Proton RBE for early intestinal tolerance in mice after fractionated irradiation

Gueulette, John; Slabbert, Jacobus; Böhm, Lothar; Coster, B M De; Rosier, Jean-François; Octave-Prignot, M; Ruifrok, Arnout; Schreuder, A; Wambersie, André; Scalliet, Pierre; Jones, D. T. L.

doi:10.1016/s0167-8140(01)00446-7

Cited by 39 publications

(35 citation statements)

References 29 publications

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“…The first study used graded single doses and reported a consistent and (sometimes) significant increase in RBE with decreasing dose, measured at the entrance and at the proximal, middle and distal positions in a 7 cm SOBP (23). The second study used 1, 3 and 10 fraction regimes and reported very consistent and similar RBEs of 1.15 6 0.04, 1.15 6 0.05 and 1.14 6 0.07, respectively (compared to 60 Co), measured at the midpoint of a 7 cm SOBP (24). The a/b value was reported as 6.2 Gy for the first experiment and 7.5 Gy for the second.…”

Section: Dose Dependence Of Rbementioning

confidence: 79%

“…Early in vivo studies at the Harvard Cyclotron (160 MeV) measured the RBE only at midpeak (10 cm SOBP) and, in some cases, at the entrance plateau (19)(20)(21)(22). Later studies by Gueulette and colleagues on two different beams [National Accelerator Center (NAC), South Africa and Paul Scherrer Institute, Switzerland] using mouse jejunum crypt regeneration, showed trends of RBE increasing with depth (23)(24)(25). Lung tolerance in mice also showed an elevated RBE in the distal peak (26).…”

Section: Rbe Dependence On Depthmentioning

confidence: 99%

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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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Section: Dose Dependence Of Rbementioning

confidence: 79%

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 aim was to estimate the RBE weighted dose in different positions within the target volume and to evaluate the RBE values of the therapeutic CNAO carbon ion beams with a reference biological system, i.e. the intestinal crypt regeneration in mice [36,37]. This experimental activity was conducted thanks to the collaboration and expertise of the radiobiology group of NIRS and to the logistic support of the animal house of the Interdepartmental Centre of Services for the Unified Management of Stabling and Radiobiology of the University of Pavia.…”

Section: Radiobiology Characterization E In Vivomentioning

confidence: 99%

The National Centre for Oncological Hadrontherapy (CNAO): Status and perspectives

Rossi

2015

Physica Medica

110

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“…Empirical evidence would indicate a dependence of RBE on linear energy transfer (LET) that is known to vary with depth along the proton track. Several investigations have measured variation in RBE with depth in a biological absorber for both in vitro 10,[18][19][20][21][22][23][24][25][26] and in vivo, [27][28][29][30][31] systems. Experimental conditions have used various cell lines with differences in sampling along the SOBP, initial beam energy, RBE calculation method, tissue type, and LET estimation.…”

Section: Discussionmentioning

confidence: 99%

“…Nonetheless, this work and the work of others 8,14,17,30,35 make it clear that although we have an excellent understanding of the dose deposition physics of charged particle irradiation, we do not have sufficient understanding of the biological responses to that energy absorption. Because it is the biological response that is driving the clinical prognosis, this uncertainty is quite compelling.…”

Section: Np4mentioning

confidence: 95%

Rapid RBE-Weighted Proton Radiation Dosimetry Risk Assessment

Qutub

Klein

Buchsbaum

2016

Technol Cancer Res Treat

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Proton therapy dose is affected by relative biological effectiveness differently than X-ray therapies. The current clinically accepted weighting factor is 1.1 at all positions along the depth-dose profile. However, the relative biological effectiveness correlates with the linear energy transfer, cell or tissue type, and the dose per fraction causing variation of relative biological effectiveness along the depth-dose profile. In this article, we present a simple relative biological effectiveness-weighted treatment planning risk assessment algorithm in 2-dimensions and compare the results with those derived using the standard relative biological effectiveness of 1.1. The isodose distribution profiles for beams were accomplished using matrices that represent coplanar intersecting beams. These matrices were combined and contoured using MATLAB to achieve the distribution of dose. There are some important differences in dose distribution between the dose profiles resulting from the use of relative biological effectiveness ¼ 1.1 and the empirically derived depth-dependent values of relative biological effectiveness. Significant hot spots of up to twice the intended dose are indicated in some beam configurations. This simple and rapid risk analysis could quickly evaluate the safety of various dose delivery schema.

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Proton RBE for early intestinal tolerance in mice after fractionated irradiation

Cited by 39 publications

References 29 publications

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

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

The National Centre for Oncological Hadrontherapy (CNAO): Status and perspectives

Rapid RBE-Weighted Proton Radiation Dosimetry Risk Assessment

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