Systematic dosimetric evaluation of risk of osteoradionecrosis (DERO): First results of dose reporting for preventing teeth osteoradionecrosis after head and neck irradiation.

PURPOSE: OsteoRadioNecrosis (ORN) is a late complication of radiation for head and neck cancer. Predicting ORN is a major challenge. We developed DERO (Dosimetric Evaluation of Risk of ORN), a semi-automatic tool which reports doses delivered to tooth-bearing sectors, to guide post-therapeutic dental care. We present the method and the first results of a 125-patient prospective cohort. MATERIAL AND METHODS: Dosimetric data of patients treated with IMRT for head and neck cancer were prospectively segmented to the DERO algorithm. Four arches corresponding to 8-tooth sectors were semi-automatically generated. Thirty-two cylindrical Regions Of Interest (ROI) corresponding to each tooth and surrounding periodontium were created by linear interpolation. Mean doses (Dmean) of ROI were extracted and included in a database, along with data about primary tumor site, laterality and dose values from organs at risk. Dmean to tooth sectors were computed for molar sectors, (teeth X5 to X8) and anterior sectors (teeth X1 to X4). An individual dose map was generated and delivered to patients and dentists. RESULTS: Dosimetric data from 125 patients treated with Tomotherapy® were prospectively collected and analyzed: 9 parotid tumors (PA), 41 Sub-Hyoid tumors (larynx, hypopharynx) (SH), 43 Oropharynx tumors (OR), 32 Oral Cavity tumors (OC). Irradiation was unilateral for 100% of PA tumors (9), 12% of OR tumors (5) and 47% of OC tumors (15). For unilateral cervical irradiation, Dmean in ipsilateral molar sectors was 54Gy for OC tumors, 45Gy for OR tumors, 20Gy for PA tumors. For Oral Cavity bilateral irradiation, Dmean was high in all tooth sectors, 49 to 55Gy. For SH tumors, Dmean in molar sectors was 27Gy. A dose gradient of 10 to 20Gy was observed between molar and anterior sectors whether radiation was uni or bilateral. CONCLUSION: Mandibular molar sectors of Oropharynx and Oral Cavity tumors were exposed to high Dmean of 40 to 50Gy. On the other hand, tooth sectors received lower doses for SH radiation. The DERO tool guide post-radiation dental care with a personalized dosimetric cartography to patient. With data update and patient follow-up, we will be able to determine ORN risk after head and neck radiation.

Vascular imaging with contrast agent in hard and soft tissues using microcomputed-tomography.

Vascularization is essential for many tissues and is a main requisite for various tissue-engineering strategies. Different techniques are used for highlighting vasculature, in vivo and ex vivo, in 2-D or 3-D including histological staining, immunohistochemistry, radiography, angiography, microscopy, computed tomography (CT) or micro-CT, both stand-alone and synchrotron system. Vascularization can be studied with or without a contrast agent. This paper presents the results obtained with the latest Skyscan micro-CT (Skyscan 1272, Bruker, Belgium) following barium sulphate injection replacing the bloodstream in comparison with results obtained with a Skyscan In Vivo 1076. Different hard and soft tissues were perfused with contrast agent and were harvested. Samples were analysed using both forms of micro-CT, and improved results were shown using this new micro-CT. This study highlights the vasculature using micro-CT methods. The results obtained with the Skyscan 1272 are clearly defined compared to results obtained with Skyscan 1076. In particular, this instrument highlights the high number of small vessels, which were not seen before at lower resolution. This new micro-CT opens broader possibilities in detection and characterization of the 3-D vascular tree to assess vascular tissue engineering strategies.

Evaluation of new bone formation in irradiated areas using association of mesenchymal stem cells and total fresh bone marrow mixed with calcium phosphate scaffold.

The consequences of the treatment of the squamous cell carcinomas of the upper aerodigestive tract (bone removal and external radiation therapy) are constant. Tissue engineering using biphasic calcium phosphate (BCP) and mesenchymal stem cells (MSC) is considered as a promising alternative. We previously demonstrated the efficacy of BCP and total fresh bone marrow (TBM) in regenerating irradiated bone defect. The aim of this study was to know if adding MSC to BCP + TBM mixture could improve the bone formation in irradiated bone defects. Twenty-four Lewis 1A rats received a single dose of 20 Gy to the hind limbs. MSC were sampled from non-irradiated donors and amplified in proliferative, and a part in osteogenic, medium. 3 weeks after, defects were created on femurs and tibias, which were filled with BCP alone, BCP + TBM, BCP + TBM + uncommitted MSC, or BCP + TBM + committed MSC. 3 weeks after, samples were removed and prepared for qualitative and quantitative analysis. The rate of bone ingrowth was significantly higher after implantation of BCP + TBM mixture. The adding of a high concentration of MSC, committed or not, didn't improve the bone regeneration. The association BCP + TBM remains the most efficient material for bone substitution in irradiated areas.