and atypical dAEs associated with this novel FDA-approved targeted therapy.” Dr. Belzer said. “As amivantamab use increases, oncologists and dermatologists need to collaborate to ensure swift diagnosis and management of dAEs.”
One trial, the authors stated, revealed more than half of patients receiving EGFR inhibitors taking preemptive treatment with moisturizers, sunscreen, topical corticosteroids, and an oral tetracycline to have more than a 50% reduction in grade 2 or higher dAEs. Belzer et al. concluded that prophylactic treatment, including sun protection, should be considered before initiating treatment with amivantamab.
A limitation of the study, Belzer et al. acknowledged, was the small sample size.
Dr. Leventhal reported receiving personal fees from the advisory boards of Sanofi, Regeneron, and La Roche-Posay as well as clinical trial funding from Azitra and OnQuality Pharmaceuticals outside the submitted work.
associated with EGFR inhibitors and atypical presentations. Toxic effects, however, were mitigated by dose interruptions, dAE management, and amivantamab dose reductions, allowing for cancer therapy continuation in all cases. Amivantamab doses were reduced in 5 out of 6 cases, according to a research letter published in JAMA Dermatology.
The EGFR exon 20 insertion–mutation portends insensitivity to EGFR tyrosine kinase inhibitors and poor prognosis. Amivantamab, a bispecific monoclonal antibody targeting EGFR and mesenchymal epithelial transition factor (MET) is Food and Drug Administration approved for this population. Acneiform eruptions and pruritus are the most common dAEs associated with EGFR inhibitors, with xerosis, fissures, and nail and hair changes occurring additionally. While no FDA-approved monoclonal antibody targets MET exclusively, capmatinib and tepotinib (both tyrosine kinase inhibitors) inhibit MET. They have been associated with photosensitivity, acneiform rash, paronychia, xerosis, pruritus, and mucositis.
The Belzer et al. letter reviewed six consecutive cases (mean age, 58) of dAEs associated with amivantamab at two academic health centers (treated June 2021 to August 2022) in order to describe dAEs associated with amivantamab use. “I suspect the rate of dAEs with amivantamab is similar to the rate of dAEs associated with first- and second-generation EGFR inhibitors, where the majority of patients, actually 75%-90%, develop cutaneous toxicity,” said Jonathan Leventhal, MD, Yale University, New Haven, Conn., corresponding author for the Belzer et al. letter.
Time from treatment initiation with amivantamab to dAE ranged from less than 1 month to 4 months. All dAEs were grade 2 or 3 and all included acneiform eruptions. These were widespread in four cases and in another case complicated by impetiginization (culture results positive for methicillin-susceptible Staphylococcus aureus), and a further case was limited to the scalp, face, upper back, and upper chest. Others with widespread acneiform eruption included the face with hyperkeratotic crust of the scalp and dermatitis of the posterior neck. Fissuring of the palms and soles was noted in two cases with widespread acneiform eruptions. Paronychia with pyogenic granulomas was reported in four cases. Another case included onycholysis with suppurative paronychia.
In five cases amivantamab was stopped but successfully reinitiated at 67%-75% of the original dose. In one case amivantamab was continued at the original dose.
Doxycycline at 100 mg twice daily was included among all of the treatments for cutaneous dAEs. Silver nitrate cautery was applied for pyogenic granulomas in clinic. The case of grade 3 acneiform eruption of the scalp and face was treated with hydrogen peroxide soaks with debridement in clinic, doxycycline, aluminum acetate soaks, and triamcinolone ointment. All dermatologic cases resolved fully without scarring.
“It is very likely that this series highlights the more severe and unusual presentations of dAEs which were referred to oncodermatology. I suspect milder presentations were likely managed by oncologists,” Dr. Leventhal said in the interview.
“It is important for dermatologists and oncologists to be aware of the more severe and atypical dAEs associated with this novel FDA-approved targeted therapy.” Dr. Belzer said. “As amivantamab use increases, oncologists and dermatologists need to collaborate to ensure swift diagnosis and management of dAEs.”
One trial, the authors stated, revealed more than half of patients receiving EGFR inhibitors taking preemptive treatment with moisturizers, sunscreen, topical corticosteroids, and an oral tetracycline to have more than a 50% reduction in grade 2 or higher dAEs. Belzer et al. concluded that prophylactic treatment, including sun protection, should be considered before initiating treatment with amivantamab.
A limitation of the study, Belzer et al. acknowledged, was the small sample size.
Dr. Leventhal reported receiving personal fees from the advisory boards of Sanofi, Regeneron, and La Roche-Posay as well as clinical trial funding from Azitra and OnQuality Pharmaceuticals outside the submitted work.
FROM JAMA DERMATOLOGY
Dermatopathologist reflects on the early history of melanoma
SAN DIEGO – Evidence of melanoma in the ancient past is rare, but according to James W. Patterson, MD, .
“Radiocarbon dating indicated that these mummies were 2,400 years old,” Dr. Patterson, professor emeritus of pathology and dermatology at the University of Virginia, Charlottesville, said at the annual Cutaneous Malignancy Update.
John Hunter, a famous British surgeon who lived from 1728 to 1793, had the first known reported encounter with melanoma in 1787. “He thought it was a form of cancerous fungus,” said Dr. Patterson, a former president of the American Board of Dermatology. “That tumor was preserved in the Hunterian Museum of the Royal College of Surgeons in London, and in 1968 it was reexamined and turned out to be melanoma.”
René Laënnec, the French physician who invented the stethoscope in 1816, is believed to be the first person to lecture on melanoma while a medical student in 1804. The lecture was published about a year later. He originated the term “melanose” (becoming black), a French word derived from the Greek language, to describe metastatic melanoma and reported metastasis to the lungs. During the early part of his career, Dr. Laënnec had studied dissection in the laboratory of the French anatomist and military surgeon Guillaume Dupuytren, best known for his description of Dupuytren’s contracture. Dr. Dupuytren took exception to Dr. Laënnec’s publication about melanoma and called foul.
“As sometimes happens these days, there was some rivalry between these two outstanding physicians of their time,” Dr. Patterson said at the meeting, hosted by Scripps MD Anderson Cancer Center. “Dupuytren was unhappy that Laënnec took credit for this because he claimed credit for originally describing melanoma. He claimed that Laënnec stole the idea from his lectures. I’m not sure that issue was ever resolved.”
In 1820, William Norris, a general practitioner from Stourbridge, England, published the first English language report of melanoma in the Edinburgh Medical and Surgical Journal. “The report was titled ‘A case of fungoid disease,’ so it appears that melanoma was often regarded as a fungal infection back then,” Dr. Patterson said. In the report, Dr. Norris described the tumor in a 59-year-old man as “nearly half the size of a hen’s egg, of a deep brown color, of a firm and fleshy feel, [and] ulcerated on its surface.” Dr. Norris authored a later work titled “Eight cases of melanosis, with pathological and therapeutical remarks on that disease.”
In 1840, a full 2 decades following the first published report from Dr. Norris, the British surgeon Samuel Cooper published a book titled “First Lines of Theory and Practice of Surgery,” in which he described patients with advanced stage melanoma as untreatable and postulated that the only chance for survival was early removal of the tumor.
Dr. Patterson reported having no relevant disclosures.
SAN DIEGO – Evidence of melanoma in the ancient past is rare, but according to James W. Patterson, MD, .
“Radiocarbon dating indicated that these mummies were 2,400 years old,” Dr. Patterson, professor emeritus of pathology and dermatology at the University of Virginia, Charlottesville, said at the annual Cutaneous Malignancy Update.
John Hunter, a famous British surgeon who lived from 1728 to 1793, had the first known reported encounter with melanoma in 1787. “He thought it was a form of cancerous fungus,” said Dr. Patterson, a former president of the American Board of Dermatology. “That tumor was preserved in the Hunterian Museum of the Royal College of Surgeons in London, and in 1968 it was reexamined and turned out to be melanoma.”
René Laënnec, the French physician who invented the stethoscope in 1816, is believed to be the first person to lecture on melanoma while a medical student in 1804. The lecture was published about a year later. He originated the term “melanose” (becoming black), a French word derived from the Greek language, to describe metastatic melanoma and reported metastasis to the lungs. During the early part of his career, Dr. Laënnec had studied dissection in the laboratory of the French anatomist and military surgeon Guillaume Dupuytren, best known for his description of Dupuytren’s contracture. Dr. Dupuytren took exception to Dr. Laënnec’s publication about melanoma and called foul.
“As sometimes happens these days, there was some rivalry between these two outstanding physicians of their time,” Dr. Patterson said at the meeting, hosted by Scripps MD Anderson Cancer Center. “Dupuytren was unhappy that Laënnec took credit for this because he claimed credit for originally describing melanoma. He claimed that Laënnec stole the idea from his lectures. I’m not sure that issue was ever resolved.”
In 1820, William Norris, a general practitioner from Stourbridge, England, published the first English language report of melanoma in the Edinburgh Medical and Surgical Journal. “The report was titled ‘A case of fungoid disease,’ so it appears that melanoma was often regarded as a fungal infection back then,” Dr. Patterson said. In the report, Dr. Norris described the tumor in a 59-year-old man as “nearly half the size of a hen’s egg, of a deep brown color, of a firm and fleshy feel, [and] ulcerated on its surface.” Dr. Norris authored a later work titled “Eight cases of melanosis, with pathological and therapeutical remarks on that disease.”
In 1840, a full 2 decades following the first published report from Dr. Norris, the British surgeon Samuel Cooper published a book titled “First Lines of Theory and Practice of Surgery,” in which he described patients with advanced stage melanoma as untreatable and postulated that the only chance for survival was early removal of the tumor.
Dr. Patterson reported having no relevant disclosures.
SAN DIEGO – Evidence of melanoma in the ancient past is rare, but according to James W. Patterson, MD, .
“Radiocarbon dating indicated that these mummies were 2,400 years old,” Dr. Patterson, professor emeritus of pathology and dermatology at the University of Virginia, Charlottesville, said at the annual Cutaneous Malignancy Update.
John Hunter, a famous British surgeon who lived from 1728 to 1793, had the first known reported encounter with melanoma in 1787. “He thought it was a form of cancerous fungus,” said Dr. Patterson, a former president of the American Board of Dermatology. “That tumor was preserved in the Hunterian Museum of the Royal College of Surgeons in London, and in 1968 it was reexamined and turned out to be melanoma.”
René Laënnec, the French physician who invented the stethoscope in 1816, is believed to be the first person to lecture on melanoma while a medical student in 1804. The lecture was published about a year later. He originated the term “melanose” (becoming black), a French word derived from the Greek language, to describe metastatic melanoma and reported metastasis to the lungs. During the early part of his career, Dr. Laënnec had studied dissection in the laboratory of the French anatomist and military surgeon Guillaume Dupuytren, best known for his description of Dupuytren’s contracture. Dr. Dupuytren took exception to Dr. Laënnec’s publication about melanoma and called foul.
