Melanoma

The calcium channel blocker amlodipine besylate was effective in reducing the number of muscle cramps caused by vismodegib, a basal cell carcinoma drug, according to a research letter from Dr. Mina Ally and her associates.

Patients who took amlodipine had the number of muscle cramps halved after 2 weeks of treatment, and this level was maintained for the 8-week medication regimen. No significant change in cramp severity, duration, or frequency of nighttime awakenings was seen. Side effects only appeared in too patients, with one reporting mild intermittent dizziness and another reporting grade 1 peripheral edema.

The control group saw a nonsignificant increase in cramp frequency, compared with the significant decrease in the amlodipine group. No change was seen in cramp severity, duration, or number of nighttime awakenings in the control group.

“Amlodipine may be effective in vismodegib-induced muscle cramps because it blocks voltage-gated calcium channels and inhibits the transport of extracellular calcium into muscle that is required for contraction,” the investigators noted.

Find the full research letter in JAMA Dermatology (doi:10.1001/jamadermatol.2015.1937).

[email protected]

The calcium channel blocker amlodipine besylate was effective in reducing the number of muscle cramps caused by vismodegib, a basal cell carcinoma drug, according to a research letter from Dr. Mina Ally and her associates.

Patients who took amlodipine had the number of muscle cramps halved after 2 weeks of treatment, and this level was maintained for the 8-week medication regimen. No significant change in cramp severity, duration, or frequency of nighttime awakenings was seen. Side effects only appeared in too patients, with one reporting mild intermittent dizziness and another reporting grade 1 peripheral edema.

The control group saw a nonsignificant increase in cramp frequency, compared with the significant decrease in the amlodipine group. No change was seen in cramp severity, duration, or number of nighttime awakenings in the control group.

“Amlodipine may be effective in vismodegib-induced muscle cramps because it blocks voltage-gated calcium channels and inhibits the transport of extracellular calcium into muscle that is required for contraction,” the investigators noted.

Find the full research letter in JAMA Dermatology (doi:10.1001/jamadermatol.2015.1937).

[email protected]

The calcium channel blocker amlodipine besylate was effective in reducing the number of muscle cramps caused by vismodegib, a basal cell carcinoma drug, according to a research letter from Dr. Mina Ally and her associates.

Patients who took amlodipine had the number of muscle cramps halved after 2 weeks of treatment, and this level was maintained for the 8-week medication regimen. No significant change in cramp severity, duration, or frequency of nighttime awakenings was seen. Side effects only appeared in too patients, with one reporting mild intermittent dizziness and another reporting grade 1 peripheral edema.

The control group saw a nonsignificant increase in cramp frequency, compared with the significant decrease in the amlodipine group. No change was seen in cramp severity, duration, or number of nighttime awakenings in the control group.

“Amlodipine may be effective in vismodegib-induced muscle cramps because it blocks voltage-gated calcium channels and inhibits the transport of extracellular calcium into muscle that is required for contraction,” the investigators noted.

Find the full research letter in JAMA Dermatology (doi:10.1001/jamadermatol.2015.1937).

[email protected]

Adding a MEK inhibitor to BRAF inhibitor treatment for metastatic melanoma is associated with a significant reduction in the risk of cutaneous squamous cell carcinoma and other cutaneous toxic effects, new data suggests.

A retrospective cohort study in 185 patients with unresectable stage IIIC and IV melanoma showed those treated with BRAF inhibitors dabrafenib or vemurafenib in combination with a MEK inhibitor had zero cases of cutaneous squamous cell carcinoma, verrucal keratosis or Grover disease but a 40% incidence of folliculitis, according to a paper published online July 22 in JAMA Dermatology.

In contrast, the rates of cutaneous squamous cell carcinoma were significantly higher among patients treated with either dabrafenib or vemurafenib alone (26.1% and 36.1%, respectively), as was the incidence of Grover disease (42.9% and 38.9%) and verrucal keratosis (66.4% and 72.2%).

“Recognition of the variety of cutaneous toxic effects associated with these different therapies, including the predisposing risk factors for their development, is important with the purpose of ensuring appropriate rapid intervention and thereby abrogating the need to delay or even withhold these essential treatments,” wrote Dr. Giuliana Carlos of Westmead Hospital, Sydney, and coauthors (JAMA Dermatology 2015, July 22 [doi:10.1001/jamadermatol.2015.1745]).

The study was supported by the Westmead Medical Research Foundation. Three authors reported travel support or consultancies with pharmaceutical companies, but there were no other conflicts of interest declared.

Adding a MEK inhibitor to BRAF inhibitor treatment for metastatic melanoma is associated with a significant reduction in the risk of cutaneous squamous cell carcinoma and other cutaneous toxic effects, new data suggests.

A retrospective cohort study in 185 patients with unresectable stage IIIC and IV melanoma showed those treated with BRAF inhibitors dabrafenib or vemurafenib in combination with a MEK inhibitor had zero cases of cutaneous squamous cell carcinoma, verrucal keratosis or Grover disease but a 40% incidence of folliculitis, according to a paper published online July 22 in JAMA Dermatology.

In contrast, the rates of cutaneous squamous cell carcinoma were significantly higher among patients treated with either dabrafenib or vemurafenib alone (26.1% and 36.1%, respectively), as was the incidence of Grover disease (42.9% and 38.9%) and verrucal keratosis (66.4% and 72.2%).

“Recognition of the variety of cutaneous toxic effects associated with these different therapies, including the predisposing risk factors for their development, is important with the purpose of ensuring appropriate rapid intervention and thereby abrogating the need to delay or even withhold these essential treatments,” wrote Dr. Giuliana Carlos of Westmead Hospital, Sydney, and coauthors (JAMA Dermatology 2015, July 22 [doi:10.1001/jamadermatol.2015.1745]).

The study was supported by the Westmead Medical Research Foundation. Three authors reported travel support or consultancies with pharmaceutical companies, but there were no other conflicts of interest declared.

Adding a MEK inhibitor to BRAF inhibitor treatment for metastatic melanoma is associated with a significant reduction in the risk of cutaneous squamous cell carcinoma and other cutaneous toxic effects, new data suggests.

