This paper studies the feasibility of using Monte Carlo (MC) for treatment planning of intraoperative electron radiation therapy (IOERT) procedure to get 3D dose by using patient's CT images. Methods: The IOERT treatment planning was performed using the following successive steps:I) The Mobetron 1000® machine was modelled with the EGSnrc MC codes. II) The MC model was validated with measurements of percentage depth doses and profiles for three energies (12, 9, 6) MeV. III) CT images were imported as DICOM files. IV) Contouring of the planning target volume (PTV) and the organs at risk was done by the radiation oncologist. V) The medical physicist with the radiation oncologist, had chosen the same parameters of IOERT procedures like energy, applicator (type, size) and using or not bolus. VI) Finally, dose calculation and analysis of 3D maps was carried out. Results: The tuning process of the MC model provides good results, as the maximum value of the root mean square deviation (RMSD) was less than 3% between the MC simulated PDDs and the measured PDDs. The contouring and dose analysis review were easy to conduct for the classical treatment planning system. The radiation oncologist had many tools for dose analysis such as DVH and color wash for all the slides. Summation of the 3D dose of IOERT with other radiotherapy plans is possible and helpful for total dose estimation. Archiving and documentation is as good as treatment planning system (TPS). Conclusions: The method displayed in this paper provides a step forward for IOERT Dosimetry and allows to obtain accurate dosimetry of treated volumes.

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Background To improve split-VMAT technique by optimizing treatment delivery time for deep-inspiration breath hold (DIBH) radiotherapy in left-sided breast cancer patients, when automatic beam-interruption devices are not available. Methods Ten consecutive patients were treated with an eight partial arcs (8paVMAT) plan, standard of care in our center. A four partial arcs (4paVMAT) plan was also created and actual LINAC outputs were measured, to evaluate whether there was a dosimetric difference between both techniques and potential impact on the delivered dose. Subsequently, ten other patients were consecutively treated with a 4paVMAT plan to compare the actual treatment delivery time between both techniques. The prescribed dose was 40.05 Gy/15 fractions on the PTV breast (breast or thoracic wall), lymph nodes (LN) and intramammary lymph node chain (IMN). Treatment delivery time, PTVs coverage, conformity index (CI), organs at risk (OAR) dose, monitor units (MU), and gamma index were compared. Results Both split-VMAT techniques resulted in similar dose coverage for the PTV Breast and LN, and similar CI. For PTV IMN we observed a 5% increased coverage for the volume receiving ≥ 36 Gy with 4paVMAT, with an identical volume receiving ≥ 32 Gy. There was no difference for the OAR sparing, with the exception of the contralateral organs: there was a 0.6 Gy decrease for contralateral breast mean (p ≤ 0.01) and 1% decrease for the volume of right lung receiving ≥ 5 Gy (p = 0.024). Overall, these results indicate a modest clinical benefit of using 4paVMAT in comparison to 8paVMAT. An increase in the number of MU per arc was observed for the 4paVMAT technique, as expected, while the total number of MU remained comparable for both techniques. All the plans were measured with the Delta4 phantom and passed the gamma index criteria with no significant differences. Finally, the main difference was seen for the treatment delivery time: there was a significant decrease from 8.9 to 5.4 min for the 4paVMAT plans (p < .05). Conclusions This study is mainly of interest for centers who are implementing the DIBH technique without automatic beam-holding devices and who therefore may require to manually switch the beam on and off during breast DIBH treatment. Split-VMAT technique with 4 partial arcs significantly reduces the treatment delivery time compared to 8 partial arcs, without compromising the target coverage and the OAR sparing. The technique decreases the number of breath holds per fraction, resulting in a shorter treatment session.

Melanoma is known to be a radioresistant cancer. Melanoma radioresistance can be due to several factors such as pigmentation, antioxidant defenses and high Deoxyribonucleic acid (DNA) repair efficacy. However, irradiation induces intracellular translocation of RTKs, including cMet, which regulates response to DNA damage activating proteins and promotes DNA repair. Accordingly, we hypothesized that co-targeting DNA repair (PARP-1) and relevant activated RTKs, c-Met in particular, may radiosensitize wild-type B-Raf Proto-Oncogene, Serine/Threonine Kinase (WTBRAF) melanomas where RTKs are often upregulated. Firstly, we found that PARP-1 is highly expressed in melanoma cell lines. PARP-1 inhibition by Olaparib or its KO mediates melanoma cell sensitivity to radiotherapy (RT). Similarly, specific inhibition of c-Met by Crizotinib or its KO radiosensitizes the melanoma cell lines. Mechanistically, we show that RT causes c-Met nuclear translocation to interact with PARP-1 promoting its activity. This can be reversed by c-Met inhibition. Accordingly, RT associated with the inhibition of both c-Met and PARP-1 resulted in a synergistic effect not only on tumor growth inhibition but also on tumor regrowth control in all animals following the stop of the treatment. We thus show that combining PARP and c-Met inhibition with RT appears a promising therapeutic approach in WTBRAF melanoma.

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Highlights The dual registration tool (DRT) aims to improve the accuracy by using two automatic image registrations sequentially; For prostate irradiation, DRT could be considered in combination with additional verification, as manual correction by the RTTs is less often needed after DRT than after chamfer matching; For prostate bed irradiation with matching on the pubic symphysis, the chamfer match together with additional verification of the RTTs remains the best choice, as it is fast and accurate.