The Spinal Cord as Organ of Risk: Assessment for Acute and Subacute Neurological Adverse Effects after Microbeam Radiotherapy in a Rodent Model

SIMPLE SUMMARY: Organs which receive an irradiation dose because they are located in the vicinity of the irradiation target are considered organs of risk. Before a new irradiation technique is tested in clinical trials, it is important to make an assessment of the potential adverse effects in these organs of risk. Microbeam radiotherapy is an innovative radiotherapy technique suitable to control tumours which are considered radioresistant with conventional, already clinically established irradiation techniques. In a small animal model, we have conducted a risk assessment in the thoracic spinal cord as organ of risk during microbeam irradiation in the thoracic cavity and determined the upper dose limit beyond which neurological signs of temporary or permanent damage occur. ABSTRACT: Microbeam radiotherapy (MRT), a high dose rate radiotherapy technique using spatial dose fractionation at the micrometre range, has shown a high therapeutic efficacy in vivo in different tumour entities, including lung cancer. We have conducted a toxicity study for the spinal cord as organ of risk during irradiation of a target in the thoracic cavity. In young adult rats, the lower thoracic spinal cord was irradiated over a length of 2 cm with an array of quasi-parallel microbeams of 50 µm width, spaced at a centre-to-centre distance of 400 µm, with MRT peak doses up to 800 Gy. No acute or subacute adverse effects were observed within the first week after irradiation up to MRT peak doses of 400 Gy. No significant differences were seen between irradiated animals and non-irradiated controls in motor function and sensitivity, open field test and somatosensory evoked potentials (SSEP). After irradiation with MRT peak doses of 450–800 Gy, dose-dependent neurologic signs occurred. Provided that long-term studies do not reveal significant morbidity due to late toxicity, an MRT dose of 400 Gy can be considered safe for the spinal cord in the tested beam geometry and field size.