Nathalie C. Zeitouni

Characterization of nonmelanoma skin cancer for light therapy using spatial frequency domain imaging

The dosimetry of light-based therapies critically depends on both optical and vascular parameters. We utilized spatial frequency domain imaging to quantify optical and vascular parameters, as well as estimated light penetration depth from 17 nonmelanoma skin cancer patients. Our data indicates that there exist substantial spatial variations in these parameters. Characterization of these parameters may inform understanding and optimization of the clinical response of light-based therapies.

Photodynamic therapy and pain: A systematic review

Photodynamic therapy (PDT) is an effective treatment for actinic keratoses and early skin cancers, and the only office procedure to control field cancerization. Procedure-associated pain limits widespread PDT use and by early termination of treatment can decrease overall therapeutic efficacy. Here we review and assess reported interventions on PDT-associated pain, in order to identify the most promising methods to manage treatment-associated pain and identify focus for future studies. Literature search was performed using MEDLINE, EMBASE, and the Cochrane Library by two independent reviewers to select publications that assessed and compared pain quantitatively during PDT treatment for actinic keratoses, basal cell carcinomas, and/or in situ squamous cell carcinomas. A total of 48 studies reporting on pain during PDT were identified and were comprised of two main categories of interventions: pain-controlling therapies and PDT parameter (photosensitizer or photo-irradiation) adjustments. Of these interventions: nerve block, subcutaneous infiltration anesthesia, cold analgesia, and transcutaneous electrical nerve stimulation, but not topical anesthetic gels, were associated with less PDT-related pain; 5-aminolevulinic acid (ALA) tended to be more painful than methyl-5-aminolevulinate (MAL); daylight PDT was less painful than conventional PDT; and lower irradiance delivery produced lower pain scores in general. There is no single crystalized protocol for management of PDT-related pain. Evidence suggests that continuous activation of low levels of PpIX with methods using lower irradiance and possibly shorter incubation times are associated with decreased pain without loss of PDT efficacy. Protocols to reduce pain should be standardized and large controlled trials are needed.

Survival in patients with primary Dermatofibrosarcoma Protuberans: National Cancer Data Base analysis

Background: The predictors of mortality, second surgery, and postoperative radiation therapy for treating dermatofibrosarcoma protuberans (DFSP) are not well described. Objective: We sought to determine the impact of patient demographics, tumor characteristics, and treatment site and modality on survival after primary DFSP. Methods: A retrospective analysis of data from the National Cancer Database was performed for patients diagnosed with DFSP during 2003–2012. Results: A total of 5249 cases were identified. Of these, 3.1% of patients died during an average of 51.4 months of follow‐up. After adjusting for relevant factors, lack of insurance, Medicaid and Medicare insurance, anaplastic histology, and positive postoperative margins all predicted mortality, while treatment at an Integrated Network Cancer Program predicted survival (P < .05). Higher odds of postoperative radiation therapy were directly associated with large tumor size, anaplastic and poorly differentiated histology, and positive postoperative margins and inversely associated with treatment at high volume facilities, and non‐head and neck tumors. Higher second surgery rates were associated with Hispanic ethnicity, and lower rates were associated with female sex. Limitations: Survival data was not cancer‐specific. Conclusion: Better understanding of factors affecting survival outcomes might help improve management of DFSP and delineate other potential causes of increased morbidity and mortality.

Neuromalignancy complicating the Muir–Torre syndrome

Keywords: brain cancer; hereditary nonpolyposis colorectal cancer; immunohistochemistry; Muir–Torre syndrome; sebaceous neoplasm

Photodynamic therapy for Bowen’s Disease (squamous cell carcinoma in situ) current review and update

The aim of this review is to provide clinicians with an overview of outcomes in the current literature concerning the use of Photodynamic Therapy to treat Bowens Disease, also known as Squamous Cell Carcinoma in situ. The review discusses clinical response, recurrence rates, cosmetic outcomes, and adverse effects. Strong evidence shows that PDT is an effective therapy for SCCis with acceptable clinical response rates and lower recurrence rates in comparison to conventional therapies such as cryotherapy and 5-fluorouracil. Furthermore, PDT is associated with superior cosmetic outcomes and is generally well tolerated by patients, with minimal side effects. PDT is especially useful in patients with multiple lesions and those whom are considered to be non-surgical candidates.

Combination vismodegib and photodynamic therapy for multiple basal cell carcinomas

BACKGROUND Oral vismodegib therapy and photodynamic therapy (PDT) are non-invasive treatments for basal cell carcinoma (BCC) with overlapping utility in widespread BCCs and patients who are poor surgical candidates. There is no published study to date investigating the combination use of PDT with vismodegib to optimize individual response rates. OBJECTIVE To evaluate the combination of red light PDT and vismodegib therapy in patients with multiple nodular BCCs. The primary objective was to determine the safety of this combination therapy. Secondary outcomes included evaluation of the overall response rate, treatment-related pain, and cosmesis. METHODS An open label pilot study of immunocompetent patients with multiple BCCs treated with 3 months of continuous vismodegib therapy (150 mg daily) and 3 consecutive ALA PDT sessions. Outcomes were assessed following each PDT session and 30 days post-treatment. RESULTS Four patients with multiple nodular BCC (median=5) were enrolled in the trial between January and August of 2016. Three patients completed the full intervention phase trial and a total of 19 lesions were treated. One patient completed 2 months of vismodegib and 2 PDT sessions. One PDT session was sufficient for small lesions, whereas larger lesions required all 3 sessions. The fifteen evaluable lesions at the end of the 3 PDT sessions showed complete responses. At 30-day follow-up, one of the treated lesions was noted to have clinical evidence of disease. Overall response rate showed 90% complete response and 10% partial response for the study. Combination therapy was well tolerated and yielded a similar or superior side effect profile to that of individual therapies with excellent cosmesis. CONCLUSION Combination PDT-vismodegib is a potential safe & effective therapy for the treatment of multiple BCCs that may enhance efficacy of individual therapies.

