Efficacy of Etanercept in the Treatment of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis.

It has been suggested that the use of etanercept for treatment of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) might provide improved mortality benefit and decreased skin healing times. This retrospective study compared the use of single-dose subcutaneous etanercept to intravenous immunoglobulin (IVIG) and supportive care alone. Thirteen patients were treated with a single dose (50 mg) of subcutaneous etanercept. Results of this study support the use of etanercept as a potentially beneficial agent in the treatment of SJS/TEN.

Sonic Hedgehog Pathway Inhibition in the Treatment of Advanced Basal Cell Carcinoma.

OPINION STATEMENT: Advanced basal cell carcinoma (BCC) represents a small proportion of BCCs that are not amenable to standard therapies due to lack of efficacy, high recurrence risk, and excessive morbidity. Implication of the Sonic hedgehog (Shh) pathway in the development of BCC has led to the development of systemic Shh pathway inhibitors, providing patients with advanced BCCs new treatment options and improved survival. There are currently two Food and Drug Administration (FDA)-approved Shh inhibitors, vismodegib and sonidegib, for advanced basal cell carcinomas. Vismodegib has approval for locally advanced BCCs (laBCC) and metastatic BCC (mBCC), while sonidegib has approval for laBCC. These agents have also been used for prevention in nevoid basal cell carcinoma syndrome and as neoadjuvant therapy before surgery, and we feel that there is a growing role of Shh inhibitors in these settings. Head-to-head randomized controlled trials comparing vismodegib to sonidegib are lacking. Adverse events can limit the utility of these medications by leading to treatment discontinuation in a large proportion of patients, and it is thus essential that prescribers be able to anticipate and manage the most frequent side effects of muscle spasms, alopecia, dysgeusia, nausea, and weight loss. Other Shh inhibitors, including the antifungal itraconazole, have been investigated in small trials, but further research is needed before recommending their routine clinical use. Additionally, there are several new agents under investigation that may have improved efficacy for resistant tumors by utilizing different mechanisms of action than the two currently approved medications.

A case of atezolizumab-induced photodistributed bullous pemphigoid.

Immunotherapy has revolutionized cancer therapy in recent years but is associated with unique immunologically mediated adverse effects. Immunotherapy-induced bullous pemphigoid (BP) is an uncommon but established reaction that portends significant management implications as in most instances systemic treatment is required. We report a case of immunotherapy-associated BP in a marked photodistribution, highlighting the diverse clinical presentations of this eruption.

The use of etanercept for treatment of toxic epidermal necrolysis when toxic shock syndrome is in the differential.

Toxic shock syndrome (TSS) can sometimes mimic Steven Johnsons syndrome/toxic epidermal necrolysis (SJS/TEN). Tumor necrosis factor (TNF) alpha is thought to play a role in the pathogenesis of both TSS and SJS/TEN. Etanercept, a TNF-alpha inhibitor has been recently shown to treat and decrease mortality of SJS/TEN. We report a 51-year-old female with history of SJS presenting with painful skin and bullae 2 days following cystoscopy with botulinum toxin injection into the bladder. Due to initial concern for SJS/TEN, the patient was treated with 50 mg of subcutaneous etanercept. Punch biopsies were not consistent with SJS, and the patient fulfilled five out of five criteria for a confirmed case of TSS. The patient ultimately had a favorable outcome despite etanercept treatment. Ultimately, TNF-alpha antagonists are an emerging therapy to treat SJS/TEN, and are unlikely to worsen TSS prognosis. Given that etanercept can be used to successfully treat SJS/TEN and TNF-alpha levels are elevated in TSS, if a dermatologist chooses to treat TEN with etanercept, consideration of TSS on the differential should not necessarily exclude etanercept as a reasonable treatment option.

Factors affecting survival and locoregional control in head and neck cSCCA with nodal metastasis.

OBJECTIVES: To determine factors affecting locoregional control (LRC) and disease-specific survival (DSS) in patients presenting with regionally metastatic cutaneous squamous cell carcinoma (cSCCA) of the head and neck. STUDY DESIGN: Retrospective review. METHODS: Upon review of institutional pathology database to identify patients with metastatic cSCCA, 62 subjects met the inclusion criteria between 2009 to 2012. Cox proportional hazard ratios for DSS and LRC were calculated for tumor, patient, lymph node, and treatment variables. These factors included primary site, primary tumor grade, primary tumor perineural invasion, extent of primary tumor invasion, age, immune status, parotid nodal status, invasion of facial nerve by parotid tumor, cervical nodal status, extracapsular spread, number of nodes involved, adjuvant radiation therapy, and chemotherapy. All variables were analyzed to determine impact on LRC and DSS. A disease-specific Kaplan-Meier curve was determined for the entire cohort. RESULTS: Five-year survival was 56% for all patients. The presence of extracapsular spread (ECS) and bone involvement of the primary tumor site resulted in statistically significant decreases in DSS (hazard ratio (HR) 41.3 and 270, respectively; P = 0.02 and P = 0.008, respectively) and LRC (HR 8.41 and 11.1, respectively; P = 0.005 and P = 0.04, respectively). The remaining factors had no statistically significant effect on DSS or LRC. CONCLUSION: The presence of ECS in the metastatic lymph node and of bone invasion by the primary tumor appear to be important to the outcome of patients with metastatic cSCCA. These factors should be considered when developing multidisciplinary care plans and future investigations. LEVEL OF EVIDENCE: 4. Laryngoscope, 1881-1886, 2018.

Initial clinical findings of a mathematical model to predict survival of head and neck cancer.

OBJECTIVES: (1) Identify clinical features that impact survival for head and neck cancer. (2) Determine the individual contribution to mortality of significant clinical features. (3) Develop a web-based calculator to integrate clinical features and predict survival outcome for individual patients. STUDY DESIGN: Analysis of a national cancer database. We fit patient data to the binary-biological model of cancer lethality, a mathematical model designed to predict cancer outcome. The model predicts the risk of cancer death, using information on tumor size, nodal status, and other prognostic factors. SUBJECTS AND METHODS: Analysis was carried out on a cohort of ~50,000 patients with head and neck cancer from the Survey, Epidemiology and End-Results (SEER) 2009 data set and validated with a cohort of ~1300 patients from an institutional Massachusetts General Hospital/Massachusetts Eye and Ear Infirmary database. We developed a web-based calculator written in JavaScript, PHP, and HTML. RESULTS: The risk of death due to head and neck cancer increases monotonically with tumor size. Each positive lymph node is associated with ~14% extra risk of death. Anatomical site, age, race, tumor extension, N stage, and extracapsular spread contribute to mortality. The lethal impact of these prognostics factors can be accurately estimated by the Size + Nodes + PrognosticMarkers (SNAP) method. CONCLUSIONS: This predictive cancer model and web-based calculator provide a basis for estimating the risk of death for head and neck cancer patients by assigning values to the lethal contributions of tumor size, number of positive nodes, anatomical site, tumor extension, N stage, extracapsular spread, age at diagnosis, and race.