Melanoma

Nonmelanoma skin cancer (NMSC) is the most common cancer in the United States, and cutaneous melanoma is projected to be the fifth most common form of cancer in 2022, with increasing incidence and high potential for mortality.^1-3 Estimates indicate that 35% to 45% of all cancers in White patients are cutaneous, with 4% to 5% occurring in Hispanic patients, 2% to 4% in Asian patients, and 1% to 2% in Black patients.⁴ Of the keratinocyte carcinomas, basal cell carcinoma (BCC) is the most prevalent, projected to affect approximately 33% to 39% of White males and 23% to 28% of White females in the United States during their lifetimes. Squamous cell carcinoma (SCC) is the second most common skin malignancy, with a lifetime risk of 9% to 14% for White males and 4% to 9% for White females in the United States.⁵ The incidence of melanoma continues to increase, with approximately 99,780 new cases expected in the United States in 2022.¹

UV-induced DNA damage plays a key role in the pathogenesis and development of various skin malignancies.⁶ UV radiation from sunlight or tanning devices causes photocarcinogenesis due to molecular and cellular effects, including the generation of reactive oxygen species, DNA damage due to the formation of cyclobutane pyrimidine dimers and pyrimidine-pyrimidone, melanogenesis, apoptosis, and the increased expression of harmful genes and proteins.⁶ The summation of this damage can result in skin malignancies, including NMSC and melanoma.^6,7 Dietary antioxidants theoretically help prevent oxidative reactions from occurring within the body, and it has been suggested that intake of dietary antioxidants may decrease DNA damage and prevent tumorigenesis secondary to UV radiation.⁸ Antioxidants exist naturally in the body but can be acquired exogenously. Investigators have studied dietary antioxidants in preventing skin cancer formation with promising results in the laboratory setting.^8-11 Recently, more robust human studies have been initiated to further delineate this relationship. We present clinical evidence of several frequently utilized antioxidant vitamins and their effects on melanoma and NMSC.

Antioxidants

Vitamin A—Vitamin A is a fat-soluble vitamin found in animal sources, including fish, liver, and eggs. Carotenoids, such as beta carotene, are provitamin A plant derivatives found in fruits and vegetables that are converted into biologically active retinol and retinoic acid.¹² Retinols play a key role in cellular growth and differentiation and are thought to be protective against skin cancer via the inactivation of free radicals and immunologic enhancement due to their antiproliferative, antioxidative, and antiapoptotic effects.^13-16 Animal studies have demonstrated this protective effect and the ability of retinoids to suppress carcinogenesis; however, human studies reveal conflicting results.^17,18

Greenberg et al¹⁹ investigated the use of beta carotene in preventing the formation of NMSC. Patients (N=1805) were randomized to receive 50 mg of beta carotene daily or placebo. Over a 5-year period, there was no significant reduction in the occurrence of NMSC (relative risk [RR], 1.05; 95% CI, 0.91-1.22).¹⁹ Frieling et al²⁰ conducted a similar randomized, double-blind, placebo-controlled trial investigating beta carotene for primary prevention of NMSC in 22,071 healthy male physicians. The study group received 50 mg of beta carotene every other day for 12 years’ duration, and there was no significant effect on the incidence of first NMSC development (RR, 0.98; 95% CI, 0.92-1.05).²⁰

A case-control study by Naldi et al²¹ found an inverse association between vitamin A intake and development of melanoma. Study participants were stratified into quartiles based on level of dietary intake and found an odds ratio (OR) of 0.71 for beta carotene (95% CI, 0.50-1.02), 0.57 for retinol (95% CI, 0.39-0.83), and 0.51 for total vitamin A (95% CI, 0.35-0.75) when comparing the upper quartile of vitamin A intake to the lower quartile. Upper-quartile cutoff values of vitamin A intake were 214 µg/d for beta carotene, 149 µg/d for retinol, and 359 µg/d for total vitamin A.²¹ More recently, a meta-analysis by Zhang et al²² pooled data from 8 case-control studies and 2 prospective studies. Intake of retinol but not total vitamin A or beta carotene was associated with a reduced risk for development of melanoma (retinol: OR, 0.80; 95% CI, 0.69-0.92; total vitamin A: OR, 0.86; 95% CI, 0.59-1.25; beta carotene: OR, 0.87; 95% CI, 0.62-1.20).²² Feskanich et al²³ demonstrated similar findings with use of food-frequency questionnaires in White women, suggesting that retinol intake from food combined with supplements may be protective for women who were otherwise at a low risk for melanoma based on nondietary factors. These factors included painful or blistering sunburns during childhood, history of more than 6 sunburns, more than 3 moles on the left arm, having red or blonde hair, and having a parent or sibling with melanoma (P=.01). However, this relationship did not hold true when looking at women at an intermediate or high risk for melanoma (P=.16 and P=.46).²³

When looking at high-risk patients, such as transplant patients, oral retinoids have been beneficial in preventing NMSC.^24-27 Bavinck et al²⁴ investigated 44 renal transplant patients with a history of more than 10 NMSCs treated with 30 mg of acitretin daily vs placebo. Patients receiving oral retinoid supplementation developed fewer NMSCs over a 6-month treatment period (P=.01).²⁴ Similarly, George et al²⁵ investigated acitretin in renal transplant patients and found a statistically significant decrease in number of SCCs in patients on supplementation (P=.002). Solomon-Cohen et al²⁶ performed a retrospective case-crossover study in solid organ transplant recipients and found that those treated with 10 mg of acitretin daily for 2 years had a significant reduction in the number of new keratinocyte carcinomas (P=.002). Other investigators have demonstrated similar results, and in 2006, Otley et al²⁷ proposed standardized dosing of acitretin for chemoprevention in high-risk patients, including patients developing 5 to 10 NMSCs per year, solid organ transplant recipients, and those with syndromes associated with the development of NMSC.^28,29 Overall, in the general population, vitamin A and related compounds have not demonstrated a significant association with decreased development of NMSC; however, oral retinoids have proven useful for high-risk patients. Furthermore, several studies have suggested a negative association between vitamin A levels and the incidence of melanoma, specifically in the retinol formulation. 

Vitamin B₃—Nicotinamide (also known as niacinamide) is a water-soluble form of vitamin B₃ and is obtained from animal-based and plant-based foods, such as meat, fish, and legumes.³⁰ Nicotinamide plays a key role in cellular metabolism, cellular signaling, and DNA repair, including protection from UV damage within keratinocytes.^31,32 Early mouse models demonstrated decreased formation of skin tumors in mice treated with topical or oral nicotinamide.^32,33 A number of human studies have revealed similar results.^34-36

Chen et al³⁴ conducted the ONTRAC study, a phase 3, double-blind, randomized controlled trial (RCT) looking at 386 participants with a history of at least 2 NMSCs in the preceding 5 years. At 12 months, those treated with 500 mg of nicotinamide twice daily demonstrated a statistically significant decreased rate of SCC formation (P=.05). A decreased incidence of BCC development was noted; however, this trend did not reach statistical significance (P=.12). Precancerous skin lesions also were found to be decreased in the treatment group, with 20% lower incidence of actinic keratoses (AKs) after 9 months of treatment (P<.001).³⁴ Drago et al³⁵ specifically studied the incidence of AKs in 38 transplant recipients—8 liver and 30 kidney—and found that previously noted AKs had decreased in size for 18 of 19 patients taking 500 mg of nicotinamide daily when originally photographed AKs were remeasured at 6-month follow-up, with 7 of these 18 patients demonstrating complete clinical regression. Of those on nicotinamide supplementation, no new AKs developed compared to the control group, which demonstrated increased size of AKs or development of new AKs in 91% of patients, with 7 AKs progressing into SCC.³⁵

Nicotinamide has been demonstrated to be useful in preventing skin cancer in high-risk populations, such as transplant patients or those with a high incidence of NMSC.^34,36 Despite promising results within the laboratory setting, nicotinamide’s effects on melanoma in humans remains less clear.^31,37 Studies suggest that nicotinamide enhances tumor-infiltrating lymphocytes and DNA repair mechanisms in melanocytes, which may translate into nicotinamide, providing chemoprevention for melanoma, but research in human patients is limited.^31,37

Vitamin B₉—Folate, the natural form of vitamin B₉, is a water-soluble compound that is found in many foods, especially green leafy vegetables, and often is supplemented because of its health benefits.^38,39 In the skin, folic acid plays a key role in cellular replication and proliferation.³⁸ Controversy exists regarding folate’s effects on cellular growth and turnover with respect to cancer incidence.^38,40 Donnenfeld et al⁴¹ conducted a prospective study assessing dietary folic acid intake and development of NMSC. A total of 5880 participants completed dietary records throughout the first 2 years of the study. After an average follow-up period of 12.6 years, there was an overall increased incidence of skin cancer in those with increased dietary folate (P=.03). Furthermore, when striating by skin cancer type, there was an increased incidence of NMSC overall as well as BCC when analyzing by type of NMSC (P=.03 for NMSC; P=.05 for BCC). However, when stratifying by gender, these findings only held true for women.⁴¹ Similar effects were observed by Fung et al,⁴² who prospectively studied the intake of various vitamins in relationship to the development of BCC in women. During 12 years of follow-up, a positive association was observed between folate intake and BCC development (OR, 1.2; 95% CI, 1.10-1.31).⁴² Fung et al⁴³ also investigated the role of several vitamins in the development of SCC and found that folate showed a negative association, which did not reach statistical significance (RR, 0.79; 95% CI, 0.56-1.11). Furthermore, Vollset et al⁴⁰ conducted a meta-analysis comparing folic acid to placebo in the incidence of various types of cancer. The study excluded NMSC but reported no significant association between the development of melanoma and folic acid supplementation.⁴⁰ In summary, the effects of folate have diverse consequences, potentially promoting the formation of NMSC, but studies suggest that an individual’s gender and other genetic and environmental factors also may play a role.

Vitamin C—Vitamin C (also known as ascorbic acid) is a water-soluble vitamin with antioxidant immune-mediating effects. It is found in various fruits and vegetables and serves as a cofactor for enzymes within the body playing a key role in immune function and collagen formation.^44,45 It has been postulated that ascorbic acid can provide protection from UV radiation damage via its intracellular activity but conversely can contribute to oxidative damage.⁴⁴ Multiple in vitro laboratory studies and animal models have demonstrated photoprotective effects of ascorbic acid.^46-48 Despite these findings, minimal photoprotective effects have been found in the human population.

Kune et al⁴⁹ performed a case-control study of 88 males with previously diagnosed NMSC undergoing surgical removal and investigated patients’ prior dietary habits. Patients with NMSC had a statistically significantly lower level of vitamin C–containing food in their diet than those without NMSC (P=.004).⁴⁹ In addition, Vural et al⁵⁰ analyzed plasma samples and blood cells of patients with AK and BCC and found a significant decrease in ascorbic acid levels in both the AK (P<.001) and BCC (P<.001) groups compared with controls. However, studies have found that consumption of certain dietary compounds can rapidly increase plasma concentration levels, which may serve as a major confounding variable in this study. Plasma concentrations of ascorbic acid and beta carotene were found to be significantly increased following consumption of a high-antioxidant diet for as short a duration as 2 weeks (P<.05).⁵¹ More recently, Heinen et al⁵² performed a prospective study on 1001 adults. In patients without a history of skin cancer, they found that vitamin C from food sources plus dietary supplements was positively associated with the development of BCC (P=.03).⁵² Similarly, Fung et al⁴² performed a study in women and found a positive association between vitamin C intake and the development of BCC (OR, 1.13; 95% CI, 1.03-1.23).

The relationship between vitamin C intake—either in dietary or supplemental form—and melanoma remains controversial. Mice-based studies found that high concentrations of orally administered vitamin C induce cytotoxicity in melanoma cell lines, but at low concentrations they promote tumor growth of malignant melanoma.⁵³ Feskanich et al²³ examined the relationship between vitamin C intake and melanoma development via food frequency questionnaires in White women and found that vitamin C was associated with a higher risk for melanoma (P=.05), and furthermore, a positive dose response with frequency of orange juice intake was observed (P=.008). Overall, despite promising laboratory studies, there is a lack of RCTs investigating the use of vitamin C supplementation for prevention of NMSC and melanoma in humans, and the oral benefits of vitamin C for chemoprevention remain unclear.

Vitamin D—Vitamin D is a fat-soluble vitamin that is found in fish, liver, egg, and cheese, and is endogenously produced when UV radiation from sun exposure interacts with the skin, triggering the synthesis of vitamin D.⁵⁴ Vitamin D is biologically inactive and must be converted to its active form 1,25-dihydroxyvitamin D after entering the body. Vitamin D modulates many genes involved in cellular proliferation and differentiation.⁵⁴ Vitamin D receptors are expressed on keratinocytes and melanocytes.⁵⁵ Animal studies have demonstrated a potentially protective effect of vitamin D in the development of NMSC.⁵⁶ In a mouse model, Ellison et al⁵⁶ found that mice without vitamin D receptors developed skin tumors more rapidly than those with vitamin D receptors.

Unfortunately, these findings have not been demonstrated in humans, and studies have even reported an increased risk for development of NMSC in patients with normal or increased vitamin D levels compared with those with low levels of vitamin D.^57-60 Eide et al⁵⁷ studied 3223 patients seeking advice for low bone density by recording their vitamin D levels at the time of presentation and monitoring development of NMSC. Vitamin D levels greater than 15 ng/mL were positively associated with the development of NMSC (OR, 1.7; 95% CI, 1.04-2.7). This association held true for both SCC and BCC, with a higher risk estimated for SCC (OR, 3.2; 95% CI, 0.4-24.0 for SCC; OR, 1.7; 95% CI, 0.5-5.8 for BCC).⁵⁷ An increased vitamin D serum level also was found to be significantly associated with a higher risk for BCC and melanoma by van der Pols et al.⁵⁸ This prospective study looked at the incidence of skin cancer over 11 years. Study participants with vitamin D levels over 75 nmol/L more frequently developed BCC (P=.01) and melanoma (P=.05). In contrast, SCC was less frequently observed in participants with these high levels of vitamin D (P=.07).⁵⁸ Furthermore, Park et al⁶⁰ looked at vitamin D and skin cancer risk for men and women in the United States and found no association with risk for SCC or melanoma but a positive association with BCC (P=.05 for total vitamin D; P<.01 for dietary vitamin D). Additional studies have been performed with inconsistent results, and multiple authors suggest the possible confounding relationship between vitamin D levels and UV radiation exposure.^59-62 Furthermore, some studies have even demonstrated a negative association between vitamin D and NMSC. Tang et al⁶³ performed a retrospective case-control study in elderly males, investigating serum levels of vitamin D and patients’ self-reported history of NMSC, which demonstrated that higher levels of vitamin D were associated with a decreased risk for NMSC. Overall, the relationship between vitamin D and skin cancer development remains unclear for both melanoma and NMSC.

Vitamin E—Vitamin E is a fat-soluble vitamin that is found in plant-based oils, nuts, seeds, fruits, and vegetables.⁶⁴ It works as an antioxidant to protect against free radicals and heighten immune function, and it also serves as a pro-oxidant.^65,66 Vitamin E naturally exists in 8 chemical forms, of which gamma-tocopherol is the most frequently obtained form in the diet, and alpha-tocopherol is the most abundant form found in the body.^64,65

Early animal studies demonstrated the inhibition of UV-induced damage in mice receiving vitamin E supplementation.^67,68 Human studies have not consistently shown these effects. Vural et al⁵⁰ investigated plasma samples and blood cells of patients with AKs and BCCs and reported a significant decrease in alpha-tocopherol levels in both the AK (P<.05) and BCC (P<.001) groups compared with controls. However, studies also have demonstrated a positive association between vitamin E intake and the development of BCC, including one by Fung et al,⁴² which found a significant association in women (OR, 1.15; 95% CI, 1.06-1.26).

Vitamin E has been found to inhibit melanin synthesis in the laboratory, suggesting a potentially protective effect in melanoma.^69,70 However, in the study performed by Feskanich et al²³ examining vitamin intake and melanoma incidence via food-frequency questionnaires, vitamin E was not associated with a lower risk for melanoma. Despite promising laboratory studies, the data surrounding the use of a vitamin E supplement for prevention of melanoma and NMSC in humans remains unclear.

Selenium—Selenium is a trace mineral found in plants, meat, and fish. It plays a key role in reproduction, hormone metabolism, DNA synthesis, and protection from oxidative damage.⁷¹ In mice studies, lack of selenium-containing proteins resulted in skin abnormalities, including the development of a hyperplastic epidermis and aberrant hair follicle morphogenesis with alopecia after birth, and numerous experimental studies have demonstrated a negative association between selenium intake and cancer.^72,73 However, human studies have yielded alternative results. 

The Nutritional Prevention of Cancer Study Group analyzed 1312 dermatology patients with a history of NMSC.⁷⁴ The study population was obtained from 7 dermatology clinics with randomization to control for confounding variables. Study participants received either 200 μg of selenium daily or placebo.⁷⁴ Baseline characteristics of each study group were overall balanced. Selenium intake was found to have no effect on the development of BCC (hazard ratio [HR], 1.09; 95% CI, 0.94-1.26) but an increased risk for developing SCC (HR, 1.25; 95% CI, 1.03-1.51) and total NMSC (HR, 1.17; 95% CI, 1.02-1.34).^74,75 Similarly, Reid et al⁷⁶ performed an RCT comparing patients treated with 400 μg/d of selenium to those treated with 200 μg/d of selenium. When compared with placebo, those treated with 200 μg/d of selenium had a statistically significantly increased incidence of NMSC (P=.006); however, those treated with 400 μg/d of selenium had no significant change in total incidence of NMSC (P=.51).⁷⁶ Furthermore, Vinceti et al⁷⁷ performed a review of 83 studies from the literature investigating the effect of dietary selenium, and from the RCTs, there was no beneficial effect of selenium in reducing cancer risk in general; however, some studies demonstrated an increased incidence of other types of cancer, including melanoma. Of the RCTs included in the study investigating NMSC incidence specifically, it was found that the incidence was not affected by selenium administration (RR, 1.16; 95% CI, 0.30-4.42; 2 studies, 2027 participants).⁷⁷ Despite data from several studies demonstrating an increased risk for NMSC, the effects of selenium on the risk for NMSC and melanoma remain unclear. 

Combination Antioxidant Studies

In addition to investigating the use of single antioxidants in skin cancer prevention, studies utilizing the combination of various antioxidants or other dietary minerals have been conducted. Hercberg et al⁷⁸ performed a randomized, double-blinded, placebo-controlled trial of 13,017 adults (7876 women and 5141 men) receiving a combination of 120 mg vitamin C, 30 mg vitamin E, 100 μg selenium, 6 mg beta carotene, and 20 mg zinc. Study participants were followed for an average of 7.5 years, and the development of skin cancers were recorded. Overall, the incidence rate of skin cancer did not differ between the 2 treatment groups; however, when segregated by gender, the study found that there was an increased risk for developing skin cancer in women taking the antioxidant supplement combination compared with placebo (P=.03). This difference was not observed in the 2 treatment groups of male patients (P=.11). When looking specifically at NMSC, there was no difference between treatment groups for male or female patients (P=.39 for males; P=.15 for females). In contrast, there was a higher incidence of melanoma identified in female patients taking the combination antioxidant supplement (P=.01), but this was not seen within the male study population (P=.51).⁷⁸ In addition, Chang et al⁷⁹ performed a meta-analysis of 10 previously published RCTs. Analysis revealed that treatment with a variety of supplements, including vitamins A, C, E, and beta carotene, were found to have no preventative effects on the incidence of skin cancer development (RR, 0.98; CI, 0.98-1.03). Notable limitations to this study included the variability in protocols of the studies included in this meta-analysis, the limited number of RCTs investigating vitamin supplementation and the risk for skin cancer development, and the influence of dietary intake on study outcomes.⁷⁹

Other Dietary Agents

Furocoumarins—Furocoumarins are botanical substances found in various fruits and plants, including many citrus products. Furocoumarins are activated by UV light radiation and can lead to development of a phototoxic eruption. Several studies have suggested a pharmacogenetic effect of furocoumarins.⁸⁰ Sun et al⁸⁰ collected dietary data from 47,453 men and 75,291 women on furocoumarin intake and correlation with the development of NMSC. Overall, the study suggested that the intake of furocoumarins may lead to an increase in the development of BCC (HR, 1.16; 95% CI, 1.11-1.21; P=.002); however, there was no significant association identified between total intake of furocoumarins in the risk for SCC or melanoma.⁸⁰ Furthermore, Sakaki et al⁸¹ conducted a survey study looking at the consumption of citrus products and the development of NMSC. The group found that there was an increased risk for NMSC in those consuming an increased amount of citrus products (P=.007).⁸¹

Conclusion

Dietary antioxidants have been investigated for their potential role in the prevention of tumorigenesis. Specific antioxidant vitamins, such as vitamin A derivatives and niacinamide, have demonstrated clinical utility in the prevention of NMSC in high-risk populations. Retinol also has been associated with a reduced incidence of melanoma. Numerous antioxidants have demonstrated promising data within the laboratory setting; however, inconsistent results have been appreciated in humans. Furthermore, several research studies suggest that folate, vitamin D, and furocoumarins may be associated with an increased risk for skin cancer development; however, these studies are inconclusive, and dietary studies are challenging to conduct. Overall, RCTs investigating the role of antioxidants for chemoprevention are limited. Moreover, the study of dietary antioxidants and vitamins may be affected by various confounding variables that can be difficult to account for because of patients’ potentially poor recall of dietary intake and the effect of dietary intake in supplemental studies. Given the increasing prevalence of skin cancer worldwide, further research into the clinical utility of antioxidants in skin cancer prevention is warranted. 

