Surface doses of flattening filter free beams with volumetric modulated arc therapy dose delivery for breast cancer

Background and purpose: Flattening filter free (FFF) beams enable high-dose rate irradiations and have the potential to speed up breast cancer radiotherapy (RT) treatments. In this work the surface doses of FFF beams were studied with various treatment plans for breast cancer RT. The near surface dose distributions were compared to the ones delivered with conventional flattening filter (FF) beams and to the calculated dose distributions. Materials and methods: The study was executed with radiochromic films. In addition to one open field, four techniques were investigated: tangential open field, tangential IMRT (IMRT), tangential VMAT (tVMAT) and continuous VMAT (cVMAT) techniques, respectively. The dose distributions were calculated with commercial Monte Carlo (MC) algorithm with energies of 6 and 10 MV with both FF and FFF. The surface areas investigated were divided into depths of 0â2, 2â5 and 5â8 mm. Results: The largest deviations (on average 5.9%) between the measured and calculated doses were recorded at the most shallowest depths (0â2 mm). At deeper depths, the differences were on average 1.4% and always less than 6%. The measured near surface doses were slightly lower (4.6%) with modulated 6MVFFF beams than with the corresponding flattened beams and on the contrary with 10 MV the surface doses by FFF were slightly higher (2.8%). Conclusions: The studied MC calculation algorithm was accurate in determine the near surface doses. There was no significant difference in measured or calculated surface doses between FFF and FF beams. With respect to surface dose uniformity the VMAT techniques overall resulted in the most uniform dose distributions. Keywords: Radiotherapy, Breast cancer, VMAT, IMRT, Flattening filter free, FFF, Surface dose

Identification of a Genetic Variation in ERAP1 Aminopeptidase that Prevents Human Cytomegalovirus miR-UL112-5p-Mediated Immunoevasion

Herein, we demonstrate that HCMV miR-UL112-5p targets ERAP1, thereby inhibiting the processing and presentation of the HCMV pp65495-503 peptide to specific CTLs. In addition, we show that the rs17481334 G variant, naturally occurring in the ERAP1 3' UTR, preserves ERAP1 from miR-UL112-5p-mediated degradation. Specifically, HCMV miR-UL112-5p binds the 3' UTR of ERAP1 A variant, but not the 3' UTR of ERAP1 G variant, and, accordingly, ERAP1 expression is reduced both at RNA and protein levels only in human fibroblasts homozygous for the A variant. Consistently, HCMV-infected GG fibroblasts were more efficient in trimming viral antigens and being lysed by HCMV-peptide-specific CTLs. Notably, a significantly decreased HCMV seropositivity was detected among GG individuals suffering from multiple sclerosis, a disease model in which HCMV is negatively associated with adult-onset disorder. Overall, our results identify a resistance mechanism to HCMV miR-UL112-5p-based immune evasion strategy with potential implications for individual susceptibility to infection and other diseases