A retrospective cohort study in 185 patients with unresectable stage IIIC and IV melanoma showed those treated with BRAF inhibitors dabrafenib or vemurafenib in combination with a MEK inhibitor had zero cases of cutaneous squamous cell carcinoma, verrucal keratosis or Grover disease but a 40% incidence of folliculitis, according to a paper published online July 22 in JAMA Dermatology.

In contrast, the rates of cutaneous squamous cell carcinoma were significantly higher among patients treated with either dabrafenib or vemurafenib alone (26.1% and 36.1%, respectively), as was the incidence of Grover disease (42.9% and 38.9%) and verrucal keratosis (66.4% and 72.2%).

“Recognition of the variety of cutaneous toxic effects associated with these different therapies, including the predisposing risk factors for their development, is important with the purpose of ensuring appropriate rapid intervention and thereby abrogating the need to delay or even withhold these essential treatments,” wrote Dr. Giuliana Carlos of Westmead Hospital, Sydney, and coauthors (JAMA Dermatology 2015, July 22 [doi:10.1001/jamadermatol.2015.1745]).

The study was supported by the Westmead Medical Research Foundation. Three authors reported travel support or consultancies with pharmaceutical companies, but there were no other conflicts of interest declared.

The Federal Trade Commission (FTC) filed complaints earlier this year against marketers of MelApp and Mole Detective for deceptively claiming their mobile applications (apps) could detect and diagnose symptoms of melanoma. The apps instructed users to photograph a mole with a smartphone camera and input other characteristics, which would enable the app to calculate the mole’s melanoma risk as low, medium, or high. The FTC alleged the marketers lacked scientific support for claims that their product could accurately analyze moles for the ABCDE symptoms of melanoma and/or increase consumers’ chances of detecting skin cancer in early stages.

The FTC reported that US sales of MelApp, whose retail price is $1.99, totaled more than $17,000 from January 2011 through July 2013. Mole Detective, which costs up to $4.99, had US sales totaling more than $50,000 from January 2012 through December 2013.

Settlements in these cases prohibit marketers from claiming that a device such as an app can detect or diagnose melanoma or its risk factors, unless the representation is truthful and supported by reliable scientific evidence in the form of human clinical testing of the device. “Truth in advertising laws apply in the mobile marketplace,” said Jessica Rich, Director of the FTC’s Bureau of Consumer Protection. “App developers and marketers must have scientific evidence to support any health or disease claims that they make for their apps.”

Patients increasingly use smartphone apps to seek health information and track personal health data. In a June 2015 Cutis article “Prevalence and Impact of Health-Related Internet and Smartphone Use Among Dermatology Patients,” Wolf et al warned that many patients may rely on online resources for information about dermatologic conditions such as melanoma instead of seeking in-person care, which could delay or prevent treatment. In their survey of 775 dermatology patients, 204 indicated they previously attempted to self-diagnose a skin condition using the Internet.

Therefore, it is important for dermatologists to guide patients to reliable online resources while emphasizing the continued need for physician evaluation. “Ideally, online forms of education will increase patients’ sense of self-efficacy while encouraging appropriate consultation for potentially harmful skin conditions,” the authors noted.

The Federal Trade Commission (FTC) filed complaints earlier this year against marketers of MelApp and Mole Detective for deceptively claiming their mobile applications (apps) could detect and diagnose symptoms of melanoma. The apps instructed users to photograph a mole with a smartphone camera and input other characteristics, which would enable the app to calculate the mole’s melanoma risk as low, medium, or high. The FTC alleged the marketers lacked scientific support for claims that their product could accurately analyze moles for the ABCDE symptoms of melanoma and/or increase consumers’ chances of detecting skin cancer in early stages.

The FTC reported that US sales of MelApp, whose retail price is $1.99, totaled more than $17,000 from January 2011 through July 2013. Mole Detective, which costs up to $4.99, had US sales totaling more than $50,000 from January 2012 through December 2013.

Settlements in these cases prohibit marketers from claiming that a device such as an app can detect or diagnose melanoma or its risk factors, unless the representation is truthful and supported by reliable scientific evidence in the form of human clinical testing of the device. “Truth in advertising laws apply in the mobile marketplace,” said Jessica Rich, Director of the FTC’s Bureau of Consumer Protection. “App developers and marketers must have scientific evidence to support any health or disease claims that they make for their apps.”

Patients increasingly use smartphone apps to seek health information and track personal health data. In a June 2015 Cutis article “Prevalence and Impact of Health-Related Internet and Smartphone Use Among Dermatology Patients,” Wolf et al warned that many patients may rely on online resources for information about dermatologic conditions such as melanoma instead of seeking in-person care, which could delay or prevent treatment. In their survey of 775 dermatology patients, 204 indicated they previously attempted to self-diagnose a skin condition using the Internet.

Therefore, it is important for dermatologists to guide patients to reliable online resources while emphasizing the continued need for physician evaluation. “Ideally, online forms of education will increase patients’ sense of self-efficacy while encouraging appropriate consultation for potentially harmful skin conditions,” the authors noted.

The Federal Trade Commission (FTC) filed complaints earlier this year against marketers of MelApp and Mole Detective for deceptively claiming their mobile applications (apps) could detect and diagnose symptoms of melanoma. The apps instructed users to photograph a mole with a smartphone camera and input other characteristics, which would enable the app to calculate the mole’s melanoma risk as low, medium, or high. The FTC alleged the marketers lacked scientific support for claims that their product could accurately analyze moles for the ABCDE symptoms of melanoma and/or increase consumers’ chances of detecting skin cancer in early stages.

The FTC reported that US sales of MelApp, whose retail price is $1.99, totaled more than $17,000 from January 2011 through July 2013. Mole Detective, which costs up to $4.99, had US sales totaling more than $50,000 from January 2012 through December 2013.

Settlements in these cases prohibit marketers from claiming that a device such as an app can detect or diagnose melanoma or its risk factors, unless the representation is truthful and supported by reliable scientific evidence in the form of human clinical testing of the device. “Truth in advertising laws apply in the mobile marketplace,” said Jessica Rich, Director of the FTC’s Bureau of Consumer Protection. “App developers and marketers must have scientific evidence to support any health or disease claims that they make for their apps.”

