Melanoma

A diagnosis of a chronic and/or serious medical condition can be a traumatic experience. Patients may experience not only intrusive thoughts but also avoidance behaviors. The affected individuals can express these trauma-associated symptoms as depression, fatigue, and sleep disturbance.

Milbury et al (J Clin Oncol. 2014;32:663-670) included 277 patients who had been diagnosed with renal cell carcinoma in a study to evaluate if writing about their deepest thoughts and feelings regarding their cancer (expressive writing) offered a quality-of-life benefit compared to writing about neutral topics (neutral writing). They found that expressive writing not only reduced the patients’ cancer-related symptoms but also improved their physical functioning.

What’s the issue?

Many of the conditions that affect dermatology patients are chronic, serious, or both. For example, psoriasis is a chronic skin condition with the potential for serious associated rheumatologic or metabolic sequelae. In addition, skin malignancies (eg, basal cell carcinoma, squamous cell carcinoma, malignant melanoma) and cutaneous lymphoma (eg, mycosis fungoides) are conditions that require chronic surveillance and possibly may have serious consequences.

Expressive writing for dermatology patients might result in remarkable improvement in emotional and physical health. Perhaps dermatologists should recommend this intervention for their patients.

We want to know your views! Tell us what you think.

A diagnosis of a chronic and/or serious medical condition can be a traumatic experience. Patients may experience not only intrusive thoughts but also avoidance behaviors. The affected individuals can express these trauma-associated symptoms as depression, fatigue, and sleep disturbance.

Milbury et al (J Clin Oncol. 2014;32:663-670) included 277 patients who had been diagnosed with renal cell carcinoma in a study to evaluate if writing about their deepest thoughts and feelings regarding their cancer (expressive writing) offered a quality-of-life benefit compared to writing about neutral topics (neutral writing). They found that expressive writing not only reduced the patients’ cancer-related symptoms but also improved their physical functioning.

What’s the issue?

Many of the conditions that affect dermatology patients are chronic, serious, or both. For example, psoriasis is a chronic skin condition with the potential for serious associated rheumatologic or metabolic sequelae. In addition, skin malignancies (eg, basal cell carcinoma, squamous cell carcinoma, malignant melanoma) and cutaneous lymphoma (eg, mycosis fungoides) are conditions that require chronic surveillance and possibly may have serious consequences.

Expressive writing for dermatology patients might result in remarkable improvement in emotional and physical health. Perhaps dermatologists should recommend this intervention for their patients.

We want to know your views! Tell us what you think.

A diagnosis of a chronic and/or serious medical condition can be a traumatic experience. Patients may experience not only intrusive thoughts but also avoidance behaviors. The affected individuals can express these trauma-associated symptoms as depression, fatigue, and sleep disturbance.

Milbury et al (J Clin Oncol. 2014;32:663-670) included 277 patients who had been diagnosed with renal cell carcinoma in a study to evaluate if writing about their deepest thoughts and feelings regarding their cancer (expressive writing) offered a quality-of-life benefit compared to writing about neutral topics (neutral writing). They found that expressive writing not only reduced the patients’ cancer-related symptoms but also improved their physical functioning.

What’s the issue?

Many of the conditions that affect dermatology patients are chronic, serious, or both. For example, psoriasis is a chronic skin condition with the potential for serious associated rheumatologic or metabolic sequelae. In addition, skin malignancies (eg, basal cell carcinoma, squamous cell carcinoma, malignant melanoma) and cutaneous lymphoma (eg, mycosis fungoides) are conditions that require chronic surveillance and possibly may have serious consequences.

Expressive writing for dermatology patients might result in remarkable improvement in emotional and physical health. Perhaps dermatologists should recommend this intervention for their patients.

We want to know your views! Tell us what you think.

1. Abstract LBA 9000, Antoni Ribas et al.

Efficacy and safety of the anti-PD-1 monoclonal antibody MK-3475 in 411 patients (pts) with melanoma (MEL).

http://abstracts.asco.org/144/AbstView_144_133842.html

2. Abstract LBA 9008, Alexander M. Eggermont et al. Ipilimumab versus placebo after complete resection of stage III melanoma: Initial efficacy and safety results from the EORTC 18071 phase III trial.

http://abstracts.asco.org/144/AbstView_144_130118.html

3. Abstract 9011, Georgina V. Long et al.

COMBI-d: A randomized, double-blinded, phase III study comparing the combination of dabrafenib and trametinib to dabrafenib and trametinib placebo as first-line therapy in patients (pts) with unresectable or metastatic BRAF^V600E/K mutation-positive cutaneous melanoma.

http://abstracts.asco.org/144/AbstView_144_128598.html

4. Abstract 9008a, Howard L. Kaufman et al.

Primary overall survival (OS) from OPTiM, a randomized phase III trial of talimogene laherparepvec (T-VEC) versus subcutaneous (SC) granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment (tx) of unresected stage IIIB/C and IV melanoma.

http://abstracts.asco.org/144/AbstView_144_133898.html

5. Abstract 9010, Keith Flaherty et al.

Updated overall survival (OS) for BRF113220, a phase 1-2 study of dabrafenib (D) alone versus combined dabrafenib and trametinib (D+T) in pts with BRAF V600 mutation-positive (+) metastatic melanoma (MM).

http://abstracts.asco.org/144/AbstView_144_134903.html

Dr. Jeffrey A. Sosman is professor of medicine and Ingram Professor for Cancer Research, Vanderbilt University Medical Center, Nashville, Tenn.

1. Abstract LBA 9000, Antoni Ribas et al.

Efficacy and safety of the anti-PD-1 monoclonal antibody MK-3475 in 411 patients (pts) with melanoma (MEL).

http://abstracts.asco.org/144/AbstView_144_133842.html

2. Abstract LBA 9008, Alexander M. Eggermont et al. Ipilimumab versus placebo after complete resection of stage III melanoma: Initial efficacy and safety results from the EORTC 18071 phase III trial.

http://abstracts.asco.org/144/AbstView_144_130118.html

3. Abstract 9011, Georgina V. Long et al.

COMBI-d: A randomized, double-blinded, phase III study comparing the combination of dabrafenib and trametinib to dabrafenib and trametinib placebo as first-line therapy in patients (pts) with unresectable or metastatic BRAF^V600E/K mutation-positive cutaneous melanoma.

http://abstracts.asco.org/144/AbstView_144_128598.html

4. Abstract 9008a, Howard L. Kaufman et al.

Primary overall survival (OS) from OPTiM, a randomized phase III trial of talimogene laherparepvec (T-VEC) versus subcutaneous (SC) granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment (tx) of unresected stage IIIB/C and IV melanoma.

http://abstracts.asco.org/144/AbstView_144_133898.html

5. Abstract 9010, Keith Flaherty et al.

Updated overall survival (OS) for BRF113220, a phase 1-2 study of dabrafenib (D) alone versus combined dabrafenib and trametinib (D+T) in pts with BRAF V600 mutation-positive (+) metastatic melanoma (MM).

http://abstracts.asco.org/144/AbstView_144_134903.html

Dr. Jeffrey A. Sosman is professor of medicine and Ingram Professor for Cancer Research, Vanderbilt University Medical Center, Nashville, Tenn.

1. Abstract LBA 9000, Antoni Ribas et al.

Efficacy and safety of the anti-PD-1 monoclonal antibody MK-3475 in 411 patients (pts) with melanoma (MEL).

http://abstracts.asco.org/144/AbstView_144_133842.html

2. Abstract LBA 9008, Alexander M. Eggermont et al. Ipilimumab versus placebo after complete resection of stage III melanoma: Initial efficacy and safety results from the EORTC 18071 phase III trial.

http://abstracts.asco.org/144/AbstView_144_130118.html

3. Abstract 9011, Georgina V. Long et al.

COMBI-d: A randomized, double-blinded, phase III study comparing the combination of dabrafenib and trametinib to dabrafenib and trametinib placebo as first-line therapy in patients (pts) with unresectable or metastatic BRAF^V600E/K mutation-positive cutaneous melanoma.

http://abstracts.asco.org/144/AbstView_144_128598.html

4. Abstract 9008a, Howard L. Kaufman et al.

Primary overall survival (OS) from OPTiM, a randomized phase III trial of talimogene laherparepvec (T-VEC) versus subcutaneous (SC) granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment (tx) of unresected stage IIIB/C and IV melanoma.

http://abstracts.asco.org/144/AbstView_144_133898.html

5. Abstract 9010, Keith Flaherty et al.

Updated overall survival (OS) for BRF113220, a phase 1-2 study of dabrafenib (D) alone versus combined dabrafenib and trametinib (D+T) in pts with BRAF V600 mutation-positive (+) metastatic melanoma (MM).

http://abstracts.asco.org/144/AbstView_144_134903.html

Dr. Jeffrey A. Sosman is professor of medicine and Ingram Professor for Cancer Research, Vanderbilt University Medical Center, Nashville, Tenn.

DENVER – As the nanotechnology field evolves, there are at least three reasons a clinician might prefer to use nanoparticles over conventional drugs, according to Dr. Jack L. Arbiser. The first is to minimize the effects of a systemic drug.

