Dendritic cell-based autologous tumor vaccines for head and neck squamous cell carcinoma.

BACKGROUND: An autologous vaccine of apoptotic tumor cells (ATCs) and dendritic cells (DCs) was administered to patients with stage III/IV head and neck squamous cell carcinoma (HNSCC) to study safety and feasibility. METHODS: Autologous DCs were generated from monocytes, loaded with ATCs, and delivered intranodally. Delayed-type hypersensitivity (DTH) and immunological endpoints were measured prevaccination and postvaccination. Clinical follow-up was required. RESULTS: Tumors obtained from 30 patients yielded 2 × 10(6) to 2 × 10(8) tumor cells. Only 19 of 30 (63%) were sterile. Ten of 30 patients (33%) had ≥1 × 10(7) sterile tumor cells required for vaccine production. Eight of 10 patients had positive recall DTH. Five of 10 patients were leukapheresed to generate DCs. Four of 5 patients were vaccinated. ATC-reactive T cells were detected in 3 of 4 patients. All 4 patients survived >5 years. The trial failed to enroll the projected 12 patients and was terminated. CONCLUSION: This vaccine was safe and immunogenic but feasible only in patients with HNSCC with positive prevaccine DTH and ≥1 × 10(7) sterile tumor cells. All vaccinated patients were long-term disease-free survivors. © 2015 Wiley Periodicals, Inc. Head Neck 38: E494-E501, 2016.

Intratumoral epidermal growth factor receptor antisense DNA therapy in head and neck cancer: first human application and potential antitumor mechanisms.

PURPOSE: Squamous cell carcinoma of the head and neck (SCCHN) is characterized by upregulation of the epidermal growth factor receptor (EGFR). We developed a novel strategy to target EGFR by using a therapeutic gene that consisted of an EGFR antisense (AS) gene sequence under U6 promoter control. A phase I clinical trial was conducted to evaluate the safety and biologic effects of EGFR AS. PATIENTS AND METHODS: Patients with advanced SCCHN who were refractory to standard therapies and who had at least one assessable and accessible lesion were enrolled. The EGFR AS dose was escalated in successive cohorts (six dose levels; 60 to 1,920 microg/injection). Patients received four weekly intratumoral EGFR AS injections. Tumor biopsies were performed before and after completion of therapy. Treatment response was assessed by tumor volume measurements (positron emission tomography/computed tomography), and levels of target proteins were assessed by immunohistochemistry. RESULTS: Seventeen assessable patients were treated. No grades 3 to 4 or dose-limiting toxicities were noted, and a maximum-tolerated dose was not reached. Five patients (29%) achieved a clinical response, which included two complete responses (CRs) and three partial responses (PRs); two additional patients had stable disease (SD) as the best response. Patients with disease control (CR + PR + SD) had tumors with higher EGFR and lower STAT3 expression at baseline compared with patients who had progressive disease (P = .0312 and P = .095, respectively). CONCLUSION: Intratumoral EGFR AS was safe and resulted in antitumor activity in patients with advanced SCCHN. Baseline levels of high EGFR and low STAT3 may be associated with antitumor effects.

State Behavioral Scale: a sedation assessment instrument for infants and young children supported on mechanical ventilation.

OBJECTIVE: To develop and test the reliability and validity of the State Behavioral Scale for use in describing sedation/agitation levels in young intubated patients supported on mechanical ventilation. DESIGN: : In this prospective, psychometric evaluation, pairs of trained pediatric critical care nurse evaluators simultaneously and independently assessed a convenience sample of pediatric intensive care unit patients along eight state/behavioral dimensions and a numeric rating scale (NRS) of 0 (extremely sedated) to 10 (extremely agitated). The eight dimensions were derived from the sedation/agitation literature and expert opinion and included respiratory drive, response to ventilation, coughing, best response to stimulation, attentiveness to careprovider, tolerance to care, consolability, and movement after consoled, each with 3-5 levels. SETTING: An 18-bed pediatric medical-surgical intensive care unit and 26-bed pediatric cardiovascular intensive care unit in a university-affiliated academic children's hospital. PATIENTS: A total of 91 intubated mechanically ventilated patients 6 wks to 6 yrs of age provided a median of two observations (interquartile range, 1-3) for a total of 198 sets of observations. Excluded were postoperative patients or those receiving neuromuscular blockade. INTERVENTIONS: Patients were observed for 1 min, and then incremental levels of stimulation were applied until patient response. After 2 mins of consoling, the state behavioral assessment and NRS were completed. MEASUREMENTS: Weighted kappa and intraclass coefficients were generated to assess interrater reliability of the eight dimension and NRS ratings. Distinct state behavior profiles were empirically identified from the dimension ratings using hierarchical cluster analysis using a squared Euclidean distance measure and between-groups linkage. Construct validity of these profiles was assessed by comparing group mean NRS scores using one-way analysis of variance. MAIN RESULTS: Weighted kappa scores for all 198 dimension ratings ranged from .44 to .76, indicating moderate to good interrater reliability. The intraclass coefficient of .79 was high for NRS ratings. Cluster analysis revealed five distinct state profiles, with mean NRS ratings of 1.1, 2.5, 4.0, 5.3, and 7.6, all of which differed significantly from each other (F = 75.8, p < .001), supporting the profiles' construct validity. CONCLUSIONS: Based on empirically derived state behavior profiles, we have constructed the State Behavioral Scale to allow systematic description of the sedation-agitation continuum in young pediatric patients supported on mechanical ventilation. Further studies including prospective validation and describing the effect of State Behavioral Scale implementation on clinical outcomes, including the quality of sedation and length of mechanical ventilation, are warranted.

Assessing the effectiveness of food worker training in Florida: opportunities and challenges.

The task of measuring the effectiveness of food worker training has historically met with many challenges. This paper considers various approaches and utilizes trends in foodborne-outbreak contributing factors to evaluate a recent change in Florida's food worker training. Results show that subsequent to training, the relative incidence of many factors that contribute to foodborne outbreaks actuay increased, while the relative incidence of other factors decreased. The overall rate of foodborne outbreaks associated with the contributing factors that the authors studied decreased subsequent to training. Results of this analysis must be interpreted with caution because of multiple confounding factors; however, it became apparent that both increases and decreases in the occurrence of contributing factors could be used to focus future training material on areas of food handler practices in which it is needed. Further work needs to be done to estabish the most useful methods and approaches for assessing effectiveness and hence the public health impact of food worker training.