“As sometimes happens these days, there was some rivalry between these two outstanding physicians of their time,” Dr. Patterson said at the meeting, hosted by Scripps MD Anderson Cancer Center. “Dupuytren was unhappy that Laënnec took credit for this because he claimed credit for originally describing melanoma. He claimed that Laënnec stole the idea from his lectures. I’m not sure that issue was ever resolved.”
In 1820, William Norris, a general practitioner from Stourbridge, England, published the first English language report of melanoma in the Edinburgh Medical and Surgical Journal. “The report was titled ‘A case of fungoid disease,’ so it appears that melanoma was often regarded as a fungal infection back then,” Dr. Patterson said. In the report, Dr. Norris described the tumor in a 59-year-old man as “nearly half the size of a hen’s egg, of a deep brown color, of a firm and fleshy feel, [and] ulcerated on its surface.” Dr. Norris authored a later work titled “Eight cases of melanosis, with pathological and therapeutical remarks on that disease.”
In 1840, a full 2 decades following the first published report from Dr. Norris, the British surgeon Samuel Cooper published a book titled “First Lines of Theory and Practice of Surgery,” in which he described patients with advanced stage melanoma as untreatable and postulated that the only chance for survival was early removal of the tumor.
Dr. Patterson reported having no relevant disclosures.
AT MELANOMA 2023
How should PRAME be used to evaluate melanocytic lesions?
SAN DIEGO – , according to Cora Humberson, MD.
“I’m a fan, but there are issues with it,” Dr. Humberson, dermatopathology coordinator in the department of pathology at Scripps MD Anderson Cancer Center, San Diego, said at the annual Cutaneous Malignancy Update. “It’s all in how you use it.”
PRAME is part of the cancer/testis (CT) antigens, of which more than 40 have now been identified. They are encoded by genes that are normally expressed only in the human germ line, but are also expressed in various tumor types, including melanoma and carcinomas of the bladder, lung, and liver. “The biological function of these antigens is not fully understood, but they may act as a repressor of retinoic acid, potentially inhibiting differentiation, inhibiting proliferation arrest – things that we associate with malignancy,” she said at the meeting, which was hosted by Scripps MD Anderson Cancer Center. “These immunogenic proteins are being pursued as targets for therapeutic cancer vaccines,” she noted.
CT antigens are also being evaluated for their role in oncogenesis, she added. Recapitulation of portions of the germline gene-expression might contribute characteristic features to the neoplastic phenotype, including immortality, invasiveness, immune evasion, and metastatic capacity.
According to Dr. Humberson, PRAME can be used to differentiate comingled nevus and melanoma, to distinguish between nevoid melanoma and nevus, and for melanoma margin assessment in sun-damaged skin. One potential pitfall is that sun-damaged melanocytes may express PRAME. “The older the person and the more sun damage [they have], the more likely you are to see this, but the melanocytes won’t be grouped, they’ll be scattered,” she said.
Another pitfall is that less than 15% of nevi may express PRAME. “PRAME can be expressed in scars, so if you’re looking at a spindle cell lesion, be aware that you might be looking at a scar if you’re seeing PRAME expression,” she added. She also noted that PRAME immunohistochemistry (IHC) expression is not a prognostic biomarker in thin melanomas.
If fewer than 25% of cells in a melanocytic lesion express PRAME, most published assessments of PRAME IHC favor nevi as the diagnosis. “If more than 75% are expressing it, it favors melanoma,” Dr. Humberson said. “There’s a big category in between. It’s not that 30% is more likely benign or that 60% is more likely malignant; you can’t really depend upon [PRAME] if you’re in this range.”
A diagnostic accuracy study found that when more than 75% of cells express PRAME, the marker has a sensitivity of 0.63 and a specificity of 0.97.
Selected PRAME-related published references she recommended include: J Cutan Pathol. 2021;48(9):1115-23; Diagnostics. 2022 Sep 9; 12(9):2197, and J Cutan Pathol. 2022;49(9):829-32.
Dr. Humberson reported having no relevant disclosures.
SAN DIEGO – , according to Cora Humberson, MD.
“I’m a fan, but there are issues with it,” Dr. Humberson, dermatopathology coordinator in the department of pathology at Scripps MD Anderson Cancer Center, San Diego, said at the annual Cutaneous Malignancy Update. “It’s all in how you use it.”
PRAME is part of the cancer/testis (CT) antigens, of which more than 40 have now been identified. They are encoded by genes that are normally expressed only in the human germ line, but are also expressed in various tumor types, including melanoma and carcinomas of the bladder, lung, and liver. “The biological function of these antigens is not fully understood, but they may act as a repressor of retinoic acid, potentially inhibiting differentiation, inhibiting proliferation arrest – things that we associate with malignancy,” she said at the meeting, which was hosted by Scripps MD Anderson Cancer Center. “These immunogenic proteins are being pursued as targets for therapeutic cancer vaccines,” she noted.
CT antigens are also being evaluated for their role in oncogenesis, she added. Recapitulation of portions of the germline gene-expression might contribute characteristic features to the neoplastic phenotype, including immortality, invasiveness, immune evasion, and metastatic capacity.
According to Dr. Humberson, PRAME can be used to differentiate comingled nevus and melanoma, to distinguish between nevoid melanoma and nevus, and for melanoma margin assessment in sun-damaged skin. One potential pitfall is that sun-damaged melanocytes may express PRAME. “The older the person and the more sun damage [they have], the more likely you are to see this, but the melanocytes won’t be grouped, they’ll be scattered,” she said.
Another pitfall is that less than 15% of nevi may express PRAME. “PRAME can be expressed in scars, so if you’re looking at a spindle cell lesion, be aware that you might be looking at a scar if you’re seeing PRAME expression,” she added. She also noted that PRAME immunohistochemistry (IHC) expression is not a prognostic biomarker in thin melanomas.
If fewer than 25% of cells in a melanocytic lesion express PRAME, most published assessments of PRAME IHC favor nevi as the diagnosis. “If more than 75% are expressing it, it favors melanoma,” Dr. Humberson said. “There’s a big category in between. It’s not that 30% is more likely benign or that 60% is more likely malignant; you can’t really depend upon [PRAME] if you’re in this range.”
A diagnostic accuracy study found that when more than 75% of cells express PRAME, the marker has a sensitivity of 0.63 and a specificity of 0.97.
Selected PRAME-related published references she recommended include: J Cutan Pathol. 2021;48(9):1115-23; Diagnostics. 2022 Sep 9; 12(9):2197, and J Cutan Pathol. 2022;49(9):829-32.
Dr. Humberson reported having no relevant disclosures.
SAN DIEGO – , according to Cora Humberson, MD.
“I’m a fan, but there are issues with it,” Dr. Humberson, dermatopathology coordinator in the department of pathology at Scripps MD Anderson Cancer Center, San Diego, said at the annual Cutaneous Malignancy Update. “It’s all in how you use it.”
PRAME is part of the cancer/testis (CT) antigens, of which more than 40 have now been identified. They are encoded by genes that are normally expressed only in the human germ line, but are also expressed in various tumor types, including melanoma and carcinomas of the bladder, lung, and liver. “The biological function of these antigens is not fully understood, but they may act as a repressor of retinoic acid, potentially inhibiting differentiation, inhibiting proliferation arrest – things that we associate with malignancy,” she said at the meeting, which was hosted by Scripps MD Anderson Cancer Center. “These immunogenic proteins are being pursued as targets for therapeutic cancer vaccines,” she noted.
CT antigens are also being evaluated for their role in oncogenesis, she added. Recapitulation of portions of the germline gene-expression might contribute characteristic features to the neoplastic phenotype, including immortality, invasiveness, immune evasion, and metastatic capacity.
According to Dr. Humberson, PRAME can be used to differentiate comingled nevus and melanoma, to distinguish between nevoid melanoma and nevus, and for melanoma margin assessment in sun-damaged skin. One potential pitfall is that sun-damaged melanocytes may express PRAME. “The older the person and the more sun damage [they have], the more likely you are to see this, but the melanocytes won’t be grouped, they’ll be scattered,” she said.
Another pitfall is that less than 15% of nevi may express PRAME. “PRAME can be expressed in scars, so if you’re looking at a spindle cell lesion, be aware that you might be looking at a scar if you’re seeing PRAME expression,” she added. She also noted that PRAME immunohistochemistry (IHC) expression is not a prognostic biomarker in thin melanomas.
If fewer than 25% of cells in a melanocytic lesion express PRAME, most published assessments of PRAME IHC favor nevi as the diagnosis. “If more than 75% are expressing it, it favors melanoma,” Dr. Humberson said. “There’s a big category in between. It’s not that 30% is more likely benign or that 60% is more likely malignant; you can’t really depend upon [PRAME] if you’re in this range.”
A diagnostic accuracy study found that when more than 75% of cells express PRAME, the marker has a sensitivity of 0.63 and a specificity of 0.97.
Selected PRAME-related published references she recommended include: J Cutan Pathol. 2021;48(9):1115-23; Diagnostics. 2022 Sep 9; 12(9):2197, and J Cutan Pathol. 2022;49(9):829-32.
Dr. Humberson reported having no relevant disclosures.
AT MELANOMA 2023
Oncologists may be too quick to refer patients to palliative care
I recently met Jane, a 53-year-old woman with metastatic breast cancer. She was referred to me by the breast oncology team, which routinely refers all metastatic patients to our palliative care clinic.
Clocking in at under 20 minutes, my consultation with Jane might have been one of my shortest on record. Not only had the breast oncology team already addressed Jane’s symptoms, which mainly consisted of hot flashes and joint pain attributable to treatment with an aromatase inhibitor, but they had already started planning ahead for the future of her illness. Jane had completed an advance directive and had a realistic and hopeful perspective on how her illness would progress. She understood the goal of her treatment was to “keep the cancer asleep,” as she put it, and she was very clear about her own goals: to live long enough to see her granddaughter graduate from high school in 2 years and to take a long-awaited trip to Australia later in 2023.
There wasn’t much for me to do. In fact, I daresay that Jane really did not need to see a palliative care specialist because the primary palliative care she was receiving from the breast oncology team was superb. Jane was receiving excellent symptom management from a nurse practitioner and oncologist, plus a social worker provided her with coping strategies. She was already having conversations with her primary medical team and her family about what to expect in the future and how to plan ahead for all possible outcomes.
When should a patient be referred to palliative care?
Integrating palliative care into routine oncologic care need not always require the time and skill of a palliative care team for every patient. Oncology providers can provide basic palliative care services without consulting a palliative care specialist.
For example, if a primary care doctor tried to refer every patient with hypertension to cardiology, the cardiologist would probably say that primary care should be able to handle basic hypertension management. In my experience from working in an oncology clinic for the past 9 years, I’ve found that oncology providers don’t need to refer every advanced cancer patient to our palliative care program. Most oncologists have good communication skills and are more than capable of managing symptoms for patients.
