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Radioresistant tumours remain complex to manage with current radiotherapy (RT) techniques. Heavy ion beams were proposed for their treatment given their advantageous radiobiological properties. However, previous studies with patients resulted in serious adverse effects in the surrounding healthy tissues. Heavy ion RT could therefore benefit from the tissue-sparing effects of minibeam radiation therapy (MBRT). To investigate the potential of this combination, here we assessed the biochemical response to neon MBRT (NeMBRT) through synchrotron-based Fourier transform infrared microspectroscopy (SR-FTIRM). Healthy (BJ) and tumour (B16-F10) cell lines were subjected to seamless (broad beam) neon RT (NeBB) and NeMBRT at HIMAC. SR-FTIRM measurements were conducted at the MIRAS beamline of ALBA Synchrotron. Principal component analysis (PCA) permitted to assess the biochemical effects after the irradiations and 24 hours post-irradiation for the different RT modalities and doses. For the healthy cells, NeMBRT resulted in the most dissimilar spectral signatures from non-irradiated cells early after irradiations, mainly due to protein conformational modifications. Nevertheless, most of the damage appeared to recover one day post-RT; conversely, protein- and nucleic acid-related IR bands were strongly affected by NeBB 24 hours after treatment, suggesting superior oxidative damage and nucleic acid degradation. Tumour cells appeared to be less sensitive to NeBB than to NeMBRT shortly after RT. Still, after one day, both NeBB and the high-dose NeMBRT regions yielded important spectral modifications, suggestive of cell death processes, protein oxidation or oxidative stress. Lipid-associated spectral changes, especially due to the NeBB and NeMBRT peak groups for the tumour cell line, were consistent with reactive oxygen species attacks. [ABSTRACT FROM AUTHOR]

Purpose: Neutron capture enhanced particle therapy (NCEPT) is a proposed augmentation of charged particle therapy that exploits thermal neutrons generated internally, within the treatment volume via nuclear fragmentation, to deliver a biochemically targeted radiation dose to cancer cells. This work is the first experimental demonstration of NCEPT, performed using both carbon and helium ion beams with 2 different targeted neutron capture agents (NCAs)., Methods and Materials: Human glioblastoma cells (T98G) were irradiated by carbon and helium ion beams in the presence of NCAs [ 10 B]-BPA and [ 157 Gd]-DOTA-TPP. Cells were positioned within a polymethyl methacrylate phantom either laterally adjacent to or within a 100 × 100 × 60 mm spread out Bragg peak (SOBP). The effect of NCAs and location relative to the SOBP on the cells was measured by cell growth and survival assays in 6 independent experiments. Neutron fluence within the phantom was characterized by quantifying the neutron activation of gold foil., Results: Cells placed inside the treatment volume reached 10% survival by 2 Gy of carbon or 2 to 3 Gy of helium in the presence of NCAs compared with 5 Gy of carbon and 7 Gy of helium with no NCA. Cells placed adjacent to the treatment volume showed a dose-dependent decrease in cell growth when treated with NCAs, reaching 10% survival by 6 Gy of carbon or helium (to the treatment volume), compared with no detectable effect on cells without NCA. The mean thermal neutron fluence at the center of the SOBP was approximately 2.2 × 10 9 n/cm 2 /Gy (relative biological effectiveness) for the carbon beam and 5.8 × 10 9 n/cm 2 /Gy (relative biological effectiveness) for the helium beam and gradually decreased in all directions., Conclusions: The addition of NCAs to cancer cells during carbon and helium beam irradiation has a measurable effect on cell survival and growth in vitro. Through the capture of internally generated neutrons, NCEPT introduces the concept of a biochemically targeted radiation dose to charged particle therapy. NCEPT enables the established pharmaceuticals and concepts of neutron capture therapy to be applied to a wider range of deeply situated and diffuse tumors, by targeting this dose to microinfiltrates and cells outside of defined treatment regions. These results also demonstrate the potential for NCEPT to provide an increased dose to tumor tissue within the treatment volume, with a reduction in radiation doses to off-target tissue., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

The stopping-power ratio (SPR) of body tissues relative to water depends on the particle energy and mean excitation energy (I value) of the tissues. Effective energies to minimize the range error in proton therapy and ion beam therapy with helium, carbon, oxygen, and neon ions and elemental I values have been updated in recent studies. We investigated the effects of these updates on SPR estimation for computed tomography-based treatment planning. The updates led to an increase of up to 0.5% in the SPRs of soft tissues, whereas they led to a decrease of up to 1.9% in the SPRs of bone tissues compared with the current clinical settings. For 44 proton beams planned for 15 randomly sampled patients, the mean water-equivalent target depth change was - 0.2 mm with a standard deviation of 0.2 mm. The maximum change was - 0.6 mm, which we consider to be insignificant in clinical practice., (© 2023. The Author(s), under exclusive licence to Japanese Society of Radiological Technology and Japan Society of Medical Physics.)

