Why RBE must be a variable and not a constant in proton therapy

Abstract

Objective: This article considered why the proton therapy (PT) relative biological effect (RBE) should be a variable rather than a constant. Methods: The reasons for a variable proton RBE are enumerated, with qualitative and quantitative arguments. The heterogeneous data sets collated by Paganetti et al (2002) and the more homogeneous data of Britten et al (2013) are further analyzed using linear regression fitting and RBE-inclusive adaptations of the linear-quadratic (LQ) radiation model.

Three Discipline Collaborative Radiation Therapy (3DCRT) Special Debate: I would treat prostate cancer with proton therapy

“…We agree that the generic use of proton RBE of 1.1 in all tissue types at all doses and LET values is not an optimal ratio for proton dose modification. However, the debate regarding this ratio is still ongoing for many reasons including the fact that it was derived almost entirely from clonogenic cell survival assays of early reacting tissues . In prostate cancer, the unusually low α/β ratio (1.5 Gy) is more reminiscent of late reacting tissues than most tumors types (~10 Gy) and is still lower than the α/β ratio of late‐responding normal rectal tissues (~3 Gy).…”

Proton relative biological effectiveness (RBE): a multiscale problem

“…Animal models are likely to prove particularly helpful in validating the performance of RBE models in terms of tolerance doses and fractionation effects. 23 Application of advanced imaging techniques may enable us to further probe RBE effects pre-clinically for relevant end points.…”

The use of a constant RBE=1.1 for proton radiotherapy is no longer appropriate

“…Despite this, variable RBE models are clinical standard for carbon ions whereas a constant RBE of 1.1 is recommended for protons . This disregards the multifactorial nature of RBE: radiobiological principles and in vitro experiments strongly indicate that proton RBE varies with biological end point, dose, linear energy transfer (LET), and tissue type …”

“…Nevertheless, it should be emphasized that the constant RBE = 1.1 is also a model, derived from experimental data in the SOBP midpoint . Consequently, as the RBE is expected to be greater than 1.1 in the distal part of the proton range, for low doses and for low α / β ‐tissues, the use of a constant RBE may underestimate potential adverse effects . On the other hand, the proponents of the constant RBE model argue that its use has not been disproved this far by clinical experience, since higher than anticipated toxicity rates have not been observed.…”