AAD 73rd Annual Meeting

av Ada Girnita, 20 - 24 mars 2015

The American Academy of Dermatology’s Annual Meeting had as always comprehensively addressed the nine content areas within the Dermatologic Core Curriculum and provided dermatologists and oncologists with high quality educational opportunities for the optimization of skin knowledge, competence and performance.

By attending the meeting I was able to update my knowledge about recent advances in the diagnosis, management and treatment of skin tumors, especially melanoma, to assess the relationship of evidence-based diagnostic approaches and therapies with new modern and most effective treatments.

More specific by attending the session about late-breaking Research: Basic Science & Clinical Oncology we were able to see data regarding inactivation of the tumor suppressor gene, phosphatase and tensin homologue (PTEN), which is a major alteration in melanoma.  Aberrant DNA methylation of promoter region of CpG islands is an alternative and frequent mechanism that leads to inactivation of PTEN in melanoma. Promoter methylation of PTEN can occur more frequently compared to BRAF, NRAS and KITmutation in some melanoma patients. When it does PTEN promoter methylation correlates to Breslow’s thickness and is an independent predictor of impaired patient  survival.

Another very interesting talk was given by Pedram Gerami about specific mutations in melanoma. By looking specifically at homozygous 9p21 deletions he was able to show that in melanoma with aggressive clinical course: 1) 9 of 11 cases with disease progression beyond the sentinel had homozygous 9p21 deletions; 2) 4 of 9 patients with ASTs with homozygous 9p21 deletion developed recurrent in transit metastasis in the skin in addition to sentinel and non-sentinel lymph node involvement all of whom are still alive.  One patient with up to 8 years of follow up.  3) Distant metastasis and death from disease from ASTs uncommon but when it does happen most cases likely to have homozygous 9p21 deletion and likely to occur with a more protracted course compared to conventional melanomas.

Merkel cell carcinoma was also the subject of discussion regarding new therapies. Kinase inhibitors: Imatinib mesylate – negative trial. KIT expressed but not activated. Pazopanib – VEGFR, PDGFR, FGFR, c-­-Kit multikinase inhibitor. Mixed case reports. Controlled trial ongoing. Cabozantinib – c-­-Met, VEGFR2. Trial ongoing. • Somatostatin analogues. MCC express somatostatin receptor 2, octreotide scintigraphy. Multiple trials. Combinations: Cixutumumab (IGF-­-1R), Everolimuse Acetate. Everolimus and atalanib (VEGFR, PDGFR, c-­-Kit). Targeted therapy: Apoptotic pathway, Oblimersen Bcl2 antisense oligonucleotide.
Negative trial?.NCAM (CD56) immunotoxin (BB-10901), DM1conjugated antibody (tubulin cytotoxin). Anti PD-1 for metastatic MerckelCC is on Phase II, single arm of MSB0010718C (Merck/ EMD Serono) as second line therapy Multicenter US and Europe.

In the melanoma update session long discussions were due to the new shift in therapy of metastatic melanoma since novel immuno- and targeted therapies have revolutionized therapy of metastatic melanoma. Actively investigated in the adjuvant setting Immunotherapy produces significant prolongation of survival, with acceptable toxicity, rapid tumor regression; use in frontline setting and no longer reserved for low-burden disease. Lately shift from IL-2/IFN>>>> Ipi>>>> PD-1. In conclusion targeted therapy produces rapid responses, but acquired drug resistance limits its long-term efficacy. It seems that combinatorial therapy is the way to go for targeted therapy, and possibly for immunotherapy.

Our contribution to the meeting was also well received and gives opportunity to interesting questions and new points of view. By participating in this meeting I feel that I gain new insights in the latest about skin cancer in general and melanoma in particular and helped me further develop my skills as a clinician and researcher.