Melanoma

Myth: Actinic keratoses are only seen in patients with lighter skin

Actinic keratoses (AKs) are precancerous lesions that may turn into squamous cell carcinoma if left untreated. UV rays cause AKs, either from outdoor sun exposure or tanning beds. According to the American Academy of Dermatology, AKs are more likely to develop in patients 40 years or older with fair skin; hair color that is naturally blonde or red; eye color that is naturally blue, green, or hazel; skin that freckles or burns when in the sun; a weakened immune system; and occupations involving substances that contain polycyclic aromatic hydrocarbons such as coal or tar.

A 2007 study compared the most common diagnoses among patients of different racial and ethnic groups in New York City. Alexis et al found that AK was in the top 10 diagnoses in white patients but not for black patients. They postulated that photoprotective factors in darkly pigmented skin such as larger and more numerous melanosomes that contain more melanin and are more dispersed throughout the epidermis result in a lower incidence of skin cancers in the skin of color (SOC) population.

RELATED ARTICLE: Common Dermatologic Disorders in Skin of Color: A Comparative Practice Survey

However, a recent skin cancer awareness study in Cutis reported that even though SOC populations have lower incidences of skin cancer such as melanoma, basal cell carcinoma, and squamous cell carcinoma, they exhibit higher death rates. Furthermore, black individuals are more likely to present with advanced-stage melanoma and acral lentiginous melanomas compared to white individuals. Kailas et al stated, “Overall, SOC patients have the poorest skin cancer prognosis, and the data suggest that the reason for this paradox is delayed diagnosis.” They evaluated several knowledge-based interventions for increasing skin cancer awareness, knowledge, and protective behaviors in SOC populations, including the use of visuals such as photographs to allow SOC patients to visualize different skin tones, educational interventions in another language, and pamphlets.

RELATED ARTICLE: Assessing the Effectiveness of Knowledge-Based Interventions in Increasing Skin Cancer Awareness, Knowledge, and Protective Behaviors in Skin of Color Populations

Dermatologists should be aware that education of SOC patients is important to eradicate the common misconception that these patients do not have to worry about AKs and other skin cancers. Remind these patients that they need to protect their skin from the sun, just as patients with fair skin do. Further research in the dermatology community should focus on educational interventions that will help increase knowledge regarding skin cancer in SOC populations.

Expert Commentary

Although more common in patients with lighter skin, actinic keratosis and skin cancer can be seen in patients of all skin types. Many patients are unaware of this risk and do not use sunscreen and other sun-protective measures. We, as a specialty, have to educate our patients and the public of the risk for actinic keratosis and skin cancer in all skin types.

—Gary Goldenberg, MD (New York, New York)

Myth: Actinic keratoses are only seen in patients with lighter skin

Actinic keratoses (AKs) are precancerous lesions that may turn into squamous cell carcinoma if left untreated. UV rays cause AKs, either from outdoor sun exposure or tanning beds. According to the American Academy of Dermatology, AKs are more likely to develop in patients 40 years or older with fair skin; hair color that is naturally blonde or red; eye color that is naturally blue, green, or hazel; skin that freckles or burns when in the sun; a weakened immune system; and occupations involving substances that contain polycyclic aromatic hydrocarbons such as coal or tar.

A 2007 study compared the most common diagnoses among patients of different racial and ethnic groups in New York City. Alexis et al found that AK was in the top 10 diagnoses in white patients but not for black patients. They postulated that photoprotective factors in darkly pigmented skin such as larger and more numerous melanosomes that contain more melanin and are more dispersed throughout the epidermis result in a lower incidence of skin cancers in the skin of color (SOC) population.

RELATED ARTICLE: Common Dermatologic Disorders in Skin of Color: A Comparative Practice Survey

However, a recent skin cancer awareness study in Cutis reported that even though SOC populations have lower incidences of skin cancer such as melanoma, basal cell carcinoma, and squamous cell carcinoma, they exhibit higher death rates. Furthermore, black individuals are more likely to present with advanced-stage melanoma and acral lentiginous melanomas compared to white individuals. Kailas et al stated, “Overall, SOC patients have the poorest skin cancer prognosis, and the data suggest that the reason for this paradox is delayed diagnosis.” They evaluated several knowledge-based interventions for increasing skin cancer awareness, knowledge, and protective behaviors in SOC populations, including the use of visuals such as photographs to allow SOC patients to visualize different skin tones, educational interventions in another language, and pamphlets.

RELATED ARTICLE: Assessing the Effectiveness of Knowledge-Based Interventions in Increasing Skin Cancer Awareness, Knowledge, and Protective Behaviors in Skin of Color Populations

Dermatologists should be aware that education of SOC patients is important to eradicate the common misconception that these patients do not have to worry about AKs and other skin cancers. Remind these patients that they need to protect their skin from the sun, just as patients with fair skin do. Further research in the dermatology community should focus on educational interventions that will help increase knowledge regarding skin cancer in SOC populations.

Expert Commentary

Although more common in patients with lighter skin, actinic keratosis and skin cancer can be seen in patients of all skin types. Many patients are unaware of this risk and do not use sunscreen and other sun-protective measures. We, as a specialty, have to educate our patients and the public of the risk for actinic keratosis and skin cancer in all skin types.

—Gary Goldenberg, MD (New York, New York)

Myth: Actinic keratoses are only seen in patients with lighter skin

Actinic keratoses (AKs) are precancerous lesions that may turn into squamous cell carcinoma if left untreated. UV rays cause AKs, either from outdoor sun exposure or tanning beds. According to the American Academy of Dermatology, AKs are more likely to develop in patients 40 years or older with fair skin; hair color that is naturally blonde or red; eye color that is naturally blue, green, or hazel; skin that freckles or burns when in the sun; a weakened immune system; and occupations involving substances that contain polycyclic aromatic hydrocarbons such as coal or tar.

A 2007 study compared the most common diagnoses among patients of different racial and ethnic groups in New York City. Alexis et al found that AK was in the top 10 diagnoses in white patients but not for black patients. They postulated that photoprotective factors in darkly pigmented skin such as larger and more numerous melanosomes that contain more melanin and are more dispersed throughout the epidermis result in a lower incidence of skin cancers in the skin of color (SOC) population.

RELATED ARTICLE: Common Dermatologic Disorders in Skin of Color: A Comparative Practice Survey

However, a recent skin cancer awareness study in Cutis reported that even though SOC populations have lower incidences of skin cancer such as melanoma, basal cell carcinoma, and squamous cell carcinoma, they exhibit higher death rates. Furthermore, black individuals are more likely to present with advanced-stage melanoma and acral lentiginous melanomas compared to white individuals. Kailas et al stated, “Overall, SOC patients have the poorest skin cancer prognosis, and the data suggest that the reason for this paradox is delayed diagnosis.” They evaluated several knowledge-based interventions for increasing skin cancer awareness, knowledge, and protective behaviors in SOC populations, including the use of visuals such as photographs to allow SOC patients to visualize different skin tones, educational interventions in another language, and pamphlets.

RELATED ARTICLE: Assessing the Effectiveness of Knowledge-Based Interventions in Increasing Skin Cancer Awareness, Knowledge, and Protective Behaviors in Skin of Color Populations

Dermatologists should be aware that education of SOC patients is important to eradicate the common misconception that these patients do not have to worry about AKs and other skin cancers. Remind these patients that they need to protect their skin from the sun, just as patients with fair skin do. Further research in the dermatology community should focus on educational interventions that will help increase knowledge regarding skin cancer in SOC populations.

Expert Commentary

Although more common in patients with lighter skin, actinic keratosis and skin cancer can be seen in patients of all skin types. Many patients are unaware of this risk and do not use sunscreen and other sun-protective measures. We, as a specialty, have to educate our patients and the public of the risk for actinic keratosis and skin cancer in all skin types.

—Gary Goldenberg, MD (New York, New York)

Malignant melanoma, basal cell carcinoma, and squamous cell carcinoma account for approximately 40% of all neoplasms among the white population in the United States. Skin cancer is the most common malignancy in the United States.¹ However, despite this occurrence, there are limited data regarding skin cancer in individuals with skin of color (SOC). The 5-year survival rates for melanoma are 58.2% for black individuals, 69.7% for Hispanics, and 70.9% for Asians compared to 79.8% for white individuals in the United States.² Even though SOC populations have lower incidences of skin cancer—melanoma, basal cell carcinoma, and squamous cell carcinoma—they exhibit higher death rates.^3-7 Nonetheless, no specific guidelines exist to address sun exposure and safety habits in SOC populations.^6,8 Furthermore, current demographics suggest that by the year 2050, approximately half of the US population will be nonwhite.⁴ Paradoxically, despite having increased sun protection from greater amounts of melanin in their skin, black individuals are more likely to present with advanced-stage melanoma (eg, stage III/IV) compared to white individuals.^8-12 Furthermore, those of nonwhite populations are more likely to present with more advanced stages of acral lentiginous melanomas than white individuals.^13,14 Hispanics also face an increasing incidence of more invasive acral lentiginous melanomas.¹⁵ Overall, SOC patients have the poorest skin cancer prognosis, and the data suggest that the reason for this paradox is delayed diagnosis.¹

Although skin cancer is largely a preventable condition, the literature suggests that lack of awareness of melanoma among ethnic minorities is one of the main reasons for their poor skin cancer prognosis.¹⁶ This lack of awareness decreases the likelihood that an SOC patient would be alert to early detection of cancerous changes.¹⁷ Because educating at-risk SOC populations is key to decreasing skin cancer risk, this study focused on determining the efficacy of major knowledge-based interventions conducted to date.¹ Overall, we sought to answer the question, do knowledge-based interventions increase skin cancer awareness, knowledge, and protective behavior among people of color?

Methods

For this review, the Cochrane method of analysis was used to conduct a thorough search of PubMed articles indexed for MEDLINE (1994-2016), as well as a search of CINAHL (1997-2016), PsycINFO (1999-2016), and Web of Science (1965-2016), using a combination of more than 100 search terms including but not limited to skin cancer, skin of color, intervention, and ethnic skin. The search yielded a total of 52 articles (Figure). Following review, only 8 articles met inclusion criteria, which were as follows: (1) study was related to skin cancer in SOC patients, which included an intervention to increase skin cancer awareness and knowledge; (2) study included adult participants or adolescents aged 12 to 18 years; (3) study was written in English; and (4) study was published in a peer-reviewed journal. Of the remaining 8 articles, 4 were excluded due to the following criteria: (1) study failed to provide both preintervention and postintervention data, (2) study failed to provide quantitative data, and (3) study included participants who worked as health care professionals or ancillary staff. As a result, a total of 4 articles were analyzed and discussed in this review (Table).

