Safety and Efficacy of Stereotactic Ablative Radiation Therapy for Renal Cell Carcinoma Extracranial Metastases.

PURPOSE: Renal cell carcinoma is refractory to conventional radiation therapy but responds to higher doses per fraction. However, the dosimetric data and clinical factors affecting local control (LC) are largely unknown. We aimed to evaluate the safety and efficacy of stereotactic ablative radiation therapy (SAbR) for extracranial renal cell carcinoma metastases. METHODS AND MATERIALS: We reviewed 175 metastatic lesions from 84 patients treated with SAbR between 2005 and 2015. LC and toxicity after SAbR were assessed with Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Predictors of local failure were analyzed with χ2, Kaplan-Meier, and log-rank tests. RESULTS: In most cases (74%), SAbR was delivered with total doses of 40 to 60 Gy, 30 to 54 Gy, and 20 to 40 Gy in 5 fractions, 3 fractions, and a single fraction, respectively. The median biologically effective dose (BED) using the universal survival model was 134.5 Gy. The 1-year LC rate after SAbR was 91.2% (95% confidence interval, 84.9%-95.0%; median follow-up, 16.7 months). Local failures were associated with prior radiation therapy (hazard ratio [HR], 10.49; P<.0001), palliative-intent radiation therapy (HR, 4.63; P=.0189), spinal location (HR, 5.36; P=.0041), previous systemic therapy status (0-1 vs >1; HR, 3.52; P=.0217), and BED <115 Gy (HR, 3.45; P=.0254). Dose received by 99% of the target volume was the strongest dosimetric predictor for LC. Upon multivariate analysis, dose received by 99% of the target volume greater than BED of 98.7 Gy and systemic therapy status remained significant (HR, 0.12 and 3.64, with P=.0014 and P=.0472, respectively). Acute and late grade 3 toxicities attributed to SAbR were observed in 3 patients (1.7%) and 5 patients (2.9%), respectively. CONCLUSIONS: SAbR demonstrated excellent LC of metastatic renal cell carcinoma with a favorable safety profile when an adequate dose and coverage were applied. Multimodality treatment with surgery should be considered for reirradiation or vertebral metastasis. A higher radiation dose may be required in patients who received previous systemic therapies.

Exposure of Acinetobacter baylyi ADP1 to the biocide chlorhexidine leads to acquired resistance to the biocide itself and to oxidants.

OBJECTIVES: The aim of this study was to determine the effect of exposure to sublethal concentrations of chlorhexidine on oxidative stress protection by Acinetobacter baylyi ADP1. METHODS: ADP1 cultures were exposed to sublethal concentrations of chlorhexidine prior to being challenged with lethal concentrations of chlorhexidine itself and by oxidants. Oxidant-sensitive dyes and a flow cytometer were used to measure the formation of reactive oxygen species. The role of efflux pumps in chlorhexidine resistance was investigated using a specific inhibitor. RESULTS: Exposure of ADP1 to low concentrations of chlorhexidine induced adaptive and cross-protective responses to chlorhexidine and oxidants (H(2)O(2) and a superoxide anion generator), respectively. Chlorhexidine treatment of ADP1 resulted in the formation of H(2)O(2) and superoxide anions that are probably responsible for the cross-protection against oxidants. CONCLUSIONS: Exposure of ADP1 to sublethal concentrations of chlorhexidine confers inducible resistance to lethal concentrations of chlorhexidine itself and to oxidants. An important link was demonstrated between exposure to a biocide and the gaining of resistance to both the biocide and oxidative stress.