But don’t get me wrong.
Palliative care for all?
In 2010, Jennifer S. Temel MD, published a landmark study in the New England Journal of Medicine that demonstrated significant improvements in quality of life and mood in patients with metastatic lung cancer who received concurrent palliative care. After the study was published many voices inside oncology and palliative care began to advocate for a “palliative care for all” approach to patients with metastatic disease. But this is often interpreted as “specialty palliative care for all,” rather than its original intended meaning that all patients with metastatic disease receive the essential elements of palliative care (biopsychosocial symptom support and conversations about goals of care) either through their primary oncology teams or, if needed, specialty palliative care teams.
The fact is that most specialty palliative care clinics do not have the manpower to meet the needs of all patients with advanced cancers, much less all patients living with serious illness. A main goal of integrating palliative care into routine outpatient health care has always been (and in my opinion, should continue to be) to enhance the primary palliative care skills of specialists, such as oncologists and cardiologists, who care for some of our sickest patients.
This could take many forms. For one, it can be helpful to screen patients for palliative care needs. The American College of Surgeons Commission on Cancer mandates distress screening for all patients as a condition of accreditation. Distress screening using a validated tool such as the National Comprehensive Cancer Network Distress Thermometer can differentiate patients who have minimal distress and may not need much additional support beyond what is provided by their oncology team from those whose distress feels unmanageable and overwhelming.
In terms of primary palliative care symptom management, most oncology teams I work with are comfortable prescribing basic medications for pain, nausea, constipation, and anxiety. They’re also comfortable referring oncology patients for nutrition needs while undergoing chemotherapy as well as to social work and spiritual care for emotional support and counseling.
Oncology teams should continually work on communications skills. They should use “Ask, Tell, Ask” to elicit prognostic awareness, convey critical information, and assess for recall and understanding at pivotal points in the cancer journey, such as when the disease progresses or the patient’s clinical condition changes. They should practice a normalizing script they can use to introduce advance care planning to their patients in the first few visits. When I meet with a patient for the first time, I usually begin by asking if they have prepared an advanced directive. If not, I ask if they’ve thought about who will make medical decisions for them should the need arise. If the patient has documented in writing their preference for care in an emergency situation, I ask for a copy for their chart.
When should patients be referred to a specialty palliative care program?
I tell our oncology teams to involve me after they have tried to intervene, but unsuccessfully because of the patient having intractable symptoms, such as pain, or the disease is not responding to treatments. Or, because there are significant communication or health literacy barriers. Or, because there are challenging family dynamics that are impeding progress in establishing goals of care.
A physician should refer to specialty palliative care when there are multiple comorbid conditions that impact a patient’s prognosis and ability to tolerate treatments. These patients will need detailed symptom management and nuanced conversations about the delicate balance of maintaining quality of life and trying to address their malignancy while also avoiding treatments that may do more harm than good.
At the end of the day, all patients with serious illnesses deserve a palliative care approach to their care from all of their clinicians, not just from the palliative care team. By continuously honing and implementing primary palliative care skills, oncology teams can feel empowered to meet the needs of their patients themselves, strengthening their bond with their patients making truly patient-centered care much more likely.
Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.
I recently met Jane, a 53-year-old woman with metastatic breast cancer. She was referred to me by the breast oncology team, which routinely refers all metastatic patients to our palliative care clinic.
Clocking in at under 20 minutes, my consultation with Jane might have been one of my shortest on record. Not only had the breast oncology team already addressed Jane’s symptoms, which mainly consisted of hot flashes and joint pain attributable to treatment with an aromatase inhibitor, but they had already started planning ahead for the future of her illness. Jane had completed an advance directive and had a realistic and hopeful perspective on how her illness would progress. She understood the goal of her treatment was to “keep the cancer asleep,” as she put it, and she was very clear about her own goals: to live long enough to see her granddaughter graduate from high school in 2 years and to take a long-awaited trip to Australia later in 2023.
There wasn’t much for me to do. In fact, I daresay that Jane really did not need to see a palliative care specialist because the primary palliative care she was receiving from the breast oncology team was superb. Jane was receiving excellent symptom management from a nurse practitioner and oncologist, plus a social worker provided her with coping strategies. She was already having conversations with her primary medical team and her family about what to expect in the future and how to plan ahead for all possible outcomes.
When should a patient be referred to palliative care?
Integrating palliative care into routine oncologic care need not always require the time and skill of a palliative care team for every patient. Oncology providers can provide basic palliative care services without consulting a palliative care specialist.
For example, if a primary care doctor tried to refer every patient with hypertension to cardiology, the cardiologist would probably say that primary care should be able to handle basic hypertension management. In my experience from working in an oncology clinic for the past 9 years, I’ve found that oncology providers don’t need to refer every advanced cancer patient to our palliative care program. Most oncologists have good communication skills and are more than capable of managing symptoms for patients.
But don’t get me wrong.
Palliative care for all?
In 2010, Jennifer S. Temel MD, published a landmark study in the New England Journal of Medicine that demonstrated significant improvements in quality of life and mood in patients with metastatic lung cancer who received concurrent palliative care. After the study was published many voices inside oncology and palliative care began to advocate for a “palliative care for all” approach to patients with metastatic disease. But this is often interpreted as “specialty palliative care for all,” rather than its original intended meaning that all patients with metastatic disease receive the essential elements of palliative care (biopsychosocial symptom support and conversations about goals of care) either through their primary oncology teams or, if needed, specialty palliative care teams.
The fact is that most specialty palliative care clinics do not have the manpower to meet the needs of all patients with advanced cancers, much less all patients living with serious illness. A main goal of integrating palliative care into routine outpatient health care has always been (and in my opinion, should continue to be) to enhance the primary palliative care skills of specialists, such as oncologists and cardiologists, who care for some of our sickest patients.
This could take many forms. For one, it can be helpful to screen patients for palliative care needs. The American College of Surgeons Commission on Cancer mandates distress screening for all patients as a condition of accreditation. Distress screening using a validated tool such as the National Comprehensive Cancer Network Distress Thermometer can differentiate patients who have minimal distress and may not need much additional support beyond what is provided by their oncology team from those whose distress feels unmanageable and overwhelming.
In terms of primary palliative care symptom management, most oncology teams I work with are comfortable prescribing basic medications for pain, nausea, constipation, and anxiety. They’re also comfortable referring oncology patients for nutrition needs while undergoing chemotherapy as well as to social work and spiritual care for emotional support and counseling.
Oncology teams should continually work on communications skills. They should use “Ask, Tell, Ask” to elicit prognostic awareness, convey critical information, and assess for recall and understanding at pivotal points in the cancer journey, such as when the disease progresses or the patient’s clinical condition changes. They should practice a normalizing script they can use to introduce advance care planning to their patients in the first few visits. When I meet with a patient for the first time, I usually begin by asking if they have prepared an advanced directive. If not, I ask if they’ve thought about who will make medical decisions for them should the need arise. If the patient has documented in writing their preference for care in an emergency situation, I ask for a copy for their chart.
When should patients be referred to a specialty palliative care program?
I tell our oncology teams to involve me after they have tried to intervene, but unsuccessfully because of the patient having intractable symptoms, such as pain, or the disease is not responding to treatments. Or, because there are significant communication or health literacy barriers. Or, because there are challenging family dynamics that are impeding progress in establishing goals of care.
A physician should refer to specialty palliative care when there are multiple comorbid conditions that impact a patient’s prognosis and ability to tolerate treatments. These patients will need detailed symptom management and nuanced conversations about the delicate balance of maintaining quality of life and trying to address their malignancy while also avoiding treatments that may do more harm than good.
At the end of the day, all patients with serious illnesses deserve a palliative care approach to their care from all of their clinicians, not just from the palliative care team. By continuously honing and implementing primary palliative care skills, oncology teams can feel empowered to meet the needs of their patients themselves, strengthening their bond with their patients making truly patient-centered care much more likely.
Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.
I recently met Jane, a 53-year-old woman with metastatic breast cancer. She was referred to me by the breast oncology team, which routinely refers all metastatic patients to our palliative care clinic.
Clocking in at under 20 minutes, my consultation with Jane might have been one of my shortest on record. Not only had the breast oncology team already addressed Jane’s symptoms, which mainly consisted of hot flashes and joint pain attributable to treatment with an aromatase inhibitor, but they had already started planning ahead for the future of her illness. Jane had completed an advance directive and had a realistic and hopeful perspective on how her illness would progress. She understood the goal of her treatment was to “keep the cancer asleep,” as she put it, and she was very clear about her own goals: to live long enough to see her granddaughter graduate from high school in 2 years and to take a long-awaited trip to Australia later in 2023.
There wasn’t much for me to do. In fact, I daresay that Jane really did not need to see a palliative care specialist because the primary palliative care she was receiving from the breast oncology team was superb. Jane was receiving excellent symptom management from a nurse practitioner and oncologist, plus a social worker provided her with coping strategies. She was already having conversations with her primary medical team and her family about what to expect in the future and how to plan ahead for all possible outcomes.
When should a patient be referred to palliative care?
Integrating palliative care into routine oncologic care need not always require the time and skill of a palliative care team for every patient. Oncology providers can provide basic palliative care services without consulting a palliative care specialist.
For example, if a primary care doctor tried to refer every patient with hypertension to cardiology, the cardiologist would probably say that primary care should be able to handle basic hypertension management. In my experience from working in an oncology clinic for the past 9 years, I’ve found that oncology providers don’t need to refer every advanced cancer patient to our palliative care program. Most oncologists have good communication skills and are more than capable of managing symptoms for patients.
But don’t get me wrong.
Palliative care for all?
In 2010, Jennifer S. Temel MD, published a landmark study in the New England Journal of Medicine that demonstrated significant improvements in quality of life and mood in patients with metastatic lung cancer who received concurrent palliative care. After the study was published many voices inside oncology and palliative care began to advocate for a “palliative care for all” approach to patients with metastatic disease. But this is often interpreted as “specialty palliative care for all,” rather than its original intended meaning that all patients with metastatic disease receive the essential elements of palliative care (biopsychosocial symptom support and conversations about goals of care) either through their primary oncology teams or, if needed, specialty palliative care teams.
The fact is that most specialty palliative care clinics do not have the manpower to meet the needs of all patients with advanced cancers, much less all patients living with serious illness. A main goal of integrating palliative care into routine outpatient health care has always been (and in my opinion, should continue to be) to enhance the primary palliative care skills of specialists, such as oncologists and cardiologists, who care for some of our sickest patients.
This could take many forms. For one, it can be helpful to screen patients for palliative care needs. The American College of Surgeons Commission on Cancer mandates distress screening for all patients as a condition of accreditation. Distress screening using a validated tool such as the National Comprehensive Cancer Network Distress Thermometer can differentiate patients who have minimal distress and may not need much additional support beyond what is provided by their oncology team from those whose distress feels unmanageable and overwhelming.