Results

Robinson et al¹⁸ conducted 12 focus groups with 120 total participants (40 black, 40 Asian, and 40 Hispanic patients). Participants engaged in a 2-hour tape-recorded focus group with a moderator guide on melanoma and skin cancer. Furthermore, they also were asked to assess skin cancer risk in 5 celebrities with different skin tones. The statistically significant preintervention results of the study (χ²=4.6, P<.001) were as follows: only 2%, 4%, and 14% correctly reported that celebrities with a very fair skin type, a fair skin type, and very dark skin type, respectively, could get sunburn, compared to 75%, 76%, and 62% post-intervention. Additionally, prior to intervention, 14% of the study population believed that dark brown skin type could get sunburn compared to 62% of the same group postintervention. This study demonstrated that the intervention helped SOC patients better identify their ability to get sunburn and identify their skin cancer risk.¹⁸

Hernandez et al¹⁹ used a video-based intervention in a Hispanic community, which was in contrast to the multiracial focus group intervention conducted by Robinson et al.¹⁸ Eighty Hispanic individuals were recruited from beauty salons to participate in the study. Participants watched two 3-minute videos in Spanish and completed a preintervention and postintervention survey. The first video emphasized the photoaging benefits of sun protection, while the second focused on skin cancer prevention. Preintervention surveys indicated that only 54 (68%) participants believed that fair-skinned Hispanics were at risk for skin cancer, which improved to 72 (90%) participants postintervention. Furthermore, initially only 44 (55%) participants thought those with darker skin types could develop skin cancer, but this number increased to 69 (86%) postintervention. For both questions regarding fair and dark skin, the agreement proportion was significantly different between the preeducation and posteducation videos (P<.0002 for the fair skin question and P<.0001 for the dark skin question). This study greatly increased awareness of skin cancer risk among Hispanics,¹⁹ similar to the Robinson et al¹⁸ study.

In contrast to 2-hour focus groups or 3-minute video–based interventions, a study by Kundu et al¹⁷ employed a 20-minute educational class-based intervention with both verbal and visual instruction. This study assessed the efficacy of an educational tutorial on improving awareness and early detection of melanoma in SOC individuals. Photographs were used to help participants recognize the ABCDEs of melanoma and to show examples of acral lentiginous melanomas in white individuals. A total of 71 participants completed a preintervention questionnaire, participated in a 20-minute class, and completed a postintervention questionnaire immediately after and 3 months following the class. The study population included 44 black, 15 Asian, 10 Hispanic, and 2 multiethnic participants. Knowledge that melanoma is a skin cancer increased from 83.9% to 100% immediately postintervention (P=.0001) and 97.2% at 3 months postintervention (P=.0075). Additionally, knowledge that people of color are at risk for melanoma increased from 48.4% preintervention to 82.8% immediately postintervention (P<.0001). However, only 40.8% of participants retained this knowledge at 3 months postintervention. Because only 1 participant reported a family history of skin cancer, the authors hypothesized that the reason for this loss of knowledge was that most participants were not personally affected by friends or family members with melanoma. A future study with an appropriate control group would be needed to support this claim. This study shed light on the potential of class-based interventions to increase both awareness and knowledge of skin cancer in SOC populations.¹⁷

A study by Chapman et al²⁰ examined the effects of a sun protection educational program on increasing awareness of skin cancer in Hispanic and black middle school students in southern Los Angeles, California. It was the only study we reviewed that focused primarily on adolescents. Furthermore, it included the largest sample size (N=148) analyzed here. Students were given a preintervention questionnaire to evaluate their awareness of skin cancer and current sun-protection practices. Based on these results, the investigators devised a set of learning goals and incorporated them into an educational pamphlet. The intervention, called “Skin Teaching Day,” was a 1-day program discussing skin cancer and the importance of sun protection. Prior to the intervention, 68% of participants reported that they used sunscreen. Three months after completing the program, 80% of participants reported sunscreen use, an increase of 12% prior to the intervention. The results of this study demonstrated the unique effectiveness and potential of pamphlets in increasing sunscreen use.²⁰

Comment

Overall, various methods of interventions such as focus groups, videos, pamphlets, and lectures improved knowledge of skin cancer risk and sun-protection behaviors in SOC populations. Furthermore, the unique differences of each study provided important insights into the successful design of an intervention.

An important characteristic of the Robinson et al¹⁸ study was the addition of photographs, which allowed participants not only to visualize different skin tones but also provided them with the opportunity to relate themselves to the photographs; by doing so, participants could effectively pick out the skin tone that best suited them. Written SOC scales are limited to mere descriptions and thus make it more difficult for participants to accurately identify the tone that best fits them. Kundu et al¹⁷ used photographs to teach skin self-examination and ABCDEs for detection of melanoma. Additionally, both studies used photographs to demonstrate examples of skin cancer.^17,18 Recent evidence suggests the use of visuals can be efficacious for improving skin cancer knowledge and awareness; a study in 16 SOC kidney transplant recipients found that the addition of photographs of squamous cell carcinoma in various skin tones to a sun-protection educational pamphlet was more effective than the original pamphlet without photographs.²¹

In contrast to the Robinson et al¹⁸ study and Hernandez et al¹⁹ study, the Kundu et al¹⁷ study showed photographs of acral lentiginous melanomas in white patients rather than SOC patients. However, SOC populations may be less likely to relate to or identify skin changes in skin types that are different from their own. This technique was still beneficial, as acral lentiginous melanoma is the most common type of melanoma in SOC populations. Another benefit of the study was that it was the only study reviewed that included a follow-up postintervention questionnaire. Such data is useful, as it demonstrates how muchinformation is retained by participants and may be more likely to predict compliance with skin cancer protective behaviors.¹⁷

The Hernandez et al¹⁹ study is unique in that it was the only one to include an educational intervention entirely in Spanish, which is important to consider, as language may be a hindrance to participants’ understanding in the other studies, particularly Hispanics, possibly leading to a lack of information retention regarding sun-protective behaviors. Furthermore, it also was the only study to utilize videos as a method for interventions. The 3-minute videos demonstrated that interventions could be efficient as compared to the 2-hour in-class intervention used by Robinson et al¹⁸ and the 20-minute intervention used by Kundu et al.¹⁷ Additionally, videos also could be more cost-effective, as incentives for large focus groups would no longer be needed. Furthermore, in the Hernandez et al¹⁹ study, there was minimal to no disruption in the participants’ daily routine, as the participants were getting cosmetic services while watching the videos, perhaps allowing them to be more attentive. In contrast, both the Robinson et al¹⁸ and Kundu et al¹⁷ studies required time out from the participants’ daily schedules. In addition, these studies were notably longer than the Hernandez et al¹⁹ study. The 8-hour intervention in the Chapman et al²⁰ study also may not be feasible for the general population because of its excessive length. However, the intervention was successful among the adolescent participants, which suggested that shorter durations are effective in the adult population and longer interventions may be more appropriate for adolescents because they benefit from peer activity.

Despite the success of the educational interventions as outlined in the 4 studies described here, a major epidemiologic flaw is that these interventions included only a small percentage of the target population. The largest total number of adults surveyed and undergoing an intervention in any of the populations was only 120.¹⁷ By failing to reach a substantial proportion of the population at risk, the number of preventable deaths likely will not decrease. The authors believe a larger-scale intervention would provide meaningful change. Australia’s SunSmart campaign to increase skin cancer awareness in the Australian population is an example of one such large-scale national intervention. The campaign focused on massive television advertisements in the summer to educate participants about the dangers of skin cancer and the importance of protective behaviors. Telephone surveys conducted from 1987 to 2011 demonstrated that more exposure to the advertisements in the SunSmart campaign meant that individuals were more likely to use sunscreen and avoid sun exposure.²² In the United States, a similar intervention would be of great benefit in educating SOC populations regarding skin cancer risk. Additionally, dermatology residents need to be adequately trained to educate patients of color about the risk for skin cancer, as survey data indicated more than 80% of Australian dermatologists desired more SOC teaching during their training and 50% indicated that they would have time to learn it during their training if offered.²³ Furthermore, one study suggested that future interventions must include primary-, secondary-, and tertiary-prevention methods to effectively reduce skin cancer risk among patients of color.²⁴ Primary prevention involves sun avoidance, secondary prevention involves detecting cancerous lesions, and tertiary prevention involves undergoing treatment of skin malignancies. However, increased knowledge does not necessarily mean increased preventative action will be employed (eg, sunscreen use, wearing sun-protective clothing and sunglasses, avoiding tanning beds and excessive sun exposure). Additional studies that demonstrate a notable increase in sun-protective behaviors related to increased knowledge are needed.

Because retention of skin cancer knowledge decreased in several postintervention surveys, there also is a dire need for continuing skin cancer education in patients of color, which may be accomplished through a combination effort of television advertisement campaigns, pamphlets, social media, community health departments, or even community members. For example, a pilot program found that Hispanic lay health workers who are educated about skin cancer may serve as a bridge between medical providers and the Hispanic community by encouraging individuals in this population to get regular skin examinations from a physician.²⁵ Overall, there are currently gaps in the understanding and treatment of skin cancer in people of color.²⁶ Identifying the advantages and disadvantages of all relevant skin cancer interventions conducted in the SOC population will hopefully guide future studies to help close these gaps by allowing others to design the best possible intervention. By doing so, researchers can generate an intervention that is precise, well-informed, and effective in decreasing mortality rates from skin cancer among SOC populations.

Conclusion

All of the studies reviewed demonstrated that instructional and educational interventions are promising methods for improving either knowledge, awareness, or safe skin practices and sun-protective behaviors in SOC populations to differing degrees (Table). Although each of the 4 interventions employed their own methods, they all increased 1 or more of the 3 aforementioned concepts—knowledge, awareness, or safe skin practices and sun-protective behaviors—when comparing postsurvey to presurvey data. However, the critically important message derived from this research is that there is a tremendous need for a substantial large-scale educational intervention to increase knowledge regarding skin cancer in SOC populations.

Malignant melanoma, basal cell carcinoma, and squamous cell carcinoma account for approximately 40% of all neoplasms among the white population in the United States. Skin cancer is the most common malignancy in the United States.¹ However, despite this occurrence, there are limited data regarding skin cancer in individuals with skin of color (SOC). The 5-year survival rates for melanoma are 58.2% for black individuals, 69.7% for Hispanics, and 70.9% for Asians compared to 79.8% for white individuals in the United States.² Even though SOC populations have lower incidences of skin cancer—melanoma, basal cell carcinoma, and squamous cell carcinoma—they exhibit higher death rates.^3-7 Nonetheless, no specific guidelines exist to address sun exposure and safety habits in SOC populations.^6,8 Furthermore, current demographics suggest that by the year 2050, approximately half of the US population will be nonwhite.⁴ Paradoxically, despite having increased sun protection from greater amounts of melanin in their skin, black individuals are more likely to present with advanced-stage melanoma (eg, stage III/IV) compared to white individuals.^8-12 Furthermore, those of nonwhite populations are more likely to present with more advanced stages of acral lentiginous melanomas than white individuals.^13,14 Hispanics also face an increasing incidence of more invasive acral lentiginous melanomas.¹⁵ Overall, SOC patients have the poorest skin cancer prognosis, and the data suggest that the reason for this paradox is delayed diagnosis.¹

Although skin cancer is largely a preventable condition, the literature suggests that lack of awareness of melanoma among ethnic minorities is one of the main reasons for their poor skin cancer prognosis.¹⁶ This lack of awareness decreases the likelihood that an SOC patient would be alert to early detection of cancerous changes.¹⁷ Because educating at-risk SOC populations is key to decreasing skin cancer risk, this study focused on determining the efficacy of major knowledge-based interventions conducted to date.¹ Overall, we sought to answer the question, do knowledge-based interventions increase skin cancer awareness, knowledge, and protective behavior among people of color?

