Background: Embryonal tumors represent a heterogeneous entity of brain tumors that need a multidisciplinary treatment including cranio-spinal irradiation (CSI), with a known impact on the acute toxicity. Proton therapy (PT) boasts a reduction in acute hematological toxicity. Methods: We retrospectively examined 20 pediatric patients affected by high-risk medulloblastoma and other rare embryonal brain tumors subjected to CSI with PT from September 2016 to April 2020. Before CSI, all patients received induction chemotherapy, and three patients additionally received two high-dose courses with thiotepa, followed by an autologous haemopoietic stem cell transplantation. We recorded the total white blood cell count, absolute neutrophil count, platelets, and hemoglobin levels for all patients during PT. Results: Leucocytes and neutrophils decreased directly after the beginning of treatment, reaching a complete recovery at the end of treatment. Hemoglobin values remained constant over the treatment course. The median platelet value decreased until reaching a plateau around halfway through therapy, followed by a slow increase. No cases of febrile neutropenia or severe infections were reported. No treatment discontinuation due to hematological toxicity was necessary. Conclusions: CSI with PT was proven to be safe in this setting of pediatric patients. Our study showed that despite all patients having undergone chemotherapy prior to irradiation, no serious hematological toxicity was reported at the end of the treatment with PT, and, therefore, no treatment was discontinued or delayed.

Silicon carbide (SiC) detectors have been widely demonstrated to be suitable alternative detectors for dosimetry in FLASH radiotherapy, showing radiation hardness and dose-rate independence at the FLASH radiotherapy instantaneous dose rates (IDRs). However, the practical use of such devices in the preclinical/clinical environment still requires the development of special handy housing enabling the quality assurance (QA) measurements under the reference dosimetric conditions. A 10 μm thick, 4.5 mm² area SiC detector produced by the STLab company was recently embedded at the INFN-Catania Division inside a plastic waterproof 15 mm diameter cylindrical housing. This encapsulated version of SiC (eSiC) allows the measurement of the dose in reference conditions and of the dose profiles in liquid/solid water phantoms for assuring high accuracy dosimetry QA procedures. Dosimetric characterizations were performed with both electron and proton beams at conventional and ultra-high dose rates (UHDR). A first experiment was carried out at the Centro Pisano for Flash Radiotherapy using UHDR 9 MeV electron beams to confirm the linearity of the charge response as a function of the dose per pulse after the encapsulation procedure. A linearity from 1.8 Gy/pulse up to about 12 Gy/pulse, corresponding to an IDR of 3 MGy s⁻¹, was found. The percentage depth dose (PDD) distribution in water of 9 MeV electron beams was also measured and compared with the PDD measured with a Freiburg Physikalisch-Technische Werkstätten Dr. Pychlau GmbH (PTW) flash diamond detector, used as reference dosimeter. The eSiC detector was also tested with proton beams accelerated by the IBA Proteus 235 cyclotron at the Trento Proton Therapy facility. A response independence on the total delivered dose (1–30 Gy) and average dose rate (50–530 Gy s⁻¹) was found using the UHDR 228 MeV proton beam available along the experimental beamline. The depth dose distribution measured with the eSiC within a liquid water phantom was successfully compared with the one simultaneously measured by the IBA PPC05 reference chamber, using 180 MeV clinical proton beams. The excellent results demonstrated that this first realized eSiC prototype can be used to accurately perform reference and relative dosimetry with UHDR electron and proton beams, contributing to support the clinical translation of FLASH radiotherapy.

Objectives: To investigate how the FLASH effect modulates radiation response on multiple developmental endpoints of zebrafish embryos under normoxic and hypoxic conditions, after irradiation with proton beams at a conventional and an ultra-high dose rate (UHDR). Methods: Embryos were obtained from adult zebrafish and irradiated with a 228 MeV proton beam 24 h post-fertilization (hpf) at a dose rate of 0.6 and 317 Gy/s. For the hypoxic group, samples were kept inside a hypoxic chamber prior to irradiation, while standard incubation was adopted for the normoxic group. After irradiation, images of single embryos were acquired, and radiation effects on larval length, yolk absorption, pericardial edema, head size, eye size, and spinal curvature were assessed at specific time points. Results: Data indicate a general trend of significantly reduced toxicity after exposure to a UHDR compared to conventional regimes, which is maintained under both normoxic and hypoxic conditions. Differences are significant for the levels of pericardial edema induced by a UHDR versus conventional irradiation in normoxic conditions, and for eye and head size in hypoxic conditions. The toxicity scoring analysis shows a tendency toward a protective effect of the UHDR, which appears to be associated with a lower percentage of embryos in the high score categories. Conclusions: A radioprotective effect at a UHDR is observed both for normoxic (pericardial edema) and hypoxic (head and eye size) conditions. These results suggest that while the UHDR may preserve a potential to reduce radiation-induced damage, its protective effects are endpoint-dependent; the role of oxygenation might also be dependent on the tissue involved.

Proton therapy represents a technologically advanced method for delivery of radiation treatments to tumors. The determination of the biological effectiveness is one of the objectives of the MoVe IT (Modeling and Verification for Ion Beam Treatment Planning) project of the National Institute for Nuclear Physics (INFN) CSN5. The aim of the present work, which is part of the project, was to evaluate the performance of the thermoluminescent dosimeters (TLDs-100) for dose verification in the proton beam line. Four irradiation experiments were performed in the experimental room at the Trento Proton Therapy Center, where a 150 MeV monoenergetic proton beam is available. A total of 80 TLDs were used. The TLDs were arranged in one or two rows and accommodated in a specially designed water-equivalent phantom. In the experimental setup, the beam enters orthogonally to the dosimeters and is distributed along the proton beam profile, while the irradiation delivers doses of 0.8 Gy or 1.5 Gy in the Bragg peak. For each irradiation stage, the depth–dose curve was determined by the TLD readings. The results showed the good performance of the TLDs-100, proving their reliability for dose recordings in future radiobiological experiments planned within the MoVe IT context.

Proton beam therapy (PBT) is an effective pediatric brain tumor treatment. However, the resulting microstructural changes within and around irradiated tumors are unknown. We retrospectively applied diffusion tensor imaging (DTI) and free-water imaging (FWI) on diffusion-weighted magnetic resonance imaging (dMRI) data to monitor microstructural changes during the PBT and after 8 months in a pilocytic astrocytoma (PA) and normal-appearing white matter (NAWM). We evaluated the conventional MRI- and dMRI-derived indices from six MRI sessions (t0–t5) in a Caucasian child with a hypothalamic PA: at baseline (t0), during the PBT (t1–t4) and after 8 months (t5). The tumor voxels were classified as “solid” or “fluid” based on the FWI. While the tumor volume remained stable during the PBT, the dMRI analyses identified two different response patterns: (i) an increase in fluid content and diffusivity with anisotropy reductions in the solid voxels at t1, followed by (ii) smaller variations in fluid content but higher anisotropy in the solid voxels at t2–t4. At follow-up (t5), the tumor volume, fluid content, and diffusivity in the solid voxels increased. The NAWM showed dose-dependent microstructural changes. The use of the dMRI and FWI showed complex dynamic microstructural changes in the irradiated mass during the PBT and at follow-up, opening new avenues in our understanding of radiation-induced pathophysiologic mechanisms in tumors and the surrounding tissues.