Patients increasingly use smartphone apps to seek health information and track personal health data. In a June 2015 Cutis article “Prevalence and Impact of Health-Related Internet and Smartphone Use Among Dermatology Patients,” Wolf et al warned that many patients may rely on online resources for information about dermatologic conditions such as melanoma instead of seeking in-person care, which could delay or prevent treatment. In their survey of 775 dermatology patients, 204 indicated they previously attempted to self-diagnose a skin condition using the Internet.

Therefore, it is important for dermatologists to guide patients to reliable online resources while emphasizing the continued need for physician evaluation. “Ideally, online forms of education will increase patients’ sense of self-efficacy while encouraging appropriate consultation for potentially harmful skin conditions,” the authors noted.

What does your patient need to know at the first visit?

Patients need a realistic approach to photoprotection based on their genetics, including Fitzpatrick skin type and family history of melanoma and nonmelanoma skin cancer; skin examination for photodamage and photoaging as well as number and type of pigmented lesions; and lifestyle history, which should include location of residence as well as occupation and recreational pursuits. This discussion should, as usual, include questions about general health, systemic and skin disease, and medication usage, with particular focus on photoaggravated diseases such as lupus and melasma as well as ongoing use of topical agents and systemic photosensitizers. These inquiries should lead to a frank discussion of the patient’s risk for developing photodamage and skin cancer and other specific conditions that alter the advice you would give.

What are your go-to treatments? Is your recommendation anecdotal or evidence based? What are the side effects?

I always recommend that my patients use a product that they like, which may sound simplistic. But if the patient doesn’t like the feel and look of the sunscreen, he/she won’t use it. Patients routinely should use a sunscreen with a sun protection factor (SPF) of 30 or higher that also carries a “broad spectrum” label. At the beach or during sweaty sports, patients should use one with a water-resistant SPF.

I prefer spray sunscreens for application on the back if the patient is alone without someone to help apply sunscreen to hard-to-reach areas and for male scalps. But you never know how much spray to use, so use a lot!

If patients are at the beach, playing sports, or watching sports outside, then they should reapply sunscreen every 2 hours. If patients work indoors and use a facial sunscreen in the morning, that’s sufficient.

Although there is no evidence that sunscreens are harmful for children older than 6 months of age and pregnant women, if patients in these special populations have concerns, I recommend using agents with inorganic compounds (physical blockers) such as titanium dioxide and zinc oxide only. Children are best protected with clothing and hats.

The evidence supports this approach. Patients really don’t need SPF 30 protection, but no one uses the amount of product that will result in the SPF listed on the bottle. So if patients use an SPF 30 or greater, they will get at least an SPF 15, which is sufficient everywhere but at the equator. Using SPF 30 the way we all apply it will give SPF 15–level protection.

There is evidence that sunscreens prevent squamous cell carcinoma, actinic keratosis, and photoaging. Early evidence, less strong but positive, also suggests protection against basal cell carcinoma and melanoma.

The biggest side effect is not using the sunscreen. Others include irritation and allergy. Irritation is common, but finding a product to use without irritation should be easy. Allergy is rarer, and when it occurs, it is usually due to the preservative or fragrance, not the active ingredients. If allergy does occur, patch testing by a dermatologist is necessary to determine the allergen.

Although it is still controversial, wearing sunscreens religiously can lead to vitamin D insufficiency or deficiency, which is particularly true for individuals with skin of color—Fitzpatrick skin types IV, V, and VI—and those cancer patients who adhere to rigorous photoprotection. These patients should be encouraged to take supplemental vitamin D₃ and I suggest 2000 IU; this recommendation is my opinion and is not evidence based.

As to the literature in the laypress about hormonal changes from benzophenone, cancer from retinoids, and nanoparticle toxicity: There is no evidence to support those claims.

How do you keep patients compliant with treatment?

Keep telling them, and then tell them again. 

What do you do if they refuse treatment?

Tell them to see someone else. 

What resources do you recommend to patients for more information?

Consult the American Academy of Dermatology Web site (www.aad.org) and the Skin Cancer Foundation (www.skincancer.org).

Editorial Note

Practical Pearls From the Cutis^® Board is a new feature that will appear in print and online (www.cutis.com). Each month a member of the Cutis Editorial Board will provide pearls relating to the practice needs of dermatologists. Future topics will include:

Looking for pearls on a specific topic? The Editorial Board welcomes your feedback on potential topics. Send an e-mail to the Editorial Office ([email protected]) with your suggestions.

What does your patient need to know at the first visit?

Patients need a realistic approach to photoprotection based on their genetics, including Fitzpatrick skin type and family history of melanoma and nonmelanoma skin cancer; skin examination for photodamage and photoaging as well as number and type of pigmented lesions; and lifestyle history, which should include location of residence as well as occupation and recreational pursuits. This discussion should, as usual, include questions about general health, systemic and skin disease, and medication usage, with particular focus on photoaggravated diseases such as lupus and melasma as well as ongoing use of topical agents and systemic photosensitizers. These inquiries should lead to a frank discussion of the patient’s risk for developing photodamage and skin cancer and other specific conditions that alter the advice you would give.

What are your go-to treatments? Is your recommendation anecdotal or evidence based? What are the side effects?

I always recommend that my patients use a product that they like, which may sound simplistic. But if the patient doesn’t like the feel and look of the sunscreen, he/she won’t use it. Patients routinely should use a sunscreen with a sun protection factor (SPF) of 30 or higher that also carries a “broad spectrum” label. At the beach or during sweaty sports, patients should use one with a water-resistant SPF.

I prefer spray sunscreens for application on the back if the patient is alone without someone to help apply sunscreen to hard-to-reach areas and for male scalps. But you never know how much spray to use, so use a lot!

If patients are at the beach, playing sports, or watching sports outside, then they should reapply sunscreen every 2 hours. If patients work indoors and use a facial sunscreen in the morning, that’s sufficient.

Although there is no evidence that sunscreens are harmful for children older than 6 months of age and pregnant women, if patients in these special populations have concerns, I recommend using agents with inorganic compounds (physical blockers) such as titanium dioxide and zinc oxide only. Children are best protected with clothing and hats.

The evidence supports this approach. Patients really don’t need SPF 30 protection, but no one uses the amount of product that will result in the SPF listed on the bottle. So if patients use an SPF 30 or greater, they will get at least an SPF 15, which is sufficient everywhere but at the equator. Using SPF 30 the way we all apply it will give SPF 15–level protection.