Methods

For this review, the Cochrane method of analysis was used to conduct a thorough search of PubMed articles indexed for MEDLINE (1994-2016), as well as a search of CINAHL (1997-2016), PsycINFO (1999-2016), and Web of Science (1965-2016), using a combination of more than 100 search terms including but not limited to skin cancer, skin of color, intervention, and ethnic skin. The search yielded a total of 52 articles (Figure). Following review, only 8 articles met inclusion criteria, which were as follows: (1) study was related to skin cancer in SOC patients, which included an intervention to increase skin cancer awareness and knowledge; (2) study included adult participants or adolescents aged 12 to 18 years; (3) study was written in English; and (4) study was published in a peer-reviewed journal. Of the remaining 8 articles, 4 were excluded due to the following criteria: (1) study failed to provide both preintervention and postintervention data, (2) study failed to provide quantitative data, and (3) study included participants who worked as health care professionals or ancillary staff. As a result, a total of 4 articles were analyzed and discussed in this review (Table).

Results

Robinson et al¹⁸ conducted 12 focus groups with 120 total participants (40 black, 40 Asian, and 40 Hispanic patients). Participants engaged in a 2-hour tape-recorded focus group with a moderator guide on melanoma and skin cancer. Furthermore, they also were asked to assess skin cancer risk in 5 celebrities with different skin tones. The statistically significant preintervention results of the study (χ²=4.6, P<.001) were as follows: only 2%, 4%, and 14% correctly reported that celebrities with a very fair skin type, a fair skin type, and very dark skin type, respectively, could get sunburn, compared to 75%, 76%, and 62% post-intervention. Additionally, prior to intervention, 14% of the study population believed that dark brown skin type could get sunburn compared to 62% of the same group postintervention. This study demonstrated that the intervention helped SOC patients better identify their ability to get sunburn and identify their skin cancer risk.¹⁸

Hernandez et al¹⁹ used a video-based intervention in a Hispanic community, which was in contrast to the multiracial focus group intervention conducted by Robinson et al.¹⁸ Eighty Hispanic individuals were recruited from beauty salons to participate in the study. Participants watched two 3-minute videos in Spanish and completed a preintervention and postintervention survey. The first video emphasized the photoaging benefits of sun protection, while the second focused on skin cancer prevention. Preintervention surveys indicated that only 54 (68%) participants believed that fair-skinned Hispanics were at risk for skin cancer, which improved to 72 (90%) participants postintervention. Furthermore, initially only 44 (55%) participants thought those with darker skin types could develop skin cancer, but this number increased to 69 (86%) postintervention. For both questions regarding fair and dark skin, the agreement proportion was significantly different between the preeducation and posteducation videos (P<.0002 for the fair skin question and P<.0001 for the dark skin question). This study greatly increased awareness of skin cancer risk among Hispanics,¹⁹ similar to the Robinson et al¹⁸ study.

In contrast to 2-hour focus groups or 3-minute video–based interventions, a study by Kundu et al¹⁷ employed a 20-minute educational class-based intervention with both verbal and visual instruction. This study assessed the efficacy of an educational tutorial on improving awareness and early detection of melanoma in SOC individuals. Photographs were used to help participants recognize the ABCDEs of melanoma and to show examples of acral lentiginous melanomas in white individuals. A total of 71 participants completed a preintervention questionnaire, participated in a 20-minute class, and completed a postintervention questionnaire immediately after and 3 months following the class. The study population included 44 black, 15 Asian, 10 Hispanic, and 2 multiethnic participants. Knowledge that melanoma is a skin cancer increased from 83.9% to 100% immediately postintervention (P=.0001) and 97.2% at 3 months postintervention (P=.0075). Additionally, knowledge that people of color are at risk for melanoma increased from 48.4% preintervention to 82.8% immediately postintervention (P<.0001). However, only 40.8% of participants retained this knowledge at 3 months postintervention. Because only 1 participant reported a family history of skin cancer, the authors hypothesized that the reason for this loss of knowledge was that most participants were not personally affected by friends or family members with melanoma. A future study with an appropriate control group would be needed to support this claim. This study shed light on the potential of class-based interventions to increase both awareness and knowledge of skin cancer in SOC populations.¹⁷

A study by Chapman et al²⁰ examined the effects of a sun protection educational program on increasing awareness of skin cancer in Hispanic and black middle school students in southern Los Angeles, California. It was the only study we reviewed that focused primarily on adolescents. Furthermore, it included the largest sample size (N=148) analyzed here. Students were given a preintervention questionnaire to evaluate their awareness of skin cancer and current sun-protection practices. Based on these results, the investigators devised a set of learning goals and incorporated them into an educational pamphlet. The intervention, called “Skin Teaching Day,” was a 1-day program discussing skin cancer and the importance of sun protection. Prior to the intervention, 68% of participants reported that they used sunscreen. Three months after completing the program, 80% of participants reported sunscreen use, an increase of 12% prior to the intervention. The results of this study demonstrated the unique effectiveness and potential of pamphlets in increasing sunscreen use.²⁰

Comment

Overall, various methods of interventions such as focus groups, videos, pamphlets, and lectures improved knowledge of skin cancer risk and sun-protection behaviors in SOC populations. Furthermore, the unique differences of each study provided important insights into the successful design of an intervention.

An important characteristic of the Robinson et al¹⁸ study was the addition of photographs, which allowed participants not only to visualize different skin tones but also provided them with the opportunity to relate themselves to the photographs; by doing so, participants could effectively pick out the skin tone that best suited them. Written SOC scales are limited to mere descriptions and thus make it more difficult for participants to accurately identify the tone that best fits them. Kundu et al¹⁷ used photographs to teach skin self-examination and ABCDEs for detection of melanoma. Additionally, both studies used photographs to demonstrate examples of skin cancer.^17,18 Recent evidence suggests the use of visuals can be efficacious for improving skin cancer knowledge and awareness; a study in 16 SOC kidney transplant recipients found that the addition of photographs of squamous cell carcinoma in various skin tones to a sun-protection educational pamphlet was more effective than the original pamphlet without photographs.²¹

In contrast to the Robinson et al¹⁸ study and Hernandez et al¹⁹ study, the Kundu et al¹⁷ study showed photographs of acral lentiginous melanomas in white patients rather than SOC patients. However, SOC populations may be less likely to relate to or identify skin changes in skin types that are different from their own. This technique was still beneficial, as acral lentiginous melanoma is the most common type of melanoma in SOC populations. Another benefit of the study was that it was the only study reviewed that included a follow-up postintervention questionnaire. Such data is useful, as it demonstrates how muchinformation is retained by participants and may be more likely to predict compliance with skin cancer protective behaviors.¹⁷

The Hernandez et al¹⁹ study is unique in that it was the only one to include an educational intervention entirely in Spanish, which is important to consider, as language may be a hindrance to participants’ understanding in the other studies, particularly Hispanics, possibly leading to a lack of information retention regarding sun-protective behaviors. Furthermore, it also was the only study to utilize videos as a method for interventions. The 3-minute videos demonstrated that interventions could be efficient as compared to the 2-hour in-class intervention used by Robinson et al¹⁸ and the 20-minute intervention used by Kundu et al.¹⁷ Additionally, videos also could be more cost-effective, as incentives for large focus groups would no longer be needed. Furthermore, in the Hernandez et al¹⁹ study, there was minimal to no disruption in the participants’ daily routine, as the participants were getting cosmetic services while watching the videos, perhaps allowing them to be more attentive. In contrast, both the Robinson et al¹⁸ and Kundu et al¹⁷ studies required time out from the participants’ daily schedules. In addition, these studies were notably longer than the Hernandez et al¹⁹ study. The 8-hour intervention in the Chapman et al²⁰ study also may not be feasible for the general population because of its excessive length. However, the intervention was successful among the adolescent participants, which suggested that shorter durations are effective in the adult population and longer interventions may be more appropriate for adolescents because they benefit from peer activity.

Despite the success of the educational interventions as outlined in the 4 studies described here, a major epidemiologic flaw is that these interventions included only a small percentage of the target population. The largest total number of adults surveyed and undergoing an intervention in any of the populations was only 120.¹⁷ By failing to reach a substantial proportion of the population at risk, the number of preventable deaths likely will not decrease. The authors believe a larger-scale intervention would provide meaningful change. Australia’s SunSmart campaign to increase skin cancer awareness in the Australian population is an example of one such large-scale national intervention. The campaign focused on massive television advertisements in the summer to educate participants about the dangers of skin cancer and the importance of protective behaviors. Telephone surveys conducted from 1987 to 2011 demonstrated that more exposure to the advertisements in the SunSmart campaign meant that individuals were more likely to use sunscreen and avoid sun exposure.²² In the United States, a similar intervention would be of great benefit in educating SOC populations regarding skin cancer risk. Additionally, dermatology residents need to be adequately trained to educate patients of color about the risk for skin cancer, as survey data indicated more than 80% of Australian dermatologists desired more SOC teaching during their training and 50% indicated that they would have time to learn it during their training if offered.²³ Furthermore, one study suggested that future interventions must include primary-, secondary-, and tertiary-prevention methods to effectively reduce skin cancer risk among patients of color.²⁴ Primary prevention involves sun avoidance, secondary prevention involves detecting cancerous lesions, and tertiary prevention involves undergoing treatment of skin malignancies. However, increased knowledge does not necessarily mean increased preventative action will be employed (eg, sunscreen use, wearing sun-protective clothing and sunglasses, avoiding tanning beds and excessive sun exposure). Additional studies that demonstrate a notable increase in sun-protective behaviors related to increased knowledge are needed.

Because retention of skin cancer knowledge decreased in several postintervention surveys, there also is a dire need for continuing skin cancer education in patients of color, which may be accomplished through a combination effort of television advertisement campaigns, pamphlets, social media, community health departments, or even community members. For example, a pilot program found that Hispanic lay health workers who are educated about skin cancer may serve as a bridge between medical providers and the Hispanic community by encouraging individuals in this population to get regular skin examinations from a physician.²⁵ Overall, there are currently gaps in the understanding and treatment of skin cancer in people of color.²⁶ Identifying the advantages and disadvantages of all relevant skin cancer interventions conducted in the SOC population will hopefully guide future studies to help close these gaps by allowing others to design the best possible intervention. By doing so, researchers can generate an intervention that is precise, well-informed, and effective in decreasing mortality rates from skin cancer among SOC populations.

Conclusion

All of the studies reviewed demonstrated that instructional and educational interventions are promising methods for improving either knowledge, awareness, or safe skin practices and sun-protective behaviors in SOC populations to differing degrees (Table). Although each of the 4 interventions employed their own methods, they all increased 1 or more of the 3 aforementioned concepts—knowledge, awareness, or safe skin practices and sun-protective behaviors—when comparing postsurvey to presurvey data. However, the critically important message derived from this research is that there is a tremendous need for a substantial large-scale educational intervention to increase knowledge regarding skin cancer in SOC populations.

