Multicentric characterisation of lateral beam profiles generated by 6FFF beam of three 0.35 T MR-linac systems.

BACKGROUND: The physical characterisation of FFF-beam profiles in the presence of a magnetic field requires a new standardization procedure and formulation. PURPOSE: The aim of this multicentric experience is to propose new normalisation factors to allow for the calculation of standard parameters typical of flattened beams, such as dosimetric field size and penumbra, for a 6 MV FFF beam from an MR-linac. METHODS: The measurements were carried out on three ViewRay-MRIdiansystems. An equal set of measurements was acquired using the same equipment. Transverse beam profiles were acquired at seven different depthsand for six beam dimensions.The inflection point was estimated as the position of the maximum of a Gaussian fit obtained from the first derivative of the profiles. The position of the minimum and maximum points of the second derivative of the above Gaussian described the fall-off region, and the external peaks of the third derivative were considered as the in-field and out-field points. The profile normalisation was determined by imposing a 55% dose level at the inflection point and the renormalisation factors were calculated. RESULTS: The position of the inflection point, and the second and third derivatives peaks were analysed,and the renormalisation factors as a function of field size and depth were determined. The values of the unflatness and the slope have been calculated for different depths and field sizes. CONCLUSION: This study represents the first multi-centric evaluation of the profiles on different low-field MR-Linac systems and theset of renormalisation parameters to analyse the FFF-beam on that system was effectively proposed.

p53 Stabilization induces cell growth inhibition and affects IGF2 pathway in response to radiotherapy in adrenocortical cancer cells.

Adrenocortical carcinoma (ACC) is a very rare endocrine tumour, with variable prognosis, depending on tumour stage and time of diagnosis. However, it is generally fatal, with an overall survival of 5 years from detection. Radiotherapy usefulness for ACC treatment has been widely debated and seems to be dependent on molecular alterations, which in turn lead to increased radio-resistance. Many studies have shown that p53 loss is an important risk factor for malignant adrenocortical tumour onset and it has been reported that somatic mutations in TP53 gene occur in 27 to 70% of adult sporadic ACCs. In this study, we investigated the role of somatic mutations of the TP53 gene in response to ionizing radiation (IR). We studied the status of p53 in two adrenocortical cell lines, H295R and SW-13, harbouring non-functioning forms of this protein, owing to the lack of exons 8 and 9 and a point mutation in exon 6, respectively. Moreover, these cell lines show high levels of p-Akt and IGF2, especially H295R. We noticed that restoration of p53 activity led to inhibition of growth after transient transfection of cells with wild type p53. Evaluation of their response to IR in terms of cell proliferation and viability was determined by means of cell count and TUNEL assay.(wt)p53 over-expression also increased cell death by apoptosis following radiation in both cell lines. Moreover, RT-PCR and Western blotting analysis of some p53 target genes, such as BCL2, IGF2 and Akt demonstrated that p53 activation following IR led to a decrease in IGF2 expression. This was associated with a reduction in the active form of Akt. Taken together, these results highlight the role of p53 in response to radiation of ACC cell lines, suggesting its importance as a predictive factor for radiotherapy in malignant adrenocortical tumours cases.