In terms of primary palliative care symptom management, most oncology teams I work with are comfortable prescribing basic medications for pain, nausea, constipation, and anxiety. They’re also comfortable referring oncology patients for nutrition needs while undergoing chemotherapy as well as to social work and spiritual care for emotional support and counseling.
Oncology teams should continually work on communications skills. They should use “Ask, Tell, Ask” to elicit prognostic awareness, convey critical information, and assess for recall and understanding at pivotal points in the cancer journey, such as when the disease progresses or the patient’s clinical condition changes. They should practice a normalizing script they can use to introduce advance care planning to their patients in the first few visits. When I meet with a patient for the first time, I usually begin by asking if they have prepared an advanced directive. If not, I ask if they’ve thought about who will make medical decisions for them should the need arise. If the patient has documented in writing their preference for care in an emergency situation, I ask for a copy for their chart.
When should patients be referred to a specialty palliative care program?
I tell our oncology teams to involve me after they have tried to intervene, but unsuccessfully because of the patient having intractable symptoms, such as pain, or the disease is not responding to treatments. Or, because there are significant communication or health literacy barriers. Or, because there are challenging family dynamics that are impeding progress in establishing goals of care.
A physician should refer to specialty palliative care when there are multiple comorbid conditions that impact a patient’s prognosis and ability to tolerate treatments. These patients will need detailed symptom management and nuanced conversations about the delicate balance of maintaining quality of life and trying to address their malignancy while also avoiding treatments that may do more harm than good.
At the end of the day, all patients with serious illnesses deserve a palliative care approach to their care from all of their clinicians, not just from the palliative care team. By continuously honing and implementing primary palliative care skills, oncology teams can feel empowered to meet the needs of their patients themselves, strengthening their bond with their patients making truly patient-centered care much more likely.
Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.
Regular vitamin D supplements may lower melanoma risk
. They also found a trend for benefit with occasional use.
The study, published in Melanoma Research, involved almost 500 individuals attending a dermatology clinic who reported on their use of vitamin D supplements.
Regular users had a significant 55% reduction in the odds of having a past or present melanoma diagnosis, while occasional use was associated with a nonsignificant 46% reduction. The reduction was similar for all skin cancer types.
However, senior author Ilkka T. Harvima, MD, PhD, department of dermatology, University of Eastern Finland and Kuopio (Finland) University Hospital, warned there are limitations to the study.
Despite adjustment for several possible confounding factors, “it is still possible that some other, yet unidentified or untested, factors can still confound the present result,” he said.
Consequently, “the causal link between vitamin D and melanoma cannot be confirmed by the present results,” Dr. Harvima said in a statement.
Even if the link were to be proven, “the question about the optimal dose of oral vitamin D in order to for it to have beneficial effects remains to be answered,” he said.
“Until we know more, national intake recommendations should be followed.”
The incidence of cutaneous malignant melanoma and other skin cancers has been increasing steadily in Western populations, particularly in immunosuppressed individuals, the authors pointed out, and they attributed the rise to an increased exposure to ultraviolet radiation.
While ultraviolet radiation exposure is a well-known risk factor, “the other side of the coin is that public sun protection campaigns have led to alerts that insufficient sun exposure is a significant public health problem, resulting in insufficient vitamin D status.”
For their study, the team reviewed the records of 498 patients aged 21-79 years at a dermatology outpatient clinic who were deemed by an experienced dermatologist to be at risk of any type of skin cancer.
Among these patients, 295 individuals had a history of past or present cutaneous malignancy, with 100 diagnosed with melanoma, 213 with basal cell carcinoma, and 41 with squamous cell carcinoma. A further 70 subjects had cancer elsewhere, including breast, prostate, kidney, bladder, intestine, and blood cancers.
A subgroup of 96 patients were immunocompromised and were considered separately.
The 402 remaining patients were categorized, based on their self-reported use of oral vitamin D preparations, as nonusers (n = 99), occasional users (n = 126), and regular users (n = 177).
Regular use of vitamin D was associated with being more educated (P = .032), less frequent outdoor working (P = .003), lower tobacco pack years (P = .001), and more frequent solarium exposure (P = .002).
There was no significant association between vitamin D use and photoaging, actinic keratoses, nevi, basal or squamous cell carcinoma, body mass index, or self-estimated lifetime exposure to sunlight or sunburns.
However, there were significant associations between regular use of vitamin D and a lower incidence of melanoma and other cancer types.
There were significantly fewer individuals in the regular vitamin D use group with a past or present history of melanoma when compared with the nonuse group, at 18.1% vs. 32.3% (P = .021), or any type of skin cancer, at 62.1% vs. 74.7% (P = .027).
Multivariate logistic regression analysis revealed that regular vitamin D use was significantly associated with a reduced melanoma risk, at an odds ratio vs. nonuse of 0.447 (P = .016).
Occasional use was associated with a reduced, albeit nonsignificant, risk, with an odds ratio versus nonuse of 0.540 (P = .08).
For any type of skin cancers, regular vitamin D use was associated with an odds ratio vs. nonuse of 0.478 (P = .032), while that for occasional vitamin D use was 0.543 (P = .061).
“Somewhat similar” results were obtained when the investigators looked at the subgroup of immunocompromised individuals, although they note that “the number of subjects was low.”
The study was supported by the Cancer Center of Eastern Finland of the University of Eastern Finland, the Finnish Cancer Research Foundation, and the VTR-funding of Kuopio University Hospital. The authors report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
. They also found a trend for benefit with occasional use.
The study, published in Melanoma Research, involved almost 500 individuals attending a dermatology clinic who reported on their use of vitamin D supplements.
Regular users had a significant 55% reduction in the odds of having a past or present melanoma diagnosis, while occasional use was associated with a nonsignificant 46% reduction. The reduction was similar for all skin cancer types.
However, senior author Ilkka T. Harvima, MD, PhD, department of dermatology, University of Eastern Finland and Kuopio (Finland) University Hospital, warned there are limitations to the study.
Despite adjustment for several possible confounding factors, “it is still possible that some other, yet unidentified or untested, factors can still confound the present result,” he said.
Consequently, “the causal link between vitamin D and melanoma cannot be confirmed by the present results,” Dr. Harvima said in a statement.
Even if the link were to be proven, “the question about the optimal dose of oral vitamin D in order to for it to have beneficial effects remains to be answered,” he said.
“Until we know more, national intake recommendations should be followed.”
The incidence of cutaneous malignant melanoma and other skin cancers has been increasing steadily in Western populations, particularly in immunosuppressed individuals, the authors pointed out, and they attributed the rise to an increased exposure to ultraviolet radiation.
While ultraviolet radiation exposure is a well-known risk factor, “the other side of the coin is that public sun protection campaigns have led to alerts that insufficient sun exposure is a significant public health problem, resulting in insufficient vitamin D status.”
For their study, the team reviewed the records of 498 patients aged 21-79 years at a dermatology outpatient clinic who were deemed by an experienced dermatologist to be at risk of any type of skin cancer.
Among these patients, 295 individuals had a history of past or present cutaneous malignancy, with 100 diagnosed with melanoma, 213 with basal cell carcinoma, and 41 with squamous cell carcinoma. A further 70 subjects had cancer elsewhere, including breast, prostate, kidney, bladder, intestine, and blood cancers.
A subgroup of 96 patients were immunocompromised and were considered separately.
The 402 remaining patients were categorized, based on their self-reported use of oral vitamin D preparations, as nonusers (n = 99), occasional users (n = 126), and regular users (n = 177).
Regular use of vitamin D was associated with being more educated (P = .032), less frequent outdoor working (P = .003), lower tobacco pack years (P = .001), and more frequent solarium exposure (P = .002).
There was no significant association between vitamin D use and photoaging, actinic keratoses, nevi, basal or squamous cell carcinoma, body mass index, or self-estimated lifetime exposure to sunlight or sunburns.
However, there were significant associations between regular use of vitamin D and a lower incidence of melanoma and other cancer types.
There were significantly fewer individuals in the regular vitamin D use group with a past or present history of melanoma when compared with the nonuse group, at 18.1% vs. 32.3% (P = .021), or any type of skin cancer, at 62.1% vs. 74.7% (P = .027).
Multivariate logistic regression analysis revealed that regular vitamin D use was significantly associated with a reduced melanoma risk, at an odds ratio vs. nonuse of 0.447 (P = .016).
Occasional use was associated with a reduced, albeit nonsignificant, risk, with an odds ratio versus nonuse of 0.540 (P = .08).
For any type of skin cancers, regular vitamin D use was associated with an odds ratio vs. nonuse of 0.478 (P = .032), while that for occasional vitamin D use was 0.543 (P = .061).
“Somewhat similar” results were obtained when the investigators looked at the subgroup of immunocompromised individuals, although they note that “the number of subjects was low.”
The study was supported by the Cancer Center of Eastern Finland of the University of Eastern Finland, the Finnish Cancer Research Foundation, and the VTR-funding of Kuopio University Hospital. The authors report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
. They also found a trend for benefit with occasional use.
The study, published in Melanoma Research, involved almost 500 individuals attending a dermatology clinic who reported on their use of vitamin D supplements.
Regular users had a significant 55% reduction in the odds of having a past or present melanoma diagnosis, while occasional use was associated with a nonsignificant 46% reduction. The reduction was similar for all skin cancer types.
However, senior author Ilkka T. Harvima, MD, PhD, department of dermatology, University of Eastern Finland and Kuopio (Finland) University Hospital, warned there are limitations to the study.
Despite adjustment for several possible confounding factors, “it is still possible that some other, yet unidentified or untested, factors can still confound the present result,” he said.
Consequently, “the causal link between vitamin D and melanoma cannot be confirmed by the present results,” Dr. Harvima said in a statement.
Even if the link were to be proven, “the question about the optimal dose of oral vitamin D in order to for it to have beneficial effects remains to be answered,” he said.
“Until we know more, national intake recommendations should be followed.”
The incidence of cutaneous malignant melanoma and other skin cancers has been increasing steadily in Western populations, particularly in immunosuppressed individuals, the authors pointed out, and they attributed the rise to an increased exposure to ultraviolet radiation.
While ultraviolet radiation exposure is a well-known risk factor, “the other side of the coin is that public sun protection campaigns have led to alerts that insufficient sun exposure is a significant public health problem, resulting in insufficient vitamin D status.”
For their study, the team reviewed the records of 498 patients aged 21-79 years at a dermatology outpatient clinic who were deemed by an experienced dermatologist to be at risk of any type of skin cancer.
Among these patients, 295 individuals had a history of past or present cutaneous malignancy, with 100 diagnosed with melanoma, 213 with basal cell carcinoma, and 41 with squamous cell carcinoma. A further 70 subjects had cancer elsewhere, including breast, prostate, kidney, bladder, intestine, and blood cancers.