Malignant melanoma, basal cell carcinoma, and squamous cell carcinoma account for approximately 40% of all neoplasms among the white population in the United States. Skin cancer is the most common malignancy in the United States.¹ However, despite this occurrence, there are limited data regarding skin cancer in individuals with skin of color (SOC). The 5-year survival rates for melanoma are 58.2% for black individuals, 69.7% for Hispanics, and 70.9% for Asians compared to 79.8% for white individuals in the United States.² Even though SOC populations have lower incidences of skin cancer—melanoma, basal cell carcinoma, and squamous cell carcinoma—they exhibit higher death rates.^3-7 Nonetheless, no specific guidelines exist to address sun exposure and safety habits in SOC populations.^6,8 Furthermore, current demographics suggest that by the year 2050, approximately half of the US population will be nonwhite.⁴ Paradoxically, despite having increased sun protection from greater amounts of melanin in their skin, black individuals are more likely to present with advanced-stage melanoma (eg, stage III/IV) compared to white individuals.^8-12 Furthermore, those of nonwhite populations are more likely to present with more advanced stages of acral lentiginous melanomas than white individuals.^13,14 Hispanics also face an increasing incidence of more invasive acral lentiginous melanomas.¹⁵ Overall, SOC patients have the poorest skin cancer prognosis, and the data suggest that the reason for this paradox is delayed diagnosis.¹

Although skin cancer is largely a preventable condition, the literature suggests that lack of awareness of melanoma among ethnic minorities is one of the main reasons for their poor skin cancer prognosis.¹⁶ This lack of awareness decreases the likelihood that an SOC patient would be alert to early detection of cancerous changes.¹⁷ Because educating at-risk SOC populations is key to decreasing skin cancer risk, this study focused on determining the efficacy of major knowledge-based interventions conducted to date.¹ Overall, we sought to answer the question, do knowledge-based interventions increase skin cancer awareness, knowledge, and protective behavior among people of color?

Methods

For this review, the Cochrane method of analysis was used to conduct a thorough search of PubMed articles indexed for MEDLINE (1994-2016), as well as a search of CINAHL (1997-2016), PsycINFO (1999-2016), and Web of Science (1965-2016), using a combination of more than 100 search terms including but not limited to skin cancer, skin of color, intervention, and ethnic skin. The search yielded a total of 52 articles (Figure). Following review, only 8 articles met inclusion criteria, which were as follows: (1) study was related to skin cancer in SOC patients, which included an intervention to increase skin cancer awareness and knowledge; (2) study included adult participants or adolescents aged 12 to 18 years; (3) study was written in English; and (4) study was published in a peer-reviewed journal. Of the remaining 8 articles, 4 were excluded due to the following criteria: (1) study failed to provide both preintervention and postintervention data, (2) study failed to provide quantitative data, and (3) study included participants who worked as health care professionals or ancillary staff. As a result, a total of 4 articles were analyzed and discussed in this review (Table).

Results

Robinson et al¹⁸ conducted 12 focus groups with 120 total participants (40 black, 40 Asian, and 40 Hispanic patients). Participants engaged in a 2-hour tape-recorded focus group with a moderator guide on melanoma and skin cancer. Furthermore, they also were asked to assess skin cancer risk in 5 celebrities with different skin tones. The statistically significant preintervention results of the study (χ²=4.6, P<.001) were as follows: only 2%, 4%, and 14% correctly reported that celebrities with a very fair skin type, a fair skin type, and very dark skin type, respectively, could get sunburn, compared to 75%, 76%, and 62% post-intervention. Additionally, prior to intervention, 14% of the study population believed that dark brown skin type could get sunburn compared to 62% of the same group postintervention. This study demonstrated that the intervention helped SOC patients better identify their ability to get sunburn and identify their skin cancer risk.¹⁸

Hernandez et al¹⁹ used a video-based intervention in a Hispanic community, which was in contrast to the multiracial focus group intervention conducted by Robinson et al.¹⁸ Eighty Hispanic individuals were recruited from beauty salons to participate in the study. Participants watched two 3-minute videos in Spanish and completed a preintervention and postintervention survey. The first video emphasized the photoaging benefits of sun protection, while the second focused on skin cancer prevention. Preintervention surveys indicated that only 54 (68%) participants believed that fair-skinned Hispanics were at risk for skin cancer, which improved to 72 (90%) participants postintervention. Furthermore, initially only 44 (55%) participants thought those with darker skin types could develop skin cancer, but this number increased to 69 (86%) postintervention. For both questions regarding fair and dark skin, the agreement proportion was significantly different between the preeducation and posteducation videos (P<.0002 for the fair skin question and P<.0001 for the dark skin question). This study greatly increased awareness of skin cancer risk among Hispanics,¹⁹ similar to the Robinson et al¹⁸ study.

In contrast to 2-hour focus groups or 3-minute video–based interventions, a study by Kundu et al¹⁷ employed a 20-minute educational class-based intervention with both verbal and visual instruction. This study assessed the efficacy of an educational tutorial on improving awareness and early detection of melanoma in SOC individuals. Photographs were used to help participants recognize the ABCDEs of melanoma and to show examples of acral lentiginous melanomas in white individuals. A total of 71 participants completed a preintervention questionnaire, participated in a 20-minute class, and completed a postintervention questionnaire immediately after and 3 months following the class. The study population included 44 black, 15 Asian, 10 Hispanic, and 2 multiethnic participants. Knowledge that melanoma is a skin cancer increased from 83.9% to 100% immediately postintervention (P=.0001) and 97.2% at 3 months postintervention (P=.0075). Additionally, knowledge that people of color are at risk for melanoma increased from 48.4% preintervention to 82.8% immediately postintervention (P<.0001). However, only 40.8% of participants retained this knowledge at 3 months postintervention. Because only 1 participant reported a family history of skin cancer, the authors hypothesized that the reason for this loss of knowledge was that most participants were not personally affected by friends or family members with melanoma. A future study with an appropriate control group would be needed to support this claim. This study shed light on the potential of class-based interventions to increase both awareness and knowledge of skin cancer in SOC populations.¹⁷

A study by Chapman et al²⁰ examined the effects of a sun protection educational program on increasing awareness of skin cancer in Hispanic and black middle school students in southern Los Angeles, California. It was the only study we reviewed that focused primarily on adolescents. Furthermore, it included the largest sample size (N=148) analyzed here. Students were given a preintervention questionnaire to evaluate their awareness of skin cancer and current sun-protection practices. Based on these results, the investigators devised a set of learning goals and incorporated them into an educational pamphlet. The intervention, called “Skin Teaching Day,” was a 1-day program discussing skin cancer and the importance of sun protection. Prior to the intervention, 68% of participants reported that they used sunscreen. Three months after completing the program, 80% of participants reported sunscreen use, an increase of 12% prior to the intervention. The results of this study demonstrated the unique effectiveness and potential of pamphlets in increasing sunscreen use.²⁰

Comment

Overall, various methods of interventions such as focus groups, videos, pamphlets, and lectures improved knowledge of skin cancer risk and sun-protection behaviors in SOC populations. Furthermore, the unique differences of each study provided important insights into the successful design of an intervention.

An important characteristic of the Robinson et al¹⁸ study was the addition of photographs, which allowed participants not only to visualize different skin tones but also provided them with the opportunity to relate themselves to the photographs; by doing so, participants could effectively pick out the skin tone that best suited them. Written SOC scales are limited to mere descriptions and thus make it more difficult for participants to accurately identify the tone that best fits them. Kundu et al¹⁷ used photographs to teach skin self-examination and ABCDEs for detection of melanoma. Additionally, both studies used photographs to demonstrate examples of skin cancer.^17,18 Recent evidence suggests the use of visuals can be efficacious for improving skin cancer knowledge and awareness; a study in 16 SOC kidney transplant recipients found that the addition of photographs of squamous cell carcinoma in various skin tones to a sun-protection educational pamphlet was more effective than the original pamphlet without photographs.²¹

In contrast to the Robinson et al¹⁸ study and Hernandez et al¹⁹ study, the Kundu et al¹⁷ study showed photographs of acral lentiginous melanomas in white patients rather than SOC patients. However, SOC populations may be less likely to relate to or identify skin changes in skin types that are different from their own. This technique was still beneficial, as acral lentiginous melanoma is the most common type of melanoma in SOC populations. Another benefit of the study was that it was the only study reviewed that included a follow-up postintervention questionnaire. Such data is useful, as it demonstrates how muchinformation is retained by participants and may be more likely to predict compliance with skin cancer protective behaviors.¹⁷

The Hernandez et al¹⁹ study is unique in that it was the only one to include an educational intervention entirely in Spanish, which is important to consider, as language may be a hindrance to participants’ understanding in the other studies, particularly Hispanics, possibly leading to a lack of information retention regarding sun-protective behaviors. Furthermore, it also was the only study to utilize videos as a method for interventions. The 3-minute videos demonstrated that interventions could be efficient as compared to the 2-hour in-class intervention used by Robinson et al¹⁸ and the 20-minute intervention used by Kundu et al.¹⁷ Additionally, videos also could be more cost-effective, as incentives for large focus groups would no longer be needed. Furthermore, in the Hernandez et al¹⁹ study, there was minimal to no disruption in the participants’ daily routine, as the participants were getting cosmetic services while watching the videos, perhaps allowing them to be more attentive. In contrast, both the Robinson et al¹⁸ and Kundu et al¹⁷ studies required time out from the participants’ daily schedules. In addition, these studies were notably longer than the Hernandez et al¹⁹ study. The 8-hour intervention in the Chapman et al²⁰ study also may not be feasible for the general population because of its excessive length. However, the intervention was successful among the adolescent participants, which suggested that shorter durations are effective in the adult population and longer interventions may be more appropriate for adolescents because they benefit from peer activity.

Despite the success of the educational interventions as outlined in the 4 studies described here, a major epidemiologic flaw is that these interventions included only a small percentage of the target population. The largest total number of adults surveyed and undergoing an intervention in any of the populations was only 120.¹⁷ By failing to reach a substantial proportion of the population at risk, the number of preventable deaths likely will not decrease. The authors believe a larger-scale intervention would provide meaningful change. Australia’s SunSmart campaign to increase skin cancer awareness in the Australian population is an example of one such large-scale national intervention. The campaign focused on massive television advertisements in the summer to educate participants about the dangers of skin cancer and the importance of protective behaviors. Telephone surveys conducted from 1987 to 2011 demonstrated that more exposure to the advertisements in the SunSmart campaign meant that individuals were more likely to use sunscreen and avoid sun exposure.²² In the United States, a similar intervention would be of great benefit in educating SOC populations regarding skin cancer risk. Additionally, dermatology residents need to be adequately trained to educate patients of color about the risk for skin cancer, as survey data indicated more than 80% of Australian dermatologists desired more SOC teaching during their training and 50% indicated that they would have time to learn it during their training if offered.²³ Furthermore, one study suggested that future interventions must include primary-, secondary-, and tertiary-prevention methods to effectively reduce skin cancer risk among patients of color.²⁴ Primary prevention involves sun avoidance, secondary prevention involves detecting cancerous lesions, and tertiary prevention involves undergoing treatment of skin malignancies. However, increased knowledge does not necessarily mean increased preventative action will be employed (eg, sunscreen use, wearing sun-protective clothing and sunglasses, avoiding tanning beds and excessive sun exposure). Additional studies that demonstrate a notable increase in sun-protective behaviors related to increased knowledge are needed.

Because retention of skin cancer knowledge decreased in several postintervention surveys, there also is a dire need for continuing skin cancer education in patients of color, which may be accomplished through a combination effort of television advertisement campaigns, pamphlets, social media, community health departments, or even community members. For example, a pilot program found that Hispanic lay health workers who are educated about skin cancer may serve as a bridge between medical providers and the Hispanic community by encouraging individuals in this population to get regular skin examinations from a physician.²⁵ Overall, there are currently gaps in the understanding and treatment of skin cancer in people of color.²⁶ Identifying the advantages and disadvantages of all relevant skin cancer interventions conducted in the SOC population will hopefully guide future studies to help close these gaps by allowing others to design the best possible intervention. By doing so, researchers can generate an intervention that is precise, well-informed, and effective in decreasing mortality rates from skin cancer among SOC populations.

