Relative biological effectiveness of proton medical beam at Moscow synchrotron determined by the Chinese hamster cells assay

Yashkin, P.N.; Silin, Dimitry I.; Zolotov, V A; Kostjuchenko, V. I.; Nichiporov, D.; Feoktistova, Tatiana P.; Martirosov, Kyrill S.; Minakova, Yelizaveta I.; Khoroshkov, V. S.; Polonski, Pavel B.; Zinovyeva, Ludmila V.

doi:10.1016/0360-3016(94)00381-t

Cited by 22 publications

(8 citation statements)

References 8 publications

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“…On the other hand, at low dose, the radiobiological effectiveness of proton was very different from that of gamma-rays (Cucinotta et al, 1991). There have also been other studies that did not definitely support the difference (Yashkin et al, 1995;Gueulette et al, 1996). We found a definite correlation between RBE and SF level or irradiation dose.…”

Section: Resultscontrasting

confidence: 65%

Comparison of radiobiological effective depths in 65-MeV modulated proton beams

Tang

Inoue²,

Yamazaki³

et al. 1997

Br J Cancer

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Summary To assess the achievement of uniformity of radiobiological effectiveness at different depths in the proton spread-out Bragg peak (SOBP), Chinese hamster ovary (CHO) cells were exposed to 65-MeV modulated proton beams at the Research Center for Nuclear Physics (RCNP) of Osaka University. We selected four different irradiation positions: 2 mm depth, corresponding to the entrance, and 10, 18 and 23 mm depths, corresponding to different positions in the SOBP. Cell survival curves were generated with the in vitro colony formation method and fitted to the linear-quadratic model. With 137CS gamma-rays as the reference irradiation, the relative biological effectiveness (RBE) values for a surviving fraction (SF) level of 0.1 are 1.05, 1.10, 1.12 and 1.19 for depths of 2, 10, 18 and 23 mm respectively. A significant difference was found between the survival curves at 10 and 23 mm (P < 0.05), but not between 18 and 10 mm or between 18 and 23 mm. There was a significant dependence of RBE on depths in modulated proton beams at the 0.1 surviving fraction level (P< 0.05). Moreover, the rise of RBEs significantly depended on increasing SF level or decreased approximately in correspondence with irradiation dose (P = 0.0001). To maintain uniformity of radiobiological effectiveness for the target volume, careful attention should be paid to the influence of depth of beam and irradiation dose.Keywords: proton; spread-out Bragg peak; relative biological effectiveness; Chinese hamster ovary cellThe depth-dose curve for the single-energy proton beam has limited applications in clinical radiation therapy owing to the excessively narrow high-dose region. This region, also known as the Bragg peak, can be modulated by appropriate selection of a distribution of proton energies to produce a spread-out Bragg peak (SOBP) or a uniform region of full dose at the depth of interest. Dose uniformity across a target volume can be achieved with multiple X-ray beams. However, each X-ray beam features a greater dose in the entrance region than a corresponding proton beam, has a dose gradient across the target volume and delivers an undesirable dose to normal tissues distal to the target. Proton beams have none of these undesirable characteristics (Suit and Urie, 1992; Munzenrider and Crowell, 1994;Raju, 1996).Although SOBP produces an excellent physical dose distribution, there is a variation of linear energy transfer (LET) values at different depths in the SOBP, known as the LET gradient, from proximal to distal SOBP. The proton is a lower LET particle than other heavy-charged particles; for example, the mean LET values of the 65-MeV modulated proton beams (SOBP) are always less than 7 keV .m-' (Courdi et al, 1994).The achievement of uniformity of radiobiological effectiveness for target volumes is always a matter of concern. In fact, there is no uniformity of LET within target volumes. One study has suggested that DNA double-strand breaks, potentially lethal damage and sublethal damage, depend on LET and are closely

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Section: Resultscontrasting

confidence: 65%

Comparison of radiobiological effective depths in 65-MeV modulated proton beams

Tang

Inoue²,

Yamazaki³

et al. 1997

Br J Cancer

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“…Several in vitro studies measured the RBE at only 2 depths: the entrance plateau and the middle of the SOBP (13)(14)(15), thus no information was obtained as to changes in RBE along the stopping peak. Among four in vitro studies examining at least two depths within the SOBP, only one (16) showed a progressive increase in RBE with depth, three showed evidence of an increase at the distal edge (10,17,18), and one reported the same RBE at three positions: entrance plateau, midpeak and distal peak of a 201 MeV beam with a 7 cm SOBP (9).…”

Section: Rbe Dependence On Depthmentioning

confidence: 99%

Radiobiological Intercomparison of the 160 MeV and 230 MeV Proton Therapy Beams at the Harvard Cyclotron Laboratory and at Massachusetts General Hospital