There is evidence that sunscreens prevent squamous cell carcinoma, actinic keratosis, and photoaging. Early evidence, less strong but positive, also suggests protection against basal cell carcinoma and melanoma.

The biggest side effect is not using the sunscreen. Others include irritation and allergy. Irritation is common, but finding a product to use without irritation should be easy. Allergy is rarer, and when it occurs, it is usually due to the preservative or fragrance, not the active ingredients. If allergy does occur, patch testing by a dermatologist is necessary to determine the allergen.

Although it is still controversial, wearing sunscreens religiously can lead to vitamin D insufficiency or deficiency, which is particularly true for individuals with skin of color—Fitzpatrick skin types IV, V, and VI—and those cancer patients who adhere to rigorous photoprotection. These patients should be encouraged to take supplemental vitamin D₃ and I suggest 2000 IU; this recommendation is my opinion and is not evidence based.

As to the literature in the laypress about hormonal changes from benzophenone, cancer from retinoids, and nanoparticle toxicity: There is no evidence to support those claims.

How do you keep patients compliant with treatment?

Keep telling them, and then tell them again. 

What do you do if they refuse treatment?

Tell them to see someone else. 

What resources do you recommend to patients for more information?

Consult the American Academy of Dermatology Web site (www.aad.org) and the Skin Cancer Foundation (www.skincancer.org).

Editorial Note

Practical Pearls From the Cutis^® Board is a new feature that will appear in print and online (www.cutis.com). Each month a member of the Cutis Editorial Board will provide pearls relating to the practice needs of dermatologists. Future topics will include:

Looking for pearls on a specific topic? The Editorial Board welcomes your feedback on potential topics. Send an e-mail to the Editorial Office ([email protected]) with your suggestions.

What does your patient need to know at the first visit?

Patients need a realistic approach to photoprotection based on their genetics, including Fitzpatrick skin type and family history of melanoma and nonmelanoma skin cancer; skin examination for photodamage and photoaging as well as number and type of pigmented lesions; and lifestyle history, which should include location of residence as well as occupation and recreational pursuits. This discussion should, as usual, include questions about general health, systemic and skin disease, and medication usage, with particular focus on photoaggravated diseases such as lupus and melasma as well as ongoing use of topical agents and systemic photosensitizers. These inquiries should lead to a frank discussion of the patient’s risk for developing photodamage and skin cancer and other specific conditions that alter the advice you would give.

What are your go-to treatments? Is your recommendation anecdotal or evidence based? What are the side effects?

I always recommend that my patients use a product that they like, which may sound simplistic. But if the patient doesn’t like the feel and look of the sunscreen, he/she won’t use it. Patients routinely should use a sunscreen with a sun protection factor (SPF) of 30 or higher that also carries a “broad spectrum” label. At the beach or during sweaty sports, patients should use one with a water-resistant SPF.

I prefer spray sunscreens for application on the back if the patient is alone without someone to help apply sunscreen to hard-to-reach areas and for male scalps. But you never know how much spray to use, so use a lot!

If patients are at the beach, playing sports, or watching sports outside, then they should reapply sunscreen every 2 hours. If patients work indoors and use a facial sunscreen in the morning, that’s sufficient.

Although there is no evidence that sunscreens are harmful for children older than 6 months of age and pregnant women, if patients in these special populations have concerns, I recommend using agents with inorganic compounds (physical blockers) such as titanium dioxide and zinc oxide only. Children are best protected with clothing and hats.

The evidence supports this approach. Patients really don’t need SPF 30 protection, but no one uses the amount of product that will result in the SPF listed on the bottle. So if patients use an SPF 30 or greater, they will get at least an SPF 15, which is sufficient everywhere but at the equator. Using SPF 30 the way we all apply it will give SPF 15–level protection.

There is evidence that sunscreens prevent squamous cell carcinoma, actinic keratosis, and photoaging. Early evidence, less strong but positive, also suggests protection against basal cell carcinoma and melanoma.

The biggest side effect is not using the sunscreen. Others include irritation and allergy. Irritation is common, but finding a product to use without irritation should be easy. Allergy is rarer, and when it occurs, it is usually due to the preservative or fragrance, not the active ingredients. If allergy does occur, patch testing by a dermatologist is necessary to determine the allergen.

Although it is still controversial, wearing sunscreens religiously can lead to vitamin D insufficiency or deficiency, which is particularly true for individuals with skin of color—Fitzpatrick skin types IV, V, and VI—and those cancer patients who adhere to rigorous photoprotection. These patients should be encouraged to take supplemental vitamin D₃ and I suggest 2000 IU; this recommendation is my opinion and is not evidence based.

As to the literature in the laypress about hormonal changes from benzophenone, cancer from retinoids, and nanoparticle toxicity: There is no evidence to support those claims.

How do you keep patients compliant with treatment?

Keep telling them, and then tell them again. 

What do you do if they refuse treatment?

Tell them to see someone else. 

What resources do you recommend to patients for more information?

Consult the American Academy of Dermatology Web site (www.aad.org) and the Skin Cancer Foundation (www.skincancer.org).

Editorial Note

Practical Pearls From the Cutis^® Board is a new feature that will appear in print and online (www.cutis.com). Each month a member of the Cutis Editorial Board will provide pearls relating to the practice needs of dermatologists. Future topics will include:

Looking for pearls on a specific topic? The Editorial Board welcomes your feedback on potential topics. Send an e-mail to the Editorial Office ([email protected]) with your suggestions.

In patients presenting with cutaneous melanoma, use of molecular data can help determine whether there is a high likelihood of nodal metastasis that warrants sentinel lymph node biopsy, according to a report published online in the Journal of Clinical Oncology.

A large number of sentinel lymph node (SLN) biopsies could be avoided if nodal metastasis in patients with primary cutaneous melanoma were better identified at the time of diagnosis, according to Dr. Alexander Meves of the department of dermatology at the Mayo Clinic in Rochester, Minn., and colleagues.

“In this study, we found that molecular data in combination with Breslow depth, tumor ulceration, and patient age were useful for discriminating between primary cutaneous melanomas that had or had not metastasized to SLN,” they wrote (J. Clin. Oncol. 2015 July 6 [doi:10.1200/JCO.2014.60.7002]).