Conclusion

All of the studies reviewed demonstrated that instructional and educational interventions are promising methods for improving either knowledge, awareness, or safe skin practices and sun-protective behaviors in SOC populations to differing degrees (Table). Although each of the 4 interventions employed their own methods, they all increased 1 or more of the 3 aforementioned concepts—knowledge, awareness, or safe skin practices and sun-protective behaviors—when comparing postsurvey to presurvey data. However, the critically important message derived from this research is that there is a tremendous need for a substantial large-scale educational intervention to increase knowledge regarding skin cancer in SOC populations.

To the Editor:

Rice and rice products, such as rice cereal and rice snacks, contain inorganic arsenic. Exposure to arsenicin utero and during early life may be associated with adverse fetal growth, adverse infant and child immune response, and adverse neurodevelopmental outcomes. Therefore, the World Health Organization, the Food and Agriculture Organization of the United Nations, the European Union, and the US Food and Drug Administration have suggested maximum arsenic ingestion recommendations for infants: 100 ng/g for inorganic arsenic in products geared toward infants. However, infants consuming only a few servings of rice products may exceed the weekly tolerable intake of arsenic.

Karagas et al¹ obtained dietary data on 759 infants who were enrolled in the New Hampshire Birth Cohort Study from 2011 to 2014. They noted that 80% of the infants had been introduced to rice cereal during the first year. Additional data on diet and total urinary arsenic at 12 months was available for 129 infants: 32.6% of these infants were fed rice snacks. In addition, the total urinary arsenic concentration was higher among infants who ate rice cereal or rice snacks as compared to infants who did not eat rice or rice products.

Chronic arsenic exposure can result in patchy dark brown hyperpigmentation with scattered pale spots referred to as “raindrops on a dusty road.” The axilla, eyelids, groin, neck, nipples, and temples often are affected. However, the hyperpigmentation can extend across the chest, abdomen, and back in severe cases.

Horizontal white lines across the nails (Mees lines) may develop. Keratoses, often on the palms (arsenic keratoses), may appear; they persist and may progress to skin cancers. In addition, patients with arsenic exposure are more susceptible to developing nonmelanoma skin cancers.²

It is unknown if exposure to inorganic arsenic in infancy predisposes these individuals to skin cancer when they become adults. Long-term longitudinal follow-up of the participants in this study may provide additional insight. Perhaps infants should not receive rice cereals and rice snacks or their parents should more carefully monitor the amount of rice and rice products that they ingest.

To the Editor:

Rice and rice products, such as rice cereal and rice snacks, contain inorganic arsenic. Exposure to arsenicin utero and during early life may be associated with adverse fetal growth, adverse infant and child immune response, and adverse neurodevelopmental outcomes. Therefore, the World Health Organization, the Food and Agriculture Organization of the United Nations, the European Union, and the US Food and Drug Administration have suggested maximum arsenic ingestion recommendations for infants: 100 ng/g for inorganic arsenic in products geared toward infants. However, infants consuming only a few servings of rice products may exceed the weekly tolerable intake of arsenic.

Karagas et al¹ obtained dietary data on 759 infants who were enrolled in the New Hampshire Birth Cohort Study from 2011 to 2014. They noted that 80% of the infants had been introduced to rice cereal during the first year. Additional data on diet and total urinary arsenic at 12 months was available for 129 infants: 32.6% of these infants were fed rice snacks. In addition, the total urinary arsenic concentration was higher among infants who ate rice cereal or rice snacks as compared to infants who did not eat rice or rice products.

Chronic arsenic exposure can result in patchy dark brown hyperpigmentation with scattered pale spots referred to as “raindrops on a dusty road.” The axilla, eyelids, groin, neck, nipples, and temples often are affected. However, the hyperpigmentation can extend across the chest, abdomen, and back in severe cases.

Horizontal white lines across the nails (Mees lines) may develop. Keratoses, often on the palms (arsenic keratoses), may appear; they persist and may progress to skin cancers. In addition, patients with arsenic exposure are more susceptible to developing nonmelanoma skin cancers.²

It is unknown if exposure to inorganic arsenic in infancy predisposes these individuals to skin cancer when they become adults. Long-term longitudinal follow-up of the participants in this study may provide additional insight. Perhaps infants should not receive rice cereals and rice snacks or their parents should more carefully monitor the amount of rice and rice products that they ingest.

To the Editor:

Rice and rice products, such as rice cereal and rice snacks, contain inorganic arsenic. Exposure to arsenicin utero and during early life may be associated with adverse fetal growth, adverse infant and child immune response, and adverse neurodevelopmental outcomes. Therefore, the World Health Organization, the Food and Agriculture Organization of the United Nations, the European Union, and the US Food and Drug Administration have suggested maximum arsenic ingestion recommendations for infants: 100 ng/g for inorganic arsenic in products geared toward infants. However, infants consuming only a few servings of rice products may exceed the weekly tolerable intake of arsenic.

Karagas et al¹ obtained dietary data on 759 infants who were enrolled in the New Hampshire Birth Cohort Study from 2011 to 2014. They noted that 80% of the infants had been introduced to rice cereal during the first year. Additional data on diet and total urinary arsenic at 12 months was available for 129 infants: 32.6% of these infants were fed rice snacks. In addition, the total urinary arsenic concentration was higher among infants who ate rice cereal or rice snacks as compared to infants who did not eat rice or rice products.

Chronic arsenic exposure can result in patchy dark brown hyperpigmentation with scattered pale spots referred to as “raindrops on a dusty road.” The axilla, eyelids, groin, neck, nipples, and temples often are affected. However, the hyperpigmentation can extend across the chest, abdomen, and back in severe cases.

Horizontal white lines across the nails (Mees lines) may develop. Keratoses, often on the palms (arsenic keratoses), may appear; they persist and may progress to skin cancers. In addition, patients with arsenic exposure are more susceptible to developing nonmelanoma skin cancers.²

It is unknown if exposure to inorganic arsenic in infancy predisposes these individuals to skin cancer when they become adults. Long-term longitudinal follow-up of the participants in this study may provide additional insight. Perhaps infants should not receive rice cereals and rice snacks or their parents should more carefully monitor the amount of rice and rice products that they ingest.

Military dermatologists are charged with caring for a diverse population of active-duty members, civilian dependents, and military retirees. Although certain risk factors for cutaneous malignancies are common in all of these groups, the active-duty population experiences unique exposures to be considered when determining their risk for skin cancer. One subset that may be at a higher risk is military pilots who fly at high altitudes on irregular schedules in austere environments. Through the unparalleled comradeship inherent in many military units, pilots “hear” from their fellow pilots that they are at increased risk for skin cancer. Do their occupational exposures translate into increased risk for cutaneous malignancy? This article will survey the literature pertaining to pilots and skin cancer so that all dermatologists may better care for this unique population.

Epidemiology

Anecdotally, we have observed basal cell carcinoma in pilots in their 20s and early 30s, earlier than would be expected in an otherwise healthy prescreened military population.¹ Woolley and Hughes² published a case report of skin cancer in a young military aviator. The patient was a 32-year-old male helicopter pilot with Fitzpatrick skin type II and no personal or family history of skin cancer who was diagnosed with a periocular nodular basal cell carcinoma. He deployed to locations with high UV radiation (UVR) indices, and his vacation time also was spent in such areas.² UV radiation exposure and Fitzpatrick skin type are known risk factors across occupations, but are there special exposures that come with military aviation service?

To better understand the risk for malignancy in this special population, the US Air Force examined the rates of all cancer types among a cohort of flying versus nonflying officers.³ Aviation personnel showed increased incidence of testicular, bladder, and all-site cancers combined. Noticeably absent was a statistically significant increased risk for malignant melanoma (MM) and nonmelanoma skin cancer (NMSC). Other epidemiological studies examined the incidence rates of MM in the US Armed Forces compared with age- and race-matched civilian populations and showed mixed results: 2 studies showed increased risk,^4,5 while a third showed decreased risk.⁶ Despite finding opposite results of MM rates in military members versus the civilian population, 2 of these studies showed US Air Force members to have higher rates of MM than those in the US Army or Navy.^4,6 Interestingly, the air force has the highest number of pilots among all the services, with 4000 more pilots than the army and navy.⁷ Further studies are needed to determine if the higher air force MM rates occur in pilots.

Although there are mixed and limited data pertaining to military flight crews, there is more robust literature concerning civilian flight personnel. One meta-analysis pooled studies related to cancer risk in cabin crews and civil and military pilots.⁸ In military pilots, they found a standardized incidence ratio (SIR) of 1.43 (95% confidence interval [CI], 1.09-1.87) for MM and 1.80 (95% CI, 1.25-2.80) for NMSC. The SIRs were higher for male cabin attendants (3.42 and 7.46, respectively) and civil pilots (2.18 and 1.88, respectively). They also found the most common cause of mortality in civilian cabin crews was AIDS, possibly explaining the higher SIRs for all types of malignancy in that population.⁸ In the United States, many civilian pilots previously were military pilots⁹ who likely served in the military for at least 10 years.¹⁰ A 2015 meta-analysis of 19 studies of more than 266,000 civil pilots and aircrew members found an SIR for MM of 2.22 (95% CI, 1.67-2.93) for civil pilots and 2.09 (95% CI, 1.67-2.62) for aircrews, stating the risk for MM is at least twice that of the general population.¹¹

Risk Factors

UV Radiation
These studies suggest flight duties increase the risk for cutaneous malignancy. UV radiation is a known risk factor for skin cancer.¹² The main body of the aircraft may protect the cabin’s crew and passengers from UVR, but pilots are exposed to more UVR, especially in aircraft with larger windshields. A government study in 2007 examined the transmittance of UVR through windscreens of 8 aircraft: 3 commercial jets, 2 commercial propeller planes, 1 private jet, and 2 small propeller planes.¹³ UVB was attenuated by all the windscreens (<1% transmittance), but 43% to 54% of UVA was transmitted, with plastic windshields attenuating more than glass. Sanlorenzo et al¹⁴ measured UVA irradiance at the pilot’s seat of a turboprop aircraft at 30,000-ft altitude. They compared this exposure to a UVA tanning bed and estimated that 57 minutes of flight at 30,000-ft altitude was equivalent to 20 minutes inside a UVA tanning booth, a startling finding.¹⁴

Cosmic Radiation
Cosmic radiation consists of neutrons and gamma rays that originate outside Earth’s atmosphere. Pilots are exposed to higher doses of cosmic radiation than nonpilots, but the health effects are difficult to study. Boice et al¹⁵ described how factors such as altitude, latitude, and flight time determine pilots’ cumulative exposure. With longer flight times at higher altitudes, a pilot’s exposure to cosmic radiation is increasing over the years.¹⁵ A 2012 review found that aircrews have low-level cosmic radiation exposure. Despite increases in MM and NMSC in pilots and increased rates of breast cancer in female aircrew, overall cancer-related mortality was lower in flying versus nonflying controls.¹⁶ Thus, cosmic radiation may not be as onerous of an occupational hazard for pilots as has been postulated.

