Title:
Potential increase in biological effectiveness from field timing optimization for stereotactic body radiation therapy.

Abstract:
Stereotactic body radiation therapy (SBRT) is a radiotherapy technique which uses high dose fractions with multiple coplanar and noncoplanar beams. Due to the large fractional doses, treatments are typically protracted and there are more fields than in conventional radiation treatment schemes. The effect of temporal optimization on the biological effectiveness of SBRT is not well established.
In a cohort of actual SBRT patient treatments, the Lea-Catcheside protraction factor (G-value) was used to determine the optimal (Δ) and the least favorable (V) field. An actual field timing delivered in the clinic was included (C) for comparison. The lethal potential lethal (LPL) model was used to quantify the difference in survival fractions. Published data from three cell lines for non-small cell lung cancers: H460, H660, and H157 were used to acquire the parameters needed by the LPL model. The results are expressed as the ratios (V:Δ)(N) and (C:Δ)(N), where N is the number fractions in the SBRT protocols and Δ, V, and C are the survival fractions calculated from the corresponding temporal patterns.
The results indicate that variability in the dose rate between fields does impact the optimization results. This dependence on dose rate, however, is small compared to the impact from the variability in doses between fields. The optimized field arrangements resembled previous studies, that maximization of cell kill is achieved by orienting the fields in a Δ shape sequence, where the fields with greatest dose are positioned in the center. Minimization of cell kill was achieved with a V-shaped orientation. Smallest dose fields were positioned centrally, and higher dose fields were placed in the beginning and end of the fraction. The survival fraction ratios calculated using the LPL demonstrated that regardless of the cell type the Δ shape had lower cell survival fractions compared to both the clinical example (C) and the V arrangement. For H460, with T(1/2) = 0.25 h, an average ratio of (C:Δ)(5)=13.9, suggesting the Δ pattern is approximately 14 times more effective than the clinical plan, after 5 fractions.
Rearranging field timing for a SBRT treatment so that maximal dose is deposited in the central fields of treatment may optimize cell kill and potentially affect overall treatment outcome.