Nonmelanoma skin cancer (NMSC) is the most common cancer in the United States, and cutaneous melanoma is projected to be the fifth most common form of cancer in 2022, with increasing incidence and high potential for mortality.^1-3 Estimates indicate that 35% to 45% of all cancers in White patients are cutaneous, with 4% to 5% occurring in Hispanic patients, 2% to 4% in Asian patients, and 1% to 2% in Black patients.⁴ Of the keratinocyte carcinomas, basal cell carcinoma (BCC) is the most prevalent, projected to affect approximately 33% to 39% of White males and 23% to 28% of White females in the United States during their lifetimes. Squamous cell carcinoma (SCC) is the second most common skin malignancy, with a lifetime risk of 9% to 14% for White males and 4% to 9% for White females in the United States.⁵ The incidence of melanoma continues to increase, with approximately 99,780 new cases expected in the United States in 2022.¹

UV-induced DNA damage plays a key role in the pathogenesis and development of various skin malignancies.⁶ UV radiation from sunlight or tanning devices causes photocarcinogenesis due to molecular and cellular effects, including the generation of reactive oxygen species, DNA damage due to the formation of cyclobutane pyrimidine dimers and pyrimidine-pyrimidone, melanogenesis, apoptosis, and the increased expression of harmful genes and proteins.⁶ The summation of this damage can result in skin malignancies, including NMSC and melanoma.^6,7 Dietary antioxidants theoretically help prevent oxidative reactions from occurring within the body, and it has been suggested that intake of dietary antioxidants may decrease DNA damage and prevent tumorigenesis secondary to UV radiation.⁸ Antioxidants exist naturally in the body but can be acquired exogenously. Investigators have studied dietary antioxidants in preventing skin cancer formation with promising results in the laboratory setting.^8-11 Recently, more robust human studies have been initiated to further delineate this relationship. We present clinical evidence of several frequently utilized antioxidant vitamins and their effects on melanoma and NMSC.

Antioxidants

Vitamin A—Vitamin A is a fat-soluble vitamin found in animal sources, including fish, liver, and eggs. Carotenoids, such as beta carotene, are provitamin A plant derivatives found in fruits and vegetables that are converted into biologically active retinol and retinoic acid.¹² Retinols play a key role in cellular growth and differentiation and are thought to be protective against skin cancer via the inactivation of free radicals and immunologic enhancement due to their antiproliferative, antioxidative, and antiapoptotic effects.^13-16 Animal studies have demonstrated this protective effect and the ability of retinoids to suppress carcinogenesis; however, human studies reveal conflicting results.^17,18

Greenberg et al¹⁹ investigated the use of beta carotene in preventing the formation of NMSC. Patients (N=1805) were randomized to receive 50 mg of beta carotene daily or placebo. Over a 5-year period, there was no significant reduction in the occurrence of NMSC (relative risk [RR], 1.05; 95% CI, 0.91-1.22).¹⁹ Frieling et al²⁰ conducted a similar randomized, double-blind, placebo-controlled trial investigating beta carotene for primary prevention of NMSC in 22,071 healthy male physicians. The study group received 50 mg of beta carotene every other day for 12 years’ duration, and there was no significant effect on the incidence of first NMSC development (RR, 0.98; 95% CI, 0.92-1.05).²⁰

A case-control study by Naldi et al²¹ found an inverse association between vitamin A intake and development of melanoma. Study participants were stratified into quartiles based on level of dietary intake and found an odds ratio (OR) of 0.71 for beta carotene (95% CI, 0.50-1.02), 0.57 for retinol (95% CI, 0.39-0.83), and 0.51 for total vitamin A (95% CI, 0.35-0.75) when comparing the upper quartile of vitamin A intake to the lower quartile. Upper-quartile cutoff values of vitamin A intake were 214 µg/d for beta carotene, 149 µg/d for retinol, and 359 µg/d for total vitamin A.²¹ More recently, a meta-analysis by Zhang et al²² pooled data from 8 case-control studies and 2 prospective studies. Intake of retinol but not total vitamin A or beta carotene was associated with a reduced risk for development of melanoma (retinol: OR, 0.80; 95% CI, 0.69-0.92; total vitamin A: OR, 0.86; 95% CI, 0.59-1.25; beta carotene: OR, 0.87; 95% CI, 0.62-1.20).²² Feskanich et al²³ demonstrated similar findings with use of food-frequency questionnaires in White women, suggesting that retinol intake from food combined with supplements may be protective for women who were otherwise at a low risk for melanoma based on nondietary factors. These factors included painful or blistering sunburns during childhood, history of more than 6 sunburns, more than 3 moles on the left arm, having red or blonde hair, and having a parent or sibling with melanoma (P=.01). However, this relationship did not hold true when looking at women at an intermediate or high risk for melanoma (P=.16 and P=.46).²³

When looking at high-risk patients, such as transplant patients, oral retinoids have been beneficial in preventing NMSC.^24-27 Bavinck et al²⁴ investigated 44 renal transplant patients with a history of more than 10 NMSCs treated with 30 mg of acitretin daily vs placebo. Patients receiving oral retinoid supplementation developed fewer NMSCs over a 6-month treatment period (P=.01).²⁴ Similarly, George et al²⁵ investigated acitretin in renal transplant patients and found a statistically significant decrease in number of SCCs in patients on supplementation (P=.002). Solomon-Cohen et al²⁶ performed a retrospective case-crossover study in solid organ transplant recipients and found that those treated with 10 mg of acitretin daily for 2 years had a significant reduction in the number of new keratinocyte carcinomas (P=.002). Other investigators have demonstrated similar results, and in 2006, Otley et al²⁷ proposed standardized dosing of acitretin for chemoprevention in high-risk patients, including patients developing 5 to 10 NMSCs per year, solid organ transplant recipients, and those with syndromes associated with the development of NMSC.^28,29 Overall, in the general population, vitamin A and related compounds have not demonstrated a significant association with decreased development of NMSC; however, oral retinoids have proven useful for high-risk patients. Furthermore, several studies have suggested a negative association between vitamin A levels and the incidence of melanoma, specifically in the retinol formulation. 

Vitamin B₃—Nicotinamide (also known as niacinamide) is a water-soluble form of vitamin B₃ and is obtained from animal-based and plant-based foods, such as meat, fish, and legumes.³⁰ Nicotinamide plays a key role in cellular metabolism, cellular signaling, and DNA repair, including protection from UV damage within keratinocytes.^31,32 Early mouse models demonstrated decreased formation of skin tumors in mice treated with topical or oral nicotinamide.^32,33 A number of human studies have revealed similar results.^34-36

Chen et al³⁴ conducted the ONTRAC study, a phase 3, double-blind, randomized controlled trial (RCT) looking at 386 participants with a history of at least 2 NMSCs in the preceding 5 years. At 12 months, those treated with 500 mg of nicotinamide twice daily demonstrated a statistically significant decreased rate of SCC formation (P=.05). A decreased incidence of BCC development was noted; however, this trend did not reach statistical significance (P=.12). Precancerous skin lesions also were found to be decreased in the treatment group, with 20% lower incidence of actinic keratoses (AKs) after 9 months of treatment (P<.001).³⁴ Drago et al³⁵ specifically studied the incidence of AKs in 38 transplant recipients—8 liver and 30 kidney—and found that previously noted AKs had decreased in size for 18 of 19 patients taking 500 mg of nicotinamide daily when originally photographed AKs were remeasured at 6-month follow-up, with 7 of these 18 patients demonstrating complete clinical regression. Of those on nicotinamide supplementation, no new AKs developed compared to the control group, which demonstrated increased size of AKs or development of new AKs in 91% of patients, with 7 AKs progressing into SCC.³⁵

Nicotinamide has been demonstrated to be useful in preventing skin cancer in high-risk populations, such as transplant patients or those with a high incidence of NMSC.^34,36 Despite promising results within the laboratory setting, nicotinamide’s effects on melanoma in humans remains less clear.^31,37 Studies suggest that nicotinamide enhances tumor-infiltrating lymphocytes and DNA repair mechanisms in melanocytes, which may translate into nicotinamide, providing chemoprevention for melanoma, but research in human patients is limited.^31,37

Vitamin B₉—Folate, the natural form of vitamin B₉, is a water-soluble compound that is found in many foods, especially green leafy vegetables, and often is supplemented because of its health benefits.^38,39 In the skin, folic acid plays a key role in cellular replication and proliferation.³⁸ Controversy exists regarding folate’s effects on cellular growth and turnover with respect to cancer incidence.^38,40 Donnenfeld et al⁴¹ conducted a prospective study assessing dietary folic acid intake and development of NMSC. A total of 5880 participants completed dietary records throughout the first 2 years of the study. After an average follow-up period of 12.6 years, there was an overall increased incidence of skin cancer in those with increased dietary folate (P=.03). Furthermore, when striating by skin cancer type, there was an increased incidence of NMSC overall as well as BCC when analyzing by type of NMSC (P=.03 for NMSC; P=.05 for BCC). However, when stratifying by gender, these findings only held true for women.⁴¹ Similar effects were observed by Fung et al,⁴² who prospectively studied the intake of various vitamins in relationship to the development of BCC in women. During 12 years of follow-up, a positive association was observed between folate intake and BCC development (OR, 1.2; 95% CI, 1.10-1.31).⁴² Fung et al⁴³ also investigated the role of several vitamins in the development of SCC and found that folate showed a negative association, which did not reach statistical significance (RR, 0.79; 95% CI, 0.56-1.11). Furthermore, Vollset et al⁴⁰ conducted a meta-analysis comparing folic acid to placebo in the incidence of various types of cancer. The study excluded NMSC but reported no significant association between the development of melanoma and folic acid supplementation.⁴⁰ In summary, the effects of folate have diverse consequences, potentially promoting the formation of NMSC, but studies suggest that an individual’s gender and other genetic and environmental factors also may play a role.

Vitamin C—Vitamin C (also known as ascorbic acid) is a water-soluble vitamin with antioxidant immune-mediating effects. It is found in various fruits and vegetables and serves as a cofactor for enzymes within the body playing a key role in immune function and collagen formation.^44,45 It has been postulated that ascorbic acid can provide protection from UV radiation damage via its intracellular activity but conversely can contribute to oxidative damage.⁴⁴ Multiple in vitro laboratory studies and animal models have demonstrated photoprotective effects of ascorbic acid.^46-48 Despite these findings, minimal photoprotective effects have been found in the human population.

Kune et al⁴⁹ performed a case-control study of 88 males with previously diagnosed NMSC undergoing surgical removal and investigated patients’ prior dietary habits. Patients with NMSC had a statistically significantly lower level of vitamin C–containing food in their diet than those without NMSC (P=.004).⁴⁹ In addition, Vural et al⁵⁰ analyzed plasma samples and blood cells of patients with AK and BCC and found a significant decrease in ascorbic acid levels in both the AK (P<.001) and BCC (P<.001) groups compared with controls. However, studies have found that consumption of certain dietary compounds can rapidly increase plasma concentration levels, which may serve as a major confounding variable in this study. Plasma concentrations of ascorbic acid and beta carotene were found to be significantly increased following consumption of a high-antioxidant diet for as short a duration as 2 weeks (P<.05).⁵¹ More recently, Heinen et al⁵² performed a prospective study on 1001 adults. In patients without a history of skin cancer, they found that vitamin C from food sources plus dietary supplements was positively associated with the development of BCC (P=.03).⁵² Similarly, Fung et al⁴² performed a study in women and found a positive association between vitamin C intake and the development of BCC (OR, 1.13; 95% CI, 1.03-1.23).

The relationship between vitamin C intake—either in dietary or supplemental form—and melanoma remains controversial. Mice-based studies found that high concentrations of orally administered vitamin C induce cytotoxicity in melanoma cell lines, but at low concentrations they promote tumor growth of malignant melanoma.⁵³ Feskanich et al²³ examined the relationship between vitamin C intake and melanoma development via food frequency questionnaires in White women and found that vitamin C was associated with a higher risk for melanoma (P=.05), and furthermore, a positive dose response with frequency of orange juice intake was observed (P=.008). Overall, despite promising laboratory studies, there is a lack of RCTs investigating the use of vitamin C supplementation for prevention of NMSC and melanoma in humans, and the oral benefits of vitamin C for chemoprevention remain unclear.

Vitamin D—Vitamin D is a fat-soluble vitamin that is found in fish, liver, egg, and cheese, and is endogenously produced when UV radiation from sun exposure interacts with the skin, triggering the synthesis of vitamin D.⁵⁴ Vitamin D is biologically inactive and must be converted to its active form 1,25-dihydroxyvitamin D after entering the body. Vitamin D modulates many genes involved in cellular proliferation and differentiation.⁵⁴ Vitamin D receptors are expressed on keratinocytes and melanocytes.⁵⁵ Animal studies have demonstrated a potentially protective effect of vitamin D in the development of NMSC.⁵⁶ In a mouse model, Ellison et al⁵⁶ found that mice without vitamin D receptors developed skin tumors more rapidly than those with vitamin D receptors.

Unfortunately, these findings have not been demonstrated in humans, and studies have even reported an increased risk for development of NMSC in patients with normal or increased vitamin D levels compared with those with low levels of vitamin D.^57-60 Eide et al⁵⁷ studied 3223 patients seeking advice for low bone density by recording their vitamin D levels at the time of presentation and monitoring development of NMSC. Vitamin D levels greater than 15 ng/mL were positively associated with the development of NMSC (OR, 1.7; 95% CI, 1.04-2.7). This association held true for both SCC and BCC, with a higher risk estimated for SCC (OR, 3.2; 95% CI, 0.4-24.0 for SCC; OR, 1.7; 95% CI, 0.5-5.8 for BCC).⁵⁷ An increased vitamin D serum level also was found to be significantly associated with a higher risk for BCC and melanoma by van der Pols et al.⁵⁸ This prospective study looked at the incidence of skin cancer over 11 years. Study participants with vitamin D levels over 75 nmol/L more frequently developed BCC (P=.01) and melanoma (P=.05). In contrast, SCC was less frequently observed in participants with these high levels of vitamin D (P=.07).⁵⁸ Furthermore, Park et al⁶⁰ looked at vitamin D and skin cancer risk for men and women in the United States and found no association with risk for SCC or melanoma but a positive association with BCC (P=.05 for total vitamin D; P<.01 for dietary vitamin D). Additional studies have been performed with inconsistent results, and multiple authors suggest the possible confounding relationship between vitamin D levels and UV radiation exposure.^59-62 Furthermore, some studies have even demonstrated a negative association between vitamin D and NMSC. Tang et al⁶³ performed a retrospective case-control study in elderly males, investigating serum levels of vitamin D and patients’ self-reported history of NMSC, which demonstrated that higher levels of vitamin D were associated with a decreased risk for NMSC. Overall, the relationship between vitamin D and skin cancer development remains unclear for both melanoma and NMSC.

Vitamin E—Vitamin E is a fat-soluble vitamin that is found in plant-based oils, nuts, seeds, fruits, and vegetables.⁶⁴ It works as an antioxidant to protect against free radicals and heighten immune function, and it also serves as a pro-oxidant.^65,66 Vitamin E naturally exists in 8 chemical forms, of which gamma-tocopherol is the most frequently obtained form in the diet, and alpha-tocopherol is the most abundant form found in the body.^64,65

Early animal studies demonstrated the inhibition of UV-induced damage in mice receiving vitamin E supplementation.^67,68 Human studies have not consistently shown these effects. Vural et al⁵⁰ investigated plasma samples and blood cells of patients with AKs and BCCs and reported a significant decrease in alpha-tocopherol levels in both the AK (P<.05) and BCC (P<.001) groups compared with controls. However, studies also have demonstrated a positive association between vitamin E intake and the development of BCC, including one by Fung et al,⁴² which found a significant association in women (OR, 1.15; 95% CI, 1.06-1.26).

Vitamin E has been found to inhibit melanin synthesis in the laboratory, suggesting a potentially protective effect in melanoma.^69,70 However, in the study performed by Feskanich et al²³ examining vitamin intake and melanoma incidence via food-frequency questionnaires, vitamin E was not associated with a lower risk for melanoma. Despite promising laboratory studies, the data surrounding the use of a vitamin E supplement for prevention of melanoma and NMSC in humans remains unclear.

Selenium—Selenium is a trace mineral found in plants, meat, and fish. It plays a key role in reproduction, hormone metabolism, DNA synthesis, and protection from oxidative damage.⁷¹ In mice studies, lack of selenium-containing proteins resulted in skin abnormalities, including the development of a hyperplastic epidermis and aberrant hair follicle morphogenesis with alopecia after birth, and numerous experimental studies have demonstrated a negative association between selenium intake and cancer.^72,73 However, human studies have yielded alternative results. 

The Nutritional Prevention of Cancer Study Group analyzed 1312 dermatology patients with a history of NMSC.⁷⁴ The study population was obtained from 7 dermatology clinics with randomization to control for confounding variables. Study participants received either 200 μg of selenium daily or placebo.⁷⁴ Baseline characteristics of each study group were overall balanced. Selenium intake was found to have no effect on the development of BCC (hazard ratio [HR], 1.09; 95% CI, 0.94-1.26) but an increased risk for developing SCC (HR, 1.25; 95% CI, 1.03-1.51) and total NMSC (HR, 1.17; 95% CI, 1.02-1.34).^74,75 Similarly, Reid et al⁷⁶ performed an RCT comparing patients treated with 400 μg/d of selenium to those treated with 200 μg/d of selenium. When compared with placebo, those treated with 200 μg/d of selenium had a statistically significantly increased incidence of NMSC (P=.006); however, those treated with 400 μg/d of selenium had no significant change in total incidence of NMSC (P=.51).⁷⁶ Furthermore, Vinceti et al⁷⁷ performed a review of 83 studies from the literature investigating the effect of dietary selenium, and from the RCTs, there was no beneficial effect of selenium in reducing cancer risk in general; however, some studies demonstrated an increased incidence of other types of cancer, including melanoma. Of the RCTs included in the study investigating NMSC incidence specifically, it was found that the incidence was not affected by selenium administration (RR, 1.16; 95% CI, 0.30-4.42; 2 studies, 2027 participants).⁷⁷ Despite data from several studies demonstrating an increased risk for NMSC, the effects of selenium on the risk for NMSC and melanoma remain unclear. 