Altered Circadian Rhythms
Aviation duties, especially in the military, require irregular work schedules that repeatedly interfere with normal sleep-wake cycles, disrupt circadian rhythms, and lead to reduced melatonin levels.⁸ Evidence suggests that low levels of melatonin could increase the risk for breast and prostate cancer—both cancers that occur more frequently in female aircrew and male pilots, respectively—by reducing melatonin’s natural protective role in such malignancies.^17,18 A World Health Organization working group categorized shift work as “probably carcinogenic” and cited alterations of melatonin levels, changes in other circadian rhythm–related gene pathways, and relative immunosuppression as likely causative factors.¹⁹ In a 2011 study, exposing mice to UVR during times when nucleotide excision repair mechanisms were at their lowest activity caused an increased rate of skin cancers.²⁰ A 2014 review discussed how epidemiological studies of shift workers such as nurses, firefighters, pilots, and flight crews found contradictory data, but molecular studies show that circadian rhythm–linked repair and tumorigenesis mechanisms are altered by aberrations in the normal sleep-wake cycle.²¹

Cockpit Instrumentation
Electromagnetic energy from the flight instruments in the cockpit also could influence malignancy risk. Nicholas et al²² found magnetic field measurements within the cockpit to be 2 to 10 times that experienced within the home or office. However, no studies examining the health effects of cockpit flight instruments and magnetic fields were found.

Final Thoughts

It is important to counsel pilots on the generally recognized, nonaviation-specific risk factors of family history, skin type, and UVR exposure in the development of skin cancer. Additionally, it is important to explain the possible role of exposure to UVR at higher altitudes, cosmic radiation, and electromagnetic energy from cockpit instruments, as well as altered sleep-wake cycles. A pilot’s risk for MM may be twice that of matched controls, and the risk for NMSC could be higher.^8,11 Although the literature lacks specific recommendations for pilots, it is reasonable to screen pilots once per year to better assess their individual risk and encourage diligent use of sunscreen and sun-protective measures when flying. It also may be important to advocate for the development of engineering controls that decrease UVR transmittance through windscreens, particularly for aircraft flying at higher altitudes for longer flights. More research is needed to determine if changes in circadian rhythm and decreases in melatonin increase skin cancer risk, which could impact how pilots’ schedules are managed. Together, we can ensure adequate surveillance, diagnosis, and treatment in this at-risk population.

Military dermatologists are charged with caring for a diverse population of active-duty members, civilian dependents, and military retirees. Although certain risk factors for cutaneous malignancies are common in all of these groups, the active-duty population experiences unique exposures to be considered when determining their risk for skin cancer. One subset that may be at a higher risk is military pilots who fly at high altitudes on irregular schedules in austere environments. Through the unparalleled comradeship inherent in many military units, pilots “hear” from their fellow pilots that they are at increased risk for skin cancer. Do their occupational exposures translate into increased risk for cutaneous malignancy? This article will survey the literature pertaining to pilots and skin cancer so that all dermatologists may better care for this unique population.

Epidemiology

Anecdotally, we have observed basal cell carcinoma in pilots in their 20s and early 30s, earlier than would be expected in an otherwise healthy prescreened military population.¹ Woolley and Hughes² published a case report of skin cancer in a young military aviator. The patient was a 32-year-old male helicopter pilot with Fitzpatrick skin type II and no personal or family history of skin cancer who was diagnosed with a periocular nodular basal cell carcinoma. He deployed to locations with high UV radiation (UVR) indices, and his vacation time also was spent in such areas.² UV radiation exposure and Fitzpatrick skin type are known risk factors across occupations, but are there special exposures that come with military aviation service?

To better understand the risk for malignancy in this special population, the US Air Force examined the rates of all cancer types among a cohort of flying versus nonflying officers.³ Aviation personnel showed increased incidence of testicular, bladder, and all-site cancers combined. Noticeably absent was a statistically significant increased risk for malignant melanoma (MM) and nonmelanoma skin cancer (NMSC). Other epidemiological studies examined the incidence rates of MM in the US Armed Forces compared with age- and race-matched civilian populations and showed mixed results: 2 studies showed increased risk,^4,5 while a third showed decreased risk.⁶ Despite finding opposite results of MM rates in military members versus the civilian population, 2 of these studies showed US Air Force members to have higher rates of MM than those in the US Army or Navy.^4,6 Interestingly, the air force has the highest number of pilots among all the services, with 4000 more pilots than the army and navy.⁷ Further studies are needed to determine if the higher air force MM rates occur in pilots.

Although there are mixed and limited data pertaining to military flight crews, there is more robust literature concerning civilian flight personnel. One meta-analysis pooled studies related to cancer risk in cabin crews and civil and military pilots.⁸ In military pilots, they found a standardized incidence ratio (SIR) of 1.43 (95% confidence interval [CI], 1.09-1.87) for MM and 1.80 (95% CI, 1.25-2.80) for NMSC. The SIRs were higher for male cabin attendants (3.42 and 7.46, respectively) and civil pilots (2.18 and 1.88, respectively). They also found the most common cause of mortality in civilian cabin crews was AIDS, possibly explaining the higher SIRs for all types of malignancy in that population.⁸ In the United States, many civilian pilots previously were military pilots⁹ who likely served in the military for at least 10 years.¹⁰ A 2015 meta-analysis of 19 studies of more than 266,000 civil pilots and aircrew members found an SIR for MM of 2.22 (95% CI, 1.67-2.93) for civil pilots and 2.09 (95% CI, 1.67-2.62) for aircrews, stating the risk for MM is at least twice that of the general population.¹¹

Risk Factors

UV Radiation
These studies suggest flight duties increase the risk for cutaneous malignancy. UV radiation is a known risk factor for skin cancer.¹² The main body of the aircraft may protect the cabin’s crew and passengers from UVR, but pilots are exposed to more UVR, especially in aircraft with larger windshields. A government study in 2007 examined the transmittance of UVR through windscreens of 8 aircraft: 3 commercial jets, 2 commercial propeller planes, 1 private jet, and 2 small propeller planes.¹³ UVB was attenuated by all the windscreens (<1% transmittance), but 43% to 54% of UVA was transmitted, with plastic windshields attenuating more than glass. Sanlorenzo et al¹⁴ measured UVA irradiance at the pilot’s seat of a turboprop aircraft at 30,000-ft altitude. They compared this exposure to a UVA tanning bed and estimated that 57 minutes of flight at 30,000-ft altitude was equivalent to 20 minutes inside a UVA tanning booth, a startling finding.¹⁴

Cosmic Radiation
Cosmic radiation consists of neutrons and gamma rays that originate outside Earth’s atmosphere. Pilots are exposed to higher doses of cosmic radiation than nonpilots, but the health effects are difficult to study. Boice et al¹⁵ described how factors such as altitude, latitude, and flight time determine pilots’ cumulative exposure. With longer flight times at higher altitudes, a pilot’s exposure to cosmic radiation is increasing over the years.¹⁵ A 2012 review found that aircrews have low-level cosmic radiation exposure. Despite increases in MM and NMSC in pilots and increased rates of breast cancer in female aircrew, overall cancer-related mortality was lower in flying versus nonflying controls.¹⁶ Thus, cosmic radiation may not be as onerous of an occupational hazard for pilots as has been postulated.

Altered Circadian Rhythms
Aviation duties, especially in the military, require irregular work schedules that repeatedly interfere with normal sleep-wake cycles, disrupt circadian rhythms, and lead to reduced melatonin levels.⁸ Evidence suggests that low levels of melatonin could increase the risk for breast and prostate cancer—both cancers that occur more frequently in female aircrew and male pilots, respectively—by reducing melatonin’s natural protective role in such malignancies.^17,18 A World Health Organization working group categorized shift work as “probably carcinogenic” and cited alterations of melatonin levels, changes in other circadian rhythm–related gene pathways, and relative immunosuppression as likely causative factors.¹⁹ In a 2011 study, exposing mice to UVR during times when nucleotide excision repair mechanisms were at their lowest activity caused an increased rate of skin cancers.²⁰ A 2014 review discussed how epidemiological studies of shift workers such as nurses, firefighters, pilots, and flight crews found contradictory data, but molecular studies show that circadian rhythm–linked repair and tumorigenesis mechanisms are altered by aberrations in the normal sleep-wake cycle.²¹

Cockpit Instrumentation
Electromagnetic energy from the flight instruments in the cockpit also could influence malignancy risk. Nicholas et al²² found magnetic field measurements within the cockpit to be 2 to 10 times that experienced within the home or office. However, no studies examining the health effects of cockpit flight instruments and magnetic fields were found.

Final Thoughts

It is important to counsel pilots on the generally recognized, nonaviation-specific risk factors of family history, skin type, and UVR exposure in the development of skin cancer. Additionally, it is important to explain the possible role of exposure to UVR at higher altitudes, cosmic radiation, and electromagnetic energy from cockpit instruments, as well as altered sleep-wake cycles. A pilot’s risk for MM may be twice that of matched controls, and the risk for NMSC could be higher.^8,11 Although the literature lacks specific recommendations for pilots, it is reasonable to screen pilots once per year to better assess their individual risk and encourage diligent use of sunscreen and sun-protective measures when flying. It also may be important to advocate for the development of engineering controls that decrease UVR transmittance through windscreens, particularly for aircraft flying at higher altitudes for longer flights. More research is needed to determine if changes in circadian rhythm and decreases in melatonin increase skin cancer risk, which could impact how pilots’ schedules are managed. Together, we can ensure adequate surveillance, diagnosis, and treatment in this at-risk population.

Military dermatologists are charged with caring for a diverse population of active-duty members, civilian dependents, and military retirees. Although certain risk factors for cutaneous malignancies are common in all of these groups, the active-duty population experiences unique exposures to be considered when determining their risk for skin cancer. One subset that may be at a higher risk is military pilots who fly at high altitudes on irregular schedules in austere environments. Through the unparalleled comradeship inherent in many military units, pilots “hear” from their fellow pilots that they are at increased risk for skin cancer. Do their occupational exposures translate into increased risk for cutaneous malignancy? This article will survey the literature pertaining to pilots and skin cancer so that all dermatologists may better care for this unique population.

Epidemiology

Anecdotally, we have observed basal cell carcinoma in pilots in their 20s and early 30s, earlier than would be expected in an otherwise healthy prescreened military population.¹ Woolley and Hughes² published a case report of skin cancer in a young military aviator. The patient was a 32-year-old male helicopter pilot with Fitzpatrick skin type II and no personal or family history of skin cancer who was diagnosed with a periocular nodular basal cell carcinoma. He deployed to locations with high UV radiation (UVR) indices, and his vacation time also was spent in such areas.² UV radiation exposure and Fitzpatrick skin type are known risk factors across occupations, but are there special exposures that come with military aviation service?

To better understand the risk for malignancy in this special population, the US Air Force examined the rates of all cancer types among a cohort of flying versus nonflying officers.³ Aviation personnel showed increased incidence of testicular, bladder, and all-site cancers combined. Noticeably absent was a statistically significant increased risk for malignant melanoma (MM) and nonmelanoma skin cancer (NMSC). Other epidemiological studies examined the incidence rates of MM in the US Armed Forces compared with age- and race-matched civilian populations and showed mixed results: 2 studies showed increased risk,^4,5 while a third showed decreased risk.⁶ Despite finding opposite results of MM rates in military members versus the civilian population, 2 of these studies showed US Air Force members to have higher rates of MM than those in the US Army or Navy.^4,6 Interestingly, the air force has the highest number of pilots among all the services, with 4000 more pilots than the army and navy.⁷ Further studies are needed to determine if the higher air force MM rates occur in pilots.