A subgroup of 96 patients were immunocompromised and were considered separately.
The 402 remaining patients were categorized, based on their self-reported use of oral vitamin D preparations, as nonusers (n = 99), occasional users (n = 126), and regular users (n = 177).
Regular use of vitamin D was associated with being more educated (P = .032), less frequent outdoor working (P = .003), lower tobacco pack years (P = .001), and more frequent solarium exposure (P = .002).
There was no significant association between vitamin D use and photoaging, actinic keratoses, nevi, basal or squamous cell carcinoma, body mass index, or self-estimated lifetime exposure to sunlight or sunburns.
However, there were significant associations between regular use of vitamin D and a lower incidence of melanoma and other cancer types.
There were significantly fewer individuals in the regular vitamin D use group with a past or present history of melanoma when compared with the nonuse group, at 18.1% vs. 32.3% (P = .021), or any type of skin cancer, at 62.1% vs. 74.7% (P = .027).
Multivariate logistic regression analysis revealed that regular vitamin D use was significantly associated with a reduced melanoma risk, at an odds ratio vs. nonuse of 0.447 (P = .016).
Occasional use was associated with a reduced, albeit nonsignificant, risk, with an odds ratio versus nonuse of 0.540 (P = .08).
For any type of skin cancers, regular vitamin D use was associated with an odds ratio vs. nonuse of 0.478 (P = .032), while that for occasional vitamin D use was 0.543 (P = .061).
“Somewhat similar” results were obtained when the investigators looked at the subgroup of immunocompromised individuals, although they note that “the number of subjects was low.”
The study was supported by the Cancer Center of Eastern Finland of the University of Eastern Finland, the Finnish Cancer Research Foundation, and the VTR-funding of Kuopio University Hospital. The authors report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM MELANOMA RESEARCH
Study spotlights clinicopathologic features, survival outcomes of pediatric melanoma
.
“Cutaneous melanomas are rare in children and much less common in adolescents than in later life,” researchers led by Mary-Ann El Sharouni, PhD, wrote in the study, which was published online in the Journal of the American Academy of Dermatology. “Management of these young patients currently follows guidelines developed for adults. Better understanding of melanoma occurring in the first 2 decades of life is, therefore, warranted.”
Drawing from two datasets – one from the Netherlands and the other from Melanoma Institute Australia (MIA) at the University of Sydney – Dr. El Sharouni of the MIA and of the department of dermatology at University Medical Center Utrecht in the Netherlands, and colleagues, evaluated all patients younger than 20 years of age who were diagnosed with invasive melanoma between January 2000 and December 2014. The pooled cohort included 397 Dutch and 117 Australian individuals. Of these, 62 were children and 452 were adolescents. To determine melanoma subtypes, the researchers reevaluated pathology reports and used multivariate Cox models to calculate recurrence-free survival (RFS) and overall survival (OS).
The median Breslow thickness was 2.7 mm in children and 1.0 mm in adolescents. Most patients (83%) had conventional melanoma, which consisted of superficial spreading, nodular, desmoplastic, and acral lentiginous forms, while 78 had spitzoid melanoma and 8 had melanoma associated with a congenital nevus. The 10-year RFS was 91.5% in children and 86.4% in adolescents (P =.32), while the 10-year OS was 100% in children and 92.7% in adolescents (P = .09).
On multivariable analysis, which was possible only for the adolescent cohort because of the small number of children, ulceration status and anatomic site were associated with RFS and OS, whereas age, sex, mitotic index, sentinel node status, and melanoma subtype were not. Breslow thickness > 4 mm was associated with worse RFS. As for affected anatomic site, those with melanomas located on the upper and lower limbs had a better overall RFS and OS compared with those who had head or neck melanomas.
The authors acknowledged certain limitation of the analysis, including its retrospective design and the small number of children. “Our data suggest that adolescent melanomas are often similar to adult-type melanomas, whilst those which occur in young children frequently occur via different molecular mechanisms,” they concluded. “In the future it is likely that further understanding of these molecular mechanisms and ability to classify melanomas based on their molecular characteristics will assist in further refining prognostic estimates and possible guiding treatment for young patients with melanoma.”
Rebecca M. Thiede, MD, assistant program director of the division of dermatology at the University of Arizona, Tucson, who was asked to comment on the study, said that the analysis “greatly contributes to dermatology, as we are still learning the differences between melanoma in children and adolescents versus adults.
This study found that adolescents with melanoma had worse survival if mitosis were present and/or located on head/neck, which could aid in aggressiveness of treatment.”
A key strength of analysis, she continued, is the large sample size of 514 patients, “given that melanoma in this population is very rare. A limitation which [the researchers] brought up is the discrepancy of diagnosis via histopathology of melanoma in children versus adults. The study relied on the pathology report given the retrospective nature of this [analysis, and it] was based on Australian and Dutch populations, which may limit its scope in other countries.”
Dr. El Sharouni was supported by a research fellowship grant from the European Academy of Dermatology and Venereology (EADV), while two of her coauthors, Richard A. Scolyer, MD, and John F. Thompson, MD, were recipients of an Australian National Health and Medical Research Council Program Grant. The study was also supported by a research program grant from Cancer Institute New South Wales. Dr. Thiede reported having no financial disclosures.
.
“Cutaneous melanomas are rare in children and much less common in adolescents than in later life,” researchers led by Mary-Ann El Sharouni, PhD, wrote in the study, which was published online in the Journal of the American Academy of Dermatology. “Management of these young patients currently follows guidelines developed for adults. Better understanding of melanoma occurring in the first 2 decades of life is, therefore, warranted.”
Drawing from two datasets – one from the Netherlands and the other from Melanoma Institute Australia (MIA) at the University of Sydney – Dr. El Sharouni of the MIA and of the department of dermatology at University Medical Center Utrecht in the Netherlands, and colleagues, evaluated all patients younger than 20 years of age who were diagnosed with invasive melanoma between January 2000 and December 2014. The pooled cohort included 397 Dutch and 117 Australian individuals. Of these, 62 were children and 452 were adolescents. To determine melanoma subtypes, the researchers reevaluated pathology reports and used multivariate Cox models to calculate recurrence-free survival (RFS) and overall survival (OS).
The median Breslow thickness was 2.7 mm in children and 1.0 mm in adolescents. Most patients (83%) had conventional melanoma, which consisted of superficial spreading, nodular, desmoplastic, and acral lentiginous forms, while 78 had spitzoid melanoma and 8 had melanoma associated with a congenital nevus. The 10-year RFS was 91.5% in children and 86.4% in adolescents (P =.32), while the 10-year OS was 100% in children and 92.7% in adolescents (P = .09).
On multivariable analysis, which was possible only for the adolescent cohort because of the small number of children, ulceration status and anatomic site were associated with RFS and OS, whereas age, sex, mitotic index, sentinel node status, and melanoma subtype were not. Breslow thickness > 4 mm was associated with worse RFS. As for affected anatomic site, those with melanomas located on the upper and lower limbs had a better overall RFS and OS compared with those who had head or neck melanomas.
The authors acknowledged certain limitation of the analysis, including its retrospective design and the small number of children. “Our data suggest that adolescent melanomas are often similar to adult-type melanomas, whilst those which occur in young children frequently occur via different molecular mechanisms,” they concluded. “In the future it is likely that further understanding of these molecular mechanisms and ability to classify melanomas based on their molecular characteristics will assist in further refining prognostic estimates and possible guiding treatment for young patients with melanoma.”
Rebecca M. Thiede, MD, assistant program director of the division of dermatology at the University of Arizona, Tucson, who was asked to comment on the study, said that the analysis “greatly contributes to dermatology, as we are still learning the differences between melanoma in children and adolescents versus adults.
This study found that adolescents with melanoma had worse survival if mitosis were present and/or located on head/neck, which could aid in aggressiveness of treatment.”
A key strength of analysis, she continued, is the large sample size of 514 patients, “given that melanoma in this population is very rare. A limitation which [the researchers] brought up is the discrepancy of diagnosis via histopathology of melanoma in children versus adults. The study relied on the pathology report given the retrospective nature of this [analysis, and it] was based on Australian and Dutch populations, which may limit its scope in other countries.”
Dr. El Sharouni was supported by a research fellowship grant from the European Academy of Dermatology and Venereology (EADV), while two of her coauthors, Richard A. Scolyer, MD, and John F. Thompson, MD, were recipients of an Australian National Health and Medical Research Council Program Grant. The study was also supported by a research program grant from Cancer Institute New South Wales. Dr. Thiede reported having no financial disclosures.
.
“Cutaneous melanomas are rare in children and much less common in adolescents than in later life,” researchers led by Mary-Ann El Sharouni, PhD, wrote in the study, which was published online in the Journal of the American Academy of Dermatology. “Management of these young patients currently follows guidelines developed for adults. Better understanding of melanoma occurring in the first 2 decades of life is, therefore, warranted.”
Drawing from two datasets – one from the Netherlands and the other from Melanoma Institute Australia (MIA) at the University of Sydney – Dr. El Sharouni of the MIA and of the department of dermatology at University Medical Center Utrecht in the Netherlands, and colleagues, evaluated all patients younger than 20 years of age who were diagnosed with invasive melanoma between January 2000 and December 2014. The pooled cohort included 397 Dutch and 117 Australian individuals. Of these, 62 were children and 452 were adolescents. To determine melanoma subtypes, the researchers reevaluated pathology reports and used multivariate Cox models to calculate recurrence-free survival (RFS) and overall survival (OS).
The median Breslow thickness was 2.7 mm in children and 1.0 mm in adolescents. Most patients (83%) had conventional melanoma, which consisted of superficial spreading, nodular, desmoplastic, and acral lentiginous forms, while 78 had spitzoid melanoma and 8 had melanoma associated with a congenital nevus. The 10-year RFS was 91.5% in children and 86.4% in adolescents (P =.32), while the 10-year OS was 100% in children and 92.7% in adolescents (P = .09).
On multivariable analysis, which was possible only for the adolescent cohort because of the small number of children, ulceration status and anatomic site were associated with RFS and OS, whereas age, sex, mitotic index, sentinel node status, and melanoma subtype were not. Breslow thickness > 4 mm was associated with worse RFS. As for affected anatomic site, those with melanomas located on the upper and lower limbs had a better overall RFS and OS compared with those who had head or neck melanomas.
The authors acknowledged certain limitation of the analysis, including its retrospective design and the small number of children. “Our data suggest that adolescent melanomas are often similar to adult-type melanomas, whilst those which occur in young children frequently occur via different molecular mechanisms,” they concluded. “In the future it is likely that further understanding of these molecular mechanisms and ability to classify melanomas based on their molecular characteristics will assist in further refining prognostic estimates and possible guiding treatment for young patients with melanoma.”
Rebecca M. Thiede, MD, assistant program director of the division of dermatology at the University of Arizona, Tucson, who was asked to comment on the study, said that the analysis “greatly contributes to dermatology, as we are still learning the differences between melanoma in children and adolescents versus adults.