Combination Antioxidant Studies

In addition to investigating the use of single antioxidants in skin cancer prevention, studies utilizing the combination of various antioxidants or other dietary minerals have been conducted. Hercberg et al⁷⁸ performed a randomized, double-blinded, placebo-controlled trial of 13,017 adults (7876 women and 5141 men) receiving a combination of 120 mg vitamin C, 30 mg vitamin E, 100 μg selenium, 6 mg beta carotene, and 20 mg zinc. Study participants were followed for an average of 7.5 years, and the development of skin cancers were recorded. Overall, the incidence rate of skin cancer did not differ between the 2 treatment groups; however, when segregated by gender, the study found that there was an increased risk for developing skin cancer in women taking the antioxidant supplement combination compared with placebo (P=.03). This difference was not observed in the 2 treatment groups of male patients (P=.11). When looking specifically at NMSC, there was no difference between treatment groups for male or female patients (P=.39 for males; P=.15 for females). In contrast, there was a higher incidence of melanoma identified in female patients taking the combination antioxidant supplement (P=.01), but this was not seen within the male study population (P=.51).⁷⁸ In addition, Chang et al⁷⁹ performed a meta-analysis of 10 previously published RCTs. Analysis revealed that treatment with a variety of supplements, including vitamins A, C, E, and beta carotene, were found to have no preventative effects on the incidence of skin cancer development (RR, 0.98; CI, 0.98-1.03). Notable limitations to this study included the variability in protocols of the studies included in this meta-analysis, the limited number of RCTs investigating vitamin supplementation and the risk for skin cancer development, and the influence of dietary intake on study outcomes.⁷⁹

Other Dietary Agents

Furocoumarins—Furocoumarins are botanical substances found in various fruits and plants, including many citrus products. Furocoumarins are activated by UV light radiation and can lead to development of a phototoxic eruption. Several studies have suggested a pharmacogenetic effect of furocoumarins.⁸⁰ Sun et al⁸⁰ collected dietary data from 47,453 men and 75,291 women on furocoumarin intake and correlation with the development of NMSC. Overall, the study suggested that the intake of furocoumarins may lead to an increase in the development of BCC (HR, 1.16; 95% CI, 1.11-1.21; P=.002); however, there was no significant association identified between total intake of furocoumarins in the risk for SCC or melanoma.⁸⁰ Furthermore, Sakaki et al⁸¹ conducted a survey study looking at the consumption of citrus products and the development of NMSC. The group found that there was an increased risk for NMSC in those consuming an increased amount of citrus products (P=.007).⁸¹

Conclusion

Dietary antioxidants have been investigated for their potential role in the prevention of tumorigenesis. Specific antioxidant vitamins, such as vitamin A derivatives and niacinamide, have demonstrated clinical utility in the prevention of NMSC in high-risk populations. Retinol also has been associated with a reduced incidence of melanoma. Numerous antioxidants have demonstrated promising data within the laboratory setting; however, inconsistent results have been appreciated in humans. Furthermore, several research studies suggest that folate, vitamin D, and furocoumarins may be associated with an increased risk for skin cancer development; however, these studies are inconclusive, and dietary studies are challenging to conduct. Overall, RCTs investigating the role of antioxidants for chemoprevention are limited. Moreover, the study of dietary antioxidants and vitamins may be affected by various confounding variables that can be difficult to account for because of patients’ potentially poor recall of dietary intake and the effect of dietary intake in supplemental studies. Given the increasing prevalence of skin cancer worldwide, further research into the clinical utility of antioxidants in skin cancer prevention is warranted. 

Nonmelanoma skin cancer (NMSC) is the most common cancer in the United States, and cutaneous melanoma is projected to be the fifth most common form of cancer in 2022, with increasing incidence and high potential for mortality.^1-3 Estimates indicate that 35% to 45% of all cancers in White patients are cutaneous, with 4% to 5% occurring in Hispanic patients, 2% to 4% in Asian patients, and 1% to 2% in Black patients.⁴ Of the keratinocyte carcinomas, basal cell carcinoma (BCC) is the most prevalent, projected to affect approximately 33% to 39% of White males and 23% to 28% of White females in the United States during their lifetimes. Squamous cell carcinoma (SCC) is the second most common skin malignancy, with a lifetime risk of 9% to 14% for White males and 4% to 9% for White females in the United States.⁵ The incidence of melanoma continues to increase, with approximately 99,780 new cases expected in the United States in 2022.¹

UV-induced DNA damage plays a key role in the pathogenesis and development of various skin malignancies.⁶ UV radiation from sunlight or tanning devices causes photocarcinogenesis due to molecular and cellular effects, including the generation of reactive oxygen species, DNA damage due to the formation of cyclobutane pyrimidine dimers and pyrimidine-pyrimidone, melanogenesis, apoptosis, and the increased expression of harmful genes and proteins.⁶ The summation of this damage can result in skin malignancies, including NMSC and melanoma.^6,7 Dietary antioxidants theoretically help prevent oxidative reactions from occurring within the body, and it has been suggested that intake of dietary antioxidants may decrease DNA damage and prevent tumorigenesis secondary to UV radiation.⁸ Antioxidants exist naturally in the body but can be acquired exogenously. Investigators have studied dietary antioxidants in preventing skin cancer formation with promising results in the laboratory setting.^8-11 Recently, more robust human studies have been initiated to further delineate this relationship. We present clinical evidence of several frequently utilized antioxidant vitamins and their effects on melanoma and NMSC.

Antioxidants

Vitamin A—Vitamin A is a fat-soluble vitamin found in animal sources, including fish, liver, and eggs. Carotenoids, such as beta carotene, are provitamin A plant derivatives found in fruits and vegetables that are converted into biologically active retinol and retinoic acid.¹² Retinols play a key role in cellular growth and differentiation and are thought to be protective against skin cancer via the inactivation of free radicals and immunologic enhancement due to their antiproliferative, antioxidative, and antiapoptotic effects.^13-16 Animal studies have demonstrated this protective effect and the ability of retinoids to suppress carcinogenesis; however, human studies reveal conflicting results.^17,18

Greenberg et al¹⁹ investigated the use of beta carotene in preventing the formation of NMSC. Patients (N=1805) were randomized to receive 50 mg of beta carotene daily or placebo. Over a 5-year period, there was no significant reduction in the occurrence of NMSC (relative risk [RR], 1.05; 95% CI, 0.91-1.22).¹⁹ Frieling et al²⁰ conducted a similar randomized, double-blind, placebo-controlled trial investigating beta carotene for primary prevention of NMSC in 22,071 healthy male physicians. The study group received 50 mg of beta carotene every other day for 12 years’ duration, and there was no significant effect on the incidence of first NMSC development (RR, 0.98; 95% CI, 0.92-1.05).²⁰

A case-control study by Naldi et al²¹ found an inverse association between vitamin A intake and development of melanoma. Study participants were stratified into quartiles based on level of dietary intake and found an odds ratio (OR) of 0.71 for beta carotene (95% CI, 0.50-1.02), 0.57 for retinol (95% CI, 0.39-0.83), and 0.51 for total vitamin A (95% CI, 0.35-0.75) when comparing the upper quartile of vitamin A intake to the lower quartile. Upper-quartile cutoff values of vitamin A intake were 214 µg/d for beta carotene, 149 µg/d for retinol, and 359 µg/d for total vitamin A.²¹ More recently, a meta-analysis by Zhang et al²² pooled data from 8 case-control studies and 2 prospective studies. Intake of retinol but not total vitamin A or beta carotene was associated with a reduced risk for development of melanoma (retinol: OR, 0.80; 95% CI, 0.69-0.92; total vitamin A: OR, 0.86; 95% CI, 0.59-1.25; beta carotene: OR, 0.87; 95% CI, 0.62-1.20).²² Feskanich et al²³ demonstrated similar findings with use of food-frequency questionnaires in White women, suggesting that retinol intake from food combined with supplements may be protective for women who were otherwise at a low risk for melanoma based on nondietary factors. These factors included painful or blistering sunburns during childhood, history of more than 6 sunburns, more than 3 moles on the left arm, having red or blonde hair, and having a parent or sibling with melanoma (P=.01). However, this relationship did not hold true when looking at women at an intermediate or high risk for melanoma (P=.16 and P=.46).²³

When looking at high-risk patients, such as transplant patients, oral retinoids have been beneficial in preventing NMSC.^24-27 Bavinck et al²⁴ investigated 44 renal transplant patients with a history of more than 10 NMSCs treated with 30 mg of acitretin daily vs placebo. Patients receiving oral retinoid supplementation developed fewer NMSCs over a 6-month treatment period (P=.01).²⁴ Similarly, George et al²⁵ investigated acitretin in renal transplant patients and found a statistically significant decrease in number of SCCs in patients on supplementation (P=.002). Solomon-Cohen et al²⁶ performed a retrospective case-crossover study in solid organ transplant recipients and found that those treated with 10 mg of acitretin daily for 2 years had a significant reduction in the number of new keratinocyte carcinomas (P=.002). Other investigators have demonstrated similar results, and in 2006, Otley et al²⁷ proposed standardized dosing of acitretin for chemoprevention in high-risk patients, including patients developing 5 to 10 NMSCs per year, solid organ transplant recipients, and those with syndromes associated with the development of NMSC.^28,29 Overall, in the general population, vitamin A and related compounds have not demonstrated a significant association with decreased development of NMSC; however, oral retinoids have proven useful for high-risk patients. Furthermore, several studies have suggested a negative association between vitamin A levels and the incidence of melanoma, specifically in the retinol formulation. 

Vitamin B₃—Nicotinamide (also known as niacinamide) is a water-soluble form of vitamin B₃ and is obtained from animal-based and plant-based foods, such as meat, fish, and legumes.³⁰ Nicotinamide plays a key role in cellular metabolism, cellular signaling, and DNA repair, including protection from UV damage within keratinocytes.^31,32 Early mouse models demonstrated decreased formation of skin tumors in mice treated with topical or oral nicotinamide.^32,33 A number of human studies have revealed similar results.^34-36

Chen et al³⁴ conducted the ONTRAC study, a phase 3, double-blind, randomized controlled trial (RCT) looking at 386 participants with a history of at least 2 NMSCs in the preceding 5 years. At 12 months, those treated with 500 mg of nicotinamide twice daily demonstrated a statistically significant decreased rate of SCC formation (P=.05). A decreased incidence of BCC development was noted; however, this trend did not reach statistical significance (P=.12). Precancerous skin lesions also were found to be decreased in the treatment group, with 20% lower incidence of actinic keratoses (AKs) after 9 months of treatment (P<.001).³⁴ Drago et al³⁵ specifically studied the incidence of AKs in 38 transplant recipients—8 liver and 30 kidney—and found that previously noted AKs had decreased in size for 18 of 19 patients taking 500 mg of nicotinamide daily when originally photographed AKs were remeasured at 6-month follow-up, with 7 of these 18 patients demonstrating complete clinical regression. Of those on nicotinamide supplementation, no new AKs developed compared to the control group, which demonstrated increased size of AKs or development of new AKs in 91% of patients, with 7 AKs progressing into SCC.³⁵

Nicotinamide has been demonstrated to be useful in preventing skin cancer in high-risk populations, such as transplant patients or those with a high incidence of NMSC.^34,36 Despite promising results within the laboratory setting, nicotinamide’s effects on melanoma in humans remains less clear.^31,37 Studies suggest that nicotinamide enhances tumor-infiltrating lymphocytes and DNA repair mechanisms in melanocytes, which may translate into nicotinamide, providing chemoprevention for melanoma, but research in human patients is limited.^31,37

Vitamin B₉—Folate, the natural form of vitamin B₉, is a water-soluble compound that is found in many foods, especially green leafy vegetables, and often is supplemented because of its health benefits.^38,39 In the skin, folic acid plays a key role in cellular replication and proliferation.³⁸ Controversy exists regarding folate’s effects on cellular growth and turnover with respect to cancer incidence.^38,40 Donnenfeld et al⁴¹ conducted a prospective study assessing dietary folic acid intake and development of NMSC. A total of 5880 participants completed dietary records throughout the first 2 years of the study. After an average follow-up period of 12.6 years, there was an overall increased incidence of skin cancer in those with increased dietary folate (P=.03). Furthermore, when striating by skin cancer type, there was an increased incidence of NMSC overall as well as BCC when analyzing by type of NMSC (P=.03 for NMSC; P=.05 for BCC). However, when stratifying by gender, these findings only held true for women.⁴¹ Similar effects were observed by Fung et al,⁴² who prospectively studied the intake of various vitamins in relationship to the development of BCC in women. During 12 years of follow-up, a positive association was observed between folate intake and BCC development (OR, 1.2; 95% CI, 1.10-1.31).⁴² Fung et al⁴³ also investigated the role of several vitamins in the development of SCC and found that folate showed a negative association, which did not reach statistical significance (RR, 0.79; 95% CI, 0.56-1.11). Furthermore, Vollset et al⁴⁰ conducted a meta-analysis comparing folic acid to placebo in the incidence of various types of cancer. The study excluded NMSC but reported no significant association between the development of melanoma and folic acid supplementation.⁴⁰ In summary, the effects of folate have diverse consequences, potentially promoting the formation of NMSC, but studies suggest that an individual’s gender and other genetic and environmental factors also may play a role.

Vitamin C—Vitamin C (also known as ascorbic acid) is a water-soluble vitamin with antioxidant immune-mediating effects. It is found in various fruits and vegetables and serves as a cofactor for enzymes within the body playing a key role in immune function and collagen formation.^44,45 It has been postulated that ascorbic acid can provide protection from UV radiation damage via its intracellular activity but conversely can contribute to oxidative damage.⁴⁴ Multiple in vitro laboratory studies and animal models have demonstrated photoprotective effects of ascorbic acid.^46-48 Despite these findings, minimal photoprotective effects have been found in the human population.

Kune et al⁴⁹ performed a case-control study of 88 males with previously diagnosed NMSC undergoing surgical removal and investigated patients’ prior dietary habits. Patients with NMSC had a statistically significantly lower level of vitamin C–containing food in their diet than those without NMSC (P=.004).⁴⁹ In addition, Vural et al⁵⁰ analyzed plasma samples and blood cells of patients with AK and BCC and found a significant decrease in ascorbic acid levels in both the AK (P<.001) and BCC (P<.001) groups compared with controls. However, studies have found that consumption of certain dietary compounds can rapidly increase plasma concentration levels, which may serve as a major confounding variable in this study. Plasma concentrations of ascorbic acid and beta carotene were found to be significantly increased following consumption of a high-antioxidant diet for as short a duration as 2 weeks (P<.05).⁵¹ More recently, Heinen et al⁵² performed a prospective study on 1001 adults. In patients without a history of skin cancer, they found that vitamin C from food sources plus dietary supplements was positively associated with the development of BCC (P=.03).⁵² Similarly, Fung et al⁴² performed a study in women and found a positive association between vitamin C intake and the development of BCC (OR, 1.13; 95% CI, 1.03-1.23).

The relationship between vitamin C intake—either in dietary or supplemental form—and melanoma remains controversial. Mice-based studies found that high concentrations of orally administered vitamin C induce cytotoxicity in melanoma cell lines, but at low concentrations they promote tumor growth of malignant melanoma.⁵³ Feskanich et al²³ examined the relationship between vitamin C intake and melanoma development via food frequency questionnaires in White women and found that vitamin C was associated with a higher risk for melanoma (P=.05), and furthermore, a positive dose response with frequency of orange juice intake was observed (P=.008). Overall, despite promising laboratory studies, there is a lack of RCTs investigating the use of vitamin C supplementation for prevention of NMSC and melanoma in humans, and the oral benefits of vitamin C for chemoprevention remain unclear.

Vitamin D—Vitamin D is a fat-soluble vitamin that is found in fish, liver, egg, and cheese, and is endogenously produced when UV radiation from sun exposure interacts with the skin, triggering the synthesis of vitamin D.⁵⁴ Vitamin D is biologically inactive and must be converted to its active form 1,25-dihydroxyvitamin D after entering the body. Vitamin D modulates many genes involved in cellular proliferation and differentiation.⁵⁴ Vitamin D receptors are expressed on keratinocytes and melanocytes.⁵⁵ Animal studies have demonstrated a potentially protective effect of vitamin D in the development of NMSC.⁵⁶ In a mouse model, Ellison et al⁵⁶ found that mice without vitamin D receptors developed skin tumors more rapidly than those with vitamin D receptors.

Unfortunately, these findings have not been demonstrated in humans, and studies have even reported an increased risk for development of NMSC in patients with normal or increased vitamin D levels compared with those with low levels of vitamin D.^57-60 Eide et al⁵⁷ studied 3223 patients seeking advice for low bone density by recording their vitamin D levels at the time of presentation and monitoring development of NMSC. Vitamin D levels greater than 15 ng/mL were positively associated with the development of NMSC (OR, 1.7; 95% CI, 1.04-2.7). This association held true for both SCC and BCC, with a higher risk estimated for SCC (OR, 3.2; 95% CI, 0.4-24.0 for SCC; OR, 1.7; 95% CI, 0.5-5.8 for BCC).⁵⁷ An increased vitamin D serum level also was found to be significantly associated with a higher risk for BCC and melanoma by van der Pols et al.⁵⁸ This prospective study looked at the incidence of skin cancer over 11 years. Study participants with vitamin D levels over 75 nmol/L more frequently developed BCC (P=.01) and melanoma (P=.05). In contrast, SCC was less frequently observed in participants with these high levels of vitamin D (P=.07).⁵⁸ Furthermore, Park et al⁶⁰ looked at vitamin D and skin cancer risk for men and women in the United States and found no association with risk for SCC or melanoma but a positive association with BCC (P=.05 for total vitamin D; P<.01 for dietary vitamin D). Additional studies have been performed with inconsistent results, and multiple authors suggest the possible confounding relationship between vitamin D levels and UV radiation exposure.^59-62 Furthermore, some studies have even demonstrated a negative association between vitamin D and NMSC. Tang et al⁶³ performed a retrospective case-control study in elderly males, investigating serum levels of vitamin D and patients’ self-reported history of NMSC, which demonstrated that higher levels of vitamin D were associated with a decreased risk for NMSC. Overall, the relationship between vitamin D and skin cancer development remains unclear for both melanoma and NMSC.

Vitamin E—Vitamin E is a fat-soluble vitamin that is found in plant-based oils, nuts, seeds, fruits, and vegetables.⁶⁴ It works as an antioxidant to protect against free radicals and heighten immune function, and it also serves as a pro-oxidant.^65,66 Vitamin E naturally exists in 8 chemical forms, of which gamma-tocopherol is the most frequently obtained form in the diet, and alpha-tocopherol is the most abundant form found in the body.^64,65

Early animal studies demonstrated the inhibition of UV-induced damage in mice receiving vitamin E supplementation.^67,68 Human studies have not consistently shown these effects. Vural et al⁵⁰ investigated plasma samples and blood cells of patients with AKs and BCCs and reported a significant decrease in alpha-tocopherol levels in both the AK (P<.05) and BCC (P<.001) groups compared with controls. However, studies also have demonstrated a positive association between vitamin E intake and the development of BCC, including one by Fung et al,⁴² which found a significant association in women (OR, 1.15; 95% CI, 1.06-1.26).

Vitamin E has been found to inhibit melanin synthesis in the laboratory, suggesting a potentially protective effect in melanoma.^69,70 However, in the study performed by Feskanich et al²³ examining vitamin intake and melanoma incidence via food-frequency questionnaires, vitamin E was not associated with a lower risk for melanoma. Despite promising laboratory studies, the data surrounding the use of a vitamin E supplement for prevention of melanoma and NMSC in humans remains unclear.

Selenium—Selenium is a trace mineral found in plants, meat, and fish. It plays a key role in reproduction, hormone metabolism, DNA synthesis, and protection from oxidative damage.⁷¹ In mice studies, lack of selenium-containing proteins resulted in skin abnormalities, including the development of a hyperplastic epidermis and aberrant hair follicle morphogenesis with alopecia after birth, and numerous experimental studies have demonstrated a negative association between selenium intake and cancer.^72,73 However, human studies have yielded alternative results. 

The Nutritional Prevention of Cancer Study Group analyzed 1312 dermatology patients with a history of NMSC.⁷⁴ The study population was obtained from 7 dermatology clinics with randomization to control for confounding variables. Study participants received either 200 μg of selenium daily or placebo.⁷⁴ Baseline characteristics of each study group were overall balanced. Selenium intake was found to have no effect on the development of BCC (hazard ratio [HR], 1.09; 95% CI, 0.94-1.26) but an increased risk for developing SCC (HR, 1.25; 95% CI, 1.03-1.51) and total NMSC (HR, 1.17; 95% CI, 1.02-1.34).^74,75 Similarly, Reid et al⁷⁶ performed an RCT comparing patients treated with 400 μg/d of selenium to those treated with 200 μg/d of selenium. When compared with placebo, those treated with 200 μg/d of selenium had a statistically significantly increased incidence of NMSC (P=.006); however, those treated with 400 μg/d of selenium had no significant change in total incidence of NMSC (P=.51).⁷⁶ Furthermore, Vinceti et al⁷⁷ performed a review of 83 studies from the literature investigating the effect of dietary selenium, and from the RCTs, there was no beneficial effect of selenium in reducing cancer risk in general; however, some studies demonstrated an increased incidence of other types of cancer, including melanoma. Of the RCTs included in the study investigating NMSC incidence specifically, it was found that the incidence was not affected by selenium administration (RR, 1.16; 95% CI, 0.30-4.42; 2 studies, 2027 participants).⁷⁷ Despite data from several studies demonstrating an increased risk for NMSC, the effects of selenium on the risk for NMSC and melanoma remain unclear. 

