Melanoma Prevention: The Latest Advances & Future Directions
Interview with Susan Swetter, MD, Professor of Dermatology, Stanford University and VA Palo Alto, and Director of the Pigmented Lesion and Melanoma Program at Stanford University Medical Center and Cancer Institute
Speaking with Dr. Susan Swetter, at the Melanoma Research Alliance Ninth Annual Scientific Retreat in Washington, DC, I inquired about the Panel Discussion she was part of titled: News from the field: What’s going well and what remains to be done?
Speaking from the prevention side, Dr. Swetter explained that researchers have not had the same breakthroughs in prevention for melanoma as they’ve had for advanced disease therapy. She adds that thousands of lives a year, worldwide, could be saved with a more pronounced focus on early stages of the disease — preventing a melanocyte from undergoing transformation to melanoma at the outset. She believes issues with prevention relate not only to using sun protection, but also to improved sun protection ingredients, many of which are not available in US sunscreens, and both physicians and individuals examining skin and detecting melanoma early.
Swetter feels increasingly hopeful about prevention since the recent development of a deep learning algorithm program initiated by artificial intelligence experts that utilizes convolutional neural networks. This new innovation tool may eventually be used to detect cancerous lesions vs. benign growths and has been tested at Stanford University relative to 21 board certified dermatologists, though not yet in a prospective, ‘real-life’ clinical setting. Swetter sees multiple levels of potential use and is excited to think about how we could incorporate artificial intelligence into early detection strategies for both patients and practitioners and expand these technologies on the prevention front to move the bar. Though the algorithm researched has not been part of a prospective validation study to establish how it fares in actual practice, the system was trained at Stanford on 130,000 plus images with 2000 plus skin type diseases.
Can you talk about your work in melanoma research at Stanford University?
Stanford’s Cutaneous Oncology Program, led by Swetter, now encompasses melanoma, pigmented lesions, cutaneous lymphoma, other solid tumors, advanced basal cell carcinoma, high-risk and squamous cell carcinoma, Merkel cell carcinoma as well as a novel skin cancer genetics clinic and unique Supportive Derma-Oncology program providing rapid evaluation and treatment of the cutaneous side of cancer therapy. The expansion of this program results in daily, close collaboration among dermatologists, oncologists, surgeons, radiation oncologists and other cancer specialists to improve patient care and quality of life. Swetter notes the importance of effective treatment for cancer-related skin conditions so patients don’t end up requiring dose reduction or cessation of medications that could be life saving.
Swetter says a central issue the Stanford Support Dermato-Oncology program is focusing on is its study into newer melanoma treatments that produce a multitude of cutaneous side effects including MAP kinase and immune checkpoint inhibitors. She explains there is an increased need for dermatologists and oncologists to work together more closely to facilitate the identification of skin findings that could serve as important biomarkers of response to the treatment, thus resulting in greater precision in treating melanoma. Swetter further considers it important to biopsy reactions on the skin in clinical trials to characterize the nature of the reaction and determine if it may predict a response. She says this collaboration has been underutilized in clinical trial settings between medical oncologists and cutaneous oncologists.
What one particular thing about melanoma research has surprised you?
“I am surprised and disappointed that we do not yet have an effective therapeutic prevention agent — that is, a candidate agent to take forward to a chemo prevention study in high-risk individuals,” says Swetter.
She explains that over the last 15 years, she and other prevention specialists developed a multi-disciplinary, national Melanoma Prevention Working Group with cooperative oncology group Infrastructure. The goal was to enhance both primary and secondary prevention strategies. A key aim is to test safe and tolerable drugs in patients who are predisposed to a melanoma based on mole pattern, p16 mutation, personal or family history of melanoma, red-hair phenotype or a combination thereof. She says a number of investigators around the country and world have examined various drugs, vitamins and other supplements and antioxidants with mixed responses and no home run as yet. She says not being able to identify which ones should be taken to a randomized trial in those at risk for melanoma is frustrating. Swetter notes that the process has been hampered a bit by resources available to study these ‘off the shelf’ agents because prevention is generally not as well funded as drug development and translational research.
Swetter says she is encouraged by prevention studies, like one presented at the MRA Scientific Retreat on mouse models that have the potential to discern the melanoma preventing effectiveness of sunscreens. She stresses that understanding more about pathways for melanoma initiation and progression can be used to guide further studies for therapeutic or precision prevention.
