Good Timing Matters: The Spatially Fractionated High Dose Rate Boost Should Come First

SIMPLE SUMMARY: The administration of X-rays with therapeutic intent (radiotherapy) can cause severe unwanted adverse effects in tissues other than those that were the intended radiation target, such as tissues located in the path of the beam or close to the target region. The results of small animal studies suggest that the risk for adverse effects may be significantly reduced if the X-ray dose is administered extremely fast, as the so-called high dose rate radiotherapy. Microbeam irradiation and pencilbeam irradiation are two new experimental concepts of high dose rate radiotherapy with spatial dose fractionation at the micrometre range. The results of our studies show how the inclusion of these concepts into a conventional broad beam radiotherapy schedule could improve cancer radiotherapy for patients with malignant brain tumours. ABSTRACT: Monoplanar microbeam irradiation (MBI) and pencilbeam irradiation (PBI) are two new concepts of high dose rate radiotherapy, combined with spatial dose fractionation at the micrometre range. In a small animal model, we have explored the concept of integrating MBI or PBI as a simultaneously integrated boost (SIB), either at the beginning or at the end of a conventional, low-dose rate schedule of 5x4 Gy broad beam (BB) whole brain radiotherapy (WBRT). MBI was administered as array of 50 µm wide, quasi-parallel microbeams. For PBI, the target was covered with an array of 50 µm × 50 µm pencilbeams. In both techniques, the centre-to-centre distance was 400 µm. To assure that the entire brain received a dose of at least 4 Gy in all irradiated animals, the peak doses were calculated based on the daily BB fraction to approximate the valley dose. The results of our study have shown that the sequence of the BB irradiation fractions and the microbeam SIB is important to limit the risk of acute adverse effects, including epileptic seizures and death. The microbeam SIB should be integrated early rather than late in the irradiation schedule.