4. Laviv May Offer Longer-Term Acne Scarring Tx: Azficel-T, an autologous cellular product, produced significant improvement in acne scarring, compared with placebo, according to new study results reported at the annual meeting of the American Society for Dermatologic Surgery. Laviv was approved by the FDA earlier this year for treating wrinkles. This video features an interview with Dr. Girish Munavalli.
The molecular profilization of melanoma is nigh. Assessment of advanced-stage, metastatic melanoma to determine whether it carries a mutation in the BRAF oncogene will turn routine soon, once physicians have the option to treat these patients with the new BRAF inhibitor drug, vemurafenib.
That might happen any day now. Reuters said on August 9 that the FDA’s approval of vemurafenib could get announced soon. Roche/Genentech submitted their NDA for vemurafenib to the FDA in May, and in June came impressive efficacy results in a phase III study that got reported at both ASCO and in a New England Journal of Medicine article.
Last week, I covered the American Academy of Dermatology’s summer meeting in New York, and melanoma specialist Dr. Richard D. Carvajal from Memorial Sloan-Kettering, New York, told me that once vemurafenib was on the market, genetic analysis of advanced melanomas to find BRAF mutations would suddenly become standard of care. Once testing for one mutation starts, several more genes can easily piggyback onto the assay, which will help to further flesh out the range of genetic mutations that can exist in metastatic melanoma and provide potential targets for new drugs.
It’s becoming a well-trodden path that’s rapidly driving the treatment of advanced cancers of all kinds into the molecular-profiling era. Just a couple of weeks ago, I blogged here on how it had already transformed advanced lung cancer management. Breast cancer and colorectal cancer have an even longer history of genetic assessment, and more cancers will likely follow this route soon.
When I wrote my blog post about lung cancer in late July, I focused on the challenge to successfully treating late-stage cancer, and I said that better alternatives were lung cancer prevention, by not smoking, and earlier diagnosis, with CT screening.
Melanoma does not pose the same screening issues as lung cancer. It’s much easier to survey the skin than to peer into a person’s lungs. And the idea of melanoma prevention by sunlight avoidance and protection has transformed the way many Americans approach outdoor activity. Over the last generation or so, SPF has become a cultural touchstone.
Despite that, cases of advanced melanoma are inevitable. Last week at the AAD meeting, Dr. Darrell S. Rigel from New York University showed evidence of a troubling, new wrinkle in melanoma epidemiology: an appreciable blip in cases that first appeared about 10 years ago in American women aged 30-34 years, a shift that Dr. Rigel attributed to an increased use of tanning salons among teenage girls that started in the 1980s.
Even if advanced-stage tumors, melanoma, or lung cancers are unstable and unlikely to respond to even the best targeted of drugs for more than a few years, those extra years of cancer control with good quality of life can make a big difference to each patient who responds to a genetically targeted treatment, Dr. Carvajal told me.
In Tanzania, where some of the oldest human fossils have been found, and where Mt. Kilimanjaro rises above the clouds, a group of international dermatologists are hoping to help a very vulnerable population.
The region has one of the highest incidences of albinism in the world. Although the condition is rare in the western world, it is quite common in sub-Saharan Africa, according to some studies. (While the incidence of this genetic condition is about 1 in 37,000 U.S. residents, the rate in this region is as high as 1 in 1,400.)
The people with albinism are also subject to discrimination, stigma and even murder.
Sun Damage to Back of an Albino Individual
But, another important concern is the health of the albinos whose pink skin is exposed to the African sunshine, and where many of the occupations are outdoors and in the field.
Many of the locals with albinism die of cancer before age 40; in fact, fewer than 2% make it to their 40th birthday. And almost all of the children with albinism show signs of sun damage before age 10.
Because of a lack of funding, many can’t afford hats to protect themselves; because of a lack of education, many don’t know the link between sun damage and cancer.
Dr. McLean has been visiting the region for the past 2 decades, helping to establish and grow the Regional Dermatology Training Centre (RDTC), an ILDS program, in the town of Moshi in Tanzania.
He is also among a group who recently spearheaded a project to make hats — the ones with 7.5-cm rim — available to the albinism population in Tanzania. [Listen to Dr. McLean below.]
Called “Hats On for Skin Health,” a collaboration between the ILDS and Stiefel, the project is a global effort to raise funds for the purchase of hats and other protective items for albinos in Tanzania.
Sun-Protective Hat on an Albino Girl
The items will be distributed by RDTC that manages a mobile skin care clinic, which regularly visits people with albinism living in the region and educates the locals, especially parents, about albinism. The lesson they try to get across, said Dr. McLean, is to let their children play outdoors, but cover them up first.
