Advances in Radiotherapy Immune Modulation: From Bench-to-Bedside and Back Again.

Pre-clinical and clinical data clearly demonstrate the immune modulatory effects of radiotherapy (RT) but clinical trials testing RT + immunotherapy have been equivocal. An improved understanding of the immune modulatory effects of RT and how practical parameters of RT delivery (site and number of lesions, dose, fractionation, timing) influence these effects are needed to optimally combine RT with immunotherapy. Additionally, increased exploration of immunotherapy combinations with RT, beyond immune checkpoint inhibitors, are needed. A "bench-to-bedside and back again" approach will improve our understanding of RT immune modulation and allow for the implementation of more effective RT + immunotherapy strategies.

Recurrence Status, Perineural Invasion, and Hypothyroidism Are Associated With Lymph Node Metastasis in Cutaneous Squamous Cell Carcinoma: A Case-Control Study.

BACKGROUND: Lymph node metastasis is a critical prognostic indicator for mortality in patients with cutaneous squamous cell carcinoma (SCC). OBJECTIVE: To identify and characterize key risk factors for SCC lymph node metastasis. METHODS: This was a multi-institutional, case-control study of 65 cutaneous SCCs with known lymph node metastasis matched with 195 cutaneous SCCs without lymph node metastasis (3:1 matching). The cases and controls were matched by anatomic location, age, and sex. Odds ratios (ORs) and their 95% confidence intervals (CIs) were generated to determine the association between specific risk factors and lymph node metastasis in a multivariate analysis. RESULTS: Recurrent tumors (p < .001), perineural invasion (p < .001), lymphovascular invasion (p = .002), size of 2 cm or greater (p = .008), and hypothyroidism (p = .03) were significantly more common in the lymph node metastasis cohort. Recurrence (OR 6.3, 95% CI 2.6-15.3), perineural invasion (OR 4.5, 95% CI 1.7-11.8), and hypothyroidism (OR 2.7, 95% CI 1.04-7.0) remained significant on performing a multivariate analysis. CONCLUSION: Lymph node metastasis in SCC is associated with recurrence, perineural invasion, lymphovascular invasion, size of 2 cm or greater, and hypothyroidism. Clinical consideration of these findings within the context of current staging systems may help improve patient outcomes.

Virtual Reality to Improve the Experience of the Mohs Patient-A Prospective Interventional Study.

BACKGROUND: Nonmelanoma skin cancer is the most common cancer in the United States with significant quality of life impact. OBJECTIVE: To assess the utility of a highly immersive virtual reality (VR) experience in the context of outpatient skin cancer surgery as a means to minimize patient-reported feelings of anxiety or pain. The authors also sought to assess the effects on patient-reported overall satisfaction. MATERIALS AND METHODS: Patients completed a pre-VR experience survey after completion of their first Mohs surgery layer, followed by a 10-minute VR experience, and a post-VR experience survey. Differences in the pre-VR survey and post-VR survey were compared using the chi-square test. The anxiety scores were compared using a t-test. RESULTS: In all but 2 questions, there was a trend toward improvement of the anxiety-related sensations after completion of the VR experience. There were statistically significant differences for 4 questions: "Are you currently feeling unable to relax" (p = .0013), "are you currently feeling fear of the worst happening" (p < .0001), "are you currently feeling terrified or afraid" (p = .0046), and "are you currently feeling nervous" (p < .0001). CONCLUSION: Virtual reality experiences during the Mohs surgical day significantly improved measures of anxiety and patient satisfaction.

A Retrospective Cohort Study of Cutaneous Squamous Cell Carcinoma With Lymph Node Metastasis: Risk Factors and Clinical Course.

BACKGROUND: The single most important prognostic indicator for mortality in patients with cutaneous squamous cell carcinoma (SCC) is the development of nodal metastasis (NM). OBJECTIVE: To characterize the risk factors for and clinical course of cutaneous SCC with NM. METHODS: Ten-year retrospective cohort study (2006-2017) at an academic tertiary care center reviewing 53 cutaneous SCC tumors with NM. RESULTS: Most patients were men (84.6%, 44/52), and almost all primary tumors were on the head and neck (96.2%, 51/53). Most primary tumors were characterized by known "high-risk features" including perineural invasion (56.6%, 30/53), diameter ≥2 cm (54.7%, 29/53), invasion beyond subcutaneous fat (43.4%, 23/53), and poor differentiation (32.1%, 17/53). In addition, many tumors were recurrent (52.8%, 28/53), and many patients were immunosuppressed (30.8%, 16/52). Disease-free survival after treatment of nodal disease was 7.5% (4/53) at 5 years. CONCLUSION: To the best of the authors' knowledge, this study is the largest retrospective cohort of cutaneous SCC with NM to date. The results verify the significance of "high-risk features" used by current staging systems while highlighting additional features that may have prognostic value. This study may be used to refine current staging systems, improve early detection, and optimize management for these aggressive tumors.

Clinical Presentations of Melanoma in African Americans, Hispanics, and Asians.

BACKGROUND: Skin cancer has traditionally been studied in Caucasian skin. Although it does occur with increased relative frequency in Caucasians, patients with skin of color suffer from elevated morbidity and mortality when diagnosed with skin cancer. OBJECTIVE: To detail the unique demographic, clinical, and genetic features of melanoma in patients with skin of color, including Hispanic, African American, and Asian patients. MATERIALS AND METHODS: A PubMed search was conducted spanning dates 1947 to June 2017. A total of 246 articles were screened, from which 69 were included in this review. RESULTS: Relative to Caucasians, melanoma has unique demographic, clinical, and genetic features in African Americans, Hispanics, and Asians that include gender and subtype predominance. CONCLUSION: Familiarization with these unique presentations of skin cancer in skin of color is imperative to accurate identification and treatment of cutaneous malignancies in these populations and ultimately to improved disease-related outcomes.

In vivo selective expression of thyroid hormone receptor α1 in endothelial cells attenuates myocardial injury in experimental myocardial infarction in mice.

Ischemic heart disease (IHD) is the single most common cause of death. New approaches to enhance myocardial perfusion are needed to improve outcomes for patients with IHD. Thyroid hormones (TH) are known to increase blood flow; however, their usefulness for increasing perfusion in IHD is limited because TH accelerates heart rate, which can be detrimental. Therefore, selective activation of TH effects is desirable. We hypothesized that cell-type-specific TH receptor (TR) expression can increase TH action in the heart, while avoiding the negative consequences of TH treatment. We generated a binary transgenic (BTG) mouse that selectively expresses TRα1 in endothelial cells in a tetracycline-inducible fashion. In BTG mice, endothelial TRα1 protein expression was increased by twofold, which, in turn, increased coronary blood flow by 77%, coronary conductance by 60%, and coronary reserve by 47% compared with wild-type mice. Systemic blood pressure was decreased by 20% in BTG mice after TRα1 expression. No effects on heart rate were observed. Endothelial TRα1 expression activated AKT/endothelial nitric oxide synthase pathway and increased A2AR adenosine receptor. Furthermore, hearts from BTG mice overexpressing TRα1 that were submitted to 20 min ischemia and 20 min reperfusion showed a 20% decline in left ventricular pressure (LVP) compared with control mice where LVP was decreased by 42%. Studies using an infarction mouse model demonstrated that endothelial overexpression of TRα1 decreased infarct size by 45%. In conclusion, selective expression of TRα1 in endothelial cells protects the heart against injury after an ischemic insult and does not result in adverse cardiac or systemic effects.