Background/aim: In vivo dosimetry can prevent dose delivery errors by directly measuring the dose of radiation administered to a patient. However, a method for in vivo dosimetry during carbon ion radiotherapy (CIRT) has not been established. Therefore, we investigated data from in vivo dosimetry of the urethra during CIRT for prostate cancer using small spherical diode dosimeters (SSDDs)., Patients and Methods: This study included five patients enrolled in a clinical trial (jRCT identifier: jRCTs032190180) on which the use of four-fraction CIRT for prostate cancer was examined. The urethral dose during CIRT for prostate cancer was measured using the SSDDs inserted into the ureteral catheter. The relative error between the in vivo and calculated doses obtained using the Xio-N treatment planning system was determined. Additionally, a dose-response stability test for the in vivo dosimeter was performed under clinical conditions., Results: The relative error between the in vivo and calculated urethral doses ranged from 6 to 12%. The dose-response stability under clinical conditions of the measured dose was ≤1%. Therefore, an error >1% would be due to an interfractional patient setup error in the large dose gradient in the urethra., Conclusion: The usefulness of in vivo dosimetry using SSDDs in CIRT and SSDDs' potential for detecting dose delivery errors during CIRT is herein highlighted., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: To evaluate the clinical relative biological effectiveness (RBE) of carbon-ion radiotherapy (C-ion RT) for prostate cancer., Methods: The records of 262 patients with low-risk prostate cancer (median age, 65 [47-80] years) treated with C-ion RT at QST Hospital, National Institutes for Quantum Science and Technology in Japan during 2000-2018 were reviewed retrospectively. Four different protocol outcomes and prostate-specific antigen (PSA) responses were evaluated. The median follow-up was 8.4 years. The Kaplan-Meier method was used to estimate the biochemical or clinical failure-free rate (BCFFR). Clinical RBE was calculated using the tumor control probability model., Results: The 5-, 7-, and 10-year BCFFRs were 91.7%, 83.8%, and 73.2%, respectively. The 10-year BCFFRs of patients who received C-ion RT at 66 Gy (RBE) in 20 fractions, 63 Gy (RBE) in 20 fractions, and 57.6 Gy (RBE) in 16 fractions were 81.4%, 70.9%, and 68.9%, respectively. The PSA level and density during follow-up were better in the patients treated with the lower fraction size. A higher PSA nadir and shorter time to PSA nadir were risk factors for biochemical or clinical failure by multivariate Cox regression. The tumor control probability analysis showed that the estimated clinical RBE values to achieve an 80% BCFFR at 10 years for 20, 16, and 12 fractions were 2.19 (2.18-2.24), 2.16 (2.14-2.23), and 2.12 (2.09-2.21), respectively., Conclusions: Using clinical data from low-risk prostate cancer patients, we showed the clinical RBE of C-ion RT decreased with increasing dose per fraction., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Time dependence of relative biological effectiveness (RBE) of carbon ions for skin damage was investigated to answer the question of whether the flat distribution of biological doses within a Spread-Out Bragg peak (SOBP) which is designed based on in vitro cell kill could also be flat for in vivo late responding tissue. Two spots of Indian ink intracutaneously injected into the legs of C3H mice were measured by calipers. An equieffective dose to produce 30% skin contraction was calculated from a dose-response curve and used to calculate the RBE of carbon ion beams. We discovered skin contraction progressed after irradiation and then reached a stable/slow progression phase. Equieffective doses decreased with time and the decrease was most prominent for gamma rays and least prominent for 100 keV/μm carbon ions. Survival parameter of alpha but not beta in the linear-quadratic model is closely related to the RBE of carbon ions. Biological doses within the SOBP increased with time but their distribution was still flat up to 1 year after irradiation. The outcomes of skin contraction studies suggest that (i) despite the higher RBE for skin contracture after carbon ions compared to gamma rays, gamma rays can result in a more severe late effect of skin contracture. This is due to the carbon effect saturating at a lower dose than gamma rays, and (ii) the biological dose distribution throughout the SOBP remains approximately the same even one year after exposure., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)