Combination Antioxidant Studies

In addition to investigating the use of single antioxidants in skin cancer prevention, studies utilizing the combination of various antioxidants or other dietary minerals have been conducted. Hercberg et al⁷⁸ performed a randomized, double-blinded, placebo-controlled trial of 13,017 adults (7876 women and 5141 men) receiving a combination of 120 mg vitamin C, 30 mg vitamin E, 100 μg selenium, 6 mg beta carotene, and 20 mg zinc. Study participants were followed for an average of 7.5 years, and the development of skin cancers were recorded. Overall, the incidence rate of skin cancer did not differ between the 2 treatment groups; however, when segregated by gender, the study found that there was an increased risk for developing skin cancer in women taking the antioxidant supplement combination compared with placebo (P=.03). This difference was not observed in the 2 treatment groups of male patients (P=.11). When looking specifically at NMSC, there was no difference between treatment groups for male or female patients (P=.39 for males; P=.15 for females). In contrast, there was a higher incidence of melanoma identified in female patients taking the combination antioxidant supplement (P=.01), but this was not seen within the male study population (P=.51).⁷⁸ In addition, Chang et al⁷⁹ performed a meta-analysis of 10 previously published RCTs. Analysis revealed that treatment with a variety of supplements, including vitamins A, C, E, and beta carotene, were found to have no preventative effects on the incidence of skin cancer development (RR, 0.98; CI, 0.98-1.03). Notable limitations to this study included the variability in protocols of the studies included in this meta-analysis, the limited number of RCTs investigating vitamin supplementation and the risk for skin cancer development, and the influence of dietary intake on study outcomes.⁷⁹

Other Dietary Agents

Furocoumarins—Furocoumarins are botanical substances found in various fruits and plants, including many citrus products. Furocoumarins are activated by UV light radiation and can lead to development of a phototoxic eruption. Several studies have suggested a pharmacogenetic effect of furocoumarins.⁸⁰ Sun et al⁸⁰ collected dietary data from 47,453 men and 75,291 women on furocoumarin intake and correlation with the development of NMSC. Overall, the study suggested that the intake of furocoumarins may lead to an increase in the development of BCC (HR, 1.16; 95% CI, 1.11-1.21; P=.002); however, there was no significant association identified between total intake of furocoumarins in the risk for SCC or melanoma.⁸⁰ Furthermore, Sakaki et al⁸¹ conducted a survey study looking at the consumption of citrus products and the development of NMSC. The group found that there was an increased risk for NMSC in those consuming an increased amount of citrus products (P=.007).⁸¹

Conclusion

Dietary antioxidants have been investigated for their potential role in the prevention of tumorigenesis. Specific antioxidant vitamins, such as vitamin A derivatives and niacinamide, have demonstrated clinical utility in the prevention of NMSC in high-risk populations. Retinol also has been associated with a reduced incidence of melanoma. Numerous antioxidants have demonstrated promising data within the laboratory setting; however, inconsistent results have been appreciated in humans. Furthermore, several research studies suggest that folate, vitamin D, and furocoumarins may be associated with an increased risk for skin cancer development; however, these studies are inconclusive, and dietary studies are challenging to conduct. Overall, RCTs investigating the role of antioxidants for chemoprevention are limited. Moreover, the study of dietary antioxidants and vitamins may be affected by various confounding variables that can be difficult to account for because of patients’ potentially poor recall of dietary intake and the effect of dietary intake in supplemental studies. Given the increasing prevalence of skin cancer worldwide, further research into the clinical utility of antioxidants in skin cancer prevention is warranted. 

Among patients with metastatic melanoma who undergo treatment with single or combination immune checkpoint inhibitors (ICIs) and who experience immune adverse events, overall survival is significantly longer, regardless of the need for hospitalization. Survival is further improved if the immunotherapy is continued after the adverse event develops, a new study confirms.

“In the largest clinical cohort to date, our data support a positive association with overall survival for patients who develop clinically significant immune-related adverse events while receiving combination immune checkpoint blockade, in keeping with other reported series,” the authors wrote.

The study was published online in JAMA Network Open.

Immune-related adverse events are common with these drugs. Severe events of grade 3 or higher occur in 59% of trial patients who receive combination ICI therapy.

The adverse events have increasingly been positively associated with survival. However, the effects for patients with metastatic melanoma, in particular, are less clear. There is little research on the effects in relation to combination therapy with ipilimumab and nivolumab, which is the standard of care for many patients with metastatic melanoma.

To investigate, Alexander S. Watson, MD, and colleagues evaluated data on 492 patients with metastatic melanoma who had been treated with one or more doses of an anti–programmed death 1 agent as single or combination immune checkpoint blockade in the multicenter Alberta Immunotherapy Database from August 2013 to May 2020.

Of these 492 patients, 198 patients (40%) developed immune-related adverse events. The mean age of the patients who developed adverse events was 61.8 years; of those who did not develop adverse events, the mean age was 65.5 years. Men made up 69.2% and 62.2%, respectively.

A total of 288 patients received pembrolizumab as their first ICI therapy, 80 received nivolumab, and 124 received combination blockade with ipilimumab-nivolumab.

Overall, with a median follow-up of 36.6 months, among patients who experienced clinically significant immune-related adverse events, defined as requiring systemic corticosteroids and/or a treatment delay, median overall survival was significantly improved, at 56.3 months, compared with 18.5 months among those who did not experience immune-related adverse events (P < .001).

In addition, among those who received combination ICI treatment, the median overall survival was 56.2 months for those who experienced adverse events versus 19.0 months for those who did not (P < .001).

There were no significant differences in overall survival between those who were and those who were not hospitalized for their immune-related adverse events (P = .53).

For patients who resumed their ICI therapy following the adverse events, overall survival was longer, compared with those who did not resume the therapy (median, 56.3 months vs. 31.5 months; P = .009).

The improvements in overall survival seen with immune-related adverse events remained consistent after adjustment in a multivariable analysis (hazard ratio for death, 0.382; P < .001).

There were no significant differences in the median number of cycles of ICIs between those with and those without the adverse events.

The risk of recurrence of immune-related adverse events following the reintroduction of therapy after initial events was a concern, so the improved overall survival among those patients is encouraging, although further investigation is needed, commented lead author Dr. Watson, from the department of oncology, University of Calgary (Alta.).

“It may be, for certain patients with immune-related adverse events, that continued immune-priming is safe and optimizes anticancer response,” he told this news organization. “However, in a retrospective analysis such as ours, selection bias can have an impact.”

“Confirming this finding and better identifying patients who may benefit from resumption will be an area for future investigation,” he said.  

Patients who developed immune-related adverse events were more likely to be younger than 50 years (21.8% vs. 13.9%), have normal albumin levels (86.4% vs. 74.8%), and have a more robust Eastern Cooperative Oncology Group status, which is consistent with other studies that have shown survival benefits among those who experience adverse events.

“We, and others, speculate this could be due to such groups having immune systems more ready to respond strongly to immunotherapy,” Dr. Watson explained.

After controlling for age and performance status in the multivariable analysis, however, “immune-related adverse events remained strongly associated with survival, potentially [indicating] that robust responses to immunotherapy lead to both cancer control and immune-related adverse events,” he said.

Overall, “we feel these findings will help clinicians in discussions with patients and in clinical decision-making after adverse events develop,” Dr. Watson said.

Dr. Watson has received personal fees from Apobiologix Canada.

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

Among patients with metastatic melanoma who undergo treatment with single or combination immune checkpoint inhibitors (ICIs) and who experience immune adverse events, overall survival is significantly longer, regardless of the need for hospitalization. Survival is further improved if the immunotherapy is continued after the adverse event develops, a new study confirms.

“In the largest clinical cohort to date, our data support a positive association with overall survival for patients who develop clinically significant immune-related adverse events while receiving combination immune checkpoint blockade, in keeping with other reported series,” the authors wrote.

The study was published online in JAMA Network Open.

Immune-related adverse events are common with these drugs. Severe events of grade 3 or higher occur in 59% of trial patients who receive combination ICI therapy.

The adverse events have increasingly been positively associated with survival. However, the effects for patients with metastatic melanoma, in particular, are less clear. There is little research on the effects in relation to combination therapy with ipilimumab and nivolumab, which is the standard of care for many patients with metastatic melanoma.

To investigate, Alexander S. Watson, MD, and colleagues evaluated data on 492 patients with metastatic melanoma who had been treated with one or more doses of an anti–programmed death 1 agent as single or combination immune checkpoint blockade in the multicenter Alberta Immunotherapy Database from August 2013 to May 2020.

Of these 492 patients, 198 patients (40%) developed immune-related adverse events. The mean age of the patients who developed adverse events was 61.8 years; of those who did not develop adverse events, the mean age was 65.5 years. Men made up 69.2% and 62.2%, respectively.

A total of 288 patients received pembrolizumab as their first ICI therapy, 80 received nivolumab, and 124 received combination blockade with ipilimumab-nivolumab.

Overall, with a median follow-up of 36.6 months, among patients who experienced clinically significant immune-related adverse events, defined as requiring systemic corticosteroids and/or a treatment delay, median overall survival was significantly improved, at 56.3 months, compared with 18.5 months among those who did not experience immune-related adverse events (P < .001).

In addition, among those who received combination ICI treatment, the median overall survival was 56.2 months for those who experienced adverse events versus 19.0 months for those who did not (P < .001).

There were no significant differences in overall survival between those who were and those who were not hospitalized for their immune-related adverse events (P = .53).

For patients who resumed their ICI therapy following the adverse events, overall survival was longer, compared with those who did not resume the therapy (median, 56.3 months vs. 31.5 months; P = .009).

The improvements in overall survival seen with immune-related adverse events remained consistent after adjustment in a multivariable analysis (hazard ratio for death, 0.382; P < .001).

There were no significant differences in the median number of cycles of ICIs between those with and those without the adverse events.

The risk of recurrence of immune-related adverse events following the reintroduction of therapy after initial events was a concern, so the improved overall survival among those patients is encouraging, although further investigation is needed, commented lead author Dr. Watson, from the department of oncology, University of Calgary (Alta.).

“It may be, for certain patients with immune-related adverse events, that continued immune-priming is safe and optimizes anticancer response,” he told this news organization. “However, in a retrospective analysis such as ours, selection bias can have an impact.”

“Confirming this finding and better identifying patients who may benefit from resumption will be an area for future investigation,” he said.  

Patients who developed immune-related adverse events were more likely to be younger than 50 years (21.8% vs. 13.9%), have normal albumin levels (86.4% vs. 74.8%), and have a more robust Eastern Cooperative Oncology Group status, which is consistent with other studies that have shown survival benefits among those who experience adverse events.

“We, and others, speculate this could be due to such groups having immune systems more ready to respond strongly to immunotherapy,” Dr. Watson explained.

After controlling for age and performance status in the multivariable analysis, however, “immune-related adverse events remained strongly associated with survival, potentially [indicating] that robust responses to immunotherapy lead to both cancer control and immune-related adverse events,” he said.

Overall, “we feel these findings will help clinicians in discussions with patients and in clinical decision-making after adverse events develop,” Dr. Watson said.

Dr. Watson has received personal fees from Apobiologix Canada.

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

Among patients with metastatic melanoma who undergo treatment with single or combination immune checkpoint inhibitors (ICIs) and who experience immune adverse events, overall survival is significantly longer, regardless of the need for hospitalization. Survival is further improved if the immunotherapy is continued after the adverse event develops, a new study confirms.

“In the largest clinical cohort to date, our data support a positive association with overall survival for patients who develop clinically significant immune-related adverse events while receiving combination immune checkpoint blockade, in keeping with other reported series,” the authors wrote.

The study was published online in JAMA Network Open.

Immune-related adverse events are common with these drugs. Severe events of grade 3 or higher occur in 59% of trial patients who receive combination ICI therapy.

The adverse events have increasingly been positively associated with survival. However, the effects for patients with metastatic melanoma, in particular, are less clear. There is little research on the effects in relation to combination therapy with ipilimumab and nivolumab, which is the standard of care for many patients with metastatic melanoma.

To investigate, Alexander S. Watson, MD, and colleagues evaluated data on 492 patients with metastatic melanoma who had been treated with one or more doses of an anti–programmed death 1 agent as single or combination immune checkpoint blockade in the multicenter Alberta Immunotherapy Database from August 2013 to May 2020.

Of these 492 patients, 198 patients (40%) developed immune-related adverse events. The mean age of the patients who developed adverse events was 61.8 years; of those who did not develop adverse events, the mean age was 65.5 years. Men made up 69.2% and 62.2%, respectively.

A total of 288 patients received pembrolizumab as their first ICI therapy, 80 received nivolumab, and 124 received combination blockade with ipilimumab-nivolumab.

Overall, with a median follow-up of 36.6 months, among patients who experienced clinically significant immune-related adverse events, defined as requiring systemic corticosteroids and/or a treatment delay, median overall survival was significantly improved, at 56.3 months, compared with 18.5 months among those who did not experience immune-related adverse events (P < .001).

In addition, among those who received combination ICI treatment, the median overall survival was 56.2 months for those who experienced adverse events versus 19.0 months for those who did not (P < .001).

There were no significant differences in overall survival between those who were and those who were not hospitalized for their immune-related adverse events (P = .53).

For patients who resumed their ICI therapy following the adverse events, overall survival was longer, compared with those who did not resume the therapy (median, 56.3 months vs. 31.5 months; P = .009).

The improvements in overall survival seen with immune-related adverse events remained consistent after adjustment in a multivariable analysis (hazard ratio for death, 0.382; P < .001).

There were no significant differences in the median number of cycles of ICIs between those with and those without the adverse events.

The risk of recurrence of immune-related adverse events following the reintroduction of therapy after initial events was a concern, so the improved overall survival among those patients is encouraging, although further investigation is needed, commented lead author Dr. Watson, from the department of oncology, University of Calgary (Alta.).

“It may be, for certain patients with immune-related adverse events, that continued immune-priming is safe and optimizes anticancer response,” he told this news organization. “However, in a retrospective analysis such as ours, selection bias can have an impact.”

“Confirming this finding and better identifying patients who may benefit from resumption will be an area for future investigation,” he said.  

Patients who developed immune-related adverse events were more likely to be younger than 50 years (21.8% vs. 13.9%), have normal albumin levels (86.4% vs. 74.8%), and have a more robust Eastern Cooperative Oncology Group status, which is consistent with other studies that have shown survival benefits among those who experience adverse events.

“We, and others, speculate this could be due to such groups having immune systems more ready to respond strongly to immunotherapy,” Dr. Watson explained.

After controlling for age and performance status in the multivariable analysis, however, “immune-related adverse events remained strongly associated with survival, potentially [indicating] that robust responses to immunotherapy lead to both cancer control and immune-related adverse events,” he said.

Overall, “we feel these findings will help clinicians in discussions with patients and in clinical decision-making after adverse events develop,” Dr. Watson said.

Dr. Watson has received personal fees from Apobiologix Canada.

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

A new generation of treatments appears to have caused U.S. melanoma mortality rates to plunge between 2013 and 2017 for the first time in 4 decades, a new study finds, although the dip appeared to stabilize over the next 2 years.

“This data is very encouraging and represents the real-world effectiveness of these newer therapies, which include immunotherapies and targeted therapies,” hematologist/oncologist Navkirat Kahlon, MD, MPH, of Seacoast Cancer Center and Massachusetts General Brigham Wentworth-Douglass Hospital, Dover, N.H., one of the study authors, said in an interview. In clinical trials, these new treatments “have been very effective ... so the timing as well as magnitude of drop seen in melanoma-specific population mortality was not at all surprising. But it’s still very exciting.”

The report, published in JAMA Network Open, tracked mortality rates for the deadliest form of skin cancer from 1975 to 2019. The researchers launched the study to better understand outcomes in cutaneous melanoma following the rise of new therapies that now provide options in addition to chemotherapy. “With the use of novel therapies, the survival of these patients has increased from a few weeks or months to many years in clinical trials,” Dr. Kahlon said. “Given the magnitude of benefit compared to traditional chemotherapy in clinical trials, we decided to see if the real-world U.S. population is deriving the same benefit.”

New drugs introduced in recent years include immunotherapy agents such as ipilimumab and targeted therapies such as vemurafenib.

The researchers analyzed age-adjusted melanoma outcome data from the Surveillance, Epidemiology, and End Results (SEER) database. In 1975, the long-term melanoma mortality rate for melanoma was 2.07 per 100,000 people (95% confidence interval [CI], 2.00-2.13). It rose to 2.65 (95% CI, 2.58-2.65) in 1988 and 2.67 (95% CI, 2.61-2.72) in 2013, then fell to 2.09 (95% CI, 2.05-2.14) in 2017 and 2.01 (95% CI, 1.97-2.06) in 2019.

Per the analysis, the rate grew at an annual percentage change (APC) of 1.65% (95% CI, 1.30%-2.00%, P < .001) from 1975 to 1988 and remained stable from 1988 to 2013 (P = .85). Then it fell by an APC of 6.28% (95% CI, –8.52% to –3.97%, P < .001) from 2013 to 2017. There was no statistically significant difference between 2017 and 2019, although “the trend was downward,” the authors noted.

“Our study didn’t study the parameters that can answer the question about how many more years of life patients are getting or how many lives aren’t lost,” Dr. Kahlon said in the interview. “But looking at other studies and clinical trial data, the prognosis of these patients with a historical median overall survival of a few weeks to months has improved to many months to years.”

But why do melanoma mortality rates remain roughly about the same as they were in 1975? “The incidence of melanoma has continued to rise,” she said. “Also, over time, we have become better at collecting more accurate information, so the [rate] in 1975 could potentially be an underestimated rate.”

In an interview, dermatologist Adewole “Ade” Adamson, MD, MPP, of the University of Texas at Austin, noted that a 2020 study examined melanoma death rates in Whites – who are most affected by melanoma – and found similar trends from 2013 to 2016. “Nothing about these [new] findings surprises me as they have been shown before. However, these confirmatory findings are reassuring because they show the powerful effect of novel treatments at a population level.”

A new generation of treatments appears to have caused U.S. melanoma mortality rates to plunge between 2013 and 2017 for the first time in 4 decades, a new study finds, although the dip appeared to stabilize over the next 2 years.

“This data is very encouraging and represents the real-world effectiveness of these newer therapies, which include immunotherapies and targeted therapies,” hematologist/oncologist Navkirat Kahlon, MD, MPH, of Seacoast Cancer Center and Massachusetts General Brigham Wentworth-Douglass Hospital, Dover, N.H., one of the study authors, said in an interview. In clinical trials, these new treatments “have been very effective ... so the timing as well as magnitude of drop seen in melanoma-specific population mortality was not at all surprising. But it’s still very exciting.”

The report, published in JAMA Network Open, tracked mortality rates for the deadliest form of skin cancer from 1975 to 2019. The researchers launched the study to better understand outcomes in cutaneous melanoma following the rise of new therapies that now provide options in addition to chemotherapy. “With the use of novel therapies, the survival of these patients has increased from a few weeks or months to many years in clinical trials,” Dr. Kahlon said. “Given the magnitude of benefit compared to traditional chemotherapy in clinical trials, we decided to see if the real-world U.S. population is deriving the same benefit.”

New drugs introduced in recent years include immunotherapy agents such as ipilimumab and targeted therapies such as vemurafenib.

The researchers analyzed age-adjusted melanoma outcome data from the Surveillance, Epidemiology, and End Results (SEER) database. In 1975, the long-term melanoma mortality rate for melanoma was 2.07 per 100,000 people (95% confidence interval [CI], 2.00-2.13). It rose to 2.65 (95% CI, 2.58-2.65) in 1988 and 2.67 (95% CI, 2.61-2.72) in 2013, then fell to 2.09 (95% CI, 2.05-2.14) in 2017 and 2.01 (95% CI, 1.97-2.06) in 2019.

Per the analysis, the rate grew at an annual percentage change (APC) of 1.65% (95% CI, 1.30%-2.00%, P < .001) from 1975 to 1988 and remained stable from 1988 to 2013 (P = .85). Then it fell by an APC of 6.28% (95% CI, –8.52% to –3.97%, P < .001) from 2013 to 2017. There was no statistically significant difference between 2017 and 2019, although “the trend was downward,” the authors noted.

“Our study didn’t study the parameters that can answer the question about how many more years of life patients are getting or how many lives aren’t lost,” Dr. Kahlon said in the interview. “But looking at other studies and clinical trial data, the prognosis of these patients with a historical median overall survival of a few weeks to months has improved to many months to years.”

