Apparent absence of a proton beam dose rate effect and possible differences in RBE between Bragg peak and plateau

Matsuura, Tetsuya; Egashira, Yasuyuki; Nishio, Teiji; Matsumoto, Yoshitaka; Wada, Mami; Koike, Sachiko; Furusawa, Yoshiya; Kohno, Ryosuke; Nishioka, Shie; Kameoka, S.; Tsuchihara, Katsuya; Kawashima, Mitsuhiko; Ogino, Takashi

doi:10.1118/1.3490086

Cited by 39 publications

(29 citation statements)

References 20 publications

(15 reference statements)

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“…Clonogenic assays in vitro have long shown that the cell killing effectiveness of sub-millisecond pulses of relativistic electrons [reviewed in (18)] or protons (4,19) does not differ significantly from that of continuous x-ray irradiation at a conventional dose rate. However, these studies did not pay attention to the mechanisms of radiationinduced cell death.…”

Section: Discussionmentioning

confidence: 99%

Ultrahigh dose-rate FLASH irradiation increases the differential response between normal and tumor tissue in mice

et al. 2014

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In vitro studies suggested that sub-millisecond pulses of radiation elicit less genomic instability than continuous, protracted irradiation at the same total dose. To determine the potential of ultrahigh dose-rate irradiation in radiotherapy, we investigated lung fibrogenesis in C57BL/6J mice exposed either to short pulses (≤ 500 ms) of radiation delivered at ultrahigh dose rate (≥ 40 Gy/s, FLASH) or to conventional dose-rate irradiation (≤ 0.03 Gy/s, CONV) in single doses. The growth of human HBCx-12A and HEp-2 tumor xenografts in nude mice and syngeneic TC-1 Luc(+) orthotopic lung tumors in C57BL/6J mice was monitored under similar radiation conditions. CONV (15 Gy) triggered lung fibrosis associated with activation of the TGF-β (transforming growth factor-β) cascade, whereas no complications developed after doses of FLASH below 20 Gy for more than 36 weeks after irradiation. FLASH irradiation also spared normal smooth muscle and epithelial cells from acute radiation-induced apoptosis, which could be reinduced by administration of systemic TNF-α (tumor necrosis factor-α) before irradiation. In contrast, FLASH was as efficient as CONV in the repression of tumor growth. Together, these results suggest that FLASH radiotherapy might allow complete eradication of lung tumors and reduce the occurrence and severity of early and late complications affecting normal tissue.

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Section: Discussionmentioning

confidence: 99%

Ultrahigh dose-rate FLASH irradiation increases the differential response between normal and tumor tissue in mice

et al. 2014

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“…Horizontal proton beams were accelerated up to 190 MeV by an Azimuthally Varying Field (AVF) cyclotron at the NCCHE (National Cancer Center Hospital East) [31]. In this experiment, we used the nozzle designed for the dual-ring scattering method [24] to obtain a flat dose profile and stable dose intensity over the target area.…”

Section: Methodsmentioning

confidence: 99%

Enhanced radiobiological effects at the distal end of a clinical proton beam: in vitro study

Matsumoto¹,

Matsuura

Wada³

et al. 2014

Journal of Radiation Research

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In the clinic, the relative biological effectiveness (RBE) value of 1.1 has usually been used in relation to the whole depth of the spread-out Bragg-peak (SOBP) of proton beams. The aim of this study was to confirm the actual biological effect in the SOBP at the very distal end of clinical proton beams using an in vitro cell system. A human salivary gland tumor cell line, HSG, was irradiated with clinical proton beams (accelerated by 190 MeV/u) and examined at different depths in the distal part and the center of the SOBP. Surviving fractions were analyzed with the colony formation assay. Cell survival curves and the survival parameters were obtained by fitting with the linear–quadratic (LQ) model. The RBE at each depth of the proton SOBP compared with that for X-rays was calculated by the biological equivalent dose, and the biological dose distribution was calculated from the RBE and the absorbed dose at each position. Although the physical dose distribution was flat in the SOBP, the RBE values calculated by the equivalent dose were significantly higher (up to 1.56 times) at the distal end than at the center of the SOBP. Additionally, the range of the isoeffective dose was extended beyond the range of the SOBP (up to 4.1 mm). From a clinical point of view, this may cause unexpected side effects to normal tissues at the distal position of the beam. It is important that the beam design and treatment planning take into consideration the biological dose distribution.

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“…3). The RBE at 10% survival for Chinese hamster fibroblasts and two human squamous cell carcinomas ranges between 1 and 1.2, much lower than the RBE values for these same cells relative to low-energy protons [20] or heavy ions [22], but similar to the value of 1.1 normally used in Bragg peak proton therapy [23] and measured in radiobiological experiments [24–26]. Similarly low RBE for 1-GeV protons has been also measured for white blood cell loss in mice [27].…”

Section: Discussionmentioning

confidence: 89%

Biophysical characterization of a relativistic proton beam for image-guided radiosurgery

Vanstalle

Tessa

et al. 2012

Journal of Radiation Research

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We measured the physical and radiobiological characteristics of 1 GeV protons for possible applications in stereotactic radiosurgery (image-guided plateau-proton radiosurgery). A proton beam was accelerated at 1 GeV at the Brookhaven National Laboratory (Upton, NY) and a target in polymethyl methacrylate (PMMA) was used. Clonogenic survival was measured after exposures to 1–10 Gy in three mammalian cell lines. Measurements and simulations demonstrate that the lateral scattering of the beam is very small. The lateral dose profile was measured with or without the 20-cm plastic target, showing no significant differences up to 2 cm from the axis A large number of secondary swift protons are produced in the target and this leads to an increase of approximately 40% in the measured dose on the beam axis at 20 cm depth. The relative biological effectiveness at 10% survival level ranged between 1.0 and 1.2 on the beam axis, and was slightly higher off-axis. The very low lateral scattering of relativistic protons and the possibility of using online proton radiography during the treatment make them attractive for image-guided plateau (non-Bragg peak) stereotactic radiosurgery.

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Apparent absence of a proton beam dose rate effect and possible differences in RBE between Bragg peak and plateau

Abstract: Present RBE can be consistently used in treatment planning of PRT using ultrahigh dose rate radiation. Because a significant increase in RBE toward the Bragg peak was observed for both UDR and CDR, further evaluation of RBE enhancement toward the Bragg peak and beyond is required.

Cited by 39 publications

References 20 publications

Ultrahigh dose-rate FLASH irradiation increases the differential response between normal and tumor tissue in mice

Ultrahigh dose-rate FLASH irradiation increases the differential response between normal and tumor tissue in mice

Enhanced radiobiological effects at the distal end of a clinical proton beam: in vitro study

Biophysical characterization of a relativistic proton beam for image-guided radiosurgery

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