To fractionate or not to fractionate? That is the question for the radiosurgery of hypoxic tumors

Abstract

ObjectThis study aimed to investigate the impact of tumor hypoxia on treatment outcome for metastases commonly treated with radiosurgery using 1 fraction of radiation and the potential gain from reoxygenation if the treatment is delivered in a few radiation fractions.MethodsIn silico metastasis-like radiosurgery targets were modeled with respect to size, density of clonogenic cells, and oxygenation. Treatment plans were produced for the targets using Leksell GammaPlan, delivering clinically relevant doses and evaluating the tumor control probability (TCP) that could be expected in each case. Fractionated schedules with 3, 4, and 5 fractions resulting in similar biological effective doses were also considered for the larger target, and TCP was determined under the assumption that local reoxygenation takes place between fractions.ResultsThe results showed that well-oxygenated small- and medium-size metastases are well controlled by radiosurgery treatments delivering 20 or 22 Gy at the periphery, with TCPs ranging from 90% to 100%. If they are moderately hypoxic, the TCP could decrease to 60%. For large metastases, the TCPs from single-fraction treatments ranged from 0% to 19%, depending on tumor oxygenation. However, for fractionated treatments, the TCP for hypoxic tumors could significantly increase up to 51%, if reoxygenation occurs between fractions.ConclusionsThis study shows that hypoxia worsens the response to single-fraction radiosurgery, especially for large tumors. However, fractionated therapy for large hypoxic tumors might considerably improve the TCP and might constitute a simple way to improve the outcome of radiosurgery for patients with hypoxic tumors.

Carbon Ion Radiobiology

“…Hypoxia can also be tackled with specific drugs (hypoxia sensitizers), some of them currently in promising clinical trials [ 142 , 143 , 144 , 145 ]. Nevertheless, it remains a negative prognostic factor and a major hindrance to radiotherapy, especially in hypofractionation, when reoxygenation is limited or absent [ 146 , 147 , 148 , 149 ].…”

Radiation-induced Vascular Damage and the Impact on the Treatment Outcome of Stereotactic Body Radiotherapy

“…Furthermore, the effect of redistribution can be disregarded given that high doses are likely to cause cellcycle arrest (5). The limited treatment time and low number of fractions also imply that reoxygenation is limited, indicating that hypoxia has an even bigger impact on the outcome of SRS and SBRT compared to conventionally fractionated radiotherapy (3,6,7). While slow reoxygenation following chronic hypoxia is typically associated with tumour shrinkage, it is highly unlikely to happen during a hypofractionated treatment course where fast reoxygenation of acute hypoxia is expected to occur between individual fractions (8).…”

Comparison of volumetric modulated arc therapy and intensity modulated radiation therapy for whole brain hippocampal sparing treatment plans based on radiobiological modeling

“…TCP calculations have been utilized for the treatment of brain tumors, both in the setting of stereotactic radiation therapy as well as with standard fractionation radiation therapy. [ 17 18 19 ] The parameters used in our model are consistent with what has been used in these reports. However, there is little information specific to the setting of HA-WBRT with IMRT or VMAT, where the overall dose distribution is more heterogeneous, and our results represent best estimates for this setting.…”