Tumor Control Probability Analysis for Single-Fraction Carbon-Ion Radiation Therapy of Early-Stage Non-small Cell Lung Cancer

Abstract

To investigate the suitability of the linear-quadratic (LQ) and universal survival curve (USC) models in describing the 3-year tumor control probability data of patients with stage I non-small cell lung cancer treated with carbon-ion radiation therapy. Carbon-ion radiation therapy was given at a total dose of 59.4 to 95.4Gy (relative biological effectiveness [RBE]) in 18 fractions, at 72Gy[RBE] in 9 fractions, at 52.8 to 60Gy[RBE] in 4 fractions, and at 28 to 50Gy[RBE] in a single fraction. A meta-analysis of published clinical data from 394 patients presenting with early-stage non-small cell lung cancer was conducted. Tumor control probability modeling based on the LQ and USC models was performed by simultaneously fitting the clinical data obtained from the different fractionation schedules while considering several spread-out Bragg peak (SOBP) sizes. Radiobiological parameters were derived from the fit. On the basis of the results, a novel SOBP was created for the single-fraction regimen that was optimized with respect to the USC model and aimed at achieving a 95% local control. The USC model gave a better fit to the 3-year local control data than the LQ modeldid. The fit using various SOBP sizes yielded transition doses between 5.6 and 7.0Gy. The results also revealed α/β ratios between 7.4 and 9.1Gy for the LQ model and between 7.4 and 9.4Gy for the USC model. The USC model provided a better estimate of the local control rate for the single-fraction course. For the schemes with a greater number of fractions, the local control rate estimates from the LQ and USC models were comparable. A USC-based SOBP design was then created for the single-fraction schedule. The updated design resulted in a flatter RBE profile compared with the conventional SOBP design. It also gave a better clinical dose prediction to optimize the tumor control rate.