This study found that adolescents with melanoma had worse survival if mitosis were present and/or located on head/neck, which could aid in aggressiveness of treatment.”
A key strength of analysis, she continued, is the large sample size of 514 patients, “given that melanoma in this population is very rare. A limitation which [the researchers] brought up is the discrepancy of diagnosis via histopathology of melanoma in children versus adults. The study relied on the pathology report given the retrospective nature of this [analysis, and it] was based on Australian and Dutch populations, which may limit its scope in other countries.”
Dr. El Sharouni was supported by a research fellowship grant from the European Academy of Dermatology and Venereology (EADV), while two of her coauthors, Richard A. Scolyer, MD, and John F. Thompson, MD, were recipients of an Australian National Health and Medical Research Council Program Grant. The study was also supported by a research program grant from Cancer Institute New South Wales. Dr. Thiede reported having no financial disclosures.
FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
Cancer clinics begin to accommodate patients demanding new cancer detection tests
Doug Flora, MD, knows the value of early cancer detection because it helped him survive kidney cancer 5 years ago. But as a medical oncologist and hematologist, and the executive medical director of oncology services at St. Elizabeth Healthcare in Edgewood, Ky., he also knows that a new era of early cancer detection testing poses big challenges for his network of six hospitals and 169 specialty and primary care offices throughout Kentucky, Ohio, and Indiana.
Multicancer early detection (MCED) tests are finally a reality and could be a potential game changer because they can screen for the possibility of up to 50 different cancers in asymptomatic individuals with one blood draw. They represent one of the fastest growing segments in medical diagnostics with a projected value of $2.77 billion by 2030, according to the market research firm Grand View Research.
These tests are different from traditional liquid biopsies, which are designed to identify actionable gene mutations to help inform treatment decisions of patients already diagnosed with cancer. Instead, MCED tests work to detect fragments of circulating free DNA that have been shed by tumors and released into the bloodstream. Detecting these cancer signals could indicate that an individual has cancer well before they ever develop symptoms.
For some cancer types, particularly those commonly diagnosed at advanced stages or those without general population screening tests, MCED testing could have a significant impact.
In its new report, Grand View Research highlights nine “prominent players” active in the MCED market; of these, two have been granted breakthrough device designation by the Food and Drug Administration: OverC MCDBT by Burning Rock on Jan. 3, 2023, and Galleri by Grail in 2019. Galleri was launched in June 2021 and can be obtained with a prescription at a cost of $949.
Yet, while patients are asking for these tests and primary care physicians are prescribing them, oncologists are grappling with how to manage the first patients whose tests tell them they may have cancer.
Ordering the tests may seem straightforward, but in reality, it is not. In fact, they are so new that most health systems have no internal guidelines for physicians. Guidelines would address when the tests should be prescribed, and whether a patient should undergo more testing or be referred to an oncologist.
Clinical trials underway
There are currently at least 17 clinical trials underway to investigate the performance and clinical utility of MCED tests. Six of these involve Grail, including NHS-Galleri, the largest study to date of 140,000 participants in the United Kingdom where participants will be followed for 3 years with annual visits at 12 and 24 months. And, the National Cancer Institute is spearheading a clinical trial of its own, according to a search of ClinicalTrials.gov.
In September 2022, Grail presented findings from its pivotal PATHFINDER study at the annual meeting of the European Society of Medical Oncology. Researchers reported that cancer signals were detected in 1.4% (92) of 6,621 participants enrolled in the study. Of the 92, 35 people were diagnosed with 36 cancers: 19 were solid tumors (2 oropharyngeal, 5 breast, l liver, 1 intrahepatic bile duct, 2 colon/rectum, 2 prostate, 1 lung, 1 pancreas, 1 small intestine, 1 uterus, 1 ovary and 1 bone) and 17 hematologic cancers (1 plasma cell myeloma/disorders, 2 lymphoid leukemia, 2 Waldenström’s macroglobulinemia, and 12 lymphoma).
Almost half of newly diagnosed cases were cancers in stage 1 or 2. Of stage 1 cancers, three were solid tumors and four were hematologic cancers. Of stage 2 cancers, three were solid tumors and four were hematologic cancers. All other cancers were in stage 3 and 4 or were listed as recurrent or no stage. Deb Schrag, MD, MPH, chair of the department of medicine at Memorial Sloan Kettering Cancer Center in New York, who presented the results from PATHFINDER at ESMO, reported that, of all diagnosed cancers, only breast, colon/rectum, prostate, and lung have established screening protocols.
The findings were so striking that the meeting scientific co-chair, Fabrice André, MD, PhD, told ESMO the oncology field must prepare for an onslaught of new patients.
“Within the next 5 years, we will need more doctors, surgeons and nurses with more diagnostic and treatment infrastructures to care for the rising number of people who will be identified by multicancer early detection tests,” said Dr. André, who is director of research at Gustave Roussy Cancer Center, Villejuif, France, and future president of ESMO (2025-2026). “We need to involve all stakeholders in deciding new pathways of care. We need to agree who will be tested and when and where tests will be carried out, and to anticipate the changes that will happen as a result of these tests.”
But first, he urged, the need for comparative trials “across all types of cancer to find out if having an early detection test affects morbidity and mortality. We also need to know how the tests benefit patients, and how to discuss the results with them,” Dr. André said.
Demand may burden health systems
Dr. Flora suggested that companies like Grail are rushing their product to market without conducting long-term sizable clinical trials.
“These diagnostic companies are a billion dollar publicly traded or venture capital-funded companies that are losing millions of dollars a quarter as they’re scaling up these tests. So, there is some pressure on the sales forces ... to start moving product long before the science has met our lowest areas for entry,” Dr. Flora said. “They are aggressively marketing to a primary care audience that knows nothing about MCEDs. It’s a sales-driven development solving a problem we all believe is real, but we don’t know if it actually solves the problem.”
There are many unanswered questions, he said. Among these include whether the tests do indeed extend survival. “What they’re suggesting – that is if the blood test detects it – that we’re going to save your life. That’s not yet been proven. This is where the providers are pushing back against these industry types to say: ‘This is the wild west right now.’ It’s very irresponsible to go out there and try to sell hundreds of millions of dollars of product to doctors who have never studied genetics,” Dr. Flora said.
Grail’s chief medical officer Jeff Venstrom, MD, however, said physicians don’t need a background in genetic testing to order or interpret Galleri because it’s not a genetic test. Genetic tests look for genetic variants associated with cancer risk, which Galleri does not. MCED tests rely on genomic profiling to identify alterations in tumors.
“Maybe there’s still confusion in the market, which is common for new technologies when they’re initially launched. This is not a 23andMe test. We do not report germline mutations that have implications for cancer risk. We’re using this blood sample to test for the presence or absence of a cancer signal. The test result is very clear and simple: One area of the report says ‘yes’ or ‘no.’ It is a binary result that says if a signal is detected or not. The second provides additional information around where that signal could be coming from,” he said.
Galleri could fill a huge unmet need in cancer prevention, Dr. Venstrom said. Not only could it detect cancer at an earlier stage, but it could serve as a screening tool for cancers like pancreatic cancer in which screening is not available.
The test is not intended to replace standard of care screening, he said. The ordering provider should have a conversation with the patient about overall cancer risk. “Are you smoking? What’s your risk of obesity-associated cancers? Do you have a family history of cancer? I think this should all be in the context of a good conversation around preventative care,” he said.
Planning and prep in Boston
In Boston, Aparna Parikh, MD, an oncologist who specializes in gastrointestinal cancers, agreed that MCED testing has forced her team at the Mass General Cancer Center global cancer care program to think outside of the box.
“We’re a major academic center and it’s not easy [because] this is all uncharted territory,” she said. “We all recognize there are more tests coming, and they are here to stay. As a health system, we have to be ready to manage not only the tests, but patient anxieties, and all the complexities that come with it. We just don’t know yet how to best navigate.”
Although Dr. Parikh’s center has set up a working group tasked with organizing an outpatient clinic for patients with positive MCED tests, the current system is haphazard.
“Right now, it gets bounced around between people,” she explained. “Sometimes, patients are getting referred to the oncology team rather than the primary care team to try to sort out where the cancer signal is coming from, that is, if it’s not immediately obvious. No one really knows who should be the right person to own it,” Dr. Parikh said. While the test is supposed to give tissue-specific results, “it’s not perfect” and sometimes imaging and other work-ups are needed to locate the source of the signa.
“A group of four or five oncologists get looped in and then we’re trying to sort it out on a case-by-case basis, but understanding that with more and more tests coming, that kind of ad hoc approach isn’t going to be sufficient. We need a happy medium between the primary care and the disease specific oncologist, someone who can kind of help think through the diagnostic workup until they have a cancer diagnosis to get them to the right place,” Dr. Parikh said.
Dr. Venstrom said Grail is committed to providing support to clinicians in these situations. “We’re doing everything we can with our medical education forums. We have this pretty intense and extensive postpositive suite of resources,” he explained. “Some of our doctors on staff call the ordering provider within 24 hours just to clarify if there are any questions or confusion from the report. For example, if it suggests the signal is coming from the lung, we provide additional support around additional workups.”
Out-of-pocket test may widen disparities in care
With the exception of a few health insurance companies that have committed to covering some of the cost for the test, Galleri is an out-of-pocket expense.
Dr. Venstrom acknowledged that broad insurance coverage for the Galleri test remains a hurdle, although “we’ve secured coverage for a handful of companies of self-insured employers and forward-thinking insurers.” This includes partnerships with Point32Health, and Alignment Health, among others, he said.
There is also growing support among more than 400 cancer organizations for the Multi-Cancer Early Detection Screening Coverage Act to accelerate coverage for Medicare beneficiaries. “We are constantly trying to understand the evidence that’s needed for payors to make sure that we get the broadest access possible for this test,” he said.
The first positive test result
Back at St. Elizabeth Healthcare where they’ve only seen one positive MCED test result thus far, Dr. Flora is more concerned about patients giving informed consent before they even get the test. “When the reps started hammering our primary care doctors, we sent communiques throughout the system saying that we would very much like to regulate this to make sure that before our patients receive accidental harm, that they at least have a conversation with somebody who understands the test,” he explained.
All 15 patients who requested the test at the hospital were first required to discuss the implications with a genetic counselor who is part of the system. “We are really pro–cancer screening,” he said, but added his hospital is “not pumped” about the Galleri test. “We’re being very cautious about overstatements made by sales guys to our primary care doctors, so we’re letting our own precision medicine people handle it.”
There’s a similar system in place at Community Health Network, a nonprofit health system with nine hospitals and 1,300 employee providers throughout Central Indiana. Patrick McGill, MD, a primary care physician and chief analytics officer for the network says they have streamlined patients with positive tests through their high-risk oncology clinic. “They don’t go straight to a medical oncologist which I know some systems are struggling with,” he said. “They get additional testing, whether it’s imaging they might need or other lab testing. We’ve had a few lung positives, and a few leukemia positives which might go straight to medical oncology. I think we had one breast that was positive so she got additional breast imaging.”