Based on samples from 160 patients that included benign nevi and primary skin melanomas with and without SLN metastasis, investigators identified genes differentially expressed between metastatic and nonmetastatic pigmented skin lesions, and found a cluster of genes associated with integrin cell adhesion. Of particular interest, the integrin cell adhesion receptor, beta-3 integrin (ITGB3), was upregulated in regionally metastatic melanoma.

Information from a cohort of 360 patients, including 74 (20.6%) with biopsy-confirmed nodal metastasis, was used to derive prediction models for SLN metastasis based on clinicopathologic factors alone and in combination with molecular data. Younger age, tumor ulceration, and greater Breslow depth contributed to the clinicopathologic model. The combined model added expression data from four genes: ITGB3, cellular tumor antigen p53 (TP53), laminin B1 chain (LAMB1), and tissue-type plasminogen activator (PLAT; protein name, t-PA). Area under the receiver operating characteristic (ROC) curve for the combined clinicopathologic plus molecular model was 0.89, compared with 0.78 for the clinicopathologic model alone (P < .001). Performance of the models on the validation cohort (n = 146) was similar, with the area under the ROC curve at 0.93. Using a 10% cutoff, the false-positive rate was 22% and the false-negative rate was 0%.

Expression data combined with clinicopathologic features can be used to calculate the predicted probability of SLN positivity at the time of primary diagnosis, which has “the potential to improve patient care by avoiding unnecessary SLN procedures,” the authors wrote.

In patients presenting with cutaneous melanoma, use of molecular data can help determine whether there is a high likelihood of nodal metastasis that warrants sentinel lymph node biopsy, according to a report published online in the Journal of Clinical Oncology.

A large number of sentinel lymph node (SLN) biopsies could be avoided if nodal metastasis in patients with primary cutaneous melanoma were better identified at the time of diagnosis, according to Dr. Alexander Meves of the department of dermatology at the Mayo Clinic in Rochester, Minn., and colleagues.

“In this study, we found that molecular data in combination with Breslow depth, tumor ulceration, and patient age were useful for discriminating between primary cutaneous melanomas that had or had not metastasized to SLN,” they wrote (J. Clin. Oncol. 2015 July 6 [doi:10.1200/JCO.2014.60.7002]).

Based on samples from 160 patients that included benign nevi and primary skin melanomas with and without SLN metastasis, investigators identified genes differentially expressed between metastatic and nonmetastatic pigmented skin lesions, and found a cluster of genes associated with integrin cell adhesion. Of particular interest, the integrin cell adhesion receptor, beta-3 integrin (ITGB3), was upregulated in regionally metastatic melanoma.

Information from a cohort of 360 patients, including 74 (20.6%) with biopsy-confirmed nodal metastasis, was used to derive prediction models for SLN metastasis based on clinicopathologic factors alone and in combination with molecular data. Younger age, tumor ulceration, and greater Breslow depth contributed to the clinicopathologic model. The combined model added expression data from four genes: ITGB3, cellular tumor antigen p53 (TP53), laminin B1 chain (LAMB1), and tissue-type plasminogen activator (PLAT; protein name, t-PA). Area under the receiver operating characteristic (ROC) curve for the combined clinicopathologic plus molecular model was 0.89, compared with 0.78 for the clinicopathologic model alone (P < .001). Performance of the models on the validation cohort (n = 146) was similar, with the area under the ROC curve at 0.93. Using a 10% cutoff, the false-positive rate was 22% and the false-negative rate was 0%.

Expression data combined with clinicopathologic features can be used to calculate the predicted probability of SLN positivity at the time of primary diagnosis, which has “the potential to improve patient care by avoiding unnecessary SLN procedures,” the authors wrote.

In patients presenting with cutaneous melanoma, use of molecular data can help determine whether there is a high likelihood of nodal metastasis that warrants sentinel lymph node biopsy, according to a report published online in the Journal of Clinical Oncology.

A large number of sentinel lymph node (SLN) biopsies could be avoided if nodal metastasis in patients with primary cutaneous melanoma were better identified at the time of diagnosis, according to Dr. Alexander Meves of the department of dermatology at the Mayo Clinic in Rochester, Minn., and colleagues.

“In this study, we found that molecular data in combination with Breslow depth, tumor ulceration, and patient age were useful for discriminating between primary cutaneous melanomas that had or had not metastasized to SLN,” they wrote (J. Clin. Oncol. 2015 July 6 [doi:10.1200/JCO.2014.60.7002]).

Based on samples from 160 patients that included benign nevi and primary skin melanomas with and without SLN metastasis, investigators identified genes differentially expressed between metastatic and nonmetastatic pigmented skin lesions, and found a cluster of genes associated with integrin cell adhesion. Of particular interest, the integrin cell adhesion receptor, beta-3 integrin (ITGB3), was upregulated in regionally metastatic melanoma.

Information from a cohort of 360 patients, including 74 (20.6%) with biopsy-confirmed nodal metastasis, was used to derive prediction models for SLN metastasis based on clinicopathologic factors alone and in combination with molecular data. Younger age, tumor ulceration, and greater Breslow depth contributed to the clinicopathologic model. The combined model added expression data from four genes: ITGB3, cellular tumor antigen p53 (TP53), laminin B1 chain (LAMB1), and tissue-type plasminogen activator (PLAT; protein name, t-PA). Area under the receiver operating characteristic (ROC) curve for the combined clinicopathologic plus molecular model was 0.89, compared with 0.78 for the clinicopathologic model alone (P < .001). Performance of the models on the validation cohort (n = 146) was similar, with the area under the ROC curve at 0.93. Using a 10% cutoff, the false-positive rate was 22% and the false-negative rate was 0%.

Expression data combined with clinicopathologic features can be used to calculate the predicted probability of SLN positivity at the time of primary diagnosis, which has “the potential to improve patient care by avoiding unnecessary SLN procedures,” the authors wrote.

Health professionals from two cohort studies who consumed citrus products more than 1.6 times a day had a 36% higher risk of developing cutaneous malignant melanoma, compared with those who consumed citrus less than twice a week, a large prospective study showed.