The group has located a hat manufacturer in Moshi, which is currently producing template models for children and adults. Many of the workers, said Dr. McLean, have albinism. “We think that’s definitely part of the solution going forward,” he said.
The cost of manufacturing a hat in Africa? Less than $2.50. The hats are expected to last for at least for 10 years.
To start the campaign, Stiefel, a subsidiary of GlaxoSmithKline, has donated $25,000, and Dr. McLean hopes that dermatologists, other professionals, and even the public, get involved with the campaign.
“Our people are on the ground there. We know what happens to every donated dollar,” said Dr. McLean.
A closely watched experimental drug has excited melanoma oncologists and patients with a 63% reduction in the relative risk of death from metastatic melanoma when compared with standard therapy in a phase III trial that had enrolled 675 newly diagnosed patients. Vemurafenib (better known as PLX4032) targets the BRAF V600E mutation found in 40%-60% of melanoma patients. It is only the second melanoma drug to extend the lives of melanoma patients in a randomized clinical study.
The first such agent, ipilimumab (Yervoy), was approved earlier this year, and the melanoma community expects the Food and Drug Administration will award an indication to vemurafenib based on the new data from the BRIM-3 trial. We talked with Dr. Paul Chapman – lead author of the BRIM-3 study — about vemurafenib. He also hypothesized how clinicians would decide which drug — vemurafenib (assuming approval) vs. ipilimumab to use for their patients.
For a while, melanoma has been a bit of a red-headed stepchild of oncology. While advances have improved survival in a number of cancers in recent years, little progress had been made in melanoma. At this year’s ASCO annual meeting, new melnoma treatments generated a lot of buzz.
These new drugs are exciting and important because of their activity — meaning that they have an impact and clinical benefit in patients with advanced melanoma.
Overall survival was 11.2 months in melanoma patients who received ipilimumab plus dacarbazine group and 9.1 months in the placebo plus dacarbazine group. The study was simultaneously published in the New England Journal of Medicine (2011 June 5 ;doi:10.1056/NEJMoa1104621). Ipilimumab was approved earlier this year as a first-line monotherapy treatment at a dosage of 3 mg/kg.
In another plenary presentation at ASCO, there was a 63% reduction in risk of death with vemurafenib, compared with dacarbazine alone, in metastatic melanoma patients with BRAF mutations. Vemurafenib is an investigational oral drug that inhibits BRAF kinase.
April showers bring May patients who may be confused about the safety of sunscreens containing nanoparticles of titanium and zinc.
To help alleviate concerns the Nanodermatology Society released a position statement on the safety of sunscreens containing nanoparticles. Dr. Adam Friedman, vice president of the Society and senior author of the position statement, spoke to our sister blog The Mole about the safety of nano-based sunscreens.
Photo credit pni via Flickr Creative Commons
The concern is that nanoparticles might interact directly with cell DNA and cause damage because of their size and their ability to not only penetrate the skin but to enter the body through the mucosa in the nose, or to be swallowed, Dr. Friedman said.
Nanoparticle penetration is limited by size. “One of the things I tell people is that the materials they are using in bench research are different than what is used in over-the-counter products,” Dr. Friedman said. “Those used in consumer products are commonly coated, so they aggregate and don’t penetrate the skin as easily.”
“Thus far, everything that has been done in terms of topical application of the skin, the particles do not penetrate to the point where they could cause problems,” said Dr. Friedman. “Clearly, more needs to be done, and certain clinical situations need to be explored, such as penetration into damaged skin,” he noted. When the nanoparticles are aggregated in solution, they are trapped in the upper layers of the skin, where they are sloughed off over time.
“A lot of the fear with respect to the bodily harm from nanomaterials comes from the lung literature and occupational hazards with respect to people inhaling asbestos,” he noted.
Another concern about nano-based sunscreens is the potential impact on the environment, Dr. Friedman said. However, a hot-off-the press study in Science of the Total Environment by A. Johnson and colleagues found no impact of titanium oxide sunscreens on the environment.
The Mohs technician – a non-physician (often even a non-healthcare worker) – occupies a unique place in the medical pantheon.
The Mohs surgeon’s right hand must be as steady as the surgeon’s own, capable of working with the most minute wafers of tissue, just a cell or two thick. A natural tinkerer who can adjust a highly complicated machine whenever its temperamental temperament gets out of whack. A perfectionist whose urge for the precision can never be shaken by deadlines, fussy patients, or cranky docs who just want to get out of here already.
At a Mohs surgery training course, sponsored by the American Society of Mohs Surgeons, I learned first-hand (no pun intended) about what the tech brings to this fascinating area of surgery.
