Heterogeneous Versus Homogeneous Radiation Dose Calculations of Twice-Daily Fractionation in Small Cell Lung Carcinoma.

Purpose The standard radiotherapy regimen for small cell lung cancer (SCLC) was determined using dose calculations without corrections for tissue heterogeneity, while modern treatments are planned using algorithms accounting for tissue heterogeneity. We assessed differences in dose delivered using heterogeneous and homogeneous dose calculations in a cohort of patients treated for limited-stage small cell lung cancer (LS-SCLC). Methods This is a retrospective analysis of 35 patients (three-dimensional conformal radiation therapy (3D-CRT), n = 22; intensity-modulated radiation therapy (IMRT), n = 13) with LS-SCLC treated with chemoradiotherapy from 2011 to 2017. Treatment plans were developed in the Eclipse Treatment Planning System (TPS) version 13.6 using the Analytical Anisotropic Algorithm (AAA). Two plans were generated for each patient with one using the unit relative electron density and the other maintaining the same monitor units (MUs) with tissue density corrections. The prescription was 45 Gy in 30 fractions of 1.5 Gy delivered twice daily. Individuals who underwent replanning within the same treatment course were evaluated using a separate corrected and uncorrected plan sum. Variations greater than 5% in dose to the tumor or organs at risk were considered clinically relevant. A two-sided paired t-test was used to evaluate the statistical significance of the dosimetric differences. Results The percent dose difference between plans without tissue heterogeneity corrections to those with corrections resulted in an overall median difference of -3% (range: -15.1% to 9.6%; p < 0.01) for the dose covering 95% of the planning target volume (PTV D95) and was -5.6% (range: -17.3% to 5.4%; p < 0.01) for lung volume receiving ≥20 Gy (lung V20). For 3D-CRT, the median difference for the PTV D95 was -0.1% (range: -4.7% to 9.6%; p = 0.62) and the lung V20 was -4.2% (range: -9.4 to 5.4; p < 0.01). For IMRT, the median difference for the PTV D95 was -10.0% (range: -15.1% to -5.3%; p < 0.01) and the lung V20 was -8.9% (range: -17.3 to -3.5; p < 0.01). Conclusion Traditional planning without tissue heterogeneity corrections results in an overall decrease in the dose delivered to the target compared with those that incorporate tissue heterogeneity corrections. These differences are modest for 3D treatment plans but may result in clinically relevant differences for the IMRT cohort (>5% deviation).

A comparative evaluation of adverse platelet outcomes among Veterans' Affairs patients receiving linezolid or vancomycin.

OBJECTIVES: The primary objectives were to compare the incidences of severe thrombocytopenia, critical thrombocytopenia and a relative decline in platelets from baseline (≥50% decline) between patients receiving linezolid and those receiving vancomycin. The secondary objective was to assess the relationship between vancomycin trough concentration and adverse platelet outcomes. METHODS: A matched cohort study was performed at the Upstate New York Veterans' Affairs Healthcare Network from January 2005 until February 2008. Eligibility criteria were: (i) receipt of linezolid or vancomycin therapy for ≥48 h; (ii) initiation of therapy as an inpatient; and (iii) baseline platelets available for evaluation. Patients who received linezolid were matched 1:1 to patients who received vancomycin. Cumulative incidences and times to event for (i) platelet count ≤50,000 cells/mm(3), (ii) platelet count ≤20,000 cells/mm(3) and (iii) ≥50% decline in platelets from baseline were evaluated. Multivariate analyses were performed. RESULTS: The study included 502 patients (251 matched pairs). The occurrences of platelet counts ≤50,000 cells/mm(3) and ≤20,000 cells/mm(3) did not differ significantly between linezolid and vancomycin patients. A ≥50% decline in platelets from baseline was observed in 78 (31.1%) patients receiving vancomycin and 43 (17.1%) patients receiving linezolid (risk ratio 0.55; 95% CI 0.40-0.77). A clear exposure-response relationship was observed between vancomycin trough concentration and ≥50% decline in platelets from baseline. CONCLUSIONS: The incidence of thrombocytopenia was low and did not differ significantly among vancomycin and linezolid patients.

Topical delivery of lycopene using microemulsions: enhanced skin penetration and tissue antioxidant activity.

Topical delivery of lycopene is a convenient way to supplement cutaneous levels of antioxidants. In this study, lycopene was incorporated (0.05%, w/w) in two microemulsions containing BRIJ-propylene glycol (2:1, w/w, surfactant blend) but different oil phases: mono/diglycerides of capric and caprylic acids (MG) or triglycerides of the same fatty acids (TG). Microemulsions containing MG and TG were isotropic, fluid, and clear, with internal phase diameters of 27 and 52 nm, respectively. Both MG- or TG-containing microemulsions markedly increased lycopene penetration in the stratum corneum (6- and 3.6-fold, respectively) and in viable layers of porcine ear skin (from undetected to 172.6 +/- 41.1 and 103.1 +/- 7.2 ng/cm(2), respectively) compared to a control solution. To assure that lycopene delivered to the skin was active, the antioxidant activity of skin treated with MG-containing microemulsion was determined by CUPRAC assay, and found to be 10-fold higher than untreated skin. The cytotoxicity of MG-containing microemulsion in cultured fibroblasts was similar to propylene glycol (considered safe) and significantly less than of sodium lauryl sulfate (a moderate-to-severe irritant) at 1-50 microg/mL. These results demonstrate that the MG-containing microemulsion is an efficient and safe system to increase lycopene delivery to the skin and the antioxidant activity in the tissue.