Swetter is equally surprised that we haven’t moved forward with regard to US standards for sunscreens compared to European and other countries, mainly due to the lack of broad-spectrum UV filters that cover the entire UV spectrum. She routinely advises her patients to purchase sunscreens abroad when they travel and provides information on how to obtain these more effective agents, which are over the counter products. If the more effective chemicals used in other countries, for decades, were approved by the FDA, she believes we could improve primary prevention efforts in the US. In addition, it concerns her that the US has proven to be woefully behind countries like Australia with regard to implementing national polices to ban tanning beds, though a number of grassroots efforts exist via the help of leading patient advocacy organizations.
How vital is policy and legislation to primary prevention of melanoma?
Dr. Swetter considers the most serious obstacle to improving primary prevention strategies to be legislative hurdles. For instance, the FDA currently requires additional safety and efficacy data for additional sunscreen ingredients, which were submitted for consideration on an expedited basis over a decade ago based on prior use without difficulties or complications. In 2015, the FDA took Mexoryl, the last sunscreen filter approved in 2006 off the market, as further scrutiny was deemed necessary, despite the Sunscreen Innovation Act’s efforts to expedite approval of newer UV filters in US sunscreens. “The US has regressed in terms of sunscreen protection. Countries like Mexico and Croatia have sunscreens offering full UVA spectrum coverage, while US sunscreen ingredients have remained stagnant,” says Swetter.
Referring to a randomized control trial out of Australia that was published in 2010, Swetter notes that sunscreens have the potential to reduce melanoma incidence by as much as 50%, with this study utilizing a less effective, lower SPF sunscreen from the early 1990s.
Dr. Swetter regards policies related to reducing harmful UV exposure in children, adolescents and young adults paramount and believes the promotion of nationwide tanning bed legislation that restricts access to minors across the country, rather than only 14 states and the District of Columbia, would be an effective way to mitigate UV exposure that leads to a significant majority of melanomas.
How has MRA funding helped your work?
Swetter says the magnitude of MRA’s funding has made a world of difference, but just as important is the support system they’ve established by bringing together investigators world-wide who can collaborate and exchange ideas, taking their research to another level.
Swetter explains that unfortunately, prevention studies are larger, extended and often more open-ended in terms of melanoma mortality reduction or finding the right biomarkers and chemo-preventative agent to determine efficacy. But, she believes MRA has changed how the melanoma community responds and how investigators conduct research by galvanizing that research. She claims MRA efforts were incredibly timely, as they helped advance the groundwork laid by worldwide investigators into novel targeted and immunotherapies.
“It’s exciting to have the ability to attack cancer in novel ways,” says Swetter. “And, with federal funding being slashed, MRA funding moved the bar more rapidly than would otherwise have been possible. Melanoma has now truly become the blueprint for study of these agents in other cancers, leaving the door open for MRA to do more for both advanced melanoma and prevention.”
Swetter is pleased there are opportunities to examine big data; to help develop artificial intelligence based detection and also improved screening methods. She believes that we can bring new technologies to the forefront, whether it is in molecular diagnostics or molecular pathology and imaging — all of which can be used to enhance cancer care.
What do you hope to see more of in the field of melanoma research?
Swetter hopes to see enhanced research efforts and funding for prevention in melanoma research as well as realistic expectations of what prevention research will take and what should be submitted for consideration of funding. She feels there are two key areas where funders can move the needle for prevention research. One involves the incorporation of novel technologies in detection, such as gene expression platforms using adhesive patch or tape stripping — that may distinguish between benign vs. malignant melanocytic neoplasms and obviate the need for a skin biopsy. In addition, the technology for individuals to image their moles and have them classified by a computer algorithm now exists and can potentially improve early detection. Swetter says funders could play a major role in supporting the development of artificial intelligence/big data and its incorporation into medical care as well as promoting research on the therapeutic prevention side. “As we consider future avenues and need for funding, MRA is ideal, as they see the big picture,” she claims.
Swetter says precision prevention — having a more precise way of profiling a patient’s tumor and treating it with particular therapies down the line or understanding if their tumor is going to recur is vital.
The most encouraging advancement on the prevention side according to Swetter is the artificial intelligence tool for prospective testing in a clinical setting, as it’s a collaborative effort that will help advance the science.
Swetter says some other exciting news on the prevention front is the existence of public health efforts that attempt to engage the melanoma community, the war on melanoma registry/repository utilized in Oregon as well as other patient advocacy groups’ work to bring together the melanoma community on the patient level so we can engage individuals in larger studies that would work for early detection in higher risk patients.
On the whole, Dr. Swetter sees a great deal of enthusiasm in the field, as there is much evolving in biomarker development and the treatment of advanced disease, molecular imaging and improved imaging probes. She says the research is tremendously exciting.
Awareness Melanoma Prevention Clinical Trials Accelerated Approval Skin Checks Advocacy biopsy dermatologist pigmented lesions MAP kinase inhibitor immune checkpoint inhibitors skin biopsy