Primary extramammary Paget's disease of the skin: treatment and survival

treatment and survival Extramammary Paget’s disease (EMPD) is a rare form of skin cancer that primarily affects perineal areas. Surgery is considered the mainstay of therapy, whereas radiotherapy is the most frequent secondary option. Despite several single-institution studies showing successful treatment of EMPD with radiotherapy, a recent meta-analysis and Surveillance, Epidemiology, and End Results (SEER) cohort study was unable to show survival benefit attributed to radiotherapy. Use of alternative modalities, including topical 5FU, imiquimod, paclitaxel, trastuzumab, and photodynamic therapy (PDT), has been reported. Imiquimod, an immune modifier used to treat basal cell carcinoma and benign epithelial growths, has been reported to induce good response when used in combination with PDT to treat EMPD. PDT is a multistep process involving application of a 5-ALA photosensitizer cream that is incubated for 4 hours and then activated by light leading to sloughing of EMPD cells. Despite various treatment options available, no effective regimen has been established. Here, we investigated the effect of treatment modality and patient demographics on overall survival (OS) in cases with primary cutaneous EMPD. The National Cancer Database (NCDB), which captures 70% of all newly diagnosed malignancies in the US annually, was queried for patients diagnosed with cutaneous EMPD from 2004 to 2012, with an average of 48 months of follow-up recorded until January 2016. Cases with a prior malignancy (n = 284, 36.1% vs. 21.4% sample mortality rate), lack of follow-up data, and unknown treatment history were excluded. A sensitivity analysis for excluded cases revealed only age of diagnosis and proportion of Medicare patients to significantly differ from population investigated. Univariate analysis was performed using Chi-squared and Student’s t test. Cox proportional hazard model was used to assess the impact of treatment approach on OS with adjustment for demographics, comorbidities, and tumor characteristics. Log-rank test was used to select variables for survival analysis. Only variables that, when excluded, did not show a significant effect on the validity of the resulting model were left out. Testing of proportion-hazard assumption and Harrell’s C statistic were done to assess validity and predictive value of the survival model, respectively. Of 628 cutaneous EMPD cases identified, 290 met our inclusion and exclusion criteria. On unadjusted analysis, individuals undergoing surgery had better OS (P = 0.002), whereas those undergoing radiotherapy (P < 0.028) and chemotherapy had poorer OS (P < 0.004) (Fig. 1). After adjusting for age, sex, race, and other factors, only radiotherapy (adjusted hazard ratio, 2.41; 95% CI, 1.04–5.55) remained independently associated with reduced OS (Table 1). Older age, presence of comorbidities, lack of insurance, large distance to treating facility, larger tumor size, and poor histological differentiation were also identified as independent predictors of reduced OS (P < 0.05).

Melanoma of the Face and Mohs Micrographic Surgery: Nationwide Mortality Data Analysis.

BACKGROUND Although Mohs micrographic surgery (MMS), narrow margin excision (NME), and wide margin excision (WME) are commonly used to treat melanoma of the face, there is a paucity of data comparing mortality outcomes for each method. OBJECTIVE To determine the association between surgical method used to treat cutaneous melanoma of the face and patient survival. MATERIALS AND METHODS A retrospective review of Surveillance, Epidemiology, and End Results registries for patients diagnosed with melanoma of the face between 2003 and 2012 was conducted. RESULTS The authors query resulted in 43,443 records. Patients with melanoma were more likely to undergo NME (57.79%) than WME (27.86%) or MMS (14.36%). Overall 5-year risk of death was higher with WME (hazard ratio [HR], 1.11; 95% confidence interval [CI], 1.00–1.23; p = .043) and NME (HR, 1.10; 95% CI, 1.00–1.20; p = .046) relative to MMS after adjusting for patient demographics, residence socioeconomic factors, and tumor characteristics. No statistically significant difference in melanoma-specific mortality was found between different surgical methods on multivariate analysis. CONCLUSION Patients with melanoma of the face treated with MMS had similar melanoma-specific mortality or overall survival outcome as patients treated by other surgical modalities.

Merkel Cell Carcinoma and Other HIV-Associated Skin Cancers

Cutaneous neoplasms are cancers that originate from the skin and are the most common malignancies in the USA. Patients with HIV and other immunocompromised diseases have not only a greater risk of developing common skin cancers such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma but also more unusual cutaneous tumors such as Merkel cell carcinoma (MCC), Kaposi’s sarcoma (KS), and certain lymphomas.