"What if steroids could be directed to the site of the pathologic lesion but not cause side effects such as glucose intolerance, bone fractures, or gastric ulcers?" he asked during a session on nanotechnology at the annual meeting of the American Academy of Dermatology. "What if propranolol could be given to patients with hemangiomas without having to worry about cardiac side effects?"

A second reason to turn to nanoparticles would be to use highly toxic substances in a safe way, continued Dr. Arbiser, a professor of dermatology at Emory University, Atlanta. "We already use Botox by injection, which is one of the most toxic substances known to man, but what if other highly toxic substances could be specifically delivered to cancers, infections, or inflammation?"

A third reason to use nanoparticles is that they may offer a way for compounds "that are not highly active be delivered to sites of disease in high enough concentration so that they have therapeutic activity and provide a high measure of safety," he said.

Dr. Arbiser discussed his nanotechnology experience as part of a research team developing a derivative of gentian violet for cancer treatment. He and his associates observed that gentian violet has potential antitumor activity through inhibition of NADPH (nicotinamide adenine dinucleotide phosphate) oxidase. However, the researchers faced early challenges, because gentian violet is not patentable by itself, and, because it is hydrophilic, it may not pass through the blood-brain barrier.

"Our solution was to synthesize and patent a more lipophilic derivative of gentian violet called imipramine blue," Dr. Arbiser explained. "We packaged it in liposomes so it has a much longer half-life and is directed to tumors because liposomes preferentially localize to leaky blood vessels."

Imipramine blue can be given weekly and is efficacious against cancer tumors. Dr. Arbiser and his associates have demonstrated that systemic delivery of imipramine blue significantly inhibited migration of glioblastoma cells into the brain parenchyma (Sci. Transl. Med. 2012;4:127ra36).

"We also see this [inhibition of spread] in prostate, breast, and melanoma cells," he said. "So it seems to be hitting the same pathway in multiple different tumor types." Such an approach targets delivery of therapeutic and diagnostic imaging agents to the site of cancer and chronic inflammation/infection, potentially reducing side effects and increasing efficacy.

"My own personal bias is that we should start using metal-based nanotechnology for severe illnesses, such as cancers, allowing the effects of these materials to be studied in humans, before widespread introduction into cosmetics," he concluded.

Dr. Arbiser disclosed that he is the cofounder of companies ABBY Therapeutics and Accuitis.

[email protected]

DENVER – As the nanotechnology field evolves, there are at least three reasons a clinician might prefer to use nanoparticles over conventional drugs, according to Dr. Jack L. Arbiser. The first is to minimize the effects of a systemic drug.

"What if steroids could be directed to the site of the pathologic lesion but not cause side effects such as glucose intolerance, bone fractures, or gastric ulcers?" he asked during a session on nanotechnology at the annual meeting of the American Academy of Dermatology. "What if propranolol could be given to patients with hemangiomas without having to worry about cardiac side effects?"

A second reason to turn to nanoparticles would be to use highly toxic substances in a safe way, continued Dr. Arbiser, a professor of dermatology at Emory University, Atlanta. "We already use Botox by injection, which is one of the most toxic substances known to man, but what if other highly toxic substances could be specifically delivered to cancers, infections, or inflammation?"

A third reason to use nanoparticles is that they may offer a way for compounds "that are not highly active be delivered to sites of disease in high enough concentration so that they have therapeutic activity and provide a high measure of safety," he said.

Dr. Arbiser discussed his nanotechnology experience as part of a research team developing a derivative of gentian violet for cancer treatment. He and his associates observed that gentian violet has potential antitumor activity through inhibition of NADPH (nicotinamide adenine dinucleotide phosphate) oxidase. However, the researchers faced early challenges, because gentian violet is not patentable by itself, and, because it is hydrophilic, it may not pass through the blood-brain barrier.

"Our solution was to synthesize and patent a more lipophilic derivative of gentian violet called imipramine blue," Dr. Arbiser explained. "We packaged it in liposomes so it has a much longer half-life and is directed to tumors because liposomes preferentially localize to leaky blood vessels."

Imipramine blue can be given weekly and is efficacious against cancer tumors. Dr. Arbiser and his associates have demonstrated that systemic delivery of imipramine blue significantly inhibited migration of glioblastoma cells into the brain parenchyma (Sci. Transl. Med. 2012;4:127ra36).

"We also see this [inhibition of spread] in prostate, breast, and melanoma cells," he said. "So it seems to be hitting the same pathway in multiple different tumor types." Such an approach targets delivery of therapeutic and diagnostic imaging agents to the site of cancer and chronic inflammation/infection, potentially reducing side effects and increasing efficacy.

"My own personal bias is that we should start using metal-based nanotechnology for severe illnesses, such as cancers, allowing the effects of these materials to be studied in humans, before widespread introduction into cosmetics," he concluded.

Dr. Arbiser disclosed that he is the cofounder of companies ABBY Therapeutics and Accuitis.

[email protected]

DENVER – As the nanotechnology field evolves, there are at least three reasons a clinician might prefer to use nanoparticles over conventional drugs, according to Dr. Jack L. Arbiser. The first is to minimize the effects of a systemic drug.

"What if steroids could be directed to the site of the pathologic lesion but not cause side effects such as glucose intolerance, bone fractures, or gastric ulcers?" he asked during a session on nanotechnology at the annual meeting of the American Academy of Dermatology. "What if propranolol could be given to patients with hemangiomas without having to worry about cardiac side effects?"

A second reason to turn to nanoparticles would be to use highly toxic substances in a safe way, continued Dr. Arbiser, a professor of dermatology at Emory University, Atlanta. "We already use Botox by injection, which is one of the most toxic substances known to man, but what if other highly toxic substances could be specifically delivered to cancers, infections, or inflammation?"

A third reason to use nanoparticles is that they may offer a way for compounds "that are not highly active be delivered to sites of disease in high enough concentration so that they have therapeutic activity and provide a high measure of safety," he said.

Dr. Arbiser discussed his nanotechnology experience as part of a research team developing a derivative of gentian violet for cancer treatment. He and his associates observed that gentian violet has potential antitumor activity through inhibition of NADPH (nicotinamide adenine dinucleotide phosphate) oxidase. However, the researchers faced early challenges, because gentian violet is not patentable by itself, and, because it is hydrophilic, it may not pass through the blood-brain barrier.

"Our solution was to synthesize and patent a more lipophilic derivative of gentian violet called imipramine blue," Dr. Arbiser explained. "We packaged it in liposomes so it has a much longer half-life and is directed to tumors because liposomes preferentially localize to leaky blood vessels."

Imipramine blue can be given weekly and is efficacious against cancer tumors. Dr. Arbiser and his associates have demonstrated that systemic delivery of imipramine blue significantly inhibited migration of glioblastoma cells into the brain parenchyma (Sci. Transl. Med. 2012;4:127ra36).

"We also see this [inhibition of spread] in prostate, breast, and melanoma cells," he said. "So it seems to be hitting the same pathway in multiple different tumor types." Such an approach targets delivery of therapeutic and diagnostic imaging agents to the site of cancer and chronic inflammation/infection, potentially reducing side effects and increasing efficacy.

"My own personal bias is that we should start using metal-based nanotechnology for severe illnesses, such as cancers, allowing the effects of these materials to be studied in humans, before widespread introduction into cosmetics," he concluded.

Dr. Arbiser disclosed that he is the cofounder of companies ABBY Therapeutics and Accuitis.

[email protected]

WAIKOLOA, HAWAII – The spectacular developments in the treatment of advanced melanoma that began with approval of ipilimumab in 2011 continue to accelerate, and these advances promise to keep dermatologists quite busy for the foreseeable future in treating the cutaneous side effects of these targeted therapies.

Cutaneous toxicities requiring medical attention are extremely common with the new therapeutic agents. The key to minimizing their effects is proactive management, Dr. James E. Sligh emphasized at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

Bruce Jancin/Frontline Medical News

"The message is that people are living longer with advanced melanoma, but you really need to work with your oncologists to get the absolute benefit patients deserve out of these advanced drugs," he said. "All patients on any of the BRAF inhibitors should receive a dermatologic evaluation prior to initiation of therapy, every 2 months while on therapy, and for 6 months following treatment discontinuation. And while I use this as a guide, there are definitely patients I see for whom 2 months is way too long between visits," he added. "If they’re growing squamous cell carcinomas or verrucous keratoses at a good clip, they need to be seen more often. I’ll see them every other week if need be," said Dr. Sligh, chief of the dermatology division at the University of Arizona, Tucson.

"This is a plea to dermatologists," he continued. "If you have a patient who’s going on a BRAF inhibitor, they need to be seen in your office regularly. And if your next available appointment isn’t until 4 months down the road, you absolutely need to make room for these patients, because after 4 months they may have very large squamous cell carcinomas."

One in four advanced melanoma patients on a BRAF inhibitor – vemurafenib and dabrenafib are the two available thus far – will develop squamous cell carcinomas, Dr. Sligh said. If it’s going to happen, it typically begins in the first month or two of therapy. Caught early, the treatment is simple removal. The same goes for verrucous keratoses, which occur in close to half of treated patients.