Although there are mixed and limited data pertaining to military flight crews, there is more robust literature concerning civilian flight personnel. One meta-analysis pooled studies related to cancer risk in cabin crews and civil and military pilots.⁸ In military pilots, they found a standardized incidence ratio (SIR) of 1.43 (95% confidence interval [CI], 1.09-1.87) for MM and 1.80 (95% CI, 1.25-2.80) for NMSC. The SIRs were higher for male cabin attendants (3.42 and 7.46, respectively) and civil pilots (2.18 and 1.88, respectively). They also found the most common cause of mortality in civilian cabin crews was AIDS, possibly explaining the higher SIRs for all types of malignancy in that population.⁸ In the United States, many civilian pilots previously were military pilots⁹ who likely served in the military for at least 10 years.¹⁰ A 2015 meta-analysis of 19 studies of more than 266,000 civil pilots and aircrew members found an SIR for MM of 2.22 (95% CI, 1.67-2.93) for civil pilots and 2.09 (95% CI, 1.67-2.62) for aircrews, stating the risk for MM is at least twice that of the general population.¹¹

Risk Factors

UV Radiation
These studies suggest flight duties increase the risk for cutaneous malignancy. UV radiation is a known risk factor for skin cancer.¹² The main body of the aircraft may protect the cabin’s crew and passengers from UVR, but pilots are exposed to more UVR, especially in aircraft with larger windshields. A government study in 2007 examined the transmittance of UVR through windscreens of 8 aircraft: 3 commercial jets, 2 commercial propeller planes, 1 private jet, and 2 small propeller planes.¹³ UVB was attenuated by all the windscreens (<1% transmittance), but 43% to 54% of UVA was transmitted, with plastic windshields attenuating more than glass. Sanlorenzo et al¹⁴ measured UVA irradiance at the pilot’s seat of a turboprop aircraft at 30,000-ft altitude. They compared this exposure to a UVA tanning bed and estimated that 57 minutes of flight at 30,000-ft altitude was equivalent to 20 minutes inside a UVA tanning booth, a startling finding.¹⁴

Cosmic Radiation
Cosmic radiation consists of neutrons and gamma rays that originate outside Earth’s atmosphere. Pilots are exposed to higher doses of cosmic radiation than nonpilots, but the health effects are difficult to study. Boice et al¹⁵ described how factors such as altitude, latitude, and flight time determine pilots’ cumulative exposure. With longer flight times at higher altitudes, a pilot’s exposure to cosmic radiation is increasing over the years.¹⁵ A 2012 review found that aircrews have low-level cosmic radiation exposure. Despite increases in MM and NMSC in pilots and increased rates of breast cancer in female aircrew, overall cancer-related mortality was lower in flying versus nonflying controls.¹⁶ Thus, cosmic radiation may not be as onerous of an occupational hazard for pilots as has been postulated.

Altered Circadian Rhythms
Aviation duties, especially in the military, require irregular work schedules that repeatedly interfere with normal sleep-wake cycles, disrupt circadian rhythms, and lead to reduced melatonin levels.⁸ Evidence suggests that low levels of melatonin could increase the risk for breast and prostate cancer—both cancers that occur more frequently in female aircrew and male pilots, respectively—by reducing melatonin’s natural protective role in such malignancies.^17,18 A World Health Organization working group categorized shift work as “probably carcinogenic” and cited alterations of melatonin levels, changes in other circadian rhythm–related gene pathways, and relative immunosuppression as likely causative factors.¹⁹ In a 2011 study, exposing mice to UVR during times when nucleotide excision repair mechanisms were at their lowest activity caused an increased rate of skin cancers.²⁰ A 2014 review discussed how epidemiological studies of shift workers such as nurses, firefighters, pilots, and flight crews found contradictory data, but molecular studies show that circadian rhythm–linked repair and tumorigenesis mechanisms are altered by aberrations in the normal sleep-wake cycle.²¹

Cockpit Instrumentation
Electromagnetic energy from the flight instruments in the cockpit also could influence malignancy risk. Nicholas et al²² found magnetic field measurements within the cockpit to be 2 to 10 times that experienced within the home or office. However, no studies examining the health effects of cockpit flight instruments and magnetic fields were found.

Final Thoughts

It is important to counsel pilots on the generally recognized, nonaviation-specific risk factors of family history, skin type, and UVR exposure in the development of skin cancer. Additionally, it is important to explain the possible role of exposure to UVR at higher altitudes, cosmic radiation, and electromagnetic energy from cockpit instruments, as well as altered sleep-wake cycles. A pilot’s risk for MM may be twice that of matched controls, and the risk for NMSC could be higher.^8,11 Although the literature lacks specific recommendations for pilots, it is reasonable to screen pilots once per year to better assess their individual risk and encourage diligent use of sunscreen and sun-protective measures when flying. It also may be important to advocate for the development of engineering controls that decrease UVR transmittance through windscreens, particularly for aircraft flying at higher altitudes for longer flights. More research is needed to determine if changes in circadian rhythm and decreases in melatonin increase skin cancer risk, which could impact how pilots’ schedules are managed. Together, we can ensure adequate surveillance, diagnosis, and treatment in this at-risk population.

The overall response rate to immune checkpoint inhibitors was 45% among cancer patients who had more than three variants of unknown significance in their circulating tumor DNA; among those with three or fewer, the response rate was 15%, according to a University of California, San Diego, investigation with 69 subjects.

Higher mutation burdens in circulating tumor DNA (ctDNA) also correlated with improved progression-free and overall survival across 20 cancer types, the investigators reported (Clin Cancer Res. 2017 Oct. 1. doi: 10.1158/1078-0432.CCR-17-1439).

Tumor mutation burdens can predict response to checkpoint inhibitors, but they are usually assessed by tissue biopsy, which is costly and invasive. The findings suggest that blood tests could replace tissue biopsies to green-light immune checkpoint inhibitor treatment.

“Our current results may be clinically exploitable. ... Liquid biopsies that assess blood-derived ctDNA are noninvasive, easily acquired, and inexpensive. The ctDNA derived from blood may also represent shed DNA from multiple metastatic sites, whereas tissue genomics reflects only the piece of tissue removed,” said investigators led by Yulian Khagi, MD, a hematology-oncology fellow at the university.

In a press statement, Dr. Khagi said “If verified by further studies, clinicians will be able to utilize the ... results of this simple blood test to make determinations about whether to use checkpoint inhibitor–based immune therapy in a variety of tumor types.”

The 69 patients were a median of 56 years old, and 43 (62.3%) were men. Melanoma, lung cancer, and head and neck cancer were the most common malignancies. The majority of patients had anti–PD-1 or PD-L1 monotherapy.

For most patients, blood samples were drawn a month or 2 before treatment. Next-generation sequencing (Guardant360) was done on ctDNA to detect alterations in cancer genes. Of the 69 patients, 20 (29%) had more than three variants of unknown significance (VUS); the rest had three or fewer.

The median overall survival was 15.3 months from the start of immunotherapy. For patients with three or fewer VUS, median overall survival was 10.72 months; for patients with more, median overall survival could not be calculated because more than half were alive at the study’s conclusion.

Median progression-fee survival was 2.07 months with three or fewer VUS, versus 3.84 months with more. The findings were statistically significant.

Similar results were found when all genomic alterations, not just VUS, were examined and dichotomized as six or more versus fewer than six.

“The number of genes assayed in our ctDNA analysis was only between 54 and 70. Unlike targeted NGS [next-generation sequencing] of tumor tissue, which often tests for hundreds of genes and allows a relatively accurate estimate of total mutational burden, targeted NGS of plasma ctDNA provides only a limited snapshot of the cancer genome. More extensive ctDNA gene panels merit investigation to determine if they increase the correlative value of our findings,” the investigators said.

The work was funded by the Joan and Irwin Jacobs Fund and the National Cancer Institute. Dr. Khagi had no industry disclosures. Three authors reported financial ties to a number of companies, including Boehringer, Merck, Guardant, and Pfizer. The senior author has ownership interests in CureMatch.

aotto@frontlinemedcom.com

The overall response rate to immune checkpoint inhibitors was 45% among cancer patients who had more than three variants of unknown significance in their circulating tumor DNA; among those with three or fewer, the response rate was 15%, according to a University of California, San Diego, investigation with 69 subjects.

Higher mutation burdens in circulating tumor DNA (ctDNA) also correlated with improved progression-free and overall survival across 20 cancer types, the investigators reported (Clin Cancer Res. 2017 Oct. 1. doi: 10.1158/1078-0432.CCR-17-1439).

Tumor mutation burdens can predict response to checkpoint inhibitors, but they are usually assessed by tissue biopsy, which is costly and invasive. The findings suggest that blood tests could replace tissue biopsies to green-light immune checkpoint inhibitor treatment.

“Our current results may be clinically exploitable. ... Liquid biopsies that assess blood-derived ctDNA are noninvasive, easily acquired, and inexpensive. The ctDNA derived from blood may also represent shed DNA from multiple metastatic sites, whereas tissue genomics reflects only the piece of tissue removed,” said investigators led by Yulian Khagi, MD, a hematology-oncology fellow at the university.

In a press statement, Dr. Khagi said “If verified by further studies, clinicians will be able to utilize the ... results of this simple blood test to make determinations about whether to use checkpoint inhibitor–based immune therapy in a variety of tumor types.”

The 69 patients were a median of 56 years old, and 43 (62.3%) were men. Melanoma, lung cancer, and head and neck cancer were the most common malignancies. The majority of patients had anti–PD-1 or PD-L1 monotherapy.

For most patients, blood samples were drawn a month or 2 before treatment. Next-generation sequencing (Guardant360) was done on ctDNA to detect alterations in cancer genes. Of the 69 patients, 20 (29%) had more than three variants of unknown significance (VUS); the rest had three or fewer.

The median overall survival was 15.3 months from the start of immunotherapy. For patients with three or fewer VUS, median overall survival was 10.72 months; for patients with more, median overall survival could not be calculated because more than half were alive at the study’s conclusion.

Median progression-fee survival was 2.07 months with three or fewer VUS, versus 3.84 months with more. The findings were statistically significant.

Similar results were found when all genomic alterations, not just VUS, were examined and dichotomized as six or more versus fewer than six.

“The number of genes assayed in our ctDNA analysis was only between 54 and 70. Unlike targeted NGS [next-generation sequencing] of tumor tissue, which often tests for hundreds of genes and allows a relatively accurate estimate of total mutational burden, targeted NGS of plasma ctDNA provides only a limited snapshot of the cancer genome. More extensive ctDNA gene panels merit investigation to determine if they increase the correlative value of our findings,” the investigators said.

The work was funded by the Joan and Irwin Jacobs Fund and the National Cancer Institute. Dr. Khagi had no industry disclosures. Three authors reported financial ties to a number of companies, including Boehringer, Merck, Guardant, and Pfizer. The senior author has ownership interests in CureMatch.

aotto@frontlinemedcom.com

The overall response rate to immune checkpoint inhibitors was 45% among cancer patients who had more than three variants of unknown significance in their circulating tumor DNA; among those with three or fewer, the response rate was 15%, according to a University of California, San Diego, investigation with 69 subjects.

