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Is "New Radiobiology" Needed to Account for the Anti-Tumor Efficacy of Hypofractionated Lung SBRT?

J Jeong

J Jeong¹*, JH Oh¹ , S Rao² , J O Deasy¹ , (1) Memorial Sloan Kettering Cancer Center, New York, NY, (2) U.C. Davis Comprehensive Cancer Center, Sacramento, CA

Presentations

WE-G-BRD-5 Wednesday 4:30PM - 6:00PM Room: Ballroom D

Purpose: The radiobiological understanding of SBRT is controversial. In this work, we modeled SBRT outcomes based on a previously published tumor control probability model, that incorporates hypoxia, proliferation and cell-cycle effects, in order to understand if non-traditional factors must be invoked to understand the efficacy of single and multiple fraction SBRT.

Methods: We extracted cohorts from Mehta et al. (PRO (2012) 2:288) with easily identifiable fractionation parameters and commensurate outcome and prescription methods (n=2617). Each RT scheme was simulated in the model, and the surviving fraction (SF) of tumor cells was estimated. Another simulation was then carried out with conventional (2Gy/fx, 5fx/wk) fractionation until the same SF was achieved, resulting in model-derived equivalent dose in 2Gy/fx for α/β=10 (EQD2₁₀(model)). In the scatter plot of the outcome vs. EQD2₁₀(model), logistic regressions were performed for the total group or separate groups (conventional RT, SBRT with 3-10 fxs, and single fx SBRT), assuming the slope of the dose response curve (γ₅₀) of 1.5. Chi-squared tests were performed to test the validity of the fit.

Results: With unfavorable hypoxic and cell-cycle effects, the effectiveness of typical SBRT regimes were predicted by the model to be significantly less effective than comparable standard fractionation regimes. The single-fraction TD₅₀ was only 55% of the conventional fractionation TD₅₀, in units of EQD2₁₀(model). The dose response curves for the separate fractionation groups seems to represent the three different groups, with a high p-value for both SBRT groups. For the lower α/β of 3, the same patterns were observed with smaller differences among the groups.

Conclusion: Based on classical radiobiology, the dose response relation of SBRT was evaluated and compared with conventional RT. Observed SBRT outcomes are inconsistent with classical radiobiology principles, suggesting the possible other effects, which increases as the fractional dose increases.


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