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

Abstract

The effect of carbon ion radiotherapy on hypoxic tumors has recently been questioned because of low linear energy transfer (LET) values in the spread-out Bragg peak (SOBP). The aim of this study was to investigate the role of hypoxia and local oxygenation changes (LOCs) in fractionated carbon ion radiotherapy. Three-dimensional tumors with hypoxic subvolumes were simulated assuming interfraction LOCs. Different fractionations were applied using a clinically relevant treatment plan with a known LET distribution. The surviving fraction was calculated, taking oxygen tension, dose and LET into account, using the repairable–conditionally repairable (RCR) damage model with parameters for human salivary gland tumor cells. The clinical oxygen enhancement ratio (OER) was defined as the ratio of doses required for a tumor control probability of 50% for hypoxic and well-oxygenated tumors. The resulting OER was well above unity for all fractionations. For the hypoxic tumor, the tumor control probability was considerably higher if LOCs were assumed, rather than static oxygenation. The beneficial effect of LOCs increased with the number of fractions. However, for very low fraction doses, the improvement related to LOCs did not compensate for the increase in total dose required for tumor control. In conclusion, our results suggest that hypoxia can influence the outcome of carbon ion radiotherapy because of the non-negligible oxygen effect at the low LETs in the SOBP. However, if LOCs occur, a relatively high level of tumor control probability is achievable with a large range of fractionation schedules for tumors with hypoxic subvolumes, but both hyperfractionation and hypofractionation should be pursued with caution.

Treatment fractionation for stereotactic radiotherapy of lung tumours: a modelling study of the influence of chronic and acute hypoxia on tumour control probability

“…By randomly re-distributing the p O 2 -values between voxels at each fraction, experimentally observed local variations in oxygenation between fractions [16] were simulated [19-21,28]. …”

Tumor Control Probability Analysis for Single-Fraction Carbon-Ion Radiation Therapy of Early-Stage Non-small Cell Lung Cancer

“…Reoxygenation of hypoxic subvolumes in the tumor between fractions can increase radiosensitivity and, therefore, improve the treatment performance. (27) Apart from this outcome, fractionation could also take advantage of the redistribution of cells within the cell cycle such that cells in a radioresistant state turn into more sensitive ones over time. (28) Thus, better tumor control can be expected for an increased number of fractions.…”

Radiobiological issues in prospective carbon ion therapy trials

“…It is beyond the scope of this article to summarize all foreseen developments of CIRT, but it is important to mention those that may involve issues regarding RBE uncertainties similar to or even more delicate than those discussed above. One issue that is currently investigated is the possibility to describe quantitatively at least some of the parameters that affect RBE, most importantly tumor hypoxia …”

“…One issue that is currently investigated is the possibility to describe quantitatively at least some of the parameters that affect RBE, most importantly tumor hypoxia. [102][103][104][105][106][107] Measuring the voxel-by-voxel degree of hypoxia and using these data to modify the voxel-by-voxel RBE could be interesting for both, to describe what is being delivered in case oxygenation without considering oxygenation in the RBEweighted dose optimization, and maybe also use this information within the optimization process. In photon RT, the only suggested modification of the treatment plan is to escalate the dose either uniformly or to increase the dose selectively in the hypoxic regions using "dose-painting."…”