Among citrus products studied, consumption of whole grapefruit, but not grapefruit juice, showed the most apparent association with melanoma risk, Shaowei Wu, Ph.D., of Brigham and Women’s Hospital, Boston, and associates reported online June 29 (J. Clin. Oncol. 2015 [doi:10.1200/JCO.2014.57.4111]).

“These findings provide evidence for the potential photocarcinogenic effect of psoralen-rich foods,” the researchers wrote. “However, previous studies have also suggested that fruit intake may have potential beneficial effects for the prevention of chronic diseases, such as breast cancer and type 2 diabetes. Although our findings are consistent with evidence from animal experiments, which revealed a potential synergistic effect between psoralens and UV radiation, further investigation is needed to confirm our findings and guide sun exposure behaviors among individuals with high citrus consumption.”

©Ls9907/Thinkstockphotos.com

For the analysis, the researchers evaluated dietary information from 63,810 women in the Nurses’ Health Study (1984-2010) and 41,622 men in the Health Professionals Follow-up Study (1986-2010). In these studies, dietary information was assessed every 2-4 years during follow-up, while incident melanoma cases were identified through self-report and confirmed by pathology.

During a follow-up period of 24-26 years, the researchers documented 1,840 incident melanomas. After adjusting for risk factors, the pooled multivariable hazard ratios for melanoma were 1.00 for overall citrus consumption less than twice per week (reference), 1.10 for two to four times per week, 1.26 for five to six times per week, 1.27 for 1-1.5 times per day, and 1.36 for 1.6 times per day or more.

“Interestingly, fresh grapefruit showed the most apparent association with melanoma among individual citrus products, which may be explained by its higher levels of psoralens and furocoumarins when compared with oranges,” wrote the researchers, who found that the pooled multivariable HR for melanoma was 1.41 for the highest consumption of grapefruit (defined as three or more times per week, versus none).

“The significant but less apparent association between [consumption of] orange juice with melanoma risk may be partly explained by its much higher consumption levels, which contributed to greater than 50% of overall citrus consumption, whereas the null association of grapefruit juice with melanoma risk may be a result of its much lower consumption levels and a large number of nonconsumers, as compared with the other individual citrus products,” they said.

In addition, Dr. Wu and associates found that the association between grapefruit consumption and melanoma was more apparent among those with a history of sunburn and higher exposure to UV radiation. The association also appeared to be stronger “for melanomas on body sites with higher continuous sun exposure (e.g., head, neck, and extremities) than for melanomas on body sites with lower continuous sun exposure (e.g., truncal sites), which may suggest a potential synergistic effect between dietary consumption and solar UV radiation.”

They acknowledged certain limitations of the study, including the fact that the dietary data were self-reported and that the two cohorts were “mostly comprised [of] white, educated U.S. health professionals, which potentially limits the generalizability of the findings.”

Dr. Wu and five coauthors reported having no financial disclosures. A seventh coauthor, Dr. Abrar A. Qureshi, disclosed that he has a consulting or advisory role with Abbvie, Novartis, Janssen Pharmaceuticals, and Pfizer. He also has received research funding from Regeneron.

[email protected]

Health professionals from two cohort studies who consumed citrus products more than 1.6 times a day had a 36% higher risk of developing cutaneous malignant melanoma, compared with those who consumed citrus less than twice a week, a large prospective study showed.

Among citrus products studied, consumption of whole grapefruit, but not grapefruit juice, showed the most apparent association with melanoma risk, Shaowei Wu, Ph.D., of Brigham and Women’s Hospital, Boston, and associates reported online June 29 (J. Clin. Oncol. 2015 [doi:10.1200/JCO.2014.57.4111]).

“These findings provide evidence for the potential photocarcinogenic effect of psoralen-rich foods,” the researchers wrote. “However, previous studies have also suggested that fruit intake may have potential beneficial effects for the prevention of chronic diseases, such as breast cancer and type 2 diabetes. Although our findings are consistent with evidence from animal experiments, which revealed a potential synergistic effect between psoralens and UV radiation, further investigation is needed to confirm our findings and guide sun exposure behaviors among individuals with high citrus consumption.”

©Ls9907/Thinkstockphotos.com

For the analysis, the researchers evaluated dietary information from 63,810 women in the Nurses’ Health Study (1984-2010) and 41,622 men in the Health Professionals Follow-up Study (1986-2010). In these studies, dietary information was assessed every 2-4 years during follow-up, while incident melanoma cases were identified through self-report and confirmed by pathology.

During a follow-up period of 24-26 years, the researchers documented 1,840 incident melanomas. After adjusting for risk factors, the pooled multivariable hazard ratios for melanoma were 1.00 for overall citrus consumption less than twice per week (reference), 1.10 for two to four times per week, 1.26 for five to six times per week, 1.27 for 1-1.5 times per day, and 1.36 for 1.6 times per day or more.

“Interestingly, fresh grapefruit showed the most apparent association with melanoma among individual citrus products, which may be explained by its higher levels of psoralens and furocoumarins when compared with oranges,” wrote the researchers, who found that the pooled multivariable HR for melanoma was 1.41 for the highest consumption of grapefruit (defined as three or more times per week, versus none).

“The significant but less apparent association between [consumption of] orange juice with melanoma risk may be partly explained by its much higher consumption levels, which contributed to greater than 50% of overall citrus consumption, whereas the null association of grapefruit juice with melanoma risk may be a result of its much lower consumption levels and a large number of nonconsumers, as compared with the other individual citrus products,” they said.

In addition, Dr. Wu and associates found that the association between grapefruit consumption and melanoma was more apparent among those with a history of sunburn and higher exposure to UV radiation. The association also appeared to be stronger “for melanomas on body sites with higher continuous sun exposure (e.g., head, neck, and extremities) than for melanomas on body sites with lower continuous sun exposure (e.g., truncal sites), which may suggest a potential synergistic effect between dietary consumption and solar UV radiation.”

They acknowledged certain limitations of the study, including the fact that the dietary data were self-reported and that the two cohorts were “mostly comprised [of] white, educated U.S. health professionals, which potentially limits the generalizability of the findings.”

Dr. Wu and five coauthors reported having no financial disclosures. A seventh coauthor, Dr. Abrar A. Qureshi, disclosed that he has a consulting or advisory role with Abbvie, Novartis, Janssen Pharmaceuticals, and Pfizer. He also has received research funding from Regeneron.

