Sarah Fitzmaurice

Metastatic melanoma – A review of current and future treatment options

Despite advances in treatment and surveillance, melanoma continues to claim approximately 9,000 lives in the US annually (SEER 2013). The National Comprehensive Cancer Network currently recommends ipilumumab, vemurafenib, dabrafenib, and high-dose IL-2 as first line agents for Stage IV melanoma. Little data exists to guide management of cutaneous and subcutaneous metastases despite the fact that they are relatively common. Existing options include intralesional Bacillus Calmette-Guérin, isolated limb perfusion/infusion, interferon-α, topical imiquimod, cryotherapy, radiation therapy, interferon therapy, and intratumoral interleukin-2 injections. Newly emerging treatments include the anti-programmed cell death 1 receptor agents (nivolumab and pembrolizumab), anti-programmed death-ligand 1 agents, and oncolytic vaccines (talimogene laherparepevec). Available treatments for select sites include adoptive T cell therapies and dendritic cell vaccines. In addition to reviewing the above agents and their mechanisms of action, this review will also focus on combination therapy as these strategies have shown promising results in clinical trials for metastatic melanoma treatment.

Effective strategies for the management of pyoderma gangrenosum: a comprehensive review.

Pyoderma gangrenosum (PG) is an inflammatory disease characterized by painful skin ulcerations with undermined and erythematous borders. The etiology of PG is not well understood, but it is generally considered to be an aberrant immune response characterized by a dermal neutrophilc infiltrate. Given the existence of only a few PG clinical trials, treatment options are largely based upon anecdotal data and small case studies. In addition to classic immunosuppressive medications, PG has been reported to respond well to the anti-TNF agents, infliximab, etanercept, adalimumab. Newer biologics such as ustekinumab (anti-IL-23), ixekizumab (anti-IL-17) and brodalumab (anti-IL-17R) are promising given the effect of IL-17 on neutrophil migration. However, the effectiveness of these newer agents remains to be rigorously evaluated. Multi-drug regimens have not been well described in the literature but are an excellent alternative for patients with refractory disease. Herein, we provide a comprehensive review of the pathophysiology of PG and of the different treatments available for managing PG patients, including the theoretical benefit of initiating multidrug regimens. We also provide one possible treatment algorithm for patients with refractory disease and give examples of refractory PG cases successfully treated with multidrug regimens.

Daylight Photodynamic Therapy: What is Known and What is Yet to be Determined.

BACKGROUND Photodynamic therapy (PDT) has been used extensively to treat actinic keratoses (AKs) and less so nonmelanoma skin cancers (NMSC). Conventional in-office treatment is limited by intensive time requirements and patient discomfort. A new trend toward the use of daylight as a light source either clinically monitored or self-supervised is gaining acceptance. OBJECTIVE To assess the current published data on daylight photodynamic therapy (dPDT) and identify knowledge gaps. METHODS AND MATERIALS A systematic search of the PubMed archives using the terms daylight PDT, daylight-PDT, daylight photodynamic therapy, and ambient light and photodynamic therapy was conducted on May 18, 2015. No restrictions were used for the search string. RESULTS Seventeen published works were identified on the use of dPDT; 8 randomized studies, 4 prospective cohort studies, 1 case series, 1 case report, and 3 retrospective studies. Complete response rates for treatment of AKs from randomized trials range from 46% to 89.2%. CONCLUSION Daylight PDT has been demonstrated to have high efficacy with results similar to conventional PDT for the treatment of AKs. Initial reports regarding treatment of NMSC indicate recurrence rates much higher than other accepted therapies. Pain associated with treatment seems to be significantly less than for conventional PDT.