The Importance of Quasi-4D Path-Integrated Dose Accumulation for More Accurate Risk Estimation in Stereotactic Liver Radiotherapy.

Intrafraction organ deformation may be accounted for by inclusion of temporal information in dose calculation models. In this article, we demonstrate a quasi-4-dimensional method for improved risk estimation. Conventional 3-dimensional and quasi-4-dimensional calculations employing dose warping for dose accumulation were undertaken for patients with liver metastases planned for 42 Gy in 6 fractions of stereotactic body radiotherapy. Normal tissue complication probabilities and stochastic risks for radiation-induced carcinogenesis and cardiac complications were evaluated for healthy peripheral structures. Hypothetical assessments of other commonly employed dose/fractionation schedules on normal tissue complication probability estimates were explored. Conventional 3-dimensional dose computation may result in significant under- or overestimation of doses to organ at risk. For instance, doses differ (on average) by 17% (σ = 14%) for the left kidney, by 14% (σ = 7%) for the right kidney, by 7% (σ = 9%) for the large bowel, and by 10% (σ = 14%) for the duodenum. Discrepancies in the excess relative risk range up to about 30%. The 3-dimensional approach was shown to result in cardiac complication risks underestimated by >20%. For liver stereotactic body radiotherapy, we have shown that conventional 3-dimensional dose calculation may significantly over-/underestimate dose to organ at risk (90%-120% of the 4-dimensional estimate for the mean dose and 20%-150% for D2%). Providing dose estimates that most closely represent the actual dose delivered will provide valuable information to improve our understanding of the dose response for partial volume irradiation using hypofractionated schedules. Excess relative risks of radiocarcinogenesis were shown to range up to approximately excess relative risk = 4 and the prediction thereof depends greatly on the use of either 3-dimensional or 4-dimensional methods (with corresponding results differing by tens of percent).