[email protected]

Health professionals from two cohort studies who consumed citrus products more than 1.6 times a day had a 36% higher risk of developing cutaneous malignant melanoma, compared with those who consumed citrus less than twice a week, a large prospective study showed.

Among citrus products studied, consumption of whole grapefruit, but not grapefruit juice, showed the most apparent association with melanoma risk, Shaowei Wu, Ph.D., of Brigham and Women’s Hospital, Boston, and associates reported online June 29 (J. Clin. Oncol. 2015 [doi:10.1200/JCO.2014.57.4111]).

“These findings provide evidence for the potential photocarcinogenic effect of psoralen-rich foods,” the researchers wrote. “However, previous studies have also suggested that fruit intake may have potential beneficial effects for the prevention of chronic diseases, such as breast cancer and type 2 diabetes. Although our findings are consistent with evidence from animal experiments, which revealed a potential synergistic effect between psoralens and UV radiation, further investigation is needed to confirm our findings and guide sun exposure behaviors among individuals with high citrus consumption.”

©Ls9907/Thinkstockphotos.com

For the analysis, the researchers evaluated dietary information from 63,810 women in the Nurses’ Health Study (1984-2010) and 41,622 men in the Health Professionals Follow-up Study (1986-2010). In these studies, dietary information was assessed every 2-4 years during follow-up, while incident melanoma cases were identified through self-report and confirmed by pathology.

During a follow-up period of 24-26 years, the researchers documented 1,840 incident melanomas. After adjusting for risk factors, the pooled multivariable hazard ratios for melanoma were 1.00 for overall citrus consumption less than twice per week (reference), 1.10 for two to four times per week, 1.26 for five to six times per week, 1.27 for 1-1.5 times per day, and 1.36 for 1.6 times per day or more.

“Interestingly, fresh grapefruit showed the most apparent association with melanoma among individual citrus products, which may be explained by its higher levels of psoralens and furocoumarins when compared with oranges,” wrote the researchers, who found that the pooled multivariable HR for melanoma was 1.41 for the highest consumption of grapefruit (defined as three or more times per week, versus none).

“The significant but less apparent association between [consumption of] orange juice with melanoma risk may be partly explained by its much higher consumption levels, which contributed to greater than 50% of overall citrus consumption, whereas the null association of grapefruit juice with melanoma risk may be a result of its much lower consumption levels and a large number of nonconsumers, as compared with the other individual citrus products,” they said.

In addition, Dr. Wu and associates found that the association between grapefruit consumption and melanoma was more apparent among those with a history of sunburn and higher exposure to UV radiation. The association also appeared to be stronger “for melanomas on body sites with higher continuous sun exposure (e.g., head, neck, and extremities) than for melanomas on body sites with lower continuous sun exposure (e.g., truncal sites), which may suggest a potential synergistic effect between dietary consumption and solar UV radiation.”

They acknowledged certain limitations of the study, including the fact that the dietary data were self-reported and that the two cohorts were “mostly comprised [of] white, educated U.S. health professionals, which potentially limits the generalizability of the findings.”

Dr. Wu and five coauthors reported having no financial disclosures. A seventh coauthor, Dr. Abrar A. Qureshi, disclosed that he has a consulting or advisory role with Abbvie, Novartis, Janssen Pharmaceuticals, and Pfizer. He also has received research funding from Regeneron.

[email protected]

People are using indoor tanning less, according to new statistics released by the Centers for Disease Control and Prevention.

“We observed significant reductions in indoor tanning from 2010 to 2013: from 5.5% to 4.2% (P < .001) among all adults, from 8.6% to 6.5% (P < .001) among women, and from 2.2% to 1.7% (P < .001) among men,” Gery P. Guy Jr., Ph.D., health economist in the Centers for Disease Control and Prevention’s Division of Cancer Prevention and Control, and his colleagues wrote in a research letter published July 1 in JAMA Dermatology (2015 July 1 [doi:10.1001/jamadermatol.2015.1568]).

The authors cite a number of possible factors contributing to the decline of indoor tanning, including increased awareness of the potential skin cancer risk, laws restricting tanning bed use by minors (that may have changed public perception on safety), and a 10% excise tax implemented in 2010.

The authors reported no conflicts of interest.

[email protected]

People are using indoor tanning less, according to new statistics released by the Centers for Disease Control and Prevention.

“We observed significant reductions in indoor tanning from 2010 to 2013: from 5.5% to 4.2% (P < .001) among all adults, from 8.6% to 6.5% (P < .001) among women, and from 2.2% to 1.7% (P < .001) among men,” Gery P. Guy Jr., Ph.D., health economist in the Centers for Disease Control and Prevention’s Division of Cancer Prevention and Control, and his colleagues wrote in a research letter published July 1 in JAMA Dermatology (2015 July 1 [doi:10.1001/jamadermatol.2015.1568]).

The authors cite a number of possible factors contributing to the decline of indoor tanning, including increased awareness of the potential skin cancer risk, laws restricting tanning bed use by minors (that may have changed public perception on safety), and a 10% excise tax implemented in 2010.

The authors reported no conflicts of interest.

[email protected]

People are using indoor tanning less, according to new statistics released by the Centers for Disease Control and Prevention.

“We observed significant reductions in indoor tanning from 2010 to 2013: from 5.5% to 4.2% (P < .001) among all adults, from 8.6% to 6.5% (P < .001) among women, and from 2.2% to 1.7% (P < .001) among men,” Gery P. Guy Jr., Ph.D., health economist in the Centers for Disease Control and Prevention’s Division of Cancer Prevention and Control, and his colleagues wrote in a research letter published July 1 in JAMA Dermatology (2015 July 1 [doi:10.1001/jamadermatol.2015.1568]).

The authors cite a number of possible factors contributing to the decline of indoor tanning, including increased awareness of the potential skin cancer risk, laws restricting tanning bed use by minors (that may have changed public perception on safety), and a 10% excise tax implemented in 2010.

The authors reported no conflicts of interest.

[email protected]

Thirty-minute infusions of ipilimumab appear to be as safe as standard 90-minute infusions for patients with metastatic melanoma and other solid tumors, with “an acceptably low incidence of infusion-related reactions,” investigators reported online in the Journal of Clinical Oncology.