"I use cryotherapy in the office, and I give patients 5-FU [5-fluorouracil] so they can start treating a lesion the day they see it, rather than waiting to show it to me a couple of months later," explained Dr. Sligh.

Other common cutaneous adverse events seen as a class effect with the BRAF inhibitors include photosensitivity reactions, seen in approximately one-third of patients in the phase III clinical trials; pruritus, seen in 23%; plantar hyperkeratosis in 10%-20%; and maculopapular rash in 9%.

The pretreatment dermatologic visit is an ideal time for patient education regarding sunscreen use, protective clothing, and the necessity to stay indoors in the event a photosensitivity rash emerges, Dr. Sligh noted. These are issues medical oncologists typically won’t counsel patients about, he said.

"The real advantage to doing this is you want these patients to maintain their optimal dose. For vemurafenib, it’s 960 mg b.i.d. There are very few things that will cause a dose reduction with these drugs, so if cutaneous toxicity is something patients are having a difficult time with, it’s our job as dermatologists to ensure that they have the best chance to make those side effects tolerable. Remaining on the drug is absolutely their best chance for survival," Dr. Sligh continued.

Serious hypersensitivity reactions, including anaphylaxis, as well as Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported in patients on a BRAF inhibitor. Such events do require permanent discontinuation of therapy. But that’s not necessarily the end of the road. "There are fantastic new options coming on board each year as alternatives for these people," according to Dr. Sligh.

New primary melanomas can arise while a patient is on BRAF inhibitor therapy. If they are detected early through those bimonthly office visits, the treatment is excision with no dosage adjustment.

Ipilimumab, which targets cytotoxic T-lymphocyte antigen 4, differs from the BRAF inhibitors in that its cutaneous adverse effects can emerge long after the drug is stopped.

"If you see a rash that’s not typical in a patient even 1 or 2 years after they were on ipilimumab, you should still consider that drug to be a likely culprit," Dr. Sligh said.

Trametinib, a MEK inhibitor, was approved last year for the treatment of melanomas with BRAF V600E or V600K mutations. Cutaneous toxicity occurs in close to 90% of patients on the drug, including a 12% rate of severe, grade 3 skin reactions. When trametinib is given in combination with vemurafenib or dabrafenib in an effort to delay emergence of tumor resistance, the result is longer progression-free survival than with either agent alone, and with a lower rate of squamous cell carcinomas and other cutaneous adverse events than with either agent as monotherapy. However, the question of whether or not combination therapy improves overall survival remains unclear, and is the subject of ongoing trials.

Close to half of melanoma patients have a BRAF mutation that makes them a potential candidate for BRAF inhibitor therapy. But in a separate presentation at the meeting, Dr. Michael Postow, an oncologist at Memorial Sloan Kettering Cancer Center in New York, urged dermatologists not to think only of the FDA-approved BRAF test when they have a patient diagnosed with melanoma.

"It’s really worthwhile to do more extensive molecular profiling of those patients, because you may find another targetable mutation," said Dr. Postow. "I would encourage you to refer any patients you have that are being diagnosed with melanoma for a larger institutional evaluation where more extensive molecular characterization of the tumor can be performed," he added.

Dr. Sligh is on the advisory board for and a consultant to Genentech, and he has received research grants from DermSpectra and SciBase. Dr. Postow reported serving as an unpaid adviser to Bristol-Myers Squibb.

SDEF and this news organization are owned by the same parent company.

[email protected]

WAIKOLOA, HAWAII – The spectacular developments in the treatment of advanced melanoma that began with approval of ipilimumab in 2011 continue to accelerate, and these advances promise to keep dermatologists quite busy for the foreseeable future in treating the cutaneous side effects of these targeted therapies.

Cutaneous toxicities requiring medical attention are extremely common with the new therapeutic agents. The key to minimizing their effects is proactive management, Dr. James E. Sligh emphasized at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

Bruce Jancin/Frontline Medical News

"The message is that people are living longer with advanced melanoma, but you really need to work with your oncologists to get the absolute benefit patients deserve out of these advanced drugs," he said. "All patients on any of the BRAF inhibitors should receive a dermatologic evaluation prior to initiation of therapy, every 2 months while on therapy, and for 6 months following treatment discontinuation. And while I use this as a guide, there are definitely patients I see for whom 2 months is way too long between visits," he added. "If they’re growing squamous cell carcinomas or verrucous keratoses at a good clip, they need to be seen more often. I’ll see them every other week if need be," said Dr. Sligh, chief of the dermatology division at the University of Arizona, Tucson.

"This is a plea to dermatologists," he continued. "If you have a patient who’s going on a BRAF inhibitor, they need to be seen in your office regularly. And if your next available appointment isn’t until 4 months down the road, you absolutely need to make room for these patients, because after 4 months they may have very large squamous cell carcinomas."

One in four advanced melanoma patients on a BRAF inhibitor – vemurafenib and dabrenafib are the two available thus far – will develop squamous cell carcinomas, Dr. Sligh said. If it’s going to happen, it typically begins in the first month or two of therapy. Caught early, the treatment is simple removal. The same goes for verrucous keratoses, which occur in close to half of treated patients.

"I use cryotherapy in the office, and I give patients 5-FU [5-fluorouracil] so they can start treating a lesion the day they see it, rather than waiting to show it to me a couple of months later," explained Dr. Sligh.

Other common cutaneous adverse events seen as a class effect with the BRAF inhibitors include photosensitivity reactions, seen in approximately one-third of patients in the phase III clinical trials; pruritus, seen in 23%; plantar hyperkeratosis in 10%-20%; and maculopapular rash in 9%.

The pretreatment dermatologic visit is an ideal time for patient education regarding sunscreen use, protective clothing, and the necessity to stay indoors in the event a photosensitivity rash emerges, Dr. Sligh noted. These are issues medical oncologists typically won’t counsel patients about, he said.

"The real advantage to doing this is you want these patients to maintain their optimal dose. For vemurafenib, it’s 960 mg b.i.d. There are very few things that will cause a dose reduction with these drugs, so if cutaneous toxicity is something patients are having a difficult time with, it’s our job as dermatologists to ensure that they have the best chance to make those side effects tolerable. Remaining on the drug is absolutely their best chance for survival," Dr. Sligh continued.

Serious hypersensitivity reactions, including anaphylaxis, as well as Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported in patients on a BRAF inhibitor. Such events do require permanent discontinuation of therapy. But that’s not necessarily the end of the road. "There are fantastic new options coming on board each year as alternatives for these people," according to Dr. Sligh.

New primary melanomas can arise while a patient is on BRAF inhibitor therapy. If they are detected early through those bimonthly office visits, the treatment is excision with no dosage adjustment.

Ipilimumab, which targets cytotoxic T-lymphocyte antigen 4, differs from the BRAF inhibitors in that its cutaneous adverse effects can emerge long after the drug is stopped.

"If you see a rash that’s not typical in a patient even 1 or 2 years after they were on ipilimumab, you should still consider that drug to be a likely culprit," Dr. Sligh said.

Trametinib, a MEK inhibitor, was approved last year for the treatment of melanomas with BRAF V600E or V600K mutations. Cutaneous toxicity occurs in close to 90% of patients on the drug, including a 12% rate of severe, grade 3 skin reactions. When trametinib is given in combination with vemurafenib or dabrafenib in an effort to delay emergence of tumor resistance, the result is longer progression-free survival than with either agent alone, and with a lower rate of squamous cell carcinomas and other cutaneous adverse events than with either agent as monotherapy. However, the question of whether or not combination therapy improves overall survival remains unclear, and is the subject of ongoing trials.

Close to half of melanoma patients have a BRAF mutation that makes them a potential candidate for BRAF inhibitor therapy. But in a separate presentation at the meeting, Dr. Michael Postow, an oncologist at Memorial Sloan Kettering Cancer Center in New York, urged dermatologists not to think only of the FDA-approved BRAF test when they have a patient diagnosed with melanoma.

"It’s really worthwhile to do more extensive molecular profiling of those patients, because you may find another targetable mutation," said Dr. Postow. "I would encourage you to refer any patients you have that are being diagnosed with melanoma for a larger institutional evaluation where more extensive molecular characterization of the tumor can be performed," he added.

Dr. Sligh is on the advisory board for and a consultant to Genentech, and he has received research grants from DermSpectra and SciBase. Dr. Postow reported serving as an unpaid adviser to Bristol-Myers Squibb.

SDEF and this news organization are owned by the same parent company.

[email protected]

WAIKOLOA, HAWAII – The spectacular developments in the treatment of advanced melanoma that began with approval of ipilimumab in 2011 continue to accelerate, and these advances promise to keep dermatologists quite busy for the foreseeable future in treating the cutaneous side effects of these targeted therapies.

Cutaneous toxicities requiring medical attention are extremely common with the new therapeutic agents. The key to minimizing their effects is proactive management, Dr. James E. Sligh emphasized at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

Bruce Jancin/Frontline Medical News

"The message is that people are living longer with advanced melanoma, but you really need to work with your oncologists to get the absolute benefit patients deserve out of these advanced drugs," he said. "All patients on any of the BRAF inhibitors should receive a dermatologic evaluation prior to initiation of therapy, every 2 months while on therapy, and for 6 months following treatment discontinuation. And while I use this as a guide, there are definitely patients I see for whom 2 months is way too long between visits," he added. "If they’re growing squamous cell carcinomas or verrucous keratoses at a good clip, they need to be seen more often. I’ll see them every other week if need be," said Dr. Sligh, chief of the dermatology division at the University of Arizona, Tucson.

