Including oxygen enhancement ratio in ion beam treatment planning: model implementation and experimental verification

Abstract

We present a method for adapting a biologically optimized treatment planning for particle beams to a spatially inhomogeneous tumor sensitivity due to hypoxia, and detected e.g., by PET functional imaging. The TRiP98 code, established treatment planning system for particles, has been extended for including explicitly the oxygen enhancement ratio (OER) in the biological effect calculation, providing the first set up of a dedicated ion beam treatment planning approach directed to hypoxic tumors, TRiP-OER, here reported together with experimental tests. A simple semi-empirical model for calculating the OER as a function of oxygen concentration and dose averaged linear energy transfer, generating input tables for the program is introduced. The code is then extended in order to import such tables coming from the present or alternative models, accordingly and to perform forward and inverse planning, i.e., predicting the survival response of differently oxygenated areas as well as optimizing the required dose for restoring a uniform survival effect in the whole irradiated target. The multiple field optimization results show how the program selects the best beam components for treating the hypoxic regions. The calculations performed for different ions, provide indications for the possible clinical advantages of a multi-ion treatment. Finally the predictivity of the code is tested through dedicated cell culture experiments on extended targets irradiation using specially designed hypoxic chambers, providing a qualitative agreement, despite some limits in full survival calculations arising from the RBE assessment. The comparison of the predictions resulting by using different model tables are also reported.

OH Radicals from the Indirect Actions of X-Rays Induce Cell Lethality and Mediate the Majority of the Oxygen Enhancement Effect

“…AA8 cells were slightly more radiosensitive compared to CHO cells under both oxic and hypoxic conditions, nevertheless, we found that the OER values at the 10% survival level (D 10 or LD 90 ) were similar for both CHO cells (2.68 6 0.15) and AA8 cells (2.76 6 0.08) ( Table 1). The OER values of approximately 3 are in concordance with other published studies and suggest that our hypoxic conditions were close to anoxic conditions used in other studies (15)(16)(17)(18)(19).…”

New challenges in high-energy particle radiobiology

“…Combinations with hypoxic sensitizers have been proposed for SBRT. 52 Owing to the reduction of OER using heavy ions, 14,53 CPTmay be an alternative. Targeting specifically hypoxic regions can be achieved with strategies of dose- 54 or LET-painting.…”

“…Targeting specifically hypoxic regions can be achieved with strategies of dose- 54 or LET-painting. 55 For oligofractionation or single fraction/high dose treatments, use of ions heavier than carbon (such as 16 O) may be beneficial, because with these ions, the OER can be further reduced in the clinically relevant hypoxia region 53 ( Figure 5). Interestingly, SBRT commonly uses a non-uniform dose distribution in the tumour to achieve sharp edges on the border of the target volume.…”

Clinical oxygen enhancement ratio of tumors in carbon ion radiotherapy: the influence of local oxygenation changes

“…Recently, Scifoni et al . presented a possible way to include tumor oxygen status in TRiP ( TR eatment plann i ng for P articles), the standard carbon ion treatment planning system at GSI (Gesellschaft für Schwerionenforschung) [7]. Uniform biological effect is achieved within the tumor by an optimization approach that compensates for the increase in survival level in the hypoxic regions by increasing the dose to these, or redistributing the LET of the beams.…”