A systematic study of the contribution of counting statistics to the final lineal energy uncertainty in microdosimetry.

Objectives.Microdosimetry is proving to be a reliable and powerful tool to be applied in different fields such as radiobiology, radiation protection and hadron therapy. However, accepted standard protocols and codes of practice are still missing. With this regard, a systematic and methodical uncertainty analysis is fundamental to build an accredited uncertainty budget of practical use. This work studied the contribution of counting statistics (i.e. number of events collected) to the final frequency-mean and dose-mean lineal energy uncertainties, aiming at providing guidelines for good experimental and simulation practice. The practical limitation of current technologies and the non-negligible probability of nuclear reactions require careful considerations and nonlinear approaches.Approach.Microdosimetric data were obtained by means of the particle tracking Monte Carlo code Geant4. The uncertainty analysis was carried out relying on a Monte Carlo based numerical analysis, as suggested by the BIPM's 'Guide to the expression of uncertainty in measurement'. Final uncertainties were systematically investigated for proton, helium and carbon ions at an increasing number of detected events, for a range of different clinical-relevant beam energies.Main results.Rare events generated by nuclear interactions in the detector sensitive volume were found to massively degrade microdosimetric uncertainties unless a very high statistics is collected. The study showed an increasing impact of such events for increasing beam energy and lighter ions. For instance, in the entrance region of a 250 MeV proton beam, about 5 ∗ 107events need to be collected to obtain a dose-mean lineal energy uncertainty below 10%.Significance.The results of this study help define the necessary conditions to achieve appropriate statistics in computational microdosimetry, pointing out the importance of properly taking into account nuclear interaction events. Their impact on microdosimetric quantities and on their uncertainty is significant and cannot be overlooked, particularly when characterising clinical beams and radiobiological response. This work prepared the ground for deeper investigations involving dedicated experiments and for the development of a method to properly evaluate the counting statistics uncertainty contribution in the uncertainty budget, whose accuracy is fundamental for the clinical transition of microdosimetry.

Clinical and Dermoscopic Factors for the Identification of Aggressive Histologic Subtypes of Basal Cell Carcinoma.

BACKGROUND: Infiltrative basal cell carcinoma (BCC) has a higher risk for post-surgical recurrence as compared to the most common low-aggressive superficial and nodular BCC. Independent diagnostic criteria for infiltrative BCC diagnosis have not been still defined. Improving the pre-surgical recognition of infiltrative BCC might significantly reduce the risk of incomplete excision and recurrence. OBJECTIVE: The aim of this study is to define clinical and dermoscopic criteria that can differentiate infiltrative BCC from the most common low-aggressive superficial and nodular BCC. METHODS: Clinical and dermoscopic images of infiltrative, superficial, and nodular BCC were retrospectively retrieved from our database and jointly evaluated by two experienced dermoscopists, blinded for the histologic subtype. Pairwise comparisons between the three histologic subtypes were performed and multivariable logistic regression models were constructed in order to define clinical and dermoscopic factors independently associated with each subtype. To validate our findings, two experienced dermoscopists not previously involved in the study were asked to evaluate clinical and dermoscopic images from an external dataset, guessing the proper BCC subtype between infiltrative, nodular and superficial, before and after being provided with the study results. RESULT: A total of 481 histopathologically proven BCCs (51.4% nodular, 33.9% superficial, and 14.8% infiltrative) were included. We found that infiltrative BCC mostly appeared on the head and neck as an amelanotic hypopigmented plaque or papule, displaying ulceration on dermoscopic examination, along with arborizing and fine superficial telangiectasia. Shiny white structures were also frequently observed. Multivariate regression analysis allowed us to define a clinical-dermoscopic profile of infiltrative BCC. CONCLUSIONS: We defined the clinical-dermoscopic profile of infiltrative BCC, allowing to differentiate this variant from superficial and nodular BCC. This will improve pre-surgical recognition of infiltrative forms, reducing the risk for post-surgical recurrence.