Higher mutation burdens in circulating tumor DNA (ctDNA) also correlated with improved progression-free and overall survival across 20 cancer types, the investigators reported (Clin Cancer Res. 2017 Oct. 1. doi: 10.1158/1078-0432.CCR-17-1439).

Tumor mutation burdens can predict response to checkpoint inhibitors, but they are usually assessed by tissue biopsy, which is costly and invasive. The findings suggest that blood tests could replace tissue biopsies to green-light immune checkpoint inhibitor treatment.

“Our current results may be clinically exploitable. ... Liquid biopsies that assess blood-derived ctDNA are noninvasive, easily acquired, and inexpensive. The ctDNA derived from blood may also represent shed DNA from multiple metastatic sites, whereas tissue genomics reflects only the piece of tissue removed,” said investigators led by Yulian Khagi, MD, a hematology-oncology fellow at the university.

In a press statement, Dr. Khagi said “If verified by further studies, clinicians will be able to utilize the ... results of this simple blood test to make determinations about whether to use checkpoint inhibitor–based immune therapy in a variety of tumor types.”

The 69 patients were a median of 56 years old, and 43 (62.3%) were men. Melanoma, lung cancer, and head and neck cancer were the most common malignancies. The majority of patients had anti–PD-1 or PD-L1 monotherapy.

For most patients, blood samples were drawn a month or 2 before treatment. Next-generation sequencing (Guardant360) was done on ctDNA to detect alterations in cancer genes. Of the 69 patients, 20 (29%) had more than three variants of unknown significance (VUS); the rest had three or fewer.

The median overall survival was 15.3 months from the start of immunotherapy. For patients with three or fewer VUS, median overall survival was 10.72 months; for patients with more, median overall survival could not be calculated because more than half were alive at the study’s conclusion.

Median progression-fee survival was 2.07 months with three or fewer VUS, versus 3.84 months with more. The findings were statistically significant.

Similar results were found when all genomic alterations, not just VUS, were examined and dichotomized as six or more versus fewer than six.

“The number of genes assayed in our ctDNA analysis was only between 54 and 70. Unlike targeted NGS [next-generation sequencing] of tumor tissue, which often tests for hundreds of genes and allows a relatively accurate estimate of total mutational burden, targeted NGS of plasma ctDNA provides only a limited snapshot of the cancer genome. More extensive ctDNA gene panels merit investigation to determine if they increase the correlative value of our findings,” the investigators said.

The work was funded by the Joan and Irwin Jacobs Fund and the National Cancer Institute. Dr. Khagi had no industry disclosures. Three authors reported financial ties to a number of companies, including Boehringer, Merck, Guardant, and Pfizer. The senior author has ownership interests in CureMatch.

aotto@frontlinemedcom.com

Adults with a history of lithium exposure had a 32% lower risk of melanoma than did those who were not exposed in an unadjusted analysis of data from more than 2 million patients.

Microarray gene profiling techniques suggest that Wnt genes, which “encode a family of secreted glycoproteins that activate cellular signaling pathways to control cell differentiation, proliferation, and motility,” may be involved in melanoma development, wrote Maryam M. Asgari, MD, of the department of dermatology at Massachusetts General Hospital and the department of population medicine at Harvard University, both in Boston, and her colleagues. In particular, “transcriptional profiling of melanoma cell lines has suggested that Wnt/beta-catenin signaling regulates a transcriptional signature predictive of less aggressive melanoma,” they wrote.

The psychiatric medication lithium activates the Wnt/beta-catenin signaling pathway and has shown an ability to inhibit the proliferation of melanoma cells in a mouse model, but “to our knowledge, no published epidemiologic studies have examined the association of melanoma risk with lithium exposure,” they wrote.

The researchers reviewed data from the Kaiser Permanente Northern California database of 2,213,848 adult white patients who were members during 1997-2012, which included 11,317 with lithium exposure. They evaluated the association between lithium exposure and both incident melanoma risk and melanoma-associated mortality (J Invest Dermatol. 2017 Oct;137[10]:2087-91.).

Individuals exposed to lithium had a 32% reduced risk of melanoma in an unadjusted analysis; in an adjusted analysis, the reduced risk was 23% and was not significant.

However, there was a significant difference in melanoma incidence per 100,000 person-years in lithium-exposed individuals, compared with unexposed individuals (67.4 vs. 92.5, respectively; P = .027).

Among patients with melanoma, those with exposure to lithium had a lower mortality rate than those not exposed (4.68 vs. 7.21 per 1,000 person-years, respectively), but the sample size for this subgroup was too small to determine statistical significance. In addition, lithium exposure was associated with reduced likelihood of developing skin tumors greater than 4 mm and of presenting with extensive disease. Among those exposed to lithium, none presented with a thick tumor (Breslow depth greater than 4 mm), and none had regional or distant disease when they were diagnosed, compared with 2.8% and 6.3%, respectively, of those not exposed to lithium.

The findings were limited by several factors, including reliance on prescription information to determine lithium exposure, a homogeneous study population, and confounding variables, such as sun exposure behaviors, the researchers noted. However, the large study population adds strength to the results, and “our conclusions provide evidence that lithium, a relatively inexpensive and readily available drug, warrants further study in melanoma,” they said.

Lead author Dr. Asgari and one of the other four authors disclosed serving as investigators for studies funded by Valeant Pharmaceuticals and Pfizer. This study was supported by the National Cancer Institute. Dr. Asgari is principal investigator in the Patient-Oriented Research in the Epidemiology of Skin Diseases lab at Massachusetts General Hospital, Boston.

Adults with a history of lithium exposure had a 32% lower risk of melanoma than did those who were not exposed in an unadjusted analysis of data from more than 2 million patients.

Microarray gene profiling techniques suggest that Wnt genes, which “encode a family of secreted glycoproteins that activate cellular signaling pathways to control cell differentiation, proliferation, and motility,” may be involved in melanoma development, wrote Maryam M. Asgari, MD, of the department of dermatology at Massachusetts General Hospital and the department of population medicine at Harvard University, both in Boston, and her colleagues. In particular, “transcriptional profiling of melanoma cell lines has suggested that Wnt/beta-catenin signaling regulates a transcriptional signature predictive of less aggressive melanoma,” they wrote.

The psychiatric medication lithium activates the Wnt/beta-catenin signaling pathway and has shown an ability to inhibit the proliferation of melanoma cells in a mouse model, but “to our knowledge, no published epidemiologic studies have examined the association of melanoma risk with lithium exposure,” they wrote.

The researchers reviewed data from the Kaiser Permanente Northern California database of 2,213,848 adult white patients who were members during 1997-2012, which included 11,317 with lithium exposure. They evaluated the association between lithium exposure and both incident melanoma risk and melanoma-associated mortality (J Invest Dermatol. 2017 Oct;137[10]:2087-91.).

Individuals exposed to lithium had a 32% reduced risk of melanoma in an unadjusted analysis; in an adjusted analysis, the reduced risk was 23% and was not significant.

However, there was a significant difference in melanoma incidence per 100,000 person-years in lithium-exposed individuals, compared with unexposed individuals (67.4 vs. 92.5, respectively; P = .027).

Among patients with melanoma, those with exposure to lithium had a lower mortality rate than those not exposed (4.68 vs. 7.21 per 1,000 person-years, respectively), but the sample size for this subgroup was too small to determine statistical significance. In addition, lithium exposure was associated with reduced likelihood of developing skin tumors greater than 4 mm and of presenting with extensive disease. Among those exposed to lithium, none presented with a thick tumor (Breslow depth greater than 4 mm), and none had regional or distant disease when they were diagnosed, compared with 2.8% and 6.3%, respectively, of those not exposed to lithium.

The findings were limited by several factors, including reliance on prescription information to determine lithium exposure, a homogeneous study population, and confounding variables, such as sun exposure behaviors, the researchers noted. However, the large study population adds strength to the results, and “our conclusions provide evidence that lithium, a relatively inexpensive and readily available drug, warrants further study in melanoma,” they said.

Lead author Dr. Asgari and one of the other four authors disclosed serving as investigators for studies funded by Valeant Pharmaceuticals and Pfizer. This study was supported by the National Cancer Institute. Dr. Asgari is principal investigator in the Patient-Oriented Research in the Epidemiology of Skin Diseases lab at Massachusetts General Hospital, Boston.

Adults with a history of lithium exposure had a 32% lower risk of melanoma than did those who were not exposed in an unadjusted analysis of data from more than 2 million patients.

Microarray gene profiling techniques suggest that Wnt genes, which “encode a family of secreted glycoproteins that activate cellular signaling pathways to control cell differentiation, proliferation, and motility,” may be involved in melanoma development, wrote Maryam M. Asgari, MD, of the department of dermatology at Massachusetts General Hospital and the department of population medicine at Harvard University, both in Boston, and her colleagues. In particular, “transcriptional profiling of melanoma cell lines has suggested that Wnt/beta-catenin signaling regulates a transcriptional signature predictive of less aggressive melanoma,” they wrote.

The psychiatric medication lithium activates the Wnt/beta-catenin signaling pathway and has shown an ability to inhibit the proliferation of melanoma cells in a mouse model, but “to our knowledge, no published epidemiologic studies have examined the association of melanoma risk with lithium exposure,” they wrote.

The researchers reviewed data from the Kaiser Permanente Northern California database of 2,213,848 adult white patients who were members during 1997-2012, which included 11,317 with lithium exposure. They evaluated the association between lithium exposure and both incident melanoma risk and melanoma-associated mortality (J Invest Dermatol. 2017 Oct;137[10]:2087-91.).

Individuals exposed to lithium had a 32% reduced risk of melanoma in an unadjusted analysis; in an adjusted analysis, the reduced risk was 23% and was not significant.

However, there was a significant difference in melanoma incidence per 100,000 person-years in lithium-exposed individuals, compared with unexposed individuals (67.4 vs. 92.5, respectively; P = .027).

Among patients with melanoma, those with exposure to lithium had a lower mortality rate than those not exposed (4.68 vs. 7.21 per 1,000 person-years, respectively), but the sample size for this subgroup was too small to determine statistical significance. In addition, lithium exposure was associated with reduced likelihood of developing skin tumors greater than 4 mm and of presenting with extensive disease. Among those exposed to lithium, none presented with a thick tumor (Breslow depth greater than 4 mm), and none had regional or distant disease when they were diagnosed, compared with 2.8% and 6.3%, respectively, of those not exposed to lithium.

The findings were limited by several factors, including reliance on prescription information to determine lithium exposure, a homogeneous study population, and confounding variables, such as sun exposure behaviors, the researchers noted. However, the large study population adds strength to the results, and “our conclusions provide evidence that lithium, a relatively inexpensive and readily available drug, warrants further study in melanoma,” they said.

Lead author Dr. Asgari and one of the other four authors disclosed serving as investigators for studies funded by Valeant Pharmaceuticals and Pfizer. This study was supported by the National Cancer Institute. Dr. Asgari is principal investigator in the Patient-Oriented Research in the Epidemiology of Skin Diseases lab at Massachusetts General Hospital, Boston.