BackgroundTo investigate the potential dosimetric and clinical benefits of Deep Inspiration Breath-Hold (DIBH) technique during radiotherapy of breast cancer compared with Free Breathing (FB).MethodsEight left-sided breast cancer patients underwent a supervised breath hold during treatment. For each patient, two CT scans were acquired with and without breath hold, and virtual simulation was performed for conventional tangential fields, utilizing 6 or 15 MV photon fields. The resulting dose–volume histograms were calculated, and the volumes of heart/lung irradiated to given doses were assessed. The left anterior descending coronary artery (LAD) mean and maximum doses were calculated, together with tumour control probability (TCP) and normal tissue complication probabilities (NTCP) for lung and heart.ResultsFor all patients a reduction of at least 16% in lung mean dose and at least 20% in irradiated pulmonary volumes was observed when DIBH was applied. Heart and LAD maximum doses were decreased by more than 78% with DIBH. The NTCP values for pneumonitis and long term cardiac mortality were also reduced by about 11% with DIBH. The NTCP values for pericarditis were zero for both DIBH and FB.ConclusionDelivering radiation in DIBH conditions the dose to the surrounding normal structures could be reduced, in particular heart, LAD and lung, due to increased distance between target and heart, and to reduced lung density.

Background Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cancer worldwide. They are typically characterized by a high incidence of local recurrence, which is the most common cause of death in HNSCC patients. TP53 is the most frequently mutated gene in HNSCC and patients carrying TP53 mutations are associated with a higher probability to develop local recurrence. MiRNAs, which are among the mediators of the oncogenic activity of mt-p53 protein, emerge as an appealing tool for screening, diagnosis and prognosis of cancer. We previously identified a signature of 12 miRNAs whose aberrant expression associated with TP53 mutations and was prognostic for HNSCC. Among them miR-96-5p emerges as an oncogenic miRNAs with prognostic significance in HNSCC. Methods To evaluate the oncogenic role of miR-96-5p in a tumoral context, we performed colony formation, cell migration and cell viability assays in two HNSCC cell lines transfected for miR-96-5p mimic or inhibitor and treated with or without radio/chemo-therapy. In addition, to identify genes positively and negatively correlated to miR-96-5p expression in HNSCC, we analyzed the correlation between gene expression and miR-96-5p level in the subset of TCGA HNSCC tumors carrying missense TP53 mutations by Spearman and Pearson correlation. To finally identify targets of miR-96-5p, we used in silico analysis and the luciferase reporter assay to confirm PTEN as direct target. Results Our data showed that overexpression of miR-96-5p led to increased cell migration and radio-resistance, chemotherapy resistance in HNSCC cells. In agreement with these results, among the most statistically significant pathways in which miR-96-5p is involved, are focal Adhesion, extracellular matrix organization and PI3K-Akt-mTOR-signaling pathway. As a direct target of miR-96-5p, we identified PTEN, the main negative regulator of PI3K-Akt signalling pathway activation. Conclusions These results highlight a new mechanism of chemo/radio-resistance insurgence in HNSCC cells and support the possibility that miR-96-5p expression could be used as a novel promising biomarker to predict radiotherapy response and local recurrence development in HNSCC patients. In addition, the identification of pathways in which miR-96-5p is involved could contribute to develop new therapeutic strategies to overcome radio-resistance. Electronic supplementary material The online version of this article (10.1186/s13046-019-1119-x) contains supplementary material, which is available to authorized users.

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The aim of this study was to investigate the dosimetric characteristics of the electron beams generated by the light intraoperative accelerator, Liac® (SORDINA, Italy), using Monte Carlo (MC) calculations. Moreover we investigated the possibility of characterizing the Liac® dosimetry with a minimal set of dosimetric data. In fact accelerator commissioning requires measurements of both percentage depth doses (PDDs) and off-axis profiles for all the possible combinations of energy, applicator diameter and bevelled angle. The Liac® geometry and water phantom were simulated in a typical measurement setup, using the MC code EGSnrc/BEAMnrc. A simulated annealing optimization algorithm was used in order to find the optimal non-monoenergetic spectrum of the initial electron beam that minimizes the differences between calculated and measured PDDs. We have concluded that, for each investigated nominal energy beam, only the PDDs of applicators with diameters of 30, 70 and 100 mm and the PDD without an applicator were needed to find the optimal spectra. Finally, the output factors of the entire set of applicator diameters/bevelled angles were calculated. The differences between calculated and experimental output factors were better than 2%, with the exception of the smallest applicator which gave differences between 3% and 4% for all energies. The code turned out to be useful for checking the experimental data from various Liac® beams and will be the basis for developing a tool based on MC simulation to support the medical physicist in the commissioning phase.

BackgroundPET/CT has recently been shown to be a viable alternative to traditional post-infusion imaging methods providing good quality images of 90Y-laden microspheres after selective internal radiation therapy (SIRT). In the present paper, first we assessed the quantitative accuracy of 90Y-PET using an anthropomorphic phantom provided with lungs, liver, spine, and a cylindrical homemade lesion located into the hepatic compartment. Then, we explored the accuracy of different computational approaches on dose calculation, including (I) direct Monte Carlo radiation transport using Raydose, (II) Kernel convolution using Philips Stratos, (III) local deposition algorithm, (IV) Monte Carlo technique (MCNP) considering a uniform activity distribution, and (V) MIRD (Medical Internal Radiation Dose) analytical approach. Finally, calculated absorbed doses were compared with those obtained performing measurements with LiF:Mg,Cu,P TLD chips in a liquid environment.ResultsOur results indicate that despite 90Y-PET being likely to provide high-resolution images, the 90Y low branch ratio, along with other image-degrading factors, may produce non-uniform activity maps, even in the presence of uniform activity. A systematic underestimation of the recovered activity, both for the tumor insert and for the liver background, was found. This is particularly true if no partial volume correction is applied through recovery coefficients. All dose algorithms performed well, the worst case scenario providing an agreement between absorbed dose evaluations within 20%. Average absorbed doses determined with the local deposition method are in excellent agreement with those obtained using the MIRD and the kernel-convolution dose calculation approach.Finally, absorbed dose assessed with MC codes are in good agreement with those obtained using TLD in liquid solution, thus confirming the soundness of both calculation approaches. This is especially true for Raydose, which provided an absorbed dose value within 3% of the measured dose, well within the stated uncertainties.ConclusionsPatient-specific dosimetry is possible even in a scenario with low true coincidences and high random fraction, as in 90Y–PET imaging, granted that accurate absolute PET calibration is performed and acquisition times are sufficiently long. Despite Monte Carlo calculations seeming to outperform all dose estimation algorithms, our data provide a strong argument for encouraging the use of the local deposition algorithm for routine 90Y dosimetry based on PET/CT imaging, due to its simplicity of implementation.

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The main hindrance to the diffusion of proton therapy facilities is the high cost for gantry installations. An alternative technical option is provided by fixed-beam treatment rooms, where the patient is rotated and translated in space with a robotic arm solution to enable beam incidence from various angles. The technological efforts based on robotic applications made up to now for patient positioning in proton beam facilities are described here, highlighting their limitations and perspectives.