But why do melanoma mortality rates remain roughly about the same as they were in 1975? “The incidence of melanoma has continued to rise,” she said. “Also, over time, we have become better at collecting more accurate information, so the [rate] in 1975 could potentially be an underestimated rate.”

In an interview, dermatologist Adewole “Ade” Adamson, MD, MPP, of the University of Texas at Austin, noted that a 2020 study examined melanoma death rates in Whites – who are most affected by melanoma – and found similar trends from 2013 to 2016. “Nothing about these [new] findings surprises me as they have been shown before. However, these confirmatory findings are reassuring because they show the powerful effect of novel treatments at a population level.”

A new generation of treatments appears to have caused U.S. melanoma mortality rates to plunge between 2013 and 2017 for the first time in 4 decades, a new study finds, although the dip appeared to stabilize over the next 2 years.

“This data is very encouraging and represents the real-world effectiveness of these newer therapies, which include immunotherapies and targeted therapies,” hematologist/oncologist Navkirat Kahlon, MD, MPH, of Seacoast Cancer Center and Massachusetts General Brigham Wentworth-Douglass Hospital, Dover, N.H., one of the study authors, said in an interview. In clinical trials, these new treatments “have been very effective ... so the timing as well as magnitude of drop seen in melanoma-specific population mortality was not at all surprising. But it’s still very exciting.”

The report, published in JAMA Network Open, tracked mortality rates for the deadliest form of skin cancer from 1975 to 2019. The researchers launched the study to better understand outcomes in cutaneous melanoma following the rise of new therapies that now provide options in addition to chemotherapy. “With the use of novel therapies, the survival of these patients has increased from a few weeks or months to many years in clinical trials,” Dr. Kahlon said. “Given the magnitude of benefit compared to traditional chemotherapy in clinical trials, we decided to see if the real-world U.S. population is deriving the same benefit.”

New drugs introduced in recent years include immunotherapy agents such as ipilimumab and targeted therapies such as vemurafenib.

The researchers analyzed age-adjusted melanoma outcome data from the Surveillance, Epidemiology, and End Results (SEER) database. In 1975, the long-term melanoma mortality rate for melanoma was 2.07 per 100,000 people (95% confidence interval [CI], 2.00-2.13). It rose to 2.65 (95% CI, 2.58-2.65) in 1988 and 2.67 (95% CI, 2.61-2.72) in 2013, then fell to 2.09 (95% CI, 2.05-2.14) in 2017 and 2.01 (95% CI, 1.97-2.06) in 2019.

Per the analysis, the rate grew at an annual percentage change (APC) of 1.65% (95% CI, 1.30%-2.00%, P < .001) from 1975 to 1988 and remained stable from 1988 to 2013 (P = .85). Then it fell by an APC of 6.28% (95% CI, –8.52% to –3.97%, P < .001) from 2013 to 2017. There was no statistically significant difference between 2017 and 2019, although “the trend was downward,” the authors noted.

“Our study didn’t study the parameters that can answer the question about how many more years of life patients are getting or how many lives aren’t lost,” Dr. Kahlon said in the interview. “But looking at other studies and clinical trial data, the prognosis of these patients with a historical median overall survival of a few weeks to months has improved to many months to years.”

But why do melanoma mortality rates remain roughly about the same as they were in 1975? “The incidence of melanoma has continued to rise,” she said. “Also, over time, we have become better at collecting more accurate information, so the [rate] in 1975 could potentially be an underestimated rate.”

In an interview, dermatologist Adewole “Ade” Adamson, MD, MPP, of the University of Texas at Austin, noted that a 2020 study examined melanoma death rates in Whites – who are most affected by melanoma – and found similar trends from 2013 to 2016. “Nothing about these [new] findings surprises me as they have been shown before. However, these confirmatory findings are reassuring because they show the powerful effect of novel treatments at a population level.”

Although melanoma is the most serious skin cancer, most patients do have high chances of survival. New research has now identified a subset of patients with early disease who have a very low risk of dying from the disease.

In a cohort of almost 11,600 patients, the overall 7-year rate of death from melanoma was 2.5%, but the risk in a subset of 25% of patients was below 1%. Conversely, the study authors were also able to identify a small subset of high‐risk patients with a greater than 20% risk for death.

Though more data are needed and the findings verified in other studies, the use of a different term such as “melanocytic neoplasm of low malignant potential” may be more appropriate and may help to begin to address the problem of overdiagnosis, they note.

“While the topic of very low-risk melanomas has been presented at national and international meetings, there have been no formal discussions to define the classification of ‘melanocytic neoplasms of low malignant potential’ at this time,” first author Megan M. Eguchi, MPH, of the department of medicine, University of California, Los Angeles, said in an interview. “Criteria would need to be established using study designs beyond those available using SEER data.”

She emphasized that currently, they do not propose any change to treatment of these lesions, just a change to the terminology. “A diagnosis of ‘MNLMP’ rather than ‘melanoma’ may potentially alleviate people’s concerns related to prognosis and begin to address the problem of overdiagnosis,” said Ms. Eguchi. The study was recently published online in Cancer.

Even though melanoma is considered to be the most common potentially lethal tumor of the skin, prognosis is often very good for those with T1 tumors, the lowest risk category. Prognostic modeling has been used to predict survival in patients with melanoma and identify prognostic variables, the authors note, with the most prominent attributes being Breslow thickness and ulceration of the primary tumor, which form the basis of the current American Joint Committee on Cancer (AJCC) staging system.

There is evidence that the increasing incidence of melanoma is partly due to overdiagnosis, meaning the diagnosis of lesions that will not lead to symptoms or death. The authors write that they were interested in identifying lesions that are currently diagnosed as melanoma but might lack the capacity for metastasis, cases that could potentially be part of the phenomenon of overdiagnosis.

Subsets with low and high risk for death

In the study, Ms. Eguchi and colleagues analyzed information from the United States Surveillance, Epidemiology, and End Results (SEER) database and identified 11,594 patients who were diagnosed in 2010 and 2011 with stage 1 melanoma that was less than or equal to 1.0 mm in thickness and had not spread to the lymph nodes. Prognostic models for risk for death from melanoma in patients with low-risk melanomas were developed, then the ability of the models to identify very‐low risk subsets of patients with melanoma‐specific survival surpassing that of T1 overall was evaluated.

The median age of the patients was 58 years, the median Breslow thickness was 0.45 mm (interquartile range, 0.30-0.65 mm), and 71% were assigned stage IA. Ulceration was present in 4% of cases, 27% were mitogenic, and 45% were Clark level II, and within this cohort, 292 (2.5%) patients died of melanoma within 7 years. In the training data set, 177 of 7,652 (2.3%) patients died of melanoma within 7 years, and numbers were similar in the testing set (115 of 3,942; 2.9%).

Overall, the investigators identified three large subsets of patients who were in the AJCC seventh edition classification for stage I (“thin”) melanoma, who had a risk for death of approximately less than 1%. This was a marked improvement from the rate of the overall sample. In the simplest model (Model 1A), patients who were younger than 70 years at diagnosis with Clark level II invasion were deemed as very low risk.

In Model 1B, the same initial classification was used, but it was further refined and limited to patients who were either age 43 years or younger or 44-69 years with Breslow thickness less than 0.40 mm. At 10 years postdiagnosis, this subset also showed a less than 1% risk for death from melanoma. The logistic regression model (Model 2) was similar, as it identified about 25% of patients with a predicted risk for death of less than 0.5%, incorporating patient age, sex, mitogenicity, Clark level, and ulceration. Model 2 was also able to further identify a small subset of patients with no deaths.

The logistic regression model was also able to identify a very small subset (0.7% and 0.8%) of patients who had a risk for death that exceeded 20%, which was markedly higher, compared with most patients with T1b tumors.

This study was supported by the National Cancer Institute. Ms. Eguchi had no disclosures to report.

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

Although melanoma is the most serious skin cancer, most patients do have high chances of survival. New research has now identified a subset of patients with early disease who have a very low risk of dying from the disease.

In a cohort of almost 11,600 patients, the overall 7-year rate of death from melanoma was 2.5%, but the risk in a subset of 25% of patients was below 1%. Conversely, the study authors were also able to identify a small subset of high‐risk patients with a greater than 20% risk for death.

Though more data are needed and the findings verified in other studies, the use of a different term such as “melanocytic neoplasm of low malignant potential” may be more appropriate and may help to begin to address the problem of overdiagnosis, they note.

“While the topic of very low-risk melanomas has been presented at national and international meetings, there have been no formal discussions to define the classification of ‘melanocytic neoplasms of low malignant potential’ at this time,” first author Megan M. Eguchi, MPH, of the department of medicine, University of California, Los Angeles, said in an interview. “Criteria would need to be established using study designs beyond those available using SEER data.”

She emphasized that currently, they do not propose any change to treatment of these lesions, just a change to the terminology. “A diagnosis of ‘MNLMP’ rather than ‘melanoma’ may potentially alleviate people’s concerns related to prognosis and begin to address the problem of overdiagnosis,” said Ms. Eguchi. The study was recently published online in Cancer.

Even though melanoma is considered to be the most common potentially lethal tumor of the skin, prognosis is often very good for those with T1 tumors, the lowest risk category. Prognostic modeling has been used to predict survival in patients with melanoma and identify prognostic variables, the authors note, with the most prominent attributes being Breslow thickness and ulceration of the primary tumor, which form the basis of the current American Joint Committee on Cancer (AJCC) staging system.

There is evidence that the increasing incidence of melanoma is partly due to overdiagnosis, meaning the diagnosis of lesions that will not lead to symptoms or death. The authors write that they were interested in identifying lesions that are currently diagnosed as melanoma but might lack the capacity for metastasis, cases that could potentially be part of the phenomenon of overdiagnosis.

Subsets with low and high risk for death

In the study, Ms. Eguchi and colleagues analyzed information from the United States Surveillance, Epidemiology, and End Results (SEER) database and identified 11,594 patients who were diagnosed in 2010 and 2011 with stage 1 melanoma that was less than or equal to 1.0 mm in thickness and had not spread to the lymph nodes. Prognostic models for risk for death from melanoma in patients with low-risk melanomas were developed, then the ability of the models to identify very‐low risk subsets of patients with melanoma‐specific survival surpassing that of T1 overall was evaluated.

The median age of the patients was 58 years, the median Breslow thickness was 0.45 mm (interquartile range, 0.30-0.65 mm), and 71% were assigned stage IA. Ulceration was present in 4% of cases, 27% were mitogenic, and 45% were Clark level II, and within this cohort, 292 (2.5%) patients died of melanoma within 7 years. In the training data set, 177 of 7,652 (2.3%) patients died of melanoma within 7 years, and numbers were similar in the testing set (115 of 3,942; 2.9%).

Overall, the investigators identified three large subsets of patients who were in the AJCC seventh edition classification for stage I (“thin”) melanoma, who had a risk for death of approximately less than 1%. This was a marked improvement from the rate of the overall sample. In the simplest model (Model 1A), patients who were younger than 70 years at diagnosis with Clark level II invasion were deemed as very low risk.

In Model 1B, the same initial classification was used, but it was further refined and limited to patients who were either age 43 years or younger or 44-69 years with Breslow thickness less than 0.40 mm. At 10 years postdiagnosis, this subset also showed a less than 1% risk for death from melanoma. The logistic regression model (Model 2) was similar, as it identified about 25% of patients with a predicted risk for death of less than 0.5%, incorporating patient age, sex, mitogenicity, Clark level, and ulceration. Model 2 was also able to further identify a small subset of patients with no deaths.

The logistic regression model was also able to identify a very small subset (0.7% and 0.8%) of patients who had a risk for death that exceeded 20%, which was markedly higher, compared with most patients with T1b tumors.

This study was supported by the National Cancer Institute. Ms. Eguchi had no disclosures to report.

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

Although melanoma is the most serious skin cancer, most patients do have high chances of survival. New research has now identified a subset of patients with early disease who have a very low risk of dying from the disease.

In a cohort of almost 11,600 patients, the overall 7-year rate of death from melanoma was 2.5%, but the risk in a subset of 25% of patients was below 1%. Conversely, the study authors were also able to identify a small subset of high‐risk patients with a greater than 20% risk for death.

Though more data are needed and the findings verified in other studies, the use of a different term such as “melanocytic neoplasm of low malignant potential” may be more appropriate and may help to begin to address the problem of overdiagnosis, they note.

“While the topic of very low-risk melanomas has been presented at national and international meetings, there have been no formal discussions to define the classification of ‘melanocytic neoplasms of low malignant potential’ at this time,” first author Megan M. Eguchi, MPH, of the department of medicine, University of California, Los Angeles, said in an interview. “Criteria would need to be established using study designs beyond those available using SEER data.”

She emphasized that currently, they do not propose any change to treatment of these lesions, just a change to the terminology. “A diagnosis of ‘MNLMP’ rather than ‘melanoma’ may potentially alleviate people’s concerns related to prognosis and begin to address the problem of overdiagnosis,” said Ms. Eguchi. The study was recently published online in Cancer.

Even though melanoma is considered to be the most common potentially lethal tumor of the skin, prognosis is often very good for those with T1 tumors, the lowest risk category. Prognostic modeling has been used to predict survival in patients with melanoma and identify prognostic variables, the authors note, with the most prominent attributes being Breslow thickness and ulceration of the primary tumor, which form the basis of the current American Joint Committee on Cancer (AJCC) staging system.

There is evidence that the increasing incidence of melanoma is partly due to overdiagnosis, meaning the diagnosis of lesions that will not lead to symptoms or death. The authors write that they were interested in identifying lesions that are currently diagnosed as melanoma but might lack the capacity for metastasis, cases that could potentially be part of the phenomenon of overdiagnosis.

Subsets with low and high risk for death

In the study, Ms. Eguchi and colleagues analyzed information from the United States Surveillance, Epidemiology, and End Results (SEER) database and identified 11,594 patients who were diagnosed in 2010 and 2011 with stage 1 melanoma that was less than or equal to 1.0 mm in thickness and had not spread to the lymph nodes. Prognostic models for risk for death from melanoma in patients with low-risk melanomas were developed, then the ability of the models to identify very‐low risk subsets of patients with melanoma‐specific survival surpassing that of T1 overall was evaluated.

The median age of the patients was 58 years, the median Breslow thickness was 0.45 mm (interquartile range, 0.30-0.65 mm), and 71% were assigned stage IA. Ulceration was present in 4% of cases, 27% were mitogenic, and 45% were Clark level II, and within this cohort, 292 (2.5%) patients died of melanoma within 7 years. In the training data set, 177 of 7,652 (2.3%) patients died of melanoma within 7 years, and numbers were similar in the testing set (115 of 3,942; 2.9%).

Overall, the investigators identified three large subsets of patients who were in the AJCC seventh edition classification for stage I (“thin”) melanoma, who had a risk for death of approximately less than 1%. This was a marked improvement from the rate of the overall sample. In the simplest model (Model 1A), patients who were younger than 70 years at diagnosis with Clark level II invasion were deemed as very low risk.

In Model 1B, the same initial classification was used, but it was further refined and limited to patients who were either age 43 years or younger or 44-69 years with Breslow thickness less than 0.40 mm. At 10 years postdiagnosis, this subset also showed a less than 1% risk for death from melanoma. The logistic regression model (Model 2) was similar, as it identified about 25% of patients with a predicted risk for death of less than 0.5%, incorporating patient age, sex, mitogenicity, Clark level, and ulceration. Model 2 was also able to further identify a small subset of patients with no deaths.

The logistic regression model was also able to identify a very small subset (0.7% and 0.8%) of patients who had a risk for death that exceeded 20%, which was markedly higher, compared with most patients with T1b tumors.

This study was supported by the National Cancer Institute. Ms. Eguchi had no disclosures to report.

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

Sunscreens marketed to individuals with skin of color are generally more expensive than products broadly marketed to consumers, and more than 40% contain a UV blocker that may create a white cast.

Ridofranz / iStock / Getty Images

Those are among the findings from a study by Michelle Xiong, a medical student at Brown University, Providence, R.I., and Erin M. Warshaw, MD, of the department of dermatology at Park Nicollet/Health Partners Health Services, Minneapolis, which was published online in the Journal of the American Academy of Dermatology.

“There is increasing awareness of the negative effects of ultraviolet (UV) light in individuals with skin of color (SOC), especially in regards to pigmentation disorders induced and/or exacerbated by UV exposure,” the authors wrote. “As a result, there has been a surge in sunscreens marketed to this population. We aimed to characterize cost, marketing claims, and potential allergenic ingredients in sunscreens marketed to individuals with SOC.”

Between December 2021 and October 2022, the researchers used the following search terms on Google: “sunscreen” plus “skin of 36 color,” “dark skin,” “brown skin,” “LatinX skin,” and/or “Black skin.” They extracted price, marketing claims, and ingredients from manufacturers’ websites and used 90 allergens contained in the American Contact Dermatitis Society 2020 Core series to identify potential allergens. Next, they combined cross-reactors/synonyms into allergen categories based on ACDS Contact Allergen Management Plan (CAMP) cross-reactor classification. If multiple ingredients in a sunscreen were represented by a single allergen category, it was counted only once. A similar approach was utilized for marketing categories.

A total of 12 sunscreens were included in the analysis: Absolute Joi, Black Girl Sunscreen, Black Girl Sunscreen Make It Matte, Bolden SPF Brightening Moisturizer, Eleven on the Defense Unrivaled Sun Serum, Kinlo Golden Rays Sunscreen, Live Tinted Hueguard 3-in-1 Mineral Sunscreen, Mele Dew The Most Sheer Moisturizer SPF30 Broad Spectrum Sunscreen, Mele No Shade Sunscreen Oil, Specific Beauty Active Radiance Day Moi, Unsun Mineral Sunscreen, and Urban Skin Rx Complexion Protection. Their average cost was $19.30 per ounce (range, $6.33-$50.00) and common marketing claims for these products were “no white cast” (91.7%), being free of an ingredient (83.3%), and “moisturizing” (75%).

Of the 12 sunscreens, 7 (58.3%) contained a chemical sunscreen agent, 5 (41.7%) contained a physical UV blocker, and all contained at least one allergen. The average number of allergens per product was 4.7, most commonly fragrance/botanicals (83.3%), tocopherol (83.3%), sodium benzoates/derivatives (58.3%), and sorbitan sesquiolate/derivatives (58.3%).

“Average cost of sunscreens marketed to individuals with SOC was $19.30/oz, much higher than the median price of $3.32/oz reported in a separate study of 65 popular sunscreens,” the study authors wrote. “As many of the sunscreens in our study were sold by smaller businesses, higher prices may be due to higher production costs or a perceived smaller market.”

The authors expressed surprise that five sunscreens marketed to individuals with SOC contained a physical UV blocker which may create a white cast. They contacted the manufacturers of these five sunscreens and confirmed that three used micronized formulations. “While ingested/inhaled nanoparticles of titanium dioxide may cause tissue effects, most studies of topical products show excellent safety,” they wrote.

They also noted that the average of 4.7 allergens per product observed in the analysis was similar to the average of 4.9 seen in a separate study of 52 popular sunscreens. “However, that study only included 34 allergens while this study evaluated 90 allergens,” the authors wrote. “Consumers and providers should be aware sunscreens marketed to individuals with SOC may cause allergic contact dermatitis,” they commented.

“It is interesting to see how costly these products are now compared to store bought and general commercially available sunscreens several years ago,” said Lawrence J. Green, clinical professor of dermatology at George Washington University, Washington, who was asked to comment on the study. “However, to me that is not surprising as products marketed and targeted to specific populations are often priced at a premium. It wasn’t clear to me how many of these specialized online SOC sunscreens are tinted. I wish the authors had compared the cost of tinted sunscreens in general to nontinted sunscreens because tinted ones are more useful for SOC, because when rubbed in, they can readily match SOC and can also offer protection in the visible light spectrum.”

The authors reported having no financial disclosures; the study had no funding source. Dr. Green disclosed that he is a speaker, consultant, or investigator for many pharmaceutical companies.

Sunscreens marketed to individuals with skin of color are generally more expensive than products broadly marketed to consumers, and more than 40% contain a UV blocker that may create a white cast.

Ridofranz / iStock / Getty Images

Those are among the findings from a study by Michelle Xiong, a medical student at Brown University, Providence, R.I., and Erin M. Warshaw, MD, of the department of dermatology at Park Nicollet/Health Partners Health Services, Minneapolis, which was published online in the Journal of the American Academy of Dermatology.

