Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of nonmelanoma skin cancer.

Nonmelanoma skin cancers (NMSCs) are some of the most commonly diagnosed malignancies. In general, early-stage NMSCs have favorable outcomes; however, a small subset of patients develop resistant, advanced, or metastatic disease, or aggressive subtypes that are more challenging to treat successfully. Recently, immune checkpoint inhibitors (ICIs) have been approved by the US Food and Drug Administration (FDA) for the treatment of Merkel cell carcinoma (MCC), cutaneous squamous cell carcinoma (CSCC), and basal cell carcinoma (BCC). Although ICIs have demonstrated activity against NMSCs, the routine clinical use of these agents may be more challenging due to a number of factors including the lack of predictive biomarkers, the need to consider special patient populations, the management of toxicity, and the assessment of atypical responses. With the goal of improving patient care by providing expert guidance to the oncology community, the Society for Immunotherapy of Cancer (SITC) convened a multidisciplinary panel of experts to develop a clinical practice guideline (CPG). The expert panel drew on the published literature as well as their own clinical experience to develop recommendations for healthcare professionals on important aspects of immunotherapeutic treatment for NMSCs, including staging, biomarker testing, patient selection, therapy selection, post-treatment response evaluation and surveillance, and patient quality of life (QOL) considerations, among others. The evidence- and consensus-based recommendations in this CPG are intended to provide guidance to cancer care professionals treating patients with NMSCs.

The scientific rationale and development of an optimized dentifrice for the treatment of dentin hypersensitivity.

PURPOSE: To describe the development of a new dentin hypersensitivity treatment, Colgate Sensitive Maximum Strength dentifrice, containing 5% potassium nitrate as the anti-hypersensitivity active agent. The objective was to develop a home-use hypersensitivity dentifrice that would be superior to the market leader, improving on what is available, which also contains 5% potassium nitrate as the anti-hypersensitivity active agent. METHODS: In vivo (clinicals, taste evaluation and rat caries), in vitro (potassium flux) and analytical (rheology, dispensed volume, scanning electron microscopy, electron scanning chemical analysis and radioactive dentin abrasion) methods were performed. RESULTS: The objective was accomplished with the development of a new activated silica technology that resulted in enhanced potassium ion activity. In vitro documentation, supported by clinical studies, demonstrated that the resulting formula is more effective than the market leader for relief of hypersensitivity pain. Fast pain relief in less than 2 weeks and long-lasting protection against pain with regular use have also been clinically documented. Furthermore, FDA-required in vivo and in vitro studies indicate that this formula, which contains 0.45% stannous fluoride (1100 ppm fluoride) as the anti-caries active agent, is effective against caries. Good taste, acceptable rheology, acceptable abrasivity, and cosmetic and chemical stability have all been engineered into this unique dentin hypersensitivity treatment. In summary, a highly efficacious consumer friendly treatment for dentin hypersensitivity has been developed.

Anticaries efficacy of a new dentifrice for hypersensitivity.

PURPOSE: To evaluate the expected anticaries efficacy of a new dentifrice containing stannous fluoride as the anticaries agent and potassium nitrate as the antihypersensitivity agent using a series of laboratory and animal studies. METHODS: Four surrogate studies were performed in this assessment including fluoride uptake in sound enamel, enamel solubility reduction, fluoride bioavailability and animal caries. RESULTS: Each of these studies indicated the new dentifrice for hypersensitivity (Colgate Sensitive Maximum Strength) was effective in inhibiting the caries process. The data demonstrate that this new dentifrice is predicted to be highly effective against caries and equivalent to a positive control dentifrice.

Relationship between dentifrice fluoride concentration and clinical caries reduction.

PURPOSE: To review the published literature on clinical caries trials of fluoride dentifrices and to combine their results in order to evaluate the correlation between fluoride concentration in dentifrice formulations and their anticaries efficacy, i.e., the dose-response relationship. METHODS: All available dentifrice caries clinical trials reported in the literature of products having at least two fluoride concentrations greater than 0 ppm were reviewed, graphed and statistically analyzed. RESULTS: The evaluation supported a linear correlation between the fluoride concentration of dentifrices between 0 and 5000 ppm F and clinical caries efficacy.

The effects of outward forced convective flow on inward diffusion of potassium across human dentin.

PURPOSE: To measure the inward flux of potassium across human dentin disks, in vitro, in the absence and then in the presence of a simulated pulpal pressure (PP), before and after brushing with two desensitizing dentifrices. MATERIALS AND METHODS: Dentin discs were made from extracted unerupted third molars and etched with 6% citric acid to remove the smear layers. The hydraulic conductance (Lp or outward fluid movement) of the discs was measured before and after brushing for 2 minutes with two desensitizing dentifrices, Colgate Sensitive Maximum Strength or Sensodyne Fresh Mint, both dentifrices containing 5% potassium nitrate. The potassium flux was measured at a pressure of 0 cm H2O, and a simulated pulpal pressure of 20 cm H2O. RESULTS: The results showed the Colgate-brushed specimens had lower Lp (P < 0.05) than specimens brushed with Sensodyne or with saline. The Colgate-brushed specimens had a corresponding lower K+ flux, at a PP = 0 cm H2O, than specimens brushed with saline, but were not significantly different than specimens brushed with Sensodyne dentifrice. However, when the pressure was increased from 0 to 20 cm H2O, to simulate outward dentin fluid pressure, there were significant decreases in K+ flux across all three treatment groups, but the K+ flux of the Colgate-brushed specimens were affected the least, resulting in the Colgate-brushed specimens having significantly (P < 0.05) greater K+ fluxes than the saline or Sensodyne dentifrice-brushed groups. The magnitude of reduction in K+ flux in going from 0 cm H2O to 20 cm H2O was demonstrated to be linearly related to the magnitude of the Lp of the brushed specimens. Hence, a small Lp corresponded to a small reduction in K+ flux, and a correspondingly large K+ flux at 20 cm H2O. An explanation of this phenomenon is that a decrease in the Lp of dentin, produced by brushing, corresponds to a decreased outward dentin fluid flow. This lowers the outward K+ convective flow and also lowers the inward K+ diffusion. However, since the decrease of the outward K+ convective flow is greater than the decrease of the inward K+ diffusion, and the net flux is the algebraic sum of these two terms, the result is greater net inward K+ flux through the dentin. Therefore, the Colgate-brushed specimens, which exhibited the lowest Lp, provided the greatest inward K+ flux at simulated dentin fluid pressure.