The approved dose for ipilimumab is 3 mg/kg infused over 90 minutes – a time period intentionally selected to be conservative when use of this monoclonal antibody began, “but not based on any specific data of which we are aware,” said Dr. Parisa Momtaz of Memorial Sloan-Kettering Cancer Center, New York, and her associates.

“Now, with extensive experience with the drug, we are in a position to reassess this guideline,” they noted.

Recent clinical trials have assessed a 10-mg/kg dose infused over 90 minutes. “We reasoned that in these patients, the standard dose of 3 mg/kg had been administered in the first 27 minutes. This suggested that a standard 3-mg/kg dose of ipilimumab might be safely administered over 30 minutes, potentially leading to improved efficiency and convenience” for patients and treatment centers alike, the investigators said.

Dr. Momtaz and her associates retrospectively assessed the incidence of infusion-related reactions among 595 patients treated at their center with either dose of the agent during a 5-year period, focusing on grade 2 and 3 symptoms of flushing, chills, pruritus, rash, nausea, dyspnea, cough, bronchospasm, fever, malaise, headache, hypotension, diaphoresis, tachycardia, and pain. The proportions of patients who had such reactions were not significantly different between the 138 who received the 10-mg/kg dose (4.3%) and the 457 who received the 3-mg/kg dose (2.2%). The standard approach at Sloan-Kettering was then changed to 30-minute rather than 90-minute infusion times for ipilimumab (J. Clin. Oncol. 2015 June 29; [doi:10.1200/JCO.2015.61.0030]).

The investigators then prospectively assessed infusion-related reactions among the next 120 patients who received 30-minute infusions of 3 mg/kg ipilimumab during the ensuing 14 months. The rate of reactions was 5.8% in this cohort, which was comparable to the previously observed rates and deemed to be “acceptably low.” These reactions typically were mild to moderate, responded to immediately with the administration of diphenhydramine and/or corticosteroids, and were never dose limiting, they noted.

Thirty-minute infusions of ipilimumab appear to be as safe as standard 90-minute infusions for patients with metastatic melanoma and other solid tumors, with “an acceptably low incidence of infusion-related reactions,” investigators reported online in the Journal of Clinical Oncology.

The approved dose for ipilimumab is 3 mg/kg infused over 90 minutes – a time period intentionally selected to be conservative when use of this monoclonal antibody began, “but not based on any specific data of which we are aware,” said Dr. Parisa Momtaz of Memorial Sloan-Kettering Cancer Center, New York, and her associates.

“Now, with extensive experience with the drug, we are in a position to reassess this guideline,” they noted.

Recent clinical trials have assessed a 10-mg/kg dose infused over 90 minutes. “We reasoned that in these patients, the standard dose of 3 mg/kg had been administered in the first 27 minutes. This suggested that a standard 3-mg/kg dose of ipilimumab might be safely administered over 30 minutes, potentially leading to improved efficiency and convenience” for patients and treatment centers alike, the investigators said.

Dr. Momtaz and her associates retrospectively assessed the incidence of infusion-related reactions among 595 patients treated at their center with either dose of the agent during a 5-year period, focusing on grade 2 and 3 symptoms of flushing, chills, pruritus, rash, nausea, dyspnea, cough, bronchospasm, fever, malaise, headache, hypotension, diaphoresis, tachycardia, and pain. The proportions of patients who had such reactions were not significantly different between the 138 who received the 10-mg/kg dose (4.3%) and the 457 who received the 3-mg/kg dose (2.2%). The standard approach at Sloan-Kettering was then changed to 30-minute rather than 90-minute infusion times for ipilimumab (J. Clin. Oncol. 2015 June 29; [doi:10.1200/JCO.2015.61.0030]).

The investigators then prospectively assessed infusion-related reactions among the next 120 patients who received 30-minute infusions of 3 mg/kg ipilimumab during the ensuing 14 months. The rate of reactions was 5.8% in this cohort, which was comparable to the previously observed rates and deemed to be “acceptably low.” These reactions typically were mild to moderate, responded to immediately with the administration of diphenhydramine and/or corticosteroids, and were never dose limiting, they noted.

Thirty-minute infusions of ipilimumab appear to be as safe as standard 90-minute infusions for patients with metastatic melanoma and other solid tumors, with “an acceptably low incidence of infusion-related reactions,” investigators reported online in the Journal of Clinical Oncology.

The approved dose for ipilimumab is 3 mg/kg infused over 90 minutes – a time period intentionally selected to be conservative when use of this monoclonal antibody began, “but not based on any specific data of which we are aware,” said Dr. Parisa Momtaz of Memorial Sloan-Kettering Cancer Center, New York, and her associates.

“Now, with extensive experience with the drug, we are in a position to reassess this guideline,” they noted.

Recent clinical trials have assessed a 10-mg/kg dose infused over 90 minutes. “We reasoned that in these patients, the standard dose of 3 mg/kg had been administered in the first 27 minutes. This suggested that a standard 3-mg/kg dose of ipilimumab might be safely administered over 30 minutes, potentially leading to improved efficiency and convenience” for patients and treatment centers alike, the investigators said.

Dr. Momtaz and her associates retrospectively assessed the incidence of infusion-related reactions among 595 patients treated at their center with either dose of the agent during a 5-year period, focusing on grade 2 and 3 symptoms of flushing, chills, pruritus, rash, nausea, dyspnea, cough, bronchospasm, fever, malaise, headache, hypotension, diaphoresis, tachycardia, and pain. The proportions of patients who had such reactions were not significantly different between the 138 who received the 10-mg/kg dose (4.3%) and the 457 who received the 3-mg/kg dose (2.2%). The standard approach at Sloan-Kettering was then changed to 30-minute rather than 90-minute infusion times for ipilimumab (J. Clin. Oncol. 2015 June 29; [doi:10.1200/JCO.2015.61.0030]).

The investigators then prospectively assessed infusion-related reactions among the next 120 patients who received 30-minute infusions of 3 mg/kg ipilimumab during the ensuing 14 months. The rate of reactions was 5.8% in this cohort, which was comparable to the previously observed rates and deemed to be “acceptably low.” These reactions typically were mild to moderate, responded to immediately with the administration of diphenhydramine and/or corticosteroids, and were never dose limiting, they noted.