“There is increasing awareness of the negative effects of ultraviolet (UV) light in individuals with skin of color (SOC), especially in regards to pigmentation disorders induced and/or exacerbated by UV exposure,” the authors wrote. “As a result, there has been a surge in sunscreens marketed to this population. We aimed to characterize cost, marketing claims, and potential allergenic ingredients in sunscreens marketed to individuals with SOC.”

Between December 2021 and October 2022, the researchers used the following search terms on Google: “sunscreen” plus “skin of 36 color,” “dark skin,” “brown skin,” “LatinX skin,” and/or “Black skin.” They extracted price, marketing claims, and ingredients from manufacturers’ websites and used 90 allergens contained in the American Contact Dermatitis Society 2020 Core series to identify potential allergens. Next, they combined cross-reactors/synonyms into allergen categories based on ACDS Contact Allergen Management Plan (CAMP) cross-reactor classification. If multiple ingredients in a sunscreen were represented by a single allergen category, it was counted only once. A similar approach was utilized for marketing categories.

A total of 12 sunscreens were included in the analysis: Absolute Joi, Black Girl Sunscreen, Black Girl Sunscreen Make It Matte, Bolden SPF Brightening Moisturizer, Eleven on the Defense Unrivaled Sun Serum, Kinlo Golden Rays Sunscreen, Live Tinted Hueguard 3-in-1 Mineral Sunscreen, Mele Dew The Most Sheer Moisturizer SPF30 Broad Spectrum Sunscreen, Mele No Shade Sunscreen Oil, Specific Beauty Active Radiance Day Moi, Unsun Mineral Sunscreen, and Urban Skin Rx Complexion Protection. Their average cost was $19.30 per ounce (range, $6.33-$50.00) and common marketing claims for these products were “no white cast” (91.7%), being free of an ingredient (83.3%), and “moisturizing” (75%).

Of the 12 sunscreens, 7 (58.3%) contained a chemical sunscreen agent, 5 (41.7%) contained a physical UV blocker, and all contained at least one allergen. The average number of allergens per product was 4.7, most commonly fragrance/botanicals (83.3%), tocopherol (83.3%), sodium benzoates/derivatives (58.3%), and sorbitan sesquiolate/derivatives (58.3%).

“Average cost of sunscreens marketed to individuals with SOC was $19.30/oz, much higher than the median price of $3.32/oz reported in a separate study of 65 popular sunscreens,” the study authors wrote. “As many of the sunscreens in our study were sold by smaller businesses, higher prices may be due to higher production costs or a perceived smaller market.”

The authors expressed surprise that five sunscreens marketed to individuals with SOC contained a physical UV blocker which may create a white cast. They contacted the manufacturers of these five sunscreens and confirmed that three used micronized formulations. “While ingested/inhaled nanoparticles of titanium dioxide may cause tissue effects, most studies of topical products show excellent safety,” they wrote.

They also noted that the average of 4.7 allergens per product observed in the analysis was similar to the average of 4.9 seen in a separate study of 52 popular sunscreens. “However, that study only included 34 allergens while this study evaluated 90 allergens,” the authors wrote. “Consumers and providers should be aware sunscreens marketed to individuals with SOC may cause allergic contact dermatitis,” they commented.

“It is interesting to see how costly these products are now compared to store bought and general commercially available sunscreens several years ago,” said Lawrence J. Green, clinical professor of dermatology at George Washington University, Washington, who was asked to comment on the study. “However, to me that is not surprising as products marketed and targeted to specific populations are often priced at a premium. It wasn’t clear to me how many of these specialized online SOC sunscreens are tinted. I wish the authors had compared the cost of tinted sunscreens in general to nontinted sunscreens because tinted ones are more useful for SOC, because when rubbed in, they can readily match SOC and can also offer protection in the visible light spectrum.”

The authors reported having no financial disclosures; the study had no funding source. Dr. Green disclosed that he is a speaker, consultant, or investigator for many pharmaceutical companies.

Sunscreens marketed to individuals with skin of color are generally more expensive than products broadly marketed to consumers, and more than 40% contain a UV blocker that may create a white cast.

Ridofranz / iStock / Getty Images

Those are among the findings from a study by Michelle Xiong, a medical student at Brown University, Providence, R.I., and Erin M. Warshaw, MD, of the department of dermatology at Park Nicollet/Health Partners Health Services, Minneapolis, which was published online in the Journal of the American Academy of Dermatology.

“There is increasing awareness of the negative effects of ultraviolet (UV) light in individuals with skin of color (SOC), especially in regards to pigmentation disorders induced and/or exacerbated by UV exposure,” the authors wrote. “As a result, there has been a surge in sunscreens marketed to this population. We aimed to characterize cost, marketing claims, and potential allergenic ingredients in sunscreens marketed to individuals with SOC.”

Between December 2021 and October 2022, the researchers used the following search terms on Google: “sunscreen” plus “skin of 36 color,” “dark skin,” “brown skin,” “LatinX skin,” and/or “Black skin.” They extracted price, marketing claims, and ingredients from manufacturers’ websites and used 90 allergens contained in the American Contact Dermatitis Society 2020 Core series to identify potential allergens. Next, they combined cross-reactors/synonyms into allergen categories based on ACDS Contact Allergen Management Plan (CAMP) cross-reactor classification. If multiple ingredients in a sunscreen were represented by a single allergen category, it was counted only once. A similar approach was utilized for marketing categories.

A total of 12 sunscreens were included in the analysis: Absolute Joi, Black Girl Sunscreen, Black Girl Sunscreen Make It Matte, Bolden SPF Brightening Moisturizer, Eleven on the Defense Unrivaled Sun Serum, Kinlo Golden Rays Sunscreen, Live Tinted Hueguard 3-in-1 Mineral Sunscreen, Mele Dew The Most Sheer Moisturizer SPF30 Broad Spectrum Sunscreen, Mele No Shade Sunscreen Oil, Specific Beauty Active Radiance Day Moi, Unsun Mineral Sunscreen, and Urban Skin Rx Complexion Protection. Their average cost was $19.30 per ounce (range, $6.33-$50.00) and common marketing claims for these products were “no white cast” (91.7%), being free of an ingredient (83.3%), and “moisturizing” (75%).

Of the 12 sunscreens, 7 (58.3%) contained a chemical sunscreen agent, 5 (41.7%) contained a physical UV blocker, and all contained at least one allergen. The average number of allergens per product was 4.7, most commonly fragrance/botanicals (83.3%), tocopherol (83.3%), sodium benzoates/derivatives (58.3%), and sorbitan sesquiolate/derivatives (58.3%).

“Average cost of sunscreens marketed to individuals with SOC was $19.30/oz, much higher than the median price of $3.32/oz reported in a separate study of 65 popular sunscreens,” the study authors wrote. “As many of the sunscreens in our study were sold by smaller businesses, higher prices may be due to higher production costs or a perceived smaller market.”

The authors expressed surprise that five sunscreens marketed to individuals with SOC contained a physical UV blocker which may create a white cast. They contacted the manufacturers of these five sunscreens and confirmed that three used micronized formulations. “While ingested/inhaled nanoparticles of titanium dioxide may cause tissue effects, most studies of topical products show excellent safety,” they wrote.

They also noted that the average of 4.7 allergens per product observed in the analysis was similar to the average of 4.9 seen in a separate study of 52 popular sunscreens. “However, that study only included 34 allergens while this study evaluated 90 allergens,” the authors wrote. “Consumers and providers should be aware sunscreens marketed to individuals with SOC may cause allergic contact dermatitis,” they commented.

“It is interesting to see how costly these products are now compared to store bought and general commercially available sunscreens several years ago,” said Lawrence J. Green, clinical professor of dermatology at George Washington University, Washington, who was asked to comment on the study. “However, to me that is not surprising as products marketed and targeted to specific populations are often priced at a premium. It wasn’t clear to me how many of these specialized online SOC sunscreens are tinted. I wish the authors had compared the cost of tinted sunscreens in general to nontinted sunscreens because tinted ones are more useful for SOC, because when rubbed in, they can readily match SOC and can also offer protection in the visible light spectrum.”

The authors reported having no financial disclosures; the study had no funding source. Dr. Green disclosed that he is a speaker, consultant, or investigator for many pharmaceutical companies.

It had only been 3 weeks since I first met this patient. She presented with an advanced case of colon cancer, but instead of treatment, we had to have a serious talk about death and dying and the goals of care. She died soon after our talk.

Within the course of 2 weeks I saw another new patient, but this time with pancreatic cancer that metastasized to the liver. “When can we start treatment?” he asked. Like my female patient with colon cancer, he was diagnosed too late as he was already in an incurable stage. He was shocked to learn that his condition was in stage 4, that achieving remission would be difficult and a cure, not likely. Certainly, standard of care treatments and clinical trials offered him hope, but they were unlikely to change the outcome.

We take a course in this – that is, in giving bad news, but every doctor has his or her own approach. Some are so uncomfortable with the talk, they choose avoidance and adopt the “look like you gotta go approach.” Or, the doctor may schedule another treatment or another test with the intention of avoiding end-of-life discussions. Other doctors opt for straight talk: “I think you should get your affairs in order. You’ve got 3 months to live.” These are extreme behaviors I wouldn’t recommend.

In my practice, I sit with my patients and explain the diagnosis. After discussing all options and the advanced stage and diagnosis, it ultimately comes down to “Win or lose, I will be here to take care of you.” Sometimes there is therapy that may help, but either way, the patient understands that death is a real possibility.

I find that people just want to know if there is hope. A different treatment regimen or a clinical trial may (or may not) extend their life. And while we cannot predict outcomes, we can give them hope. You can’t shut down hope. True for some people the cup is always half empty, but most people want to live and are optimistic no matter how small the chances are.

These conversations are very difficult. I don’t like them, but then I don’t avoid them either. Fortunately, patients don’t usually come to my office for the first visit presenting with advanced disease. In the cases I described above, one patient had been experiencing unexplained weight loss, but didn’t share it with a physician. And, for the patient with pancreatic cancer, other than some discomfort in the last couple of weeks, the disease was not associated with other symptoms. But the absence of symptoms should not in any way rule out a malignant disease. A diagnosis should be based on a complete evaluation of signs and symptoms followed by testing.

We’ve got to be able to take the time to listen to our patients during these encounters. We may not spend as much time as we should because we’re so busy now and we’re slaves to EMRs. It helps if we take more time to probe symptoms a little longer, especially in the primary care setting.

It is possible for a patient with cancer to be asymptomatic up until the later stages of the disease. A study published in ESMO Open in 2020 found that fewer than half of patients with stage 4 non–small cell lung cancer have only one or two symptoms at diagnosis regardless of whether the patient was a smoker. In this study only 33% of patients reported having a cough and 25% had chest pain.

A study presented in October at the United European Gastroenterology Week found that of 600 pancreatic cancer cases, 46 of these were not detected by CT or MRI conducted 3-18 months prior to diagnosis. Of the 46 cases, 26% were not picked up by the radiologist and the rest were largely as a result of imaging changes over time. Radiology techniques are good, but they cannot pick up lesions that are too small. And some lesions, particularly in pancreatic cancer, can grow and metastasize rather quickly.

When a patient is diagnosed with advanced disease, it is most often simply because of the nature of the disease. But sometimes patients put off scheduling a doctor visit because of fear of the potential for bad news or fear of the doctor belittling their symptoms. Some tell me they were “just hoping the symptoms would disappear.” Waiting too long to see a doctor is never a good idea because timing is crucial. In many cases, there is a small window of opportunity to treat disease if remission is to be achieved.


Dr. Henry is a practicing clinical oncologist with PennMedicine in Philadelphia where he also serves as Vice Chair of the Department of Medicine at Pennsylvania Hospital.
 

This article was updated 12/7/22.

It had only been 3 weeks since I first met this patient. She presented with an advanced case of colon cancer, but instead of treatment, we had to have a serious talk about death and dying and the goals of care. She died soon after our talk.

Within the course of 2 weeks I saw another new patient, but this time with pancreatic cancer that metastasized to the liver. “When can we start treatment?” he asked. Like my female patient with colon cancer, he was diagnosed too late as he was already in an incurable stage. He was shocked to learn that his condition was in stage 4, that achieving remission would be difficult and a cure, not likely. Certainly, standard of care treatments and clinical trials offered him hope, but they were unlikely to change the outcome.

We take a course in this – that is, in giving bad news, but every doctor has his or her own approach. Some are so uncomfortable with the talk, they choose avoidance and adopt the “look like you gotta go approach.” Or, the doctor may schedule another treatment or another test with the intention of avoiding end-of-life discussions. Other doctors opt for straight talk: “I think you should get your affairs in order. You’ve got 3 months to live.” These are extreme behaviors I wouldn’t recommend.

In my practice, I sit with my patients and explain the diagnosis. After discussing all options and the advanced stage and diagnosis, it ultimately comes down to “Win or lose, I will be here to take care of you.” Sometimes there is therapy that may help, but either way, the patient understands that death is a real possibility.

I find that people just want to know if there is hope. A different treatment regimen or a clinical trial may (or may not) extend their life. And while we cannot predict outcomes, we can give them hope. You can’t shut down hope. True for some people the cup is always half empty, but most people want to live and are optimistic no matter how small the chances are.

These conversations are very difficult. I don’t like them, but then I don’t avoid them either. Fortunately, patients don’t usually come to my office for the first visit presenting with advanced disease. In the cases I described above, one patient had been experiencing unexplained weight loss, but didn’t share it with a physician. And, for the patient with pancreatic cancer, other than some discomfort in the last couple of weeks, the disease was not associated with other symptoms. But the absence of symptoms should not in any way rule out a malignant disease. A diagnosis should be based on a complete evaluation of signs and symptoms followed by testing.

We’ve got to be able to take the time to listen to our patients during these encounters. We may not spend as much time as we should because we’re so busy now and we’re slaves to EMRs. It helps if we take more time to probe symptoms a little longer, especially in the primary care setting.

It is possible for a patient with cancer to be asymptomatic up until the later stages of the disease. A study published in ESMO Open in 2020 found that fewer than half of patients with stage 4 non–small cell lung cancer have only one or two symptoms at diagnosis regardless of whether the patient was a smoker. In this study only 33% of patients reported having a cough and 25% had chest pain.

A study presented in October at the United European Gastroenterology Week found that of 600 pancreatic cancer cases, 46 of these were not detected by CT or MRI conducted 3-18 months prior to diagnosis. Of the 46 cases, 26% were not picked up by the radiologist and the rest were largely as a result of imaging changes over time. Radiology techniques are good, but they cannot pick up lesions that are too small. And some lesions, particularly in pancreatic cancer, can grow and metastasize rather quickly.

When a patient is diagnosed with advanced disease, it is most often simply because of the nature of the disease. But sometimes patients put off scheduling a doctor visit because of fear of the potential for bad news or fear of the doctor belittling their symptoms. Some tell me they were “just hoping the symptoms would disappear.” Waiting too long to see a doctor is never a good idea because timing is crucial. In many cases, there is a small window of opportunity to treat disease if remission is to be achieved.


Dr. Henry is a practicing clinical oncologist with PennMedicine in Philadelphia where he also serves as Vice Chair of the Department of Medicine at Pennsylvania Hospital.
 

This article was updated 12/7/22.

It had only been 3 weeks since I first met this patient. She presented with an advanced case of colon cancer, but instead of treatment, we had to have a serious talk about death and dying and the goals of care. She died soon after our talk.

Within the course of 2 weeks I saw another new patient, but this time with pancreatic cancer that metastasized to the liver. “When can we start treatment?” he asked. Like my female patient with colon cancer, he was diagnosed too late as he was already in an incurable stage. He was shocked to learn that his condition was in stage 4, that achieving remission would be difficult and a cure, not likely. Certainly, standard of care treatments and clinical trials offered him hope, but they were unlikely to change the outcome.

We take a course in this – that is, in giving bad news, but every doctor has his or her own approach. Some are so uncomfortable with the talk, they choose avoidance and adopt the “look like you gotta go approach.” Or, the doctor may schedule another treatment or another test with the intention of avoiding end-of-life discussions. Other doctors opt for straight talk: “I think you should get your affairs in order. You’ve got 3 months to live.” These are extreme behaviors I wouldn’t recommend.

In my practice, I sit with my patients and explain the diagnosis. After discussing all options and the advanced stage and diagnosis, it ultimately comes down to “Win or lose, I will be here to take care of you.” Sometimes there is therapy that may help, but either way, the patient understands that death is a real possibility.

I find that people just want to know if there is hope. A different treatment regimen or a clinical trial may (or may not) extend their life. And while we cannot predict outcomes, we can give them hope. You can’t shut down hope. True for some people the cup is always half empty, but most people want to live and are optimistic no matter how small the chances are.

These conversations are very difficult. I don’t like them, but then I don’t avoid them either. Fortunately, patients don’t usually come to my office for the first visit presenting with advanced disease. In the cases I described above, one patient had been experiencing unexplained weight loss, but didn’t share it with a physician. And, for the patient with pancreatic cancer, other than some discomfort in the last couple of weeks, the disease was not associated with other symptoms. But the absence of symptoms should not in any way rule out a malignant disease. A diagnosis should be based on a complete evaluation of signs and symptoms followed by testing.

We’ve got to be able to take the time to listen to our patients during these encounters. We may not spend as much time as we should because we’re so busy now and we’re slaves to EMRs. It helps if we take more time to probe symptoms a little longer, especially in the primary care setting.

It is possible for a patient with cancer to be asymptomatic up until the later stages of the disease. A study published in ESMO Open in 2020 found that fewer than half of patients with stage 4 non–small cell lung cancer have only one or two symptoms at diagnosis regardless of whether the patient was a smoker. In this study only 33% of patients reported having a cough and 25% had chest pain.

A study presented in October at the United European Gastroenterology Week found that of 600 pancreatic cancer cases, 46 of these were not detected by CT or MRI conducted 3-18 months prior to diagnosis. Of the 46 cases, 26% were not picked up by the radiologist and the rest were largely as a result of imaging changes over time. Radiology techniques are good, but they cannot pick up lesions that are too small. And some lesions, particularly in pancreatic cancer, can grow and metastasize rather quickly.

When a patient is diagnosed with advanced disease, it is most often simply because of the nature of the disease. But sometimes patients put off scheduling a doctor visit because of fear of the potential for bad news or fear of the doctor belittling their symptoms. Some tell me they were “just hoping the symptoms would disappear.” Waiting too long to see a doctor is never a good idea because timing is crucial. In many cases, there is a small window of opportunity to treat disease if remission is to be achieved.


Dr. Henry is a practicing clinical oncologist with PennMedicine in Philadelphia where he also serves as Vice Chair of the Department of Medicine at Pennsylvania Hospital.
 

This article was updated 12/7/22.

Among adults undergoing Mohs micrographic surgery, individuals most prone to preprocedural anxiety were younger, female, and those with a history of anxiety confirmed by a health care provider (HCP), results from a single-center survey demonstrated.

“Higher patient-reported anxiety in hospital settings is significantly linked to lower patient satisfaction with the quality of care and higher patient-reported postoperative pain,” corresponding author Ally-Khan Somani, MD, PhD, and colleagues wrote in the study, which was published online in Dermatologic Surgery. “Identifying factors associated with perioperative patient anxiety could improve outcomes and patient satisfaction.”

Dr. Somani, director of dermatologic surgery and cutaneous oncology in the department of dermatology at the University of Indiana, Indianapolis, and coauthors surveyed 145 patients who underwent Mohs micrographic surgery (MMS) at the university from February 2018 to March 2020. They collected patient self-reported demographics, medical history, and administered a 10-point visual analog scale assessment of anxiety at multiple stages. They also sought HCP-perceived assessments of anxiety and used a stepwise regression mode to explore factors that potentially contributed to anxiety outcomes. The mean age of the 145 patients was 63 years, 60% were female, and 77% had no self-reported anxiety confirmed by a prior HCP’s diagnosis.

Two-thirds of patients (66%) received a pre-MMS consultation with the surgeon, 59% had a history of skin cancer removal surgery, and 86% had 1-2 layers removed during the current MMS.

Prior to MMS, the researchers found that significant risk factors for increased anxiety included younger age, female sex, and self-reported history of anxiety confirmed by an HCP (P < .05), while intraoperatively, HCP-perceived patient anxiety increased with younger patient age and more layers removed. Following MMS, patient anxiety increased significantly with more layers removed and higher self-reported preoperative anxiety levels. “Although existing research is divided regarding the efficacy of pre-MMS consultation for anxiety reduction, these findings suggest that patient-reported and HCP-perceived anxiety were not significantly affected by in-person pre-MMS consultation with the surgeon,” Dr. Somani and colleagues wrote. “Thus, routinely recommending consultations may not be the best approach for improving anxiety outcomes.”