Wouters

Skarsgard²,

Gerweck

et al. 2015

Radiation Research

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The purpose of this study was to determine the relative biological effectiveness (RBE) along the axis of two range-modulated proton beams (160 and 230 MeV). Both the depth and the dose dependence of RBE were investigated. Chinese hamster V79-WNRE cells, suspended in medium containing gelatin and cooled to 2 °C, were used to obtain complete survival curves at multiple positions throughout the entrance and 10 cm spread-out Bragg peak (SOBP). Simultaneous measurements of the survival response to (60)Co gamma rays served as the reference data for the proton RBE determinations. For both beams the RBE increased significantly with depth in the 10 cm SOBP, particularly in the distal half of the SOBP, then rose even more sharply at the distal edge, the most distal position measured. At a 4 Gy dose of gamma radiation (S = 0.34) the average RBE values for the entrance, proximal half, distal half and distal edge were 1.07 ± 0.01, 1.10 ± 0.01, 1.17 ± 0.01 and 1.21 ± 0.01, respectively, and essentially the same for both beams. At a 2 Gy dose of gamma radiation (S = 0.71) the average RBE values rose to 1.13 ± 0.03, 1.15 ± 0.02, 1.26 ± 0.02 and 1.30 ± 0.02, respectively, for the same four regions of the SOBP. The difference between the 4 Gy and 2 Gy RBE values reflects the dose dependence of RBE as measured in these V79-WNRE cells, which have a low α/β value, as do other widely used cell lines that also show dose-dependent RBE values. Late-responding tissues are also characterized by low α/β values, so it is possible that these cell lines may be predictive for the response of such tissues (e.g., spinal cord, optic nerve, kidney, liver, lung). However, in the very small number of studies of late-responding tissues performed to date there appears to be no evidence of an increased RBE for protons at low doses. Similarly, RBE measurements using early responding in vivo systems (mostly mouse jejunum, an early-responding tissue which has a large α/β ∼ 10 Gy) have generally shown little or no detectable dose dependence. It is useful to compare the RBE values reported here to the commonly used generic clinical RBE of 1.1, which assumes no dependence on depth or on dose. Our proximal RBEs obviously avoid the depth-related increase in RBE and for doses of 4 Gy or more, the low-dose increase in RBE is also minimized, as shown in this article. Thus the proximal RBE at a 4 Gy dose of 1.10 ± 0.01, quoted above, represents an interesting point of congruence with the clinical RBE for conditions where it could reasonably be expected in the measurements reported here. The depth dependence of RBE reported here is consistent with the majority of measurements, both in vitro and in vivo, by other investigators. The dose dependence of RBE, on the other hand, is tissue specific but has not yet been demonstrated for protons by RBE values in late-responding normal tissue systems. This indicates a need for additional RBE determination as function of dose, especially in late-responding tissues.

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“…Similarly, several in vitro Chinese hamster cell survival studies have not indicated any change in RBE as the dose decreased, such as the studies of Yashkin et al (1995) who irradiated clone 431 cells with 179 MeV protons, or of Gueulette et al (1996) in CHO cells exposed to 85 MeV protons. Over the centre of the SOBP, Yashkin et al (1995) obtained RBE values of 1.07 and 1.08 at SF = 0.1 and SF = 0.37, respectively.…”

Section: Discussionmentioning

confidence: 99%

Relative biological effectiveness of the 60-MeV therapeutic proton beam at the Institute of Nuclear Physics (IFJ PAN) in Kraków, Poland

Słonina

Biesaga

Swakoń

et al. 2014

Radiat Environ Biophys

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The aim of the study was to determine the relative biological effectiveness (RBE) of a 60-MeV proton radiotherapy beam at the Institute of Nuclear Physics, Polish Academy of Sciences (IFJ PAN) in Kraków, the first one to operate in Poland. RBE was assessed at the surviving fractions (SFs) of 0.01, 0.1, and 0.37, for normal human fibroblasts from three cancer patients. The cells were irradiated near the Bragg peak of the pristine beam and at three depths within a 28.4-mm spread-out Bragg peak (SOBP). Reference radiation was provided by 6-MV X-rays. The mean RBE value at SF = 0.01 for fibroblasts irradiated near the Bragg peak of pristine beam ranged between 1.06 and 1.15. The mean RBE values at SF = 0.01 for these cells exposed at depths of 2, 15, and 27 mm of the SOBP ranged between 0.95–1.00, 0.97–1.02, and 1.05–1.11, respectively. A trend was observed for RBE values to increase with survival level and with depth in the SOBP: at SF = 0.37 and at the depth of 27 mm, RBE values attained their maximum (1.19–1.24). The RBE values estimated at SF = 0.01 using normal human fibroblasts for the 60-MeV proton radiotherapy beam at the IFJ PAN in Kraków are close to values of 1.0 and 1.1, used in clinical practice.

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Relative biological effectiveness of proton medical beam at Moscow synchrotron determined by the Chinese hamster cells assay

Cited by 22 publications

References 8 publications

Comparison of radiobiological effective depths in 65-MeV modulated proton beams

Comparison of radiobiological effective depths in 65-MeV modulated proton beams

Radiobiological Intercomparison of the 160 MeV and 230 MeV Proton Therapy Beams at the Harvard Cyclotron Laboratory and at Massachusetts General Hospital

Relative biological effectiveness of the 60-MeV therapeutic proton beam at the Institute of Nuclear Physics (IFJ PAN) in Kraków, Poland

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