Radiobiological characterization of the very high dose rate and dose per pulse electron beams produced by an IORT (intra operative radiation therapy) dedicated linac

Background: Intra operative radiation therapy (IORT) is a cancer treatment modality combining surgery and radiation therapy that permits the delivery of a large single dose of radiation at the time of the tumour resection. During the last years, IORT has become a widespread technique in clinical routine. This was possible thanks to the recent development of small dedicated, and hence very flexible, electron accelerators suitable for a surgical operation environment. However, the electron beams produced by these dedicated linacs are different with respect to those produced by linacs used in conventional radiation therapy in terms of dose rate (dose delivered/time of irradiation), dose per pulse (dose delivered per emitted beam pulse) and energy spectrum. In particular the very high dose rate and dose per pulse (i.e., respectively about 20 and 100 times greater than those of conventional radiation therapy) pose some radiobiological questions that have not yet been fully investigated. The aim of this work was to evaluate the relative biological effectiveness (RBE) of the IORT beams through the experimental construction of dose-response curves for cell survival. Methods: Since breast cancer represents the elective malignancy for treatment by IORT, clonogenic survival was assayed in the MCF-7 cell line from breast tissue malignant adenocarcinoma as a function of dose for different dose rates (5, 25 and 75 Gy/min) and doses per pulse (4.2 and 7.4 cGy/pulse). Irradiations were performed at the IORT accelerator Novac7 (Hitesys SpA, Italy) delivering electrons at the nominal energy of 7 MeV. For comparison, irradiations were also carried out with a conventional radiotherapy accelerator (ClinacR DHX, Varian), providing a 6 MeV pulsed electron beam and 6 MV X-rays (dose rate and dose-per-pulse 2 Gy/min and 0.1 cGy/pulse respectively) as reference irradiations. Results: The IORT beam effectiveness was found almost the same with varying dose rate (5, 25 and 75 Gy/min) and dose per pulse (4.2 and 7.4 cGy/pulse). No significant difference was also found between IORT and conventional electron beams, while 6 MV X-rays (beam used in the conventional treatment of breast cancer) proved to be more effective. Conclusions: Data show that cell killing effectiveness of the electron beams from the IORT accelerator does not differ significantly from that of an electron beam used in conventional radiotherapy. This suggests that changes in the dose rate and dose per pulse, up to the values of 75 Gy/min and 7.4 cGy/pulse, do not affect the radiobiological characteristics of the beam. In the light of our results, new experimental data are needed to better compare the RBE of a IORT breast cancer treatment (5- 9 MeV electron beams, 21 Gy at the 90% isodose level in single fraction) and the RBE of a conventional breast cancer treatment (6 MV X- rays, 2 Gy per fraction, 30 fractions).