"This is a plea to dermatologists," he continued. "If you have a patient who’s going on a BRAF inhibitor, they need to be seen in your office regularly. And if your next available appointment isn’t until 4 months down the road, you absolutely need to make room for these patients, because after 4 months they may have very large squamous cell carcinomas."

One in four advanced melanoma patients on a BRAF inhibitor – vemurafenib and dabrenafib are the two available thus far – will develop squamous cell carcinomas, Dr. Sligh said. If it’s going to happen, it typically begins in the first month or two of therapy. Caught early, the treatment is simple removal. The same goes for verrucous keratoses, which occur in close to half of treated patients.

"I use cryotherapy in the office, and I give patients 5-FU [5-fluorouracil] so they can start treating a lesion the day they see it, rather than waiting to show it to me a couple of months later," explained Dr. Sligh.

Other common cutaneous adverse events seen as a class effect with the BRAF inhibitors include photosensitivity reactions, seen in approximately one-third of patients in the phase III clinical trials; pruritus, seen in 23%; plantar hyperkeratosis in 10%-20%; and maculopapular rash in 9%.

The pretreatment dermatologic visit is an ideal time for patient education regarding sunscreen use, protective clothing, and the necessity to stay indoors in the event a photosensitivity rash emerges, Dr. Sligh noted. These are issues medical oncologists typically won’t counsel patients about, he said.

"The real advantage to doing this is you want these patients to maintain their optimal dose. For vemurafenib, it’s 960 mg b.i.d. There are very few things that will cause a dose reduction with these drugs, so if cutaneous toxicity is something patients are having a difficult time with, it’s our job as dermatologists to ensure that they have the best chance to make those side effects tolerable. Remaining on the drug is absolutely their best chance for survival," Dr. Sligh continued.

Serious hypersensitivity reactions, including anaphylaxis, as well as Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported in patients on a BRAF inhibitor. Such events do require permanent discontinuation of therapy. But that’s not necessarily the end of the road. "There are fantastic new options coming on board each year as alternatives for these people," according to Dr. Sligh.

New primary melanomas can arise while a patient is on BRAF inhibitor therapy. If they are detected early through those bimonthly office visits, the treatment is excision with no dosage adjustment.

Ipilimumab, which targets cytotoxic T-lymphocyte antigen 4, differs from the BRAF inhibitors in that its cutaneous adverse effects can emerge long after the drug is stopped.

"If you see a rash that’s not typical in a patient even 1 or 2 years after they were on ipilimumab, you should still consider that drug to be a likely culprit," Dr. Sligh said.

Trametinib, a MEK inhibitor, was approved last year for the treatment of melanomas with BRAF V600E or V600K mutations. Cutaneous toxicity occurs in close to 90% of patients on the drug, including a 12% rate of severe, grade 3 skin reactions. When trametinib is given in combination with vemurafenib or dabrafenib in an effort to delay emergence of tumor resistance, the result is longer progression-free survival than with either agent alone, and with a lower rate of squamous cell carcinomas and other cutaneous adverse events than with either agent as monotherapy. However, the question of whether or not combination therapy improves overall survival remains unclear, and is the subject of ongoing trials.

Close to half of melanoma patients have a BRAF mutation that makes them a potential candidate for BRAF inhibitor therapy. But in a separate presentation at the meeting, Dr. Michael Postow, an oncologist at Memorial Sloan Kettering Cancer Center in New York, urged dermatologists not to think only of the FDA-approved BRAF test when they have a patient diagnosed with melanoma.

"It’s really worthwhile to do more extensive molecular profiling of those patients, because you may find another targetable mutation," said Dr. Postow. "I would encourage you to refer any patients you have that are being diagnosed with melanoma for a larger institutional evaluation where more extensive molecular characterization of the tumor can be performed," he added.

Dr. Sligh is on the advisory board for and a consultant to Genentech, and he has received research grants from DermSpectra and SciBase. Dr. Postow reported serving as an unpaid adviser to Bristol-Myers Squibb.

SDEF and this news organization are owned by the same parent company.

[email protected]

An analysis of 20 sunscreens by Consumer Reports found that only two provided the SPF protection claimed on the label.

The analysis – and rating of overall performance of those sunscreens – was released by the advocacy organization just ahead of Memorial Day weekend, the unofficial start of summer.

Courtesy U.S. Food and Drug Administration

According to a survey of 1,000 adults conducted by the Consumer Reports National Research Center, a product’s sun protection factor (SPF) was the most important factor in determining what sunscreen to purchase.

Consumer Reports decided to put those SPF claims to the test in its own labs. The only two that tested at the SPF level claimed were BullFrog WaterArmor Sport InstaCool SPF 50-plus and Coppertone Sensitive Skin SPF 50. One product, Beyond Coastal Natural SPF 30, tested at half its claim. The other products tested at 4%-40% below the claimed SPF.

"We can’t say why our test results differ from the manufacturers’ claims, but they show that SPF isn’t always carved in stone," the Consumer Reports authors wrote.

The group also debunked some of what it called the "myths" about sunscreens, including that sprays provide the best coverage, and that "natural" sunscreens are safer than other sunscreens. In addition, mineral-based sunscreens are no more effective than other sunscreens, says Consumer Reports.

Also, the article said that there is no practical or meaningful difference between a sunscreen labeled for children and one for adults. In most cases, the active ingredients and the concentration of those ingredients are exactly the same. Some of the kids’ sunscreens contain only zinc oxide or titanium dioxide, which may be less irritating than products that contain chemical sunscreens such as avobenzone, according to the article.

The organization tested UVB protection by spreading a standard amount of sunscreen on a volunteer’s back, immersing them in a tub of water for a bit, and then exposing them to six intensities of UVB light from a sun simulator for a standard period of time. The skin patches were examined the next day for redness and the measured SPF was used to calculate the UVB scores.

For UVA, Consumer Reports conducted a critical wavelength test similar to what the Food and Drug Administration requires of manufacturers. The test assesses how well UV rays are absorbed by clear plastic plates that have been treated with the sunscreen.

The overall performance score was based on both the UVA and UVB results.

Among lotions, the best-performing product was Coppertone’s Water Babies SPF 50. Walmart’s less-expensive Equate Ultra Protection SPF 50 was the second-best performer. BullFrog’s WaterArmor Sport InstaCool SPF 50-plus was the top performing spray, followed by Target’s Up & Up Sport SPF 50. Banana Boat Ultra Defense Max Skin Protect SPF 110 spray and Neutrogena Ultimate Sport SPF 70-plus lotion were the highest-performing products with ultra-high SPFs.

The article and ratings are available online to subscribers and will be published in the group’s July 2014 print publication, Consumer Reports.

[email protected]

On Twitter @aliciaault

An analysis of 20 sunscreens by Consumer Reports found that only two provided the SPF protection claimed on the label.

The analysis – and rating of overall performance of those sunscreens – was released by the advocacy organization just ahead of Memorial Day weekend, the unofficial start of summer.

Courtesy U.S. Food and Drug Administration

According to a survey of 1,000 adults conducted by the Consumer Reports National Research Center, a product’s sun protection factor (SPF) was the most important factor in determining what sunscreen to purchase.

Consumer Reports decided to put those SPF claims to the test in its own labs. The only two that tested at the SPF level claimed were BullFrog WaterArmor Sport InstaCool SPF 50-plus and Coppertone Sensitive Skin SPF 50. One product, Beyond Coastal Natural SPF 30, tested at half its claim. The other products tested at 4%-40% below the claimed SPF.

"We can’t say why our test results differ from the manufacturers’ claims, but they show that SPF isn’t always carved in stone," the Consumer Reports authors wrote.

The group also debunked some of what it called the "myths" about sunscreens, including that sprays provide the best coverage, and that "natural" sunscreens are safer than other sunscreens. In addition, mineral-based sunscreens are no more effective than other sunscreens, says Consumer Reports.

Also, the article said that there is no practical or meaningful difference between a sunscreen labeled for children and one for adults. In most cases, the active ingredients and the concentration of those ingredients are exactly the same. Some of the kids’ sunscreens contain only zinc oxide or titanium dioxide, which may be less irritating than products that contain chemical sunscreens such as avobenzone, according to the article.

The organization tested UVB protection by spreading a standard amount of sunscreen on a volunteer’s back, immersing them in a tub of water for a bit, and then exposing them to six intensities of UVB light from a sun simulator for a standard period of time. The skin patches were examined the next day for redness and the measured SPF was used to calculate the UVB scores.

For UVA, Consumer Reports conducted a critical wavelength test similar to what the Food and Drug Administration requires of manufacturers. The test assesses how well UV rays are absorbed by clear plastic plates that have been treated with the sunscreen.

The overall performance score was based on both the UVA and UVB results.

