On the effect of dose delivery temporal domain on the biological effectiveness of central nervous system CyberKnife radiosurgery applications: theoretical assessment using the concept of biologically effective dose

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Objective: The diversity in technical configuration between clinically available radiosurgery systems, results in accordingly diverse treatment times for the same physical dose prescription, spanning from several min to more than 1 h. This, combined with evidence supporting the impact of dose delivery temporal pattern on the bio-effectiveness of low-LET radiation treatments, challenges the ‘acute exposure’ assumption adopted clinically to estimate the biological outcome of a given treatment scheme under the concept of biologically effective dose (BED). Approach: In this work, the treatment plans of 30 patients underwent CyberKnife radiosurgery for vestibular schwannoma (VS), prescribing a marginal dose of 13 Gy to the tumor, were retrospectively reviewed and the corresponding dose distributions were resolved in the temporal domain. For this purpose, the dose delivery timeline for each treatment was calculated based on relevant treatment plan data and technical specifications of the CyberKnife system, while dosimetry data were independently acquired on a CT-based digital model of each patient using an in-house developed dose calculation algorithm. Main results: Results showed that CyberKnife delivers highly inhomogeneous dose rate distributions in the temporo-spatial domain. This influences the delivered BED levels due to alterations in the sublethal damage repair (SLR) occurring within the treatment session. Using a BED framework involving SLR effects, it was shown that each physical dose iso-surface is associated with a BEDslr range. For the patient cohort studied, a typical range of 2%, with respect to the mean BEDslr value was found at 1σ. Significance: The marginal BEDslr delivered to the tumor by the prescription dose iso-surface deteriorates with treatment time, involving both beam-on time and beam-off gaps. For treatment time, T, between 21 and 50 min, this can be expressed by Compared to the acute exposure approach, a BED ‘loss’ of 21% is associated with the delivery of 13 Gy to the VS-tumor in 35 min.