They acknowledged certain limitations of their analysis, including its single-center design, enrollment of demographically similar patients, and the fact that no objective measurements of anxiety such as heart rate or blood pressure were taken.

“One of the main benefits of Mohs surgery is that we are able to operate under local anesthesia, but this also means that our patients are acutely aware of everything going on around them,” said Patricia M. Richey, MD, who practices Mohs surgery and cosmetic dermatology in Washington, D.C., and was asked to comment on the study.

“I think it is so important that this study is primarily focusing on the patient experience,” she said. “While this study did not find that a pre-op consult impacted patient anxiety levels, I do think we can infer that it is critical to connect with your patients on some level prior to surgery, as it helps you tailor your process to make the day more tolerable for them [such as] playing music, determining the need for an oral anxiolytic, etc.”

Neither the researchers nor Dr. Richey reported having financial disclosures.

Among adults undergoing Mohs micrographic surgery, individuals most prone to preprocedural anxiety were younger, female, and those with a history of anxiety confirmed by a health care provider (HCP), results from a single-center survey demonstrated.

“Higher patient-reported anxiety in hospital settings is significantly linked to lower patient satisfaction with the quality of care and higher patient-reported postoperative pain,” corresponding author Ally-Khan Somani, MD, PhD, and colleagues wrote in the study, which was published online in Dermatologic Surgery. “Identifying factors associated with perioperative patient anxiety could improve outcomes and patient satisfaction.”

Dr. Somani, director of dermatologic surgery and cutaneous oncology in the department of dermatology at the University of Indiana, Indianapolis, and coauthors surveyed 145 patients who underwent Mohs micrographic surgery (MMS) at the university from February 2018 to March 2020. They collected patient self-reported demographics, medical history, and administered a 10-point visual analog scale assessment of anxiety at multiple stages. They also sought HCP-perceived assessments of anxiety and used a stepwise regression mode to explore factors that potentially contributed to anxiety outcomes. The mean age of the 145 patients was 63 years, 60% were female, and 77% had no self-reported anxiety confirmed by a prior HCP’s diagnosis.

Two-thirds of patients (66%) received a pre-MMS consultation with the surgeon, 59% had a history of skin cancer removal surgery, and 86% had 1-2 layers removed during the current MMS.

Prior to MMS, the researchers found that significant risk factors for increased anxiety included younger age, female sex, and self-reported history of anxiety confirmed by an HCP (P < .05), while intraoperatively, HCP-perceived patient anxiety increased with younger patient age and more layers removed. Following MMS, patient anxiety increased significantly with more layers removed and higher self-reported preoperative anxiety levels. “Although existing research is divided regarding the efficacy of pre-MMS consultation for anxiety reduction, these findings suggest that patient-reported and HCP-perceived anxiety were not significantly affected by in-person pre-MMS consultation with the surgeon,” Dr. Somani and colleagues wrote. “Thus, routinely recommending consultations may not be the best approach for improving anxiety outcomes.”

They acknowledged certain limitations of their analysis, including its single-center design, enrollment of demographically similar patients, and the fact that no objective measurements of anxiety such as heart rate or blood pressure were taken.

“One of the main benefits of Mohs surgery is that we are able to operate under local anesthesia, but this also means that our patients are acutely aware of everything going on around them,” said Patricia M. Richey, MD, who practices Mohs surgery and cosmetic dermatology in Washington, D.C., and was asked to comment on the study.

“I think it is so important that this study is primarily focusing on the patient experience,” she said. “While this study did not find that a pre-op consult impacted patient anxiety levels, I do think we can infer that it is critical to connect with your patients on some level prior to surgery, as it helps you tailor your process to make the day more tolerable for them [such as] playing music, determining the need for an oral anxiolytic, etc.”

Neither the researchers nor Dr. Richey reported having financial disclosures.

Among adults undergoing Mohs micrographic surgery, individuals most prone to preprocedural anxiety were younger, female, and those with a history of anxiety confirmed by a health care provider (HCP), results from a single-center survey demonstrated.

“Higher patient-reported anxiety in hospital settings is significantly linked to lower patient satisfaction with the quality of care and higher patient-reported postoperative pain,” corresponding author Ally-Khan Somani, MD, PhD, and colleagues wrote in the study, which was published online in Dermatologic Surgery. “Identifying factors associated with perioperative patient anxiety could improve outcomes and patient satisfaction.”

Dr. Somani, director of dermatologic surgery and cutaneous oncology in the department of dermatology at the University of Indiana, Indianapolis, and coauthors surveyed 145 patients who underwent Mohs micrographic surgery (MMS) at the university from February 2018 to March 2020. They collected patient self-reported demographics, medical history, and administered a 10-point visual analog scale assessment of anxiety at multiple stages. They also sought HCP-perceived assessments of anxiety and used a stepwise regression mode to explore factors that potentially contributed to anxiety outcomes. The mean age of the 145 patients was 63 years, 60% were female, and 77% had no self-reported anxiety confirmed by a prior HCP’s diagnosis.

Two-thirds of patients (66%) received a pre-MMS consultation with the surgeon, 59% had a history of skin cancer removal surgery, and 86% had 1-2 layers removed during the current MMS.

Prior to MMS, the researchers found that significant risk factors for increased anxiety included younger age, female sex, and self-reported history of anxiety confirmed by an HCP (P < .05), while intraoperatively, HCP-perceived patient anxiety increased with younger patient age and more layers removed. Following MMS, patient anxiety increased significantly with more layers removed and higher self-reported preoperative anxiety levels. “Although existing research is divided regarding the efficacy of pre-MMS consultation for anxiety reduction, these findings suggest that patient-reported and HCP-perceived anxiety were not significantly affected by in-person pre-MMS consultation with the surgeon,” Dr. Somani and colleagues wrote. “Thus, routinely recommending consultations may not be the best approach for improving anxiety outcomes.”

They acknowledged certain limitations of their analysis, including its single-center design, enrollment of demographically similar patients, and the fact that no objective measurements of anxiety such as heart rate or blood pressure were taken.

“One of the main benefits of Mohs surgery is that we are able to operate under local anesthesia, but this also means that our patients are acutely aware of everything going on around them,” said Patricia M. Richey, MD, who practices Mohs surgery and cosmetic dermatology in Washington, D.C., and was asked to comment on the study.

“I think it is so important that this study is primarily focusing on the patient experience,” she said. “While this study did not find that a pre-op consult impacted patient anxiety levels, I do think we can infer that it is critical to connect with your patients on some level prior to surgery, as it helps you tailor your process to make the day more tolerable for them [such as] playing music, determining the need for an oral anxiolytic, etc.”

Neither the researchers nor Dr. Richey reported having financial disclosures.

Individuals with a primary melanoma may be more likely to develop a second primary melanoma if they have certain characteristics, a new study suggests.

In a cohort study of more than 38,000 patients, those diagnosed with a second primary melanoma were significantly more likely to have a “nevus-prone” phenotype and a high polygenic risk score for melanoma.

Notably, the researchers also found only limited evidence that elevated levels of sun exposure contributed to second melanoma risk.

Overall, the findings suggest that “within the general population, the presence of many nevi and having a high genetic predisposition to melanoma were associated with the highest risks of developing second primary melanoma,” Catherine M. Olsen, PhD, of the University of Queensland, Australia, and colleagues concluded.

The study was published online in JAMA Dermatology.

People with melanoma are believed to be at high risk for developing subsequent tumors, yet most never do. Population-based studies indicate that only about 8%-18% of patients are diagnosed with a second primary melanoma.

Previous studies using modified case-control design have identified several factors associated with developing multiple primary melanomas, including older age, male sex, a family history of melanoma, high nevus counts or presence of atypical nevi, higher ambient UV radiation and personal sun exposure, as well as certain inherited genetic variants.

However, these studies aren’t equipped to assess the magnitude of risk of developing multiple melanomas among those who have not yet had melanoma.

In the current analysis, Dr. Olsen and colleagues set out to understand the level of risk using a prospective cohort study design. The cohort comprised participants in the QSkin Sun and Health Study and included 38,845 patients with a baseline median age of 56 years, followed for a median of 7.4 years. Among these participants, 1,212 (3.1%) had only one primary melanoma diagnosis, and 245 (0.6%) had two or more primary melanomas. Of those with more primary melanomas, 59 had synchronous primary melanoma, meaning first and second primary melanomas were diagnosed on the same day.

The investigators compared the clinical characteristics of patients with first and second melanomas, looking at demographic, phenotypic, sun exposure, and genetic factors. The team found that the median time between first and second melanoma, excluding cases of synchronous primary melanoma, was 18.4 months.

Those who developed second melanomas were older at baseline than those who developed only one (59.3 years vs. 58.2 years, respectively; P < .001), and were more likely to have a sun-sensitive phenotype, a self-reported history of excisions for nonmelanoma skin cancers, and a high polygenic risk score for melanoma. Among people who developed second primary melanomas, the second melanomas were more likely to be in situ and of the lentigo maligna subtype.

Notably, factors including age, sex, sunburn tendency, and family history of melanoma had similarly elevated effect sizes among those diagnosed with first and second melanomas. The authors also found similar associations with baseline measures for personal sun exposure – including sunburns and cumulative sun exposure; however, the number of past skin cancer excisions was more strongly associated with second primaries (P = .05).

The team did identify two factors associated with a higher risk of developing a second primary melanoma. A nevus phenotype was more strongly associated with developing a second primary melanoma (hazard ratio, 6.36) than the initial one (HR, 3.46). And second primary melanomas had stronger associations with high melanoma polygenic risk scores than first primary melanomas (HR, 3.28 vs HR, 2.06; P = .03).

The authors noted several limitations to the study, including the generalizability of the findings outside of Australia and the relatively small number of people with second primary melanomas.

Still, the investigators note that the data “offer unique insights that differ from earlier efforts.” Namely, the “findings showed that many of the classic phenotypic risk factors for melanoma were similarly associated with risk of first and second melanomas; however, high numbers of nevi and high genetic predisposition were more strongly associated with second [rather] than first primary melanomas.”

This work was supported by grants from the National Health and Medical Research Council of Australia. Dr. Olsen reports no relevant financial relationships. Coauthor Rachel Neale, PhD, reported grants from Viatris and the National Health and Medical Research Council of Australia outside the submitted work. Coauthor David Whiteman, MBBS, PhD, reported personal fees from Pierre Fabre (speaker fees for conference presentation) outside the submitted work. No other disclosures were reported.

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

Individuals with a primary melanoma may be more likely to develop a second primary melanoma if they have certain characteristics, a new study suggests.

In a cohort study of more than 38,000 patients, those diagnosed with a second primary melanoma were significantly more likely to have a “nevus-prone” phenotype and a high polygenic risk score for melanoma.

Notably, the researchers also found only limited evidence that elevated levels of sun exposure contributed to second melanoma risk.

Overall, the findings suggest that “within the general population, the presence of many nevi and having a high genetic predisposition to melanoma were associated with the highest risks of developing second primary melanoma,” Catherine M. Olsen, PhD, of the University of Queensland, Australia, and colleagues concluded.

The study was published online in JAMA Dermatology.

People with melanoma are believed to be at high risk for developing subsequent tumors, yet most never do. Population-based studies indicate that only about 8%-18% of patients are diagnosed with a second primary melanoma.

Previous studies using modified case-control design have identified several factors associated with developing multiple primary melanomas, including older age, male sex, a family history of melanoma, high nevus counts or presence of atypical nevi, higher ambient UV radiation and personal sun exposure, as well as certain inherited genetic variants.

However, these studies aren’t equipped to assess the magnitude of risk of developing multiple melanomas among those who have not yet had melanoma.

In the current analysis, Dr. Olsen and colleagues set out to understand the level of risk using a prospective cohort study design. The cohort comprised participants in the QSkin Sun and Health Study and included 38,845 patients with a baseline median age of 56 years, followed for a median of 7.4 years. Among these participants, 1,212 (3.1%) had only one primary melanoma diagnosis, and 245 (0.6%) had two or more primary melanomas. Of those with more primary melanomas, 59 had synchronous primary melanoma, meaning first and second primary melanomas were diagnosed on the same day.

The investigators compared the clinical characteristics of patients with first and second melanomas, looking at demographic, phenotypic, sun exposure, and genetic factors. The team found that the median time between first and second melanoma, excluding cases of synchronous primary melanoma, was 18.4 months.

Those who developed second melanomas were older at baseline than those who developed only one (59.3 years vs. 58.2 years, respectively; P < .001), and were more likely to have a sun-sensitive phenotype, a self-reported history of excisions for nonmelanoma skin cancers, and a high polygenic risk score for melanoma. Among people who developed second primary melanomas, the second melanomas were more likely to be in situ and of the lentigo maligna subtype.

Notably, factors including age, sex, sunburn tendency, and family history of melanoma had similarly elevated effect sizes among those diagnosed with first and second melanomas. The authors also found similar associations with baseline measures for personal sun exposure – including sunburns and cumulative sun exposure; however, the number of past skin cancer excisions was more strongly associated with second primaries (P = .05).

The team did identify two factors associated with a higher risk of developing a second primary melanoma. A nevus phenotype was more strongly associated with developing a second primary melanoma (hazard ratio, 6.36) than the initial one (HR, 3.46). And second primary melanomas had stronger associations with high melanoma polygenic risk scores than first primary melanomas (HR, 3.28 vs HR, 2.06; P = .03).

The authors noted several limitations to the study, including the generalizability of the findings outside of Australia and the relatively small number of people with second primary melanomas.

Still, the investigators note that the data “offer unique insights that differ from earlier efforts.” Namely, the “findings showed that many of the classic phenotypic risk factors for melanoma were similarly associated with risk of first and second melanomas; however, high numbers of nevi and high genetic predisposition were more strongly associated with second [rather] than first primary melanomas.”

This work was supported by grants from the National Health and Medical Research Council of Australia. Dr. Olsen reports no relevant financial relationships. Coauthor Rachel Neale, PhD, reported grants from Viatris and the National Health and Medical Research Council of Australia outside the submitted work. Coauthor David Whiteman, MBBS, PhD, reported personal fees from Pierre Fabre (speaker fees for conference presentation) outside the submitted work. No other disclosures were reported.

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

Individuals with a primary melanoma may be more likely to develop a second primary melanoma if they have certain characteristics, a new study suggests.

In a cohort study of more than 38,000 patients, those diagnosed with a second primary melanoma were significantly more likely to have a “nevus-prone” phenotype and a high polygenic risk score for melanoma.

Notably, the researchers also found only limited evidence that elevated levels of sun exposure contributed to second melanoma risk.

Overall, the findings suggest that “within the general population, the presence of many nevi and having a high genetic predisposition to melanoma were associated with the highest risks of developing second primary melanoma,” Catherine M. Olsen, PhD, of the University of Queensland, Australia, and colleagues concluded.

The study was published online in JAMA Dermatology.

People with melanoma are believed to be at high risk for developing subsequent tumors, yet most never do. Population-based studies indicate that only about 8%-18% of patients are diagnosed with a second primary melanoma.

Previous studies using modified case-control design have identified several factors associated with developing multiple primary melanomas, including older age, male sex, a family history of melanoma, high nevus counts or presence of atypical nevi, higher ambient UV radiation and personal sun exposure, as well as certain inherited genetic variants.

However, these studies aren’t equipped to assess the magnitude of risk of developing multiple melanomas among those who have not yet had melanoma.

In the current analysis, Dr. Olsen and colleagues set out to understand the level of risk using a prospective cohort study design. The cohort comprised participants in the QSkin Sun and Health Study and included 38,845 patients with a baseline median age of 56 years, followed for a median of 7.4 years. Among these participants, 1,212 (3.1%) had only one primary melanoma diagnosis, and 245 (0.6%) had two or more primary melanomas. Of those with more primary melanomas, 59 had synchronous primary melanoma, meaning first and second primary melanomas were diagnosed on the same day.

The investigators compared the clinical characteristics of patients with first and second melanomas, looking at demographic, phenotypic, sun exposure, and genetic factors. The team found that the median time between first and second melanoma, excluding cases of synchronous primary melanoma, was 18.4 months.

Those who developed second melanomas were older at baseline than those who developed only one (59.3 years vs. 58.2 years, respectively; P < .001), and were more likely to have a sun-sensitive phenotype, a self-reported history of excisions for nonmelanoma skin cancers, and a high polygenic risk score for melanoma. Among people who developed second primary melanomas, the second melanomas were more likely to be in situ and of the lentigo maligna subtype.

Notably, factors including age, sex, sunburn tendency, and family history of melanoma had similarly elevated effect sizes among those diagnosed with first and second melanomas. The authors also found similar associations with baseline measures for personal sun exposure – including sunburns and cumulative sun exposure; however, the number of past skin cancer excisions was more strongly associated with second primaries (P = .05).

The team did identify two factors associated with a higher risk of developing a second primary melanoma. A nevus phenotype was more strongly associated with developing a second primary melanoma (hazard ratio, 6.36) than the initial one (HR, 3.46). And second primary melanomas had stronger associations with high melanoma polygenic risk scores than first primary melanomas (HR, 3.28 vs HR, 2.06; P = .03).

The authors noted several limitations to the study, including the generalizability of the findings outside of Australia and the relatively small number of people with second primary melanomas.

Still, the investigators note that the data “offer unique insights that differ from earlier efforts.” Namely, the “findings showed that many of the classic phenotypic risk factors for melanoma were similarly associated with risk of first and second melanomas; however, high numbers of nevi and high genetic predisposition were more strongly associated with second [rather] than first primary melanomas.”

This work was supported by grants from the National Health and Medical Research Council of Australia. Dr. Olsen reports no relevant financial relationships. Coauthor Rachel Neale, PhD, reported grants from Viatris and the National Health and Medical Research Council of Australia outside the submitted work. Coauthor David Whiteman, MBBS, PhD, reported personal fees from Pierre Fabre (speaker fees for conference presentation) outside the submitted work. No other disclosures were reported.

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

Latinx individuals have a lower overall risk of melanoma than non-Latinx Whites (NLW), but they are more likely to be diagnosed with advanced disease, and experience greater mortality. A new qualitative study of Latinx and low-income NLW individuals in California has revealed some of the socioeconomic and community factors that may play a role in preventing early access to care.

Thicker melanomas, which are more likely to be lethal, are on the rise in the United States among people with lower socioeconomic status (SES), as well as African Americans and Hispanics, and both Black and Latinx people are more likely than NLW people to present with stage 3 or stage 4 disease. “That has really prompted us to look at community engagement and outreach and then really understand the qualitative aspects that are driving individuals into higher risk for melanoma, apart from just limited insurance and access to health care,” said Susan Swetter, MD, who presented the results of the study at the annual meeting of the American Society of Clinical Oncology.

Other studies, such as a Boston-area survey published in 2020, suggest that Hispanics are less likely than Whites to know the meaning of the term melanoma (odds ratio, 0.27; P =.0037), suggesting the need for educational efforts. The authors of that study noted that knowledge of melanoma in 2017, when the survey was conducted, remained essentially unchanged since a previous study was published in 1996.

“Our results support a need for better public educational programs, particularly those geared toward minority populations. Educational programs that are culturally relevant and include specific sections for skin of color have been shown to better promote early melanoma detection in individuals of ethnic minorities and may help decrease the ethnic disparities in melanoma-related mortality. At the patient-physician level, dermatologists may educate their patients, including Hispanic patients, should they choose to perform (skin self-examinations) to specifically inspect the extremities and acral areas, given the higher incidence rates of melanoma on those areas in this population,” the authors wrote.

The goal of the new study is to get a better understanding of the factors that affect attitudes toward health care, and the researchers found a complex mixture that including ethnicity, cultural, gender identity, geography, skin color, gender norms, and socioeconomic status (SES). “Qualitative research can inform our preventive and early detection strategies. For instance, in the Latinx group, there’s a lot of mistrust of health systems, medical providers, and who is providing that knowledge. We have to figure out ways to provide a trusted source of information. Doctors and physicians and health providers tend to be trusted, but there are many barriers to getting lower SES patients into care. We’re now investigating the use of community health workers and even individuals in various settings and community centers, religious settings or religious leaders, where we’ve determined through this focus group research that there is increased trust,” Dr. Swetter said.

The researchers assembled 19 focus groups with 176 total adult participants, interviewing them about perceptions of melanoma risk, prevention and screening strategies and their acceptability, and barriers to melanoma prevention and care. The sample include people from urban and semirural areas; 55%-62% of participants self-identified as Latinx or Hispanic and 26%-27% as NLW.