Among lotions, the best-performing product was Coppertone’s Water Babies SPF 50. Walmart’s less-expensive Equate Ultra Protection SPF 50 was the second-best performer. BullFrog’s WaterArmor Sport InstaCool SPF 50-plus was the top performing spray, followed by Target’s Up & Up Sport SPF 50. Banana Boat Ultra Defense Max Skin Protect SPF 110 spray and Neutrogena Ultimate Sport SPF 70-plus lotion were the highest-performing products with ultra-high SPFs.

The article and ratings are available online to subscribers and will be published in the group’s July 2014 print publication, Consumer Reports.

[email protected]

On Twitter @aliciaault

An analysis of 20 sunscreens by Consumer Reports found that only two provided the SPF protection claimed on the label.

The analysis – and rating of overall performance of those sunscreens – was released by the advocacy organization just ahead of Memorial Day weekend, the unofficial start of summer.

Courtesy U.S. Food and Drug Administration

According to a survey of 1,000 adults conducted by the Consumer Reports National Research Center, a product’s sun protection factor (SPF) was the most important factor in determining what sunscreen to purchase.

Consumer Reports decided to put those SPF claims to the test in its own labs. The only two that tested at the SPF level claimed were BullFrog WaterArmor Sport InstaCool SPF 50-plus and Coppertone Sensitive Skin SPF 50. One product, Beyond Coastal Natural SPF 30, tested at half its claim. The other products tested at 4%-40% below the claimed SPF.

"We can’t say why our test results differ from the manufacturers’ claims, but they show that SPF isn’t always carved in stone," the Consumer Reports authors wrote.

The group also debunked some of what it called the "myths" about sunscreens, including that sprays provide the best coverage, and that "natural" sunscreens are safer than other sunscreens. In addition, mineral-based sunscreens are no more effective than other sunscreens, says Consumer Reports.

Also, the article said that there is no practical or meaningful difference between a sunscreen labeled for children and one for adults. In most cases, the active ingredients and the concentration of those ingredients are exactly the same. Some of the kids’ sunscreens contain only zinc oxide or titanium dioxide, which may be less irritating than products that contain chemical sunscreens such as avobenzone, according to the article.

The organization tested UVB protection by spreading a standard amount of sunscreen on a volunteer’s back, immersing them in a tub of water for a bit, and then exposing them to six intensities of UVB light from a sun simulator for a standard period of time. The skin patches were examined the next day for redness and the measured SPF was used to calculate the UVB scores.

For UVA, Consumer Reports conducted a critical wavelength test similar to what the Food and Drug Administration requires of manufacturers. The test assesses how well UV rays are absorbed by clear plastic plates that have been treated with the sunscreen.

The overall performance score was based on both the UVA and UVB results.

Among lotions, the best-performing product was Coppertone’s Water Babies SPF 50. Walmart’s less-expensive Equate Ultra Protection SPF 50 was the second-best performer. BullFrog’s WaterArmor Sport InstaCool SPF 50-plus was the top performing spray, followed by Target’s Up & Up Sport SPF 50. Banana Boat Ultra Defense Max Skin Protect SPF 110 spray and Neutrogena Ultimate Sport SPF 70-plus lotion were the highest-performing products with ultra-high SPFs.

The article and ratings are available online to subscribers and will be published in the group’s July 2014 print publication, Consumer Reports.

[email protected]

On Twitter @aliciaault

ALBUQUERQUE – Postmenopausal women who reported a history of nonmelanoma skin cancer were almost 16% more likely to sustain a lower arm fracture than were women without a skin cancer history, according to a large, prospective, longitudinal study.

Women with prior nonmelanoma skin cancers (NMSCs) also were more likely to suffer a subsequent hip fracture, although the association did not reach statistical significance, said Eric Anderson of the dermatology department at Stanford (Calif.) University School of Medicine.

"These results suggest that prior history of NMSC is associated with an increased risk of subsequent bone fracture, contrary to our hypothesis," noted Mr. Anderson. He presented the findings at the annual meeting of the Society for Investigational Dermatology.

Nonmelanoma skin cancer has been correlated with decreased fracture risk in at least one small cohort study, Mr. Anderson said (Osteoporos. Int. 2007;18:687-92). However, patients with NMSC also have been shown to wear more sunscreen and limit their sun exposure after diagnosis, which might lower their vitamin D levels and increase their fracture risk, Mr. Anderson noted (Cancer Causes Control 2012;23:133-40).

To better clarify the relationship between NMSC and fracture risk, Mr. Anderson and his associates compared prospective data from 4,289 women with self-reported NMSC and 67,470 women who did not report a history of NMSC at baseline. The participants were from the Womens Health Initiative, a prospective longitudinal cohort study of postmenopausal women aged 50-79 years who were enrolled at 40 centers in the United States. Participants were followed for more than 10 years, and new spine, hip, and lower arm fractures were recorded, Mr. Anderson said.

In age-adjusted Cox proportional hazards models, women with a history of NMSC were 1.55 times more likely to sustain a hip fracture (95% confidence interval, 1.31-1.85; P < 0.0001), 1.29 times more likely to suffer a spine fracture (95% CI, 1.10-1.51; P = 0.0018), and 1.28 times more likely to sustain a lower arm fracture (95% CI, 1.13-1.45; P < 0.0001) than were women who did not report a history of NMSC at baseline, Mr. Anderson and his associates reported.

After adjusting for sun exposure, sunscreen use, vitamin D intake, physical activity, and other risk factors for fracture, only lower arm fracture remained statistically significant (hazard ratio, 1.16; 95% CI, 1.31-1.85; P = 0.02), although hip fracture was borderline significant (HR, 1.18; 95% CI, 0.99-1.41; P = 0.06), the investigators reported. Baseline hip bone marrow density was not associated with risk of NMSC in a subgroup analysis of 4,267 women with available data, Mr. Anderson said.

"We’re inclined to believe that this increased fracture risk may be due to sun exposure avoidance after NMSC diagnosis," said Mr. Anderson. He added that, in future studies, the investigators would compare serum vitamin D levels between participants with and without a history of NMSC, and explore temporal relationships between diagnosis of NMSC and fracture occurrence.

The National Institutes of Health and the Medical Scholars Research Program at Stanford University funded the research. Mr. Anderson reported no conflicts of interest.

ALBUQUERQUE – Postmenopausal women who reported a history of nonmelanoma skin cancer were almost 16% more likely to sustain a lower arm fracture than were women without a skin cancer history, according to a large, prospective, longitudinal study.

Women with prior nonmelanoma skin cancers (NMSCs) also were more likely to suffer a subsequent hip fracture, although the association did not reach statistical significance, said Eric Anderson of the dermatology department at Stanford (Calif.) University School of Medicine.

"These results suggest that prior history of NMSC is associated with an increased risk of subsequent bone fracture, contrary to our hypothesis," noted Mr. Anderson. He presented the findings at the annual meeting of the Society for Investigational Dermatology.

Nonmelanoma skin cancer has been correlated with decreased fracture risk in at least one small cohort study, Mr. Anderson said (Osteoporos. Int. 2007;18:687-92). However, patients with NMSC also have been shown to wear more sunscreen and limit their sun exposure after diagnosis, which might lower their vitamin D levels and increase their fracture risk, Mr. Anderson noted (Cancer Causes Control 2012;23:133-40).

To better clarify the relationship between NMSC and fracture risk, Mr. Anderson and his associates compared prospective data from 4,289 women with self-reported NMSC and 67,470 women who did not report a history of NMSC at baseline. The participants were from the Womens Health Initiative, a prospective longitudinal cohort study of postmenopausal women aged 50-79 years who were enrolled at 40 centers in the United States. Participants were followed for more than 10 years, and new spine, hip, and lower arm fractures were recorded, Mr. Anderson said.

In age-adjusted Cox proportional hazards models, women with a history of NMSC were 1.55 times more likely to sustain a hip fracture (95% confidence interval, 1.31-1.85; P < 0.0001), 1.29 times more likely to suffer a spine fracture (95% CI, 1.10-1.51; P = 0.0018), and 1.28 times more likely to sustain a lower arm fracture (95% CI, 1.13-1.45; P < 0.0001) than were women who did not report a history of NMSC at baseline, Mr. Anderson and his associates reported.

After adjusting for sun exposure, sunscreen use, vitamin D intake, physical activity, and other risk factors for fracture, only lower arm fracture remained statistically significant (hazard ratio, 1.16; 95% CI, 1.31-1.85; P = 0.02), although hip fracture was borderline significant (HR, 1.18; 95% CI, 0.99-1.41; P = 0.06), the investigators reported. Baseline hip bone marrow density was not associated with risk of NMSC in a subgroup analysis of 4,267 women with available data, Mr. Anderson said.

"We’re inclined to believe that this increased fracture risk may be due to sun exposure avoidance after NMSC diagnosis," said Mr. Anderson. He added that, in future studies, the investigators would compare serum vitamin D levels between participants with and without a history of NMSC, and explore temporal relationships between diagnosis of NMSC and fracture occurrence.

The National Institutes of Health and the Medical Scholars Research Program at Stanford University funded the research. Mr. Anderson reported no conflicts of interest.

