Influence of gray level discretization on radiomic feature stability for different CT scanners, tube currents and slice thicknesses: a comprehensive phantom study, Acta Oncologica, 56:11, 1544-1553, DOI: 10.1080 Background: Radiomic analyses of CT images provide prognostic information that can potentially be used for personalized treatment. However, heterogeneity of acquisition-and reconstruction protocols influences robustness of radiomic analyses. The aim of this study was to investigate the influence of different CT-scanners, slice thicknesses, exposures and gray-level discretization on radiomic feature values and their stability. Material and methods: A texture phantom with ten different inserts was scanned on nine different CT-scanners with varying tube currents. Scans were reconstructed with 1.5 mm or 3 mm slice thickness. Image pre-processing comprised gray-level discretization in ten different bin widths ranging from 5 to 50 HU and different resampling methods (i.e., linear, cubic and nearest neighbor interpolation to 1 Â 1 Â 3 mm 3 voxels) were investigated. Subsequently, 114 textural radiomic features were extracted from a 2.1 cm 3 sphere in the center of each insert. The influence of slice thickness, exposure and bin width on feature values was investigated. Feature stability was assessed by calculating the concordance correlation coefficient (CCC) in a test-retest setting and for different combinations of scanners, tube currents and slice thicknesses. Results: Bin width influenced feature values, but this only had a marginal effect on the total number of stable features (CCC > 0.85) when comparing different scanners, slice thicknesses or exposures. Most radiomic features were affected by slice thickness, but this effect could be reduced by resampling the CT-images before feature extraction. Statistics feature 'energy' was the most dependent on slice thickness. No clear correlation between feature values and exposures was observed. Conclusions: CT-scanner, slice thickness and bin width affected radiomic feature values, whereas no effect of exposure was observed. Optimization of gray-level discretization to potentially improve prognostic value can be performed without compromising feature stability. Resampling images prior to feature extraction decreases the variability of radiomic features.

Purpose: Our purpose was to report the feasibility and safety of diffusing alpha-emitter radiation therapy (DaRT), which entails the interstitial implantation of a novel alpha-emitting brachytherapy source, for the treatment of locally advanced and recurrent squamous cancers of the skin and head and neck. Methods and Materials: This prospective first-inhuman , multicenter clinical study evaluated 31 lesions in 28 patients. The primary objective was to determine the feasibility and safety of this approach, and the secondary objectives were to evaluate the initial tumor response and local progression-free survival. Eligibility criteria included all patients with biopsy-proven squamous cancers of the skin and head and neck with either primary tumors or recurrent/previously treated disease by either surgery or prior external beam radiation therapy; 13 of 31 lesions (42%) had received prior radiation therapy. Toxicity was evaluated according to the Common Terminology Criteria for Adverse Events version 4.03. Tumor response was assessed at 30 to 45 days at a follow-up visit using the Response Evaluation Criteria in Solid Tumors, version 1.1. Median follow-up time was 6.7 months. Results: Acute toxicity included mostly local pain and erythema at the implantation site followed by swelling and mild skin ulceration. For pain and grade 2 skin ulcerations, 90% of patients had resolution within 3 to 5 weeks. Complete response to the Ra-224 DaRT treatment was observed in 22 lesions (22/28; 78.6%); 6 lesions (6/28, 21.4%) manifested a partial response (>30% tumor reduction). Among the 22 lesions with a complete response, 5 (22%) developed a subsequent local relapse at the site of DaRT implantation at a median time of 4.9 months (range, 2.43-5.52 months). The 1-year local progression-free survival probability at the implanted site was 44% overall (confidence interval [CI], 20.3%-64.3%) and 60% (95% CI,

Purpose: Alpha particle treatments could enhance the probability of an immune response, which can lead to abscopal effects (AE). We report a case of a patient affected by multiple cutaneous squamous cell carcinoma (cSCC). After the treatment with diffusing alpha emitters radiation therapy (DaRT) of one lesion, an AE was observed on at least two distant ones.Material and methods: We investigated a case of a 65-year-old female patient with multiple synchronous lesions of the skin of lower limbs confirmed by a biopsy. Patient was enrolled in a clinical trial N.CTP-SCC-00 (NCT03015883), with the objective to assess effectiveness of DaRT technique. DaRT is based on the insertion of locally 224 Ra-loaded seeds in a clinical target volume (CTV). Treatment plan with positron emission tomography/computed tomography (PET/CT) was used to entirely cover the CTV. Follow-up and biopsy evaluations were employed to outline the patient outcome.Results: We performed seeds implantation according to the Paris system. At 28 th day, an evident lesion shrinkage with a persistent minimal area of hyperkeratosis was noted. 76 days after implantation, a complete remission of the treated lesion was observed and an evident reduction of the area with two more distant lesion, which could be associated to an immune-mediated response. One year after the treatment, a complete remission of treated lesion was observed as well as spontaneous regression of untreated distant ones.Conclusions: In this study, we reported evidences of an AE in cSCC stimulated by radiation and possibly mediated by immune system. In the next DaRT treatments, our intent is to monitor T-lymphocytes variations in peripheral blood in order to demonstrate indirect activation of the immune system mediated by radiation also in patients with solitary lesions, in which, by definition, an AE cannot be observed.