Latinx and semirural participants reported having minimal conversations with family about melanoma prevention, and those who reported having darker skin perceived their risk from skin cancer as lower. Participants who lived in rural areas, were Latinx, or of low SES status indicated that health care access challenges included out-of-pocket costs, past experiences of physicians showing less concern about them, and little confidence that rural physicians had the needed expertise or would make an appropriate referral.

The study is just the first step in a series of efforts to improve melanoma outcomes in high-risk populations, which is being pursued through Stanford University’s Wipe Out Melanoma–California statewide initiative and research consortium. “What we aim to do is use this knowledge to now design programs to reach the populations who are more likely to present with worse disease, and to prevent that disease from happening. These qualitative analyses are few and far between in the world of melanoma, and we’re really happy to really push this envelope and change the way we deliver preventive and early detection efforts,” said Dr. Swetter, who is a professor of dermatology and director of the pigmented lesion/melanoma and cutaneous oncology programs at Stanford (Calif.) University Medical Center. Dr. Swetter also chairs the National Comprehensive Cancer Network guidelines for cutaneous melanoma.

The study could also improve care of advanced melanoma. “There’s clear evidence that many of these patient and SES factors, economic and knowledge barriers are the same when it comes to getting patients with advanced melanoma into appropriate care and on clinical trials, and that’s true across all races and ethnicities,” said Dr. Swetter.

The ultimate goal of these approaches is to give individuals greater “self-efficacy, such that a person feels more competent to manage his or her own health outcomes. One aspect of this approach is the use of novel technology such as smartphone apps that can track moles or help visualize lesions during teledermatology. “I think that the future of melanoma prevention and early detection is bright, especially if we incorporate novel technologies and engage patients and their communities in the effort. It’s a different strategy, as opposed to the top-down approach of physicians imparting knowledge and providing the exam. Increasing community engagement is critical to reaching the populations at highest risk for advanced disease and getting them into care and detection early,” Dr. Swetter said.

Dr. Swetter has no relevant financial disclosures.

Latinx individuals have a lower overall risk of melanoma than non-Latinx Whites (NLW), but they are more likely to be diagnosed with advanced disease, and experience greater mortality. A new qualitative study of Latinx and low-income NLW individuals in California has revealed some of the socioeconomic and community factors that may play a role in preventing early access to care.

Thicker melanomas, which are more likely to be lethal, are on the rise in the United States among people with lower socioeconomic status (SES), as well as African Americans and Hispanics, and both Black and Latinx people are more likely than NLW people to present with stage 3 or stage 4 disease. “That has really prompted us to look at community engagement and outreach and then really understand the qualitative aspects that are driving individuals into higher risk for melanoma, apart from just limited insurance and access to health care,” said Susan Swetter, MD, who presented the results of the study at the annual meeting of the American Society of Clinical Oncology.

Other studies, such as a Boston-area survey published in 2020, suggest that Hispanics are less likely than Whites to know the meaning of the term melanoma (odds ratio, 0.27; P =.0037), suggesting the need for educational efforts. The authors of that study noted that knowledge of melanoma in 2017, when the survey was conducted, remained essentially unchanged since a previous study was published in 1996.

“Our results support a need for better public educational programs, particularly those geared toward minority populations. Educational programs that are culturally relevant and include specific sections for skin of color have been shown to better promote early melanoma detection in individuals of ethnic minorities and may help decrease the ethnic disparities in melanoma-related mortality. At the patient-physician level, dermatologists may educate their patients, including Hispanic patients, should they choose to perform (skin self-examinations) to specifically inspect the extremities and acral areas, given the higher incidence rates of melanoma on those areas in this population,” the authors wrote.

The goal of the new study is to get a better understanding of the factors that affect attitudes toward health care, and the researchers found a complex mixture that including ethnicity, cultural, gender identity, geography, skin color, gender norms, and socioeconomic status (SES). “Qualitative research can inform our preventive and early detection strategies. For instance, in the Latinx group, there’s a lot of mistrust of health systems, medical providers, and who is providing that knowledge. We have to figure out ways to provide a trusted source of information. Doctors and physicians and health providers tend to be trusted, but there are many barriers to getting lower SES patients into care. We’re now investigating the use of community health workers and even individuals in various settings and community centers, religious settings or religious leaders, where we’ve determined through this focus group research that there is increased trust,” Dr. Swetter said.

The researchers assembled 19 focus groups with 176 total adult participants, interviewing them about perceptions of melanoma risk, prevention and screening strategies and their acceptability, and barriers to melanoma prevention and care. The sample include people from urban and semirural areas; 55%-62% of participants self-identified as Latinx or Hispanic and 26%-27% as NLW.

Latinx and semirural participants reported having minimal conversations with family about melanoma prevention, and those who reported having darker skin perceived their risk from skin cancer as lower. Participants who lived in rural areas, were Latinx, or of low SES status indicated that health care access challenges included out-of-pocket costs, past experiences of physicians showing less concern about them, and little confidence that rural physicians had the needed expertise or would make an appropriate referral.

The study is just the first step in a series of efforts to improve melanoma outcomes in high-risk populations, which is being pursued through Stanford University’s Wipe Out Melanoma–California statewide initiative and research consortium. “What we aim to do is use this knowledge to now design programs to reach the populations who are more likely to present with worse disease, and to prevent that disease from happening. These qualitative analyses are few and far between in the world of melanoma, and we’re really happy to really push this envelope and change the way we deliver preventive and early detection efforts,” said Dr. Swetter, who is a professor of dermatology and director of the pigmented lesion/melanoma and cutaneous oncology programs at Stanford (Calif.) University Medical Center. Dr. Swetter also chairs the National Comprehensive Cancer Network guidelines for cutaneous melanoma.

The study could also improve care of advanced melanoma. “There’s clear evidence that many of these patient and SES factors, economic and knowledge barriers are the same when it comes to getting patients with advanced melanoma into appropriate care and on clinical trials, and that’s true across all races and ethnicities,” said Dr. Swetter.

The ultimate goal of these approaches is to give individuals greater “self-efficacy, such that a person feels more competent to manage his or her own health outcomes. One aspect of this approach is the use of novel technology such as smartphone apps that can track moles or help visualize lesions during teledermatology. “I think that the future of melanoma prevention and early detection is bright, especially if we incorporate novel technologies and engage patients and their communities in the effort. It’s a different strategy, as opposed to the top-down approach of physicians imparting knowledge and providing the exam. Increasing community engagement is critical to reaching the populations at highest risk for advanced disease and getting them into care and detection early,” Dr. Swetter said.

Dr. Swetter has no relevant financial disclosures.

Latinx individuals have a lower overall risk of melanoma than non-Latinx Whites (NLW), but they are more likely to be diagnosed with advanced disease, and experience greater mortality. A new qualitative study of Latinx and low-income NLW individuals in California has revealed some of the socioeconomic and community factors that may play a role in preventing early access to care.

Thicker melanomas, which are more likely to be lethal, are on the rise in the United States among people with lower socioeconomic status (SES), as well as African Americans and Hispanics, and both Black and Latinx people are more likely than NLW people to present with stage 3 or stage 4 disease. “That has really prompted us to look at community engagement and outreach and then really understand the qualitative aspects that are driving individuals into higher risk for melanoma, apart from just limited insurance and access to health care,” said Susan Swetter, MD, who presented the results of the study at the annual meeting of the American Society of Clinical Oncology.

Other studies, such as a Boston-area survey published in 2020, suggest that Hispanics are less likely than Whites to know the meaning of the term melanoma (odds ratio, 0.27; P =.0037), suggesting the need for educational efforts. The authors of that study noted that knowledge of melanoma in 2017, when the survey was conducted, remained essentially unchanged since a previous study was published in 1996.

“Our results support a need for better public educational programs, particularly those geared toward minority populations. Educational programs that are culturally relevant and include specific sections for skin of color have been shown to better promote early melanoma detection in individuals of ethnic minorities and may help decrease the ethnic disparities in melanoma-related mortality. At the patient-physician level, dermatologists may educate their patients, including Hispanic patients, should they choose to perform (skin self-examinations) to specifically inspect the extremities and acral areas, given the higher incidence rates of melanoma on those areas in this population,” the authors wrote.

The goal of the new study is to get a better understanding of the factors that affect attitudes toward health care, and the researchers found a complex mixture that including ethnicity, cultural, gender identity, geography, skin color, gender norms, and socioeconomic status (SES). “Qualitative research can inform our preventive and early detection strategies. For instance, in the Latinx group, there’s a lot of mistrust of health systems, medical providers, and who is providing that knowledge. We have to figure out ways to provide a trusted source of information. Doctors and physicians and health providers tend to be trusted, but there are many barriers to getting lower SES patients into care. We’re now investigating the use of community health workers and even individuals in various settings and community centers, religious settings or religious leaders, where we’ve determined through this focus group research that there is increased trust,” Dr. Swetter said.

The researchers assembled 19 focus groups with 176 total adult participants, interviewing them about perceptions of melanoma risk, prevention and screening strategies and their acceptability, and barriers to melanoma prevention and care. The sample include people from urban and semirural areas; 55%-62% of participants self-identified as Latinx or Hispanic and 26%-27% as NLW.

Latinx and semirural participants reported having minimal conversations with family about melanoma prevention, and those who reported having darker skin perceived their risk from skin cancer as lower. Participants who lived in rural areas, were Latinx, or of low SES status indicated that health care access challenges included out-of-pocket costs, past experiences of physicians showing less concern about them, and little confidence that rural physicians had the needed expertise or would make an appropriate referral.

The study is just the first step in a series of efforts to improve melanoma outcomes in high-risk populations, which is being pursued through Stanford University’s Wipe Out Melanoma–California statewide initiative and research consortium. “What we aim to do is use this knowledge to now design programs to reach the populations who are more likely to present with worse disease, and to prevent that disease from happening. These qualitative analyses are few and far between in the world of melanoma, and we’re really happy to really push this envelope and change the way we deliver preventive and early detection efforts,” said Dr. Swetter, who is a professor of dermatology and director of the pigmented lesion/melanoma and cutaneous oncology programs at Stanford (Calif.) University Medical Center. Dr. Swetter also chairs the National Comprehensive Cancer Network guidelines for cutaneous melanoma.

The study could also improve care of advanced melanoma. “There’s clear evidence that many of these patient and SES factors, economic and knowledge barriers are the same when it comes to getting patients with advanced melanoma into appropriate care and on clinical trials, and that’s true across all races and ethnicities,” said Dr. Swetter.

The ultimate goal of these approaches is to give individuals greater “self-efficacy, such that a person feels more competent to manage his or her own health outcomes. One aspect of this approach is the use of novel technology such as smartphone apps that can track moles or help visualize lesions during teledermatology. “I think that the future of melanoma prevention and early detection is bright, especially if we incorporate novel technologies and engage patients and their communities in the effort. It’s a different strategy, as opposed to the top-down approach of physicians imparting knowledge and providing the exam. Increasing community engagement is critical to reaching the populations at highest risk for advanced disease and getting them into care and detection early,” Dr. Swetter said.

Dr. Swetter has no relevant financial disclosures.

The combination of nivolumab and vidutolimod led to a high rate of pathologic complete response and pathologic major response in a phase 2 trial of patients with stage 3 resectable melanoma. The result led researchers to call for a future study comparing the regimen against a suitable control group.

“We were very excited to see the ability of intratumoral vidutolimod to augment T-cell infiltrate. (Pathologic) response was associated with a dense infiltrate of CD8 T cells. We were also able to demonstrate for what I think may be the first time, that intratumoral CpG resulted in clear evidence of CD303+ plasmacytoid dendritic cells [pDCs],” said Diwakar Davar, MD, assistant professor of medicine at the University of Pittsburgh, during a presentation of the results at the annual meeting of the Society for Immunotherapy of Cancer. He noted that pDCs represent a very rare cell population, less than 0.4% of circulating peripheral blood mononuclear cells, and tend to be found in lymph nodes.

The current standard of care for stage 3 melanoma is up-front surgery followed by adjuvant therapy – anti–PD-1 therapy for patients with wild-type or BRAF-mutant cancers, and targeted therapy with BRAF/MEK inhibitors in patients with BRAF mutations. However, preclinical studies suggest that neoadjuvant immunotherapy could lead to a stronger antitumor T-cell response than adjuvant immunotherapy.

Vidutolimod targets the toll-like receptor 9 (TLR-9) endosomal receptor found in B cells and pDC cells. The formulation is a virus-like particle (VLP) that contains unmethylated cytosine guanine–rich oligonucleotides (CpG ODN). Bacterial and viral genomes tend to be enriched in CpG ODN, and this acts as a TLR-9 agonist. TLR-9 activation in turn triggers an interferon response, and this may help overcome PD-1 blockade resistance in metastatic melanoma.

The researchers conducted a nonrandomized, open-label trial that included 30 patients with stage 3 melanoma (14 women; median age, 61 years). Patients received neoadjuvant nivolumab and vidutolimod for 8 weeks, then were evaluated for surgery. Patients continued both drugs in the adjuvant setting for 48 weeks. 47% experienced complete pathologic response, 10% a major pathologic response, and 10% a partial pathologic response.

Analysis of resected samples revealed clear evidence of an immune response, Dr. Davar said during a press conference held in advance of the meeting. “Pathologic response was associated with compelling evidence of immune activation both peripherally and within the tumor, with clear evidence of pDC infiltrate and pDC activation – something that has not previously been seen in human specimens.”

The study regimen appeared safe, with no dose-limiting toxicities or grade 4 or 5 adverse events. He noted that the regimen is now being tested in the phase 2 ECOG-ACRIN trial.

The results are “very exciting,” said Pamela Ohashi, PhD, who commented on the study during the press conference. The virus-like nature of vidutolimod may be an important element of the therapy. “I think scientifically we would have predicted that the VLP carrying the CPG would be very good at activating the CD8 cells, which in fact is what you’re seeing. So I think it’s very exciting and has lots of potential for future combinations,” said Dr. Ohashi, who is director of the tumor immunotherapy program at the Princess Margaret Cancer Centre, Toronto.

The study was funded by Checkmate Pharmaceuticals. Dr. Davar has financial relationships with Checkmate Pharmaceuticals and Regeneron, which has acquired Checkmate Pharmaceuticals.

The combination of nivolumab and vidutolimod led to a high rate of pathologic complete response and pathologic major response in a phase 2 trial of patients with stage 3 resectable melanoma. The result led researchers to call for a future study comparing the regimen against a suitable control group.

“We were very excited to see the ability of intratumoral vidutolimod to augment T-cell infiltrate. (Pathologic) response was associated with a dense infiltrate of CD8 T cells. We were also able to demonstrate for what I think may be the first time, that intratumoral CpG resulted in clear evidence of CD303+ plasmacytoid dendritic cells [pDCs],” said Diwakar Davar, MD, assistant professor of medicine at the University of Pittsburgh, during a presentation of the results at the annual meeting of the Society for Immunotherapy of Cancer. He noted that pDCs represent a very rare cell population, less than 0.4% of circulating peripheral blood mononuclear cells, and tend to be found in lymph nodes.

The current standard of care for stage 3 melanoma is up-front surgery followed by adjuvant therapy – anti–PD-1 therapy for patients with wild-type or BRAF-mutant cancers, and targeted therapy with BRAF/MEK inhibitors in patients with BRAF mutations. However, preclinical studies suggest that neoadjuvant immunotherapy could lead to a stronger antitumor T-cell response than adjuvant immunotherapy.

Vidutolimod targets the toll-like receptor 9 (TLR-9) endosomal receptor found in B cells and pDC cells. The formulation is a virus-like particle (VLP) that contains unmethylated cytosine guanine–rich oligonucleotides (CpG ODN). Bacterial and viral genomes tend to be enriched in CpG ODN, and this acts as a TLR-9 agonist. TLR-9 activation in turn triggers an interferon response, and this may help overcome PD-1 blockade resistance in metastatic melanoma.

The researchers conducted a nonrandomized, open-label trial that included 30 patients with stage 3 melanoma (14 women; median age, 61 years). Patients received neoadjuvant nivolumab and vidutolimod for 8 weeks, then were evaluated for surgery. Patients continued both drugs in the adjuvant setting for 48 weeks. 47% experienced complete pathologic response, 10% a major pathologic response, and 10% a partial pathologic response.

Analysis of resected samples revealed clear evidence of an immune response, Dr. Davar said during a press conference held in advance of the meeting. “Pathologic response was associated with compelling evidence of immune activation both peripherally and within the tumor, with clear evidence of pDC infiltrate and pDC activation – something that has not previously been seen in human specimens.”

The study regimen appeared safe, with no dose-limiting toxicities or grade 4 or 5 adverse events. He noted that the regimen is now being tested in the phase 2 ECOG-ACRIN trial.

The results are “very exciting,” said Pamela Ohashi, PhD, who commented on the study during the press conference. The virus-like nature of vidutolimod may be an important element of the therapy. “I think scientifically we would have predicted that the VLP carrying the CPG would be very good at activating the CD8 cells, which in fact is what you’re seeing. So I think it’s very exciting and has lots of potential for future combinations,” said Dr. Ohashi, who is director of the tumor immunotherapy program at the Princess Margaret Cancer Centre, Toronto.

The study was funded by Checkmate Pharmaceuticals. Dr. Davar has financial relationships with Checkmate Pharmaceuticals and Regeneron, which has acquired Checkmate Pharmaceuticals.

The combination of nivolumab and vidutolimod led to a high rate of pathologic complete response and pathologic major response in a phase 2 trial of patients with stage 3 resectable melanoma. The result led researchers to call for a future study comparing the regimen against a suitable control group.

“We were very excited to see the ability of intratumoral vidutolimod to augment T-cell infiltrate. (Pathologic) response was associated with a dense infiltrate of CD8 T cells. We were also able to demonstrate for what I think may be the first time, that intratumoral CpG resulted in clear evidence of CD303+ plasmacytoid dendritic cells [pDCs],” said Diwakar Davar, MD, assistant professor of medicine at the University of Pittsburgh, during a presentation of the results at the annual meeting of the Society for Immunotherapy of Cancer. He noted that pDCs represent a very rare cell population, less than 0.4% of circulating peripheral blood mononuclear cells, and tend to be found in lymph nodes.

The current standard of care for stage 3 melanoma is up-front surgery followed by adjuvant therapy – anti–PD-1 therapy for patients with wild-type or BRAF-mutant cancers, and targeted therapy with BRAF/MEK inhibitors in patients with BRAF mutations. However, preclinical studies suggest that neoadjuvant immunotherapy could lead to a stronger antitumor T-cell response than adjuvant immunotherapy.

Vidutolimod targets the toll-like receptor 9 (TLR-9) endosomal receptor found in B cells and pDC cells. The formulation is a virus-like particle (VLP) that contains unmethylated cytosine guanine–rich oligonucleotides (CpG ODN). Bacterial and viral genomes tend to be enriched in CpG ODN, and this acts as a TLR-9 agonist. TLR-9 activation in turn triggers an interferon response, and this may help overcome PD-1 blockade resistance in metastatic melanoma.

The researchers conducted a nonrandomized, open-label trial that included 30 patients with stage 3 melanoma (14 women; median age, 61 years). Patients received neoadjuvant nivolumab and vidutolimod for 8 weeks, then were evaluated for surgery. Patients continued both drugs in the adjuvant setting for 48 weeks. 47% experienced complete pathologic response, 10% a major pathologic response, and 10% a partial pathologic response.

Analysis of resected samples revealed clear evidence of an immune response, Dr. Davar said during a press conference held in advance of the meeting. “Pathologic response was associated with compelling evidence of immune activation both peripherally and within the tumor, with clear evidence of pDC infiltrate and pDC activation – something that has not previously been seen in human specimens.”

The study regimen appeared safe, with no dose-limiting toxicities or grade 4 or 5 adverse events. He noted that the regimen is now being tested in the phase 2 ECOG-ACRIN trial.

The results are “very exciting,” said Pamela Ohashi, PhD, who commented on the study during the press conference. The virus-like nature of vidutolimod may be an important element of the therapy. “I think scientifically we would have predicted that the VLP carrying the CPG would be very good at activating the CD8 cells, which in fact is what you’re seeing. So I think it’s very exciting and has lots of potential for future combinations,” said Dr. Ohashi, who is director of the tumor immunotherapy program at the Princess Margaret Cancer Centre, Toronto.

The study was funded by Checkmate Pharmaceuticals. Dr. Davar has financial relationships with Checkmate Pharmaceuticals and Regeneron, which has acquired Checkmate Pharmaceuticals.