ALBUQUERQUE – Postmenopausal women who reported a history of nonmelanoma skin cancer were almost 16% more likely to sustain a lower arm fracture than were women without a skin cancer history, according to a large, prospective, longitudinal study.

Women with prior nonmelanoma skin cancers (NMSCs) also were more likely to suffer a subsequent hip fracture, although the association did not reach statistical significance, said Eric Anderson of the dermatology department at Stanford (Calif.) University School of Medicine.

"These results suggest that prior history of NMSC is associated with an increased risk of subsequent bone fracture, contrary to our hypothesis," noted Mr. Anderson. He presented the findings at the annual meeting of the Society for Investigational Dermatology.

Nonmelanoma skin cancer has been correlated with decreased fracture risk in at least one small cohort study, Mr. Anderson said (Osteoporos. Int. 2007;18:687-92). However, patients with NMSC also have been shown to wear more sunscreen and limit their sun exposure after diagnosis, which might lower their vitamin D levels and increase their fracture risk, Mr. Anderson noted (Cancer Causes Control 2012;23:133-40).

To better clarify the relationship between NMSC and fracture risk, Mr. Anderson and his associates compared prospective data from 4,289 women with self-reported NMSC and 67,470 women who did not report a history of NMSC at baseline. The participants were from the Womens Health Initiative, a prospective longitudinal cohort study of postmenopausal women aged 50-79 years who were enrolled at 40 centers in the United States. Participants were followed for more than 10 years, and new spine, hip, and lower arm fractures were recorded, Mr. Anderson said.

In age-adjusted Cox proportional hazards models, women with a history of NMSC were 1.55 times more likely to sustain a hip fracture (95% confidence interval, 1.31-1.85; P < 0.0001), 1.29 times more likely to suffer a spine fracture (95% CI, 1.10-1.51; P = 0.0018), and 1.28 times more likely to sustain a lower arm fracture (95% CI, 1.13-1.45; P < 0.0001) than were women who did not report a history of NMSC at baseline, Mr. Anderson and his associates reported.

After adjusting for sun exposure, sunscreen use, vitamin D intake, physical activity, and other risk factors for fracture, only lower arm fracture remained statistically significant (hazard ratio, 1.16; 95% CI, 1.31-1.85; P = 0.02), although hip fracture was borderline significant (HR, 1.18; 95% CI, 0.99-1.41; P = 0.06), the investigators reported. Baseline hip bone marrow density was not associated with risk of NMSC in a subgroup analysis of 4,267 women with available data, Mr. Anderson said.

"We’re inclined to believe that this increased fracture risk may be due to sun exposure avoidance after NMSC diagnosis," said Mr. Anderson. He added that, in future studies, the investigators would compare serum vitamin D levels between participants with and without a history of NMSC, and explore temporal relationships between diagnosis of NMSC and fracture occurrence.

The National Institutes of Health and the Medical Scholars Research Program at Stanford University funded the research. Mr. Anderson reported no conflicts of interest.

ALBUQUERQUE – Adding topical tazarotene did not improve response to 5% imiquimod in lentigo maligna, based on data from nearly 300 patients.

But patients with higher levels of inflammation in response to topical therapy had significantly smaller surgical defects, required fewer surgical stages, and had improved clearance rates, said Nicholas Blickenstaff, a third-year medical student at the University of Utah and a former researcher at the Huntsman Cancer Institute, both in Salt Lake City.

Surgical excision with negative margins is the standard treatment for lentigo maligna, but the cancer’s predilection for the head and neck can cause disfigurement, especially with large tumors. Patients sometimes elect nonsurgical treatment because of cosmetic concerns, comorbidities, or both, Mr. Blickenstaff said at the annual meeting of the Society for Investigative Dermatology.

A prior study found that adding the topical retinoid tazarotene to 5% imiquimod showed a trend toward improved clearance in lentigo maligna, but the association did not reach statistical significance (Arch. Dermatol. 2012;148:592-6).

Based on those data, "we looked at a larger treatment cohort to determine if adding tazarotene to topical imiquimod increased clearance rates of lentigo maligna, as defined by the presence or absence of residual tumor at the time of surgical removal," said Mr. Blickenstaff.

He and his associates at the Huntsman Cancer Institute and the University of Utah School of Medicine conducted a retrospective chart study of 282 patients with an average age of 68 years and biopsy-confirmed lentigo maligna.

A total of 188 patients with 194 lesions received imiquimod 5% cream 5 days a week for 1-3 months, depending on the amount of inflammation observed, said Mr. Blickenstaff. Another group of 94 patients with 98 lesions received the same treatment plus tazarotene 0.1% gel twice weekly. Patients then underwent conservative staged excisions using Melan-A immunostaining on frozen sections to confirm negative margins. The investigators followed patients for an average of 43 months.

Using chart data, the investigators graded patients’ inflammatory responses to topical therapy on a 0-3 scale, with 0 interpreted as no erythema, 1 as mild erythema, 2 as moderate erythema, and 3 as severe erythema with possible surface erosions, said Mr. Blickenstaff.

The researchers found no difference between the two topical regimens in terms of presurgical clearance (P = 0.97). However, patients with higher levels of inflammation (scores of 2 or 3) were significantly more likely to be free of tumor at surgery than were other patients (odds ratio, 2.8; P = 0.002). Patients with more inflammation also had decreased postsurgical defect sizes (P = 0.023), and needed fewer stages to achieve clear margins (P = 0.015), Mr. Blickenstaff and his associates reported.

Patients required an average of 1.5 stages and a maximum of five stages to achieve clearance, Mr. Blickenstaff added. A total of four patients (1.4%) had a recurrence of lentigo maligna, and there were no deaths related to treatment or lentigo maligna, he said.

Based on the findings, "studies should evaluate whether the quality of the inflammatory response with 5% imiquimod is unique and required for efficacy," said Mr. Blickenstaff.

He is now a research fellow at UCSF Medical Center in San Francisco. He reported no conflicts of interest. The Huntsman Cancer Institute funded the study.

ALBUQUERQUE – Adding topical tazarotene did not improve response to 5% imiquimod in lentigo maligna, based on data from nearly 300 patients.

But patients with higher levels of inflammation in response to topical therapy had significantly smaller surgical defects, required fewer surgical stages, and had improved clearance rates, said Nicholas Blickenstaff, a third-year medical student at the University of Utah and a former researcher at the Huntsman Cancer Institute, both in Salt Lake City.

Surgical excision with negative margins is the standard treatment for lentigo maligna, but the cancer’s predilection for the head and neck can cause disfigurement, especially with large tumors. Patients sometimes elect nonsurgical treatment because of cosmetic concerns, comorbidities, or both, Mr. Blickenstaff said at the annual meeting of the Society for Investigative Dermatology.

A prior study found that adding the topical retinoid tazarotene to 5% imiquimod showed a trend toward improved clearance in lentigo maligna, but the association did not reach statistical significance (Arch. Dermatol. 2012;148:592-6).

Based on those data, "we looked at a larger treatment cohort to determine if adding tazarotene to topical imiquimod increased clearance rates of lentigo maligna, as defined by the presence or absence of residual tumor at the time of surgical removal," said Mr. Blickenstaff.

He and his associates at the Huntsman Cancer Institute and the University of Utah School of Medicine conducted a retrospective chart study of 282 patients with an average age of 68 years and biopsy-confirmed lentigo maligna.

A total of 188 patients with 194 lesions received imiquimod 5% cream 5 days a week for 1-3 months, depending on the amount of inflammation observed, said Mr. Blickenstaff. Another group of 94 patients with 98 lesions received the same treatment plus tazarotene 0.1% gel twice weekly. Patients then underwent conservative staged excisions using Melan-A immunostaining on frozen sections to confirm negative margins. The investigators followed patients for an average of 43 months.

Using chart data, the investigators graded patients’ inflammatory responses to topical therapy on a 0-3 scale, with 0 interpreted as no erythema, 1 as mild erythema, 2 as moderate erythema, and 3 as severe erythema with possible surface erosions, said Mr. Blickenstaff.

The researchers found no difference between the two topical regimens in terms of presurgical clearance (P = 0.97). However, patients with higher levels of inflammation (scores of 2 or 3) were significantly more likely to be free of tumor at surgery than were other patients (odds ratio, 2.8; P = 0.002). Patients with more inflammation also had decreased postsurgical defect sizes (P = 0.023), and needed fewer stages to achieve clear margins (P = 0.015), Mr. Blickenstaff and his associates reported.

Patients required an average of 1.5 stages and a maximum of five stages to achieve clearance, Mr. Blickenstaff added. A total of four patients (1.4%) had a recurrence of lentigo maligna, and there were no deaths related to treatment or lentigo maligna, he said.

Based on the findings, "studies should evaluate whether the quality of the inflammatory response with 5% imiquimod is unique and required for efficacy," said Mr. Blickenstaff.

He is now a research fellow at UCSF Medical Center in San Francisco. He reported no conflicts of interest. The Huntsman Cancer Institute funded the study.

ALBUQUERQUE – Adding topical tazarotene did not improve response to 5% imiquimod in lentigo maligna, based on data from nearly 300 patients.

