Dose distribution changes with shielding disc misalignments and wrong orientations in breast IOERT: a Monte Carlo - GEANT4 and experimental study.

One of the most relevant risks in breast intraoperative electron radiotherapy (IOERT) is the incorrect positioning of the shielding disc. If such a setup error occurs, the treatment zone could receive a nonuniform dose delivery, and a considerable part of the electron beam could hit - and irradiate - the patient's healthy tissue. However misalignment and tilt angle of the shielding disc can be evaluated, but it is not possible to measure the corresponding in vivo dose distribution. This led us to develop a simulation using the Geant4 Monte Carlo toolkit to study the effects of disc configuration on dose distribution. Some parameters were investigated: the shielding factor (SF), the radiation back scattering factor (BSF), the volume-dose histogram in the treatment zone, and the maximum leakage dose (MLD) in normal tissue. A lateral shift of the disc (in the plane perpendicular to the beam axis) causes a decrease in SF (from 4% for a misalignment of 5 mm to 40% for a misalignment of 40 mm), but no relevant dose variations were found for a tilt angle until 10°. In the same uncorrected disc positions, the BSF shows no significant change. MLD rises to 3.45 Gy for a 14 mm misalignment and 4.60 Gy for 30° tilt angle when the prescribed dose is 21 Gy. The simulation results are compared with the experimental ones, and allow an a posteriori estimation of the dose distribution in the breast target and underlying healthy tissue. This information could help the surgical team choose a more correct clinical setup, and assist in quantifying the degree of success or failure of an IOERT breast treatment.

Gene Expression Profiling of MCF10A Breast Epithelial Cells Exposed to IOERT.

BACKGROUND/AIM: Intraoperative electron radiation therapy (IOERT) is a therapeutic approach that delivers a single high dose of ionizing radiation (IR) directly to the tumor bed during cancer surgery. The main goal of IOERT is to counteract tumor growth by acting on residual cancer cells as well as to preserve healthy surrounding tissue from the side-effects of radiation therapy. The radiobiology of the healthy tissue response to IR is a topic of interest which may contribute to avoiding impairment of normal tissue and organ function and to reducing the risks of secondary cancer. The purpose of the study was to highlight cell and gene expression responses following IOERT treatment in the human non-tumorigenic MCF10A cell line in order to find new potential biomarkers of radiosensitivity/radioresistance. MATERIAL AND METHODS: Gene-expression profiling of MCF10A cells treated with 9 and 23 Gy doses (IOERT boost and exclusive treatment, respectively), was performed by whole-genome cDNA microarrays. Real-time quantitative reverse transcription (qRT-PCR), immunofluorescence and immunoblot experiments were carried out to validate candidate IOERT biomarkers. Clonogenic tests and morphological evaluations to examine cellular effects induced by radiation were also conducted. RESULTS: The study revealed a dose-dependent gene-expression profile and specific key genes that may be proposed as novel markers of radiosensitivity. Our results show consistent differences in non-tumorigenic cell tolerance and in the molecular response of MCF10A cells to different IOERTs. In particular, after 9 Gy of exposure, the selection of a radioresistant cell fraction was observed. CONCLUSION: The possibility of clarifying the molecular strategies adopted by cells in choosing between death or survival after IR-induced damage opens-up new avenues for the selection of a proper personalized therapy schedule.

High-intensity focused ultrasound plus concomitant radiotherapy: a new weapon in oncology?

The potential impact of high-intensity focused ultrasound (HIFU) to general medicine and oncology seems very high. However, while in the research area, the development of this technique is very rapid and unchallenged. The direct application of HIFU to human tumour therapy is hampered by various technical difficulties, which may confine its role to a marginal device in the surgery armamentarium. To deploy the full potential of focused ultrasound in oncology, it seems necessary to review the basic relationship between HIFU and external beam radiotherapy. This is the aim of the present work.