Alexander Lutz, the owner of Travel Tech Mohs Services, Inc., Carson, Calif., put it well during his talk on the issue: “It’s a rare relationship between and physician and non-physician, even more so than a surgeon with his surgical nurse or tech. The nurse might be helping the surgeon, but you aren’t depending on them to complete the surgery. With a Mohs technician, you are.”
A physician who wants to learn Mohs surgery can choose to hire and train a formally educated lab tech or histotechnician – or pick a staff person to train. It can be a nurse or medical assistant, or even the office manager.
Photo courtesy Loggie-log/Wikimedia Commons
Mr. Lutz gave some pointers on picking the right trainee. Two characteristics are key: manual dexterity and a perfectionist personality. “In my experience, good Mohs techs have these things in common. I always ask if they have a hobby that shows dexterity-like knitting, musical instruments, or even juggling.”
And though the perfectionist personality part might drive the doc nuts in a personal relationship, it will serve both well in the surgical suite. The success of Mohs surgery – and even the life of a human being – depends on those beautiful clear margins. The surgeon can only create those margins if there are plenty of beautiful slides to guide the surgery. And only a dedicated, skilled technician can make those beautiful slides.
How long people live after a diagnosis of thin melanoma varies.
Dr. Christopher J. Miller
“Most patients do well–at five years, 95% are doing fine,” Dr. Christopher J. Miller said at a summer symposium of the Alabama Dermatology Society.
This figure comes from an Archives of Dermatology study where researchers found 95.3% of patients survived at least 5 years if they had thin (< 1 mm) melanoma, stage II/III disease, with no ulceration.
“About 10% are not doing as well,” Dr. Miller said, referring to a different group with thin melanoma (<1 mm, stage IV/V with ulceration). In this group, study researchers found a 90.9% five-year survival.
So how do you estimate prognosis for your individual patient? Dr. Miller recommended a website that has a fast and easy-to-use (I tried it!) instrument to estimate survival based on a few characteristics.
“This is a great tool … and a useful thing to have for your patients,” said Dr. Miller, Director of Dermatologic Surgery at the University of Pennsylvania in Philadelphia. Using a number of factors to calculate survival is more accurate than relying on just one measure or using survival curves, he said.
I tried the site for a hypothetical patient with localized melanoma. I found that a 45-year-old with a 1 mm ulcerated lesion located on axial site would have an estimated:
The month of May marked 25 years since dermatologists began using the ABCD rule to help screen for melanoma, and advances in diagnosis since then have leaned toward newer and better use of imaging technology instead of clinical mnemonics.
Left side, top to bottom: melanomas showing (A) asymmetry, (B) irregular border, (C) unusual coloring, and (D) diameter that had changed in size. Right column: Normal moles. Images from National Cancer Institute via Skin Cancer Foundation, merged by WikiMedia Commons user Stevenfruitsmaak.
You do know your ABCDs, don’t you? Moles with ”A” for asymmetry, “B” for border irregularity, “C” for uneven color, or “D” for diameter greater than 6 mm. If you see these, think melanoma.
Advances over the quarter-century since then have focused on helping physicians “see” melanoma better. Dr. Darrel Rigel described some of these at the annual meeting of the American Society for Mohs Surgery. Dermoscopy allowed non-invasive imaging of melanomas. Digital photography came along, and some dermatologists began using serial digital imaging to track changes in moles over time. Most recently, various groups have been trying to add assessments using infrared (non-visible) light through computer-aided programs to aide diagnosis.
As a woman of letters, I have to admit a fondness for the ABCDs. But the imaging advances do have more of a new-school, digital-age feel to them. I think both can happily co-exist in dermatology. Time will tell if that’s old-school thinking as the digital age advances.
One of these things is not like the others,
One of these things just doesn’t belong,
Can you tell which thing is not like the others
By the time I finish my song? (Words and Music by Joe Raposo and Jon Stone, Sesame Street)
The current public health message to patients is to look for the ABCD’s of melanoma. But how many people do you think can actually remember what that mnemonic stands for?
The ugly duckling sign of melanoma was first described in 1998 by Dr. Jean-Jacques Grob of the University of Marsielle in Provence, France. It holds that nevi on a given individual tend to resemble each other, said Dr. Ashfaq A. Marghoob, at today’s meeting at the annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation. Most individuals harbor nevi that resemble each other like brothers. And when a lesion breaks that common mold, it becomes an ugly duckling…
This post first appeared in our sister blog, The Mole: the Skin & Allergy News blog. To read the whole post by managing editor Amy Pfeiffer, go here.
A long-acting intramuscular formulation of testosterone has been approved by the Food and Drug Administration for treating hypogonadism, with a label that includes a boxed warning about the risks of pulmonary oil microembolism and anaphylaxis associated with treatment.