But patients with higher levels of inflammation in response to topical therapy had significantly smaller surgical defects, required fewer surgical stages, and had improved clearance rates, said Nicholas Blickenstaff, a third-year medical student at the University of Utah and a former researcher at the Huntsman Cancer Institute, both in Salt Lake City.

Surgical excision with negative margins is the standard treatment for lentigo maligna, but the cancer’s predilection for the head and neck can cause disfigurement, especially with large tumors. Patients sometimes elect nonsurgical treatment because of cosmetic concerns, comorbidities, or both, Mr. Blickenstaff said at the annual meeting of the Society for Investigative Dermatology.

A prior study found that adding the topical retinoid tazarotene to 5% imiquimod showed a trend toward improved clearance in lentigo maligna, but the association did not reach statistical significance (Arch. Dermatol. 2012;148:592-6).

Based on those data, "we looked at a larger treatment cohort to determine if adding tazarotene to topical imiquimod increased clearance rates of lentigo maligna, as defined by the presence or absence of residual tumor at the time of surgical removal," said Mr. Blickenstaff.

He and his associates at the Huntsman Cancer Institute and the University of Utah School of Medicine conducted a retrospective chart study of 282 patients with an average age of 68 years and biopsy-confirmed lentigo maligna.

A total of 188 patients with 194 lesions received imiquimod 5% cream 5 days a week for 1-3 months, depending on the amount of inflammation observed, said Mr. Blickenstaff. Another group of 94 patients with 98 lesions received the same treatment plus tazarotene 0.1% gel twice weekly. Patients then underwent conservative staged excisions using Melan-A immunostaining on frozen sections to confirm negative margins. The investigators followed patients for an average of 43 months.

Using chart data, the investigators graded patients’ inflammatory responses to topical therapy on a 0-3 scale, with 0 interpreted as no erythema, 1 as mild erythema, 2 as moderate erythema, and 3 as severe erythema with possible surface erosions, said Mr. Blickenstaff.

The researchers found no difference between the two topical regimens in terms of presurgical clearance (P = 0.97). However, patients with higher levels of inflammation (scores of 2 or 3) were significantly more likely to be free of tumor at surgery than were other patients (odds ratio, 2.8; P = 0.002). Patients with more inflammation also had decreased postsurgical defect sizes (P = 0.023), and needed fewer stages to achieve clear margins (P = 0.015), Mr. Blickenstaff and his associates reported.

Patients required an average of 1.5 stages and a maximum of five stages to achieve clearance, Mr. Blickenstaff added. A total of four patients (1.4%) had a recurrence of lentigo maligna, and there were no deaths related to treatment or lentigo maligna, he said.

Based on the findings, "studies should evaluate whether the quality of the inflammatory response with 5% imiquimod is unique and required for efficacy," said Mr. Blickenstaff.

He is now a research fellow at UCSF Medical Center in San Francisco. He reported no conflicts of interest. The Huntsman Cancer Institute funded the study.

ALBUQUERQUE – A long-wave infrared system distinguished malignant and benign skin lesions with a sensitivity of 96.97% and a specificity of 78.05%, with skin biopsies used as a benchmark, in a pilot study of 74 patients.

The results "suggest the technique is promising as a noninvasive screening tool" and merits continued research and development to improve sensitivity, specificity, and statistical confidence, reported Stephen Myers, Ph.D., of Skinfrared, and his associates.

Recent advances in infrared technology have led to the development of imaging devices that noninvasively detect tumors, based on differential thermal properties of malignant versus healthy tissue. The long-wave infrared detection device used in the pilot study was designed to identify thermal signatures of suspicious lesions and surrounding skin after the application of a temperature stimulus, Dr. Myers said at the annual conference of the Society for Investigative Dermatology.

In the United States skin cancers are diagnosed more often than all other cancers combined, noted Dr. Myers, but screening for them "requires the skill of a highly trained dermatologist," who must assess a range of morphologic characteristics. "This is a rather subjective approach that causes many biopsies to be performed on benign lesions," Dr. Myers added.

To test the device, investigators at the University of New Mexico, Albuquerque, Dermatology Clinic offered patients with suspicious skin lesions the option of being evaluated with the infrared device before undergoing biopsy.

The device has infrared and visible cameras, as well as a registration marker, a cold air source, and a computer and software to guide image acquisition and analysis, Dr. Myers said. Investigators placed the registration marker near the skin lesion of interest, captured a visible image of the lesion, and then took a 15-second baseline thermal image sequence. After cooling the lesions and surrounding skin to 10° C, they measured and compared 3-minute thermal recovery rates for the lesion and surrounding skin.

Participants averaged 55 years of age, and 53% were male. A total of 102 suspicious lesions were tested. Based on biopsy results, 55% were benign, 34% were basal cell carcinomas, 7% were squamous cell carcinomas, and 4% were melanomas, Dr. Myers reported. The receiver operating curve – calculated to assess the test’s ability to classify skin lesions – had an area under the curve of 95.3% (95% confidence interval, 90.0-99.0). Using biopsy results as a benchmark, the infrared device had a sensitivity of 96.97% and a specificity of 78.05%, Dr. Myers said.

The study was supported by the National Science Foundation and Skinfrared, which makes the device. Dr. Myers is an employee of Skinfrared.

ALBUQUERQUE – A long-wave infrared system distinguished malignant and benign skin lesions with a sensitivity of 96.97% and a specificity of 78.05%, with skin biopsies used as a benchmark, in a pilot study of 74 patients.

The results "suggest the technique is promising as a noninvasive screening tool" and merits continued research and development to improve sensitivity, specificity, and statistical confidence, reported Stephen Myers, Ph.D., of Skinfrared, and his associates.

Recent advances in infrared technology have led to the development of imaging devices that noninvasively detect tumors, based on differential thermal properties of malignant versus healthy tissue. The long-wave infrared detection device used in the pilot study was designed to identify thermal signatures of suspicious lesions and surrounding skin after the application of a temperature stimulus, Dr. Myers said at the annual conference of the Society for Investigative Dermatology.

In the United States skin cancers are diagnosed more often than all other cancers combined, noted Dr. Myers, but screening for them "requires the skill of a highly trained dermatologist," who must assess a range of morphologic characteristics. "This is a rather subjective approach that causes many biopsies to be performed on benign lesions," Dr. Myers added.

To test the device, investigators at the University of New Mexico, Albuquerque, Dermatology Clinic offered patients with suspicious skin lesions the option of being evaluated with the infrared device before undergoing biopsy.

The device has infrared and visible cameras, as well as a registration marker, a cold air source, and a computer and software to guide image acquisition and analysis, Dr. Myers said. Investigators placed the registration marker near the skin lesion of interest, captured a visible image of the lesion, and then took a 15-second baseline thermal image sequence. After cooling the lesions and surrounding skin to 10° C, they measured and compared 3-minute thermal recovery rates for the lesion and surrounding skin.

Participants averaged 55 years of age, and 53% were male. A total of 102 suspicious lesions were tested. Based on biopsy results, 55% were benign, 34% were basal cell carcinomas, 7% were squamous cell carcinomas, and 4% were melanomas, Dr. Myers reported. The receiver operating curve – calculated to assess the test’s ability to classify skin lesions – had an area under the curve of 95.3% (95% confidence interval, 90.0-99.0). Using biopsy results as a benchmark, the infrared device had a sensitivity of 96.97% and a specificity of 78.05%, Dr. Myers said.

The study was supported by the National Science Foundation and Skinfrared, which makes the device. Dr. Myers is an employee of Skinfrared.

ALBUQUERQUE – A long-wave infrared system distinguished malignant and benign skin lesions with a sensitivity of 96.97% and a specificity of 78.05%, with skin biopsies used as a benchmark, in a pilot study of 74 patients.

The results "suggest the technique is promising as a noninvasive screening tool" and merits continued research and development to improve sensitivity, specificity, and statistical confidence, reported Stephen Myers, Ph.D., of Skinfrared, and his associates.

Recent advances in infrared technology have led to the development of imaging devices that noninvasively detect tumors, based on differential thermal properties of malignant versus healthy tissue. The long-wave infrared detection device used in the pilot study was designed to identify thermal signatures of suspicious lesions and surrounding skin after the application of a temperature stimulus, Dr. Myers said at the annual conference of the Society for Investigative Dermatology.

In the United States skin cancers are diagnosed more often than all other cancers combined, noted Dr. Myers, but screening for them "requires the skill of a highly trained dermatologist," who must assess a range of morphologic characteristics. "This is a rather subjective approach that causes many biopsies to be performed on benign lesions," Dr. Myers added.

To test the device, investigators at the University of New Mexico, Albuquerque, Dermatology Clinic offered patients with suspicious skin lesions the option of being evaluated with the infrared device before undergoing biopsy.

The device has infrared and visible cameras, as well as a registration marker, a cold air source, and a computer and software to guide image acquisition and analysis, Dr. Myers said. Investigators placed the registration marker near the skin lesion of interest, captured a visible image of the lesion, and then took a 15-second baseline thermal image sequence. After cooling the lesions and surrounding skin to 10° C, they measured and compared 3-minute thermal recovery rates for the lesion and surrounding skin.