Through its foundation, CHN will offer 2,000 tests free of charge. “We decided to take cost off the table with this funding,” Dr. McGill said. “A lot of health systems I talk to are always concerned that insurance doesn’t cover it and it’s cost prohibitive. Is it creating additional disparities because only people who can afford it can get the test?”
Dr. Schrag serves as an uncompensated advisor for Grail. Previously, while with the Dana-Farber Cancer Institute, she received research funding from Grail.
Doug Flora, MD, knows the value of early cancer detection because it helped him survive kidney cancer 5 years ago. But as a medical oncologist and hematologist, and the executive medical director of oncology services at St. Elizabeth Healthcare in Edgewood, Ky., he also knows that a new era of early cancer detection testing poses big challenges for his network of six hospitals and 169 specialty and primary care offices throughout Kentucky, Ohio, and Indiana.
Multicancer early detection (MCED) tests are finally a reality and could be a potential game changer because they can screen for the possibility of up to 50 different cancers in asymptomatic individuals with one blood draw. They represent one of the fastest growing segments in medical diagnostics with a projected value of $2.77 billion by 2030, according to the market research firm Grand View Research.
These tests are different from traditional liquid biopsies, which are designed to identify actionable gene mutations to help inform treatment decisions of patients already diagnosed with cancer. Instead, MCED tests work to detect fragments of circulating free DNA that have been shed by tumors and released into the bloodstream. Detecting these cancer signals could indicate that an individual has cancer well before they ever develop symptoms.
For some cancer types, particularly those commonly diagnosed at advanced stages or those without general population screening tests, MCED testing could have a significant impact.
In its new report, Grand View Research highlights nine “prominent players” active in the MCED market; of these, two have been granted breakthrough device designation by the Food and Drug Administration: OverC MCDBT by Burning Rock on Jan. 3, 2023, and Galleri by Grail in 2019. Galleri was launched in June 2021 and can be obtained with a prescription at a cost of $949.
Yet, while patients are asking for these tests and primary care physicians are prescribing them, oncologists are grappling with how to manage the first patients whose tests tell them they may have cancer.
Ordering the tests may seem straightforward, but in reality, it is not. In fact, they are so new that most health systems have no internal guidelines for physicians. Guidelines would address when the tests should be prescribed, and whether a patient should undergo more testing or be referred to an oncologist.
Clinical trials underway
There are currently at least 17 clinical trials underway to investigate the performance and clinical utility of MCED tests. Six of these involve Grail, including NHS-Galleri, the largest study to date of 140,000 participants in the United Kingdom where participants will be followed for 3 years with annual visits at 12 and 24 months. And, the National Cancer Institute is spearheading a clinical trial of its own, according to a search of ClinicalTrials.gov.
In September 2022, Grail presented findings from its pivotal PATHFINDER study at the annual meeting of the European Society of Medical Oncology. Researchers reported that cancer signals were detected in 1.4% (92) of 6,621 participants enrolled in the study. Of the 92, 35 people were diagnosed with 36 cancers: 19 were solid tumors (2 oropharyngeal, 5 breast, l liver, 1 intrahepatic bile duct, 2 colon/rectum, 2 prostate, 1 lung, 1 pancreas, 1 small intestine, 1 uterus, 1 ovary and 1 bone) and 17 hematologic cancers (1 plasma cell myeloma/disorders, 2 lymphoid leukemia, 2 Waldenström’s macroglobulinemia, and 12 lymphoma).
Almost half of newly diagnosed cases were cancers in stage 1 or 2. Of stage 1 cancers, three were solid tumors and four were hematologic cancers. Of stage 2 cancers, three were solid tumors and four were hematologic cancers. All other cancers were in stage 3 and 4 or were listed as recurrent or no stage. Deb Schrag, MD, MPH, chair of the department of medicine at Memorial Sloan Kettering Cancer Center in New York, who presented the results from PATHFINDER at ESMO, reported that, of all diagnosed cancers, only breast, colon/rectum, prostate, and lung have established screening protocols.
The findings were so striking that the meeting scientific co-chair, Fabrice André, MD, PhD, told ESMO the oncology field must prepare for an onslaught of new patients.
“Within the next 5 years, we will need more doctors, surgeons and nurses with more diagnostic and treatment infrastructures to care for the rising number of people who will be identified by multicancer early detection tests,” said Dr. André, who is director of research at Gustave Roussy Cancer Center, Villejuif, France, and future president of ESMO (2025-2026). “We need to involve all stakeholders in deciding new pathways of care. We need to agree who will be tested and when and where tests will be carried out, and to anticipate the changes that will happen as a result of these tests.”
But first, he urged, the need for comparative trials “across all types of cancer to find out if having an early detection test affects morbidity and mortality. We also need to know how the tests benefit patients, and how to discuss the results with them,” Dr. André said.
Demand may burden health systems
Dr. Flora suggested that companies like Grail are rushing their product to market without conducting long-term sizable clinical trials.
“These diagnostic companies are a billion dollar publicly traded or venture capital-funded companies that are losing millions of dollars a quarter as they’re scaling up these tests. So, there is some pressure on the sales forces ... to start moving product long before the science has met our lowest areas for entry,” Dr. Flora said. “They are aggressively marketing to a primary care audience that knows nothing about MCEDs. It’s a sales-driven development solving a problem we all believe is real, but we don’t know if it actually solves the problem.”
There are many unanswered questions, he said. Among these include whether the tests do indeed extend survival. “What they’re suggesting – that is if the blood test detects it – that we’re going to save your life. That’s not yet been proven. This is where the providers are pushing back against these industry types to say: ‘This is the wild west right now.’ It’s very irresponsible to go out there and try to sell hundreds of millions of dollars of product to doctors who have never studied genetics,” Dr. Flora said.
Grail’s chief medical officer Jeff Venstrom, MD, however, said physicians don’t need a background in genetic testing to order or interpret Galleri because it’s not a genetic test. Genetic tests look for genetic variants associated with cancer risk, which Galleri does not. MCED tests rely on genomic profiling to identify alterations in tumors.
“Maybe there’s still confusion in the market, which is common for new technologies when they’re initially launched. This is not a 23andMe test. We do not report germline mutations that have implications for cancer risk. We’re using this blood sample to test for the presence or absence of a cancer signal. The test result is very clear and simple: One area of the report says ‘yes’ or ‘no.’ It is a binary result that says if a signal is detected or not. The second provides additional information around where that signal could be coming from,” he said.
Galleri could fill a huge unmet need in cancer prevention, Dr. Venstrom said. Not only could it detect cancer at an earlier stage, but it could serve as a screening tool for cancers like pancreatic cancer in which screening is not available.
The test is not intended to replace standard of care screening, he said. The ordering provider should have a conversation with the patient about overall cancer risk. “Are you smoking? What’s your risk of obesity-associated cancers? Do you have a family history of cancer? I think this should all be in the context of a good conversation around preventative care,” he said.
Planning and prep in Boston
In Boston, Aparna Parikh, MD, an oncologist who specializes in gastrointestinal cancers, agreed that MCED testing has forced her team at the Mass General Cancer Center global cancer care program to think outside of the box.
“We’re a major academic center and it’s not easy [because] this is all uncharted territory,” she said. “We all recognize there are more tests coming, and they are here to stay. As a health system, we have to be ready to manage not only the tests, but patient anxieties, and all the complexities that come with it. We just don’t know yet how to best navigate.”
Although Dr. Parikh’s center has set up a working group tasked with organizing an outpatient clinic for patients with positive MCED tests, the current system is haphazard.
“Right now, it gets bounced around between people,” she explained. “Sometimes, patients are getting referred to the oncology team rather than the primary care team to try to sort out where the cancer signal is coming from, that is, if it’s not immediately obvious. No one really knows who should be the right person to own it,” Dr. Parikh said. While the test is supposed to give tissue-specific results, “it’s not perfect” and sometimes imaging and other work-ups are needed to locate the source of the signa.
“A group of four or five oncologists get looped in and then we’re trying to sort it out on a case-by-case basis, but understanding that with more and more tests coming, that kind of ad hoc approach isn’t going to be sufficient. We need a happy medium between the primary care and the disease specific oncologist, someone who can kind of help think through the diagnostic workup until they have a cancer diagnosis to get them to the right place,” Dr. Parikh said.
Dr. Venstrom said Grail is committed to providing support to clinicians in these situations. “We’re doing everything we can with our medical education forums. We have this pretty intense and extensive postpositive suite of resources,” he explained. “Some of our doctors on staff call the ordering provider within 24 hours just to clarify if there are any questions or confusion from the report. For example, if it suggests the signal is coming from the lung, we provide additional support around additional workups.”
Out-of-pocket test may widen disparities in care
With the exception of a few health insurance companies that have committed to covering some of the cost for the test, Galleri is an out-of-pocket expense.
Dr. Venstrom acknowledged that broad insurance coverage for the Galleri test remains a hurdle, although “we’ve secured coverage for a handful of companies of self-insured employers and forward-thinking insurers.” This includes partnerships with Point32Health, and Alignment Health, among others, he said.
There is also growing support among more than 400 cancer organizations for the Multi-Cancer Early Detection Screening Coverage Act to accelerate coverage for Medicare beneficiaries. “We are constantly trying to understand the evidence that’s needed for payors to make sure that we get the broadest access possible for this test,” he said.
The first positive test result
Back at St. Elizabeth Healthcare where they’ve only seen one positive MCED test result thus far, Dr. Flora is more concerned about patients giving informed consent before they even get the test. “When the reps started hammering our primary care doctors, we sent communiques throughout the system saying that we would very much like to regulate this to make sure that before our patients receive accidental harm, that they at least have a conversation with somebody who understands the test,” he explained.
All 15 patients who requested the test at the hospital were first required to discuss the implications with a genetic counselor who is part of the system. “We are really pro–cancer screening,” he said, but added his hospital is “not pumped” about the Galleri test. “We’re being very cautious about overstatements made by sales guys to our primary care doctors, so we’re letting our own precision medicine people handle it.”
There’s a similar system in place at Community Health Network, a nonprofit health system with nine hospitals and 1,300 employee providers throughout Central Indiana. Patrick McGill, MD, a primary care physician and chief analytics officer for the network says they have streamlined patients with positive tests through their high-risk oncology clinic. “They don’t go straight to a medical oncologist which I know some systems are struggling with,” he said. “They get additional testing, whether it’s imaging they might need or other lab testing. We’ve had a few lung positives, and a few leukemia positives which might go straight to medical oncology. I think we had one breast that was positive so she got additional breast imaging.”