Participants averaged 55 years of age, and 53% were male. A total of 102 suspicious lesions were tested. Based on biopsy results, 55% were benign, 34% were basal cell carcinomas, 7% were squamous cell carcinomas, and 4% were melanomas, Dr. Myers reported. The receiver operating curve – calculated to assess the test’s ability to classify skin lesions – had an area under the curve of 95.3% (95% confidence interval, 90.0-99.0). Using biopsy results as a benchmark, the infrared device had a sensitivity of 96.97% and a specificity of 78.05%, Dr. Myers said.

The study was supported by the National Science Foundation and Skinfrared, which makes the device. Dr. Myers is an employee of Skinfrared.

ALBUQUERQUE – Single-fraction radiotherapy of distant metastatic Merkel cell carcinomas led to complete response rates ranging from 52% to 81%, and caused no adverse effects except rare transient pain flares, according to a single-center, single-arm study of 26 patients.

The rate of initial response was 94%, and three-quarters of responders never progressed during the study period, Dr. Paul Nghiem said at the annual meeting of the Society for Investigative Dermatology.

Merkel cell carcinoma (MCC) creates a "terribly frustrating situation" when it metastasizes because although two-thirds of patients initially respond to chemotherapy, the effect is short-lived, with a median progression-free survival of only 94 days, said Dr. Nghiem, professor of dermatology at the University of Washington, Seattle.

Radiation therapy is often used as an adjuvant or palliative treatment in MCC, but it is almost always fractionated, requiring multiple visits and potentially killing T cells that function in tumor immunity, Dr. Nghiem said. In light of evidence that single-fraction radiotherapy (SFRT) enhanced tumor immunity in mice, he and his colleagues at the University of Washington and the Fred Hutchinson Cancer Research Center in Seattle decided to "think outside the box and do something different."

Therefore, in 2010, the researchers began using 8-Gy SFRT on distant MCC metastases. In all, they targeted 93 tumors in 26 patients (median age, 68 years). Survivors were followed for a median of 252 days (range, 76-699 days). The median tumor size was 4 cm (range, 1-19 cm), and patients had 1-28 tumors, with an average of 3.5 tumors per patient.

The investigators classified half of patients (n = 13) as high risk because they were immunosuppressed and/or had prior chemotherapy. Other patients were categorized as low risk. High-risk patients had 60 tumors and a 3.5-month median interval from chemotherapy to start of SFRT. The low-risk group had 33 tumors.

A complete response was seen in 81% of tumors in low-risk patients and 52% of tumors in high-risk patients (P = .008), Dr. Nghiem reported. No tumor that completely responded ever recurred, regardless of risk, he said. In one case, a patient with a 5-cm metastasis compressing the trachea reported greater ease of breathing several days after SFRT, and subsequent imaging studies showed complete response with no recurrence at 20 months, he said, adding that the patient remained on an immunostimulant.

The rate of recurrence also was significantly lower in low-risk (9%) versus high-risk patients (30%; P = .02), Dr. Nghiem said. The P value "was statistically significant in this midsize trial, suggesting that the immune system really matters in controlling these lesions," he said, adding that Merkel cell carcinoma, "maybe more than most other cancers, is extremely linked to immune function. As we increase radiation dose, we see more cancer killing [activity], and more immune cell activation at lower doses."

The investigators did not perform post-treatment biopsies to quantify abscopal effects, Dr. Nghiem noted.

The National Cancer Institute, the American Cancer Society, and the National Institutes of Health funded the research. Dr. Nghiem reported no relevant conflicts of interest.

ALBUQUERQUE – Single-fraction radiotherapy of distant metastatic Merkel cell carcinomas led to complete response rates ranging from 52% to 81%, and caused no adverse effects except rare transient pain flares, according to a single-center, single-arm study of 26 patients.

The rate of initial response was 94%, and three-quarters of responders never progressed during the study period, Dr. Paul Nghiem said at the annual meeting of the Society for Investigative Dermatology.

Merkel cell carcinoma (MCC) creates a "terribly frustrating situation" when it metastasizes because although two-thirds of patients initially respond to chemotherapy, the effect is short-lived, with a median progression-free survival of only 94 days, said Dr. Nghiem, professor of dermatology at the University of Washington, Seattle.

Radiation therapy is often used as an adjuvant or palliative treatment in MCC, but it is almost always fractionated, requiring multiple visits and potentially killing T cells that function in tumor immunity, Dr. Nghiem said. In light of evidence that single-fraction radiotherapy (SFRT) enhanced tumor immunity in mice, he and his colleagues at the University of Washington and the Fred Hutchinson Cancer Research Center in Seattle decided to "think outside the box and do something different."

Therefore, in 2010, the researchers began using 8-Gy SFRT on distant MCC metastases. In all, they targeted 93 tumors in 26 patients (median age, 68 years). Survivors were followed for a median of 252 days (range, 76-699 days). The median tumor size was 4 cm (range, 1-19 cm), and patients had 1-28 tumors, with an average of 3.5 tumors per patient.

The investigators classified half of patients (n = 13) as high risk because they were immunosuppressed and/or had prior chemotherapy. Other patients were categorized as low risk. High-risk patients had 60 tumors and a 3.5-month median interval from chemotherapy to start of SFRT. The low-risk group had 33 tumors.

A complete response was seen in 81% of tumors in low-risk patients and 52% of tumors in high-risk patients (P = .008), Dr. Nghiem reported. No tumor that completely responded ever recurred, regardless of risk, he said. In one case, a patient with a 5-cm metastasis compressing the trachea reported greater ease of breathing several days after SFRT, and subsequent imaging studies showed complete response with no recurrence at 20 months, he said, adding that the patient remained on an immunostimulant.

The rate of recurrence also was significantly lower in low-risk (9%) versus high-risk patients (30%; P = .02), Dr. Nghiem said. The P value "was statistically significant in this midsize trial, suggesting that the immune system really matters in controlling these lesions," he said, adding that Merkel cell carcinoma, "maybe more than most other cancers, is extremely linked to immune function. As we increase radiation dose, we see more cancer killing [activity], and more immune cell activation at lower doses."

The investigators did not perform post-treatment biopsies to quantify abscopal effects, Dr. Nghiem noted.

The National Cancer Institute, the American Cancer Society, and the National Institutes of Health funded the research. Dr. Nghiem reported no relevant conflicts of interest.

ALBUQUERQUE – Single-fraction radiotherapy of distant metastatic Merkel cell carcinomas led to complete response rates ranging from 52% to 81%, and caused no adverse effects except rare transient pain flares, according to a single-center, single-arm study of 26 patients.

The rate of initial response was 94%, and three-quarters of responders never progressed during the study period, Dr. Paul Nghiem said at the annual meeting of the Society for Investigative Dermatology.

Merkel cell carcinoma (MCC) creates a "terribly frustrating situation" when it metastasizes because although two-thirds of patients initially respond to chemotherapy, the effect is short-lived, with a median progression-free survival of only 94 days, said Dr. Nghiem, professor of dermatology at the University of Washington, Seattle.

Radiation therapy is often used as an adjuvant or palliative treatment in MCC, but it is almost always fractionated, requiring multiple visits and potentially killing T cells that function in tumor immunity, Dr. Nghiem said. In light of evidence that single-fraction radiotherapy (SFRT) enhanced tumor immunity in mice, he and his colleagues at the University of Washington and the Fred Hutchinson Cancer Research Center in Seattle decided to "think outside the box and do something different."

Therefore, in 2010, the researchers began using 8-Gy SFRT on distant MCC metastases. In all, they targeted 93 tumors in 26 patients (median age, 68 years). Survivors were followed for a median of 252 days (range, 76-699 days). The median tumor size was 4 cm (range, 1-19 cm), and patients had 1-28 tumors, with an average of 3.5 tumors per patient.

The investigators classified half of patients (n = 13) as high risk because they were immunosuppressed and/or had prior chemotherapy. Other patients were categorized as low risk. High-risk patients had 60 tumors and a 3.5-month median interval from chemotherapy to start of SFRT. The low-risk group had 33 tumors.

A complete response was seen in 81% of tumors in low-risk patients and 52% of tumors in high-risk patients (P = .008), Dr. Nghiem reported. No tumor that completely responded ever recurred, regardless of risk, he said. In one case, a patient with a 5-cm metastasis compressing the trachea reported greater ease of breathing several days after SFRT, and subsequent imaging studies showed complete response with no recurrence at 20 months, he said, adding that the patient remained on an immunostimulant.

The rate of recurrence also was significantly lower in low-risk (9%) versus high-risk patients (30%; P = .02), Dr. Nghiem said. The P value "was statistically significant in this midsize trial, suggesting that the immune system really matters in controlling these lesions," he said, adding that Merkel cell carcinoma, "maybe more than most other cancers, is extremely linked to immune function. As we increase radiation dose, we see more cancer killing [activity], and more immune cell activation at lower doses."

The investigators did not perform post-treatment biopsies to quantify abscopal effects, Dr. Nghiem noted.

The National Cancer Institute, the American Cancer Society, and the National Institutes of Health funded the research. Dr. Nghiem reported no relevant conflicts of interest.