Through its foundation, CHN will offer 2,000 tests free of charge. “We decided to take cost off the table with this funding,” Dr. McGill said. “A lot of health systems I talk to are always concerned that insurance doesn’t cover it and it’s cost prohibitive. Is it creating additional disparities because only people who can afford it can get the test?”
Dr. Schrag serves as an uncompensated advisor for Grail. Previously, while with the Dana-Farber Cancer Institute, she received research funding from Grail.
Doug Flora, MD, knows the value of early cancer detection because it helped him survive kidney cancer 5 years ago. But as a medical oncologist and hematologist, and the executive medical director of oncology services at St. Elizabeth Healthcare in Edgewood, Ky., he also knows that a new era of early cancer detection testing poses big challenges for his network of six hospitals and 169 specialty and primary care offices throughout Kentucky, Ohio, and Indiana.
Multicancer early detection (MCED) tests are finally a reality and could be a potential game changer because they can screen for the possibility of up to 50 different cancers in asymptomatic individuals with one blood draw. They represent one of the fastest growing segments in medical diagnostics with a projected value of $2.77 billion by 2030, according to the market research firm Grand View Research.
These tests are different from traditional liquid biopsies, which are designed to identify actionable gene mutations to help inform treatment decisions of patients already diagnosed with cancer. Instead, MCED tests work to detect fragments of circulating free DNA that have been shed by tumors and released into the bloodstream. Detecting these cancer signals could indicate that an individual has cancer well before they ever develop symptoms.
For some cancer types, particularly those commonly diagnosed at advanced stages or those without general population screening tests, MCED testing could have a significant impact.
In its new report, Grand View Research highlights nine “prominent players” active in the MCED market; of these, two have been granted breakthrough device designation by the Food and Drug Administration: OverC MCDBT by Burning Rock on Jan. 3, 2023, and Galleri by Grail in 2019. Galleri was launched in June 2021 and can be obtained with a prescription at a cost of $949.
Yet, while patients are asking for these tests and primary care physicians are prescribing them, oncologists are grappling with how to manage the first patients whose tests tell them they may have cancer.
Ordering the tests may seem straightforward, but in reality, it is not. In fact, they are so new that most health systems have no internal guidelines for physicians. Guidelines would address when the tests should be prescribed, and whether a patient should undergo more testing or be referred to an oncologist.
Clinical trials underway
There are currently at least 17 clinical trials underway to investigate the performance and clinical utility of MCED tests. Six of these involve Grail, including NHS-Galleri, the largest study to date of 140,000 participants in the United Kingdom where participants will be followed for 3 years with annual visits at 12 and 24 months. And, the National Cancer Institute is spearheading a clinical trial of its own, according to a search of ClinicalTrials.gov.
In September 2022, Grail presented findings from its pivotal PATHFINDER study at the annual meeting of the European Society of Medical Oncology. Researchers reported that cancer signals were detected in 1.4% (92) of 6,621 participants enrolled in the study. Of the 92, 35 people were diagnosed with 36 cancers: 19 were solid tumors (2 oropharyngeal, 5 breast, l liver, 1 intrahepatic bile duct, 2 colon/rectum, 2 prostate, 1 lung, 1 pancreas, 1 small intestine, 1 uterus, 1 ovary and 1 bone) and 17 hematologic cancers (1 plasma cell myeloma/disorders, 2 lymphoid leukemia, 2 Waldenström’s macroglobulinemia, and 12 lymphoma).
Almost half of newly diagnosed cases were cancers in stage 1 or 2. Of stage 1 cancers, three were solid tumors and four were hematologic cancers. Of stage 2 cancers, three were solid tumors and four were hematologic cancers. All other cancers were in stage 3 and 4 or were listed as recurrent or no stage. Deb Schrag, MD, MPH, chair of the department of medicine at Memorial Sloan Kettering Cancer Center in New York, who presented the results from PATHFINDER at ESMO, reported that, of all diagnosed cancers, only breast, colon/rectum, prostate, and lung have established screening protocols.
The findings were so striking that the meeting scientific co-chair, Fabrice André, MD, PhD, told ESMO the oncology field must prepare for an onslaught of new patients.
“Within the next 5 years, we will need more doctors, surgeons and nurses with more diagnostic and treatment infrastructures to care for the rising number of people who will be identified by multicancer early detection tests,” said Dr. André, who is director of research at Gustave Roussy Cancer Center, Villejuif, France, and future president of ESMO (2025-2026). “We need to involve all stakeholders in deciding new pathways of care. We need to agree who will be tested and when and where tests will be carried out, and to anticipate the changes that will happen as a result of these tests.”
But first, he urged, the need for comparative trials “across all types of cancer to find out if having an early detection test affects morbidity and mortality. We also need to know how the tests benefit patients, and how to discuss the results with them,” Dr. André said.
Demand may burden health systems
Dr. Flora suggested that companies like Grail are rushing their product to market without conducting long-term sizable clinical trials.
“These diagnostic companies are a billion dollar publicly traded or venture capital-funded companies that are losing millions of dollars a quarter as they’re scaling up these tests. So, there is some pressure on the sales forces ... to start moving product long before the science has met our lowest areas for entry,” Dr. Flora said. “They are aggressively marketing to a primary care audience that knows nothing about MCEDs. It’s a sales-driven development solving a problem we all believe is real, but we don’t know if it actually solves the problem.”
There are many unanswered questions, he said. Among these include whether the tests do indeed extend survival. “What they’re suggesting – that is if the blood test detects it – that we’re going to save your life. That’s not yet been proven. This is where the providers are pushing back against these industry types to say: ‘This is the wild west right now.’ It’s very irresponsible to go out there and try to sell hundreds of millions of dollars of product to doctors who have never studied genetics,” Dr. Flora said.
Grail’s chief medical officer Jeff Venstrom, MD, however, said physicians don’t need a background in genetic testing to order or interpret Galleri because it’s not a genetic test. Genetic tests look for genetic variants associated with cancer risk, which Galleri does not. MCED tests rely on genomic profiling to identify alterations in tumors.
“Maybe there’s still confusion in the market, which is common for new technologies when they’re initially launched. This is not a 23andMe test. We do not report germline mutations that have implications for cancer risk. We’re using this blood sample to test for the presence or absence of a cancer signal. The test result is very clear and simple: One area of the report says ‘yes’ or ‘no.’ It is a binary result that says if a signal is detected or not. The second provides additional information around where that signal could be coming from,” he said.
Galleri could fill a huge unmet need in cancer prevention, Dr. Venstrom said. Not only could it detect cancer at an earlier stage, but it could serve as a screening tool for cancers like pancreatic cancer in which screening is not available.
The test is not intended to replace standard of care screening, he said. The ordering provider should have a conversation with the patient about overall cancer risk. “Are you smoking? What’s your risk of obesity-associated cancers? Do you have a family history of cancer? I think this should all be in the context of a good conversation around preventative care,” he said.
Planning and prep in Boston
In Boston, Aparna Parikh, MD, an oncologist who specializes in gastrointestinal cancers, agreed that MCED testing has forced her team at the Mass General Cancer Center global cancer care program to think outside of the box.
“We’re a major academic center and it’s not easy [because] this is all uncharted territory,” she said. “We all recognize there are more tests coming, and they are here to stay. As a health system, we have to be ready to manage not only the tests, but patient anxieties, and all the complexities that come with it. We just don’t know yet how to best navigate.”
Although Dr. Parikh’s center has set up a working group tasked with organizing an outpatient clinic for patients with positive MCED tests, the current system is haphazard.
“Right now, it gets bounced around between people,” she explained. “Sometimes, patients are getting referred to the oncology team rather than the primary care team to try to sort out where the cancer signal is coming from, that is, if it’s not immediately obvious. No one really knows who should be the right person to own it,” Dr. Parikh said. While the test is supposed to give tissue-specific results, “it’s not perfect” and sometimes imaging and other work-ups are needed to locate the source of the signa.
“A group of four or five oncologists get looped in and then we’re trying to sort it out on a case-by-case basis, but understanding that with more and more tests coming, that kind of ad hoc approach isn’t going to be sufficient. We need a happy medium between the primary care and the disease specific oncologist, someone who can kind of help think through the diagnostic workup until they have a cancer diagnosis to get them to the right place,” Dr. Parikh said.
Dr. Venstrom said Grail is committed to providing support to clinicians in these situations. “We’re doing everything we can with our medical education forums. We have this pretty intense and extensive postpositive suite of resources,” he explained. “Some of our doctors on staff call the ordering provider within 24 hours just to clarify if there are any questions or confusion from the report. For example, if it suggests the signal is coming from the lung, we provide additional support around additional workups.”
Out-of-pocket test may widen disparities in care
With the exception of a few health insurance companies that have committed to covering some of the cost for the test, Galleri is an out-of-pocket expense.
Dr. Venstrom acknowledged that broad insurance coverage for the Galleri test remains a hurdle, although “we’ve secured coverage for a handful of companies of self-insured employers and forward-thinking insurers.” This includes partnerships with Point32Health, and Alignment Health, among others, he said.
There is also growing support among more than 400 cancer organizations for the Multi-Cancer Early Detection Screening Coverage Act to accelerate coverage for Medicare beneficiaries. “We are constantly trying to understand the evidence that’s needed for payors to make sure that we get the broadest access possible for this test,” he said.
The first positive test result
Back at St. Elizabeth Healthcare where they’ve only seen one positive MCED test result thus far, Dr. Flora is more concerned about patients giving informed consent before they even get the test. “When the reps started hammering our primary care doctors, we sent communiques throughout the system saying that we would very much like to regulate this to make sure that before our patients receive accidental harm, that they at least have a conversation with somebody who understands the test,” he explained.
All 15 patients who requested the test at the hospital were first required to discuss the implications with a genetic counselor who is part of the system. “We are really pro–cancer screening,” he said, but added his hospital is “not pumped” about the Galleri test. “We’re being very cautious about overstatements made by sales guys to our primary care doctors, so we’re letting our own precision medicine people handle it.”
There’s a similar system in place at Community Health Network, a nonprofit health system with nine hospitals and 1,300 employee providers throughout Central Indiana. Patrick McGill, MD, a primary care physician and chief analytics officer for the network says they have streamlined patients with positive tests through their high-risk oncology clinic. “They don’t go straight to a medical oncologist which I know some systems are struggling with,” he said. “They get additional testing, whether it’s imaging they might need or other lab testing. We’ve had a few lung positives, and a few leukemia positives which might go straight to medical oncology. I think we had one breast that was positive so she got additional breast imaging.”
Through its foundation, CHN will offer 2,000 tests free of charge. “We decided to take cost off the table with this funding,” Dr. McGill said. “A lot of health systems I talk to are always concerned that insurance doesn’t cover it and it’s cost prohibitive. Is it creating additional disparities because only people who can afford it can get the test?”
Dr. Schrag serves as an uncompensated advisor for Grail. Previously, while with the Dana-Farber Cancer Institute, she received research funding from Grail.