Abstract

Cássia O. Ribeiro¹, Erik W. Korevaar¹, Sabine Visser¹, Adriaan C. Hengeveld¹, Gabriel G. Marmitt¹, Johannes A. Langendijk¹, Robin Wijsman¹, Antje Knopf¹, Arturs Meijers¹, Stefan Both¹

¹University Medical Center Groningen, Department of Radiation Oncology, Groningen, The Netherlands

Despite the anticipated clinical benefits of intensity-modulated proton therapy (IMPT), plan robustness may be compromised due to its sensitivity to patient treatment uncertainties. Especially for tumours with large motion amplitudes, respiratory-induced dosimetric impacts may be assessed through 4D dose accumulation based on 4DCT images. To prospectively verify our IMPT planning protocol, we developed a 4D robustness evaluation method (4DREM) to predict the influence of possible disturbances on the treatment course dose for thoracic indications. Here we aim to verify if the pre-clinical 4DREM dose is representative for the actual clinical 4D accumulated dose delivery for tumours with motion over 10 mm.

For 9 lung and 1 thymoma cancer patients referred for proton therapy, planning and weekly verification 4DCTs were collected. Point maximum CTV motion on the planning 4DCT was extracted for all patients (Table 1). Layered rescanned (x5) 3D robust optimised IMPT (IMPT_3D) plans were generated on the averaged planning 4DCT, and approved clinically, for all patients. All plans were delivered in dry runs at our proton facility to obtain pre-treatment log files, and subsequently evaluated through our 4DREM. With this method, for each evaluated plan, 14 4D accumulated scenario doses were obtained, representing 14 possible fractionated treatment courses. Throughout the patient clinical treatment, breathing pattern records (from the Anzai belt system) and log files were acquired for all fractions. This patient treatment delivery information was used for a fraction-wise 4D dose reconstruction, and a subsequent dose accumulation (4DREAL), which estimates the entire clinical treatment course dose. The accumulated 4DREAL dose was then used to confirm the pre-clinical 4DREM dose for all patients.

No clinically relevant differences in target coverage between 4DREM and accumulated 4DREAL dose distributions were observed (Fig. 1A). Inter-patient variability of V₉₅(CTV) values and target homogeneity (D₂-D₉₈(CTV)) was consistent between both methods (Fig. 1B.I). However, relative to the 4DREM, the 4DREAL mostly showed lower D₂-D₉₈(CTV) values, with a mean difference of 0.20 ± 0.24 Gy_RBE over all patients. This can be due to the fact that residual setup errors and range uncertainties are simulated in the 4DREM, through error scenarios resulting in voxel-wise dose distributions. Furthermore, averaged D_mean(lungs-GTV) and D_mean(heart) over all 4DREM scenarios changed only slightly (maximum SD = 0.59 Gy_RBE), and were comparable to the respective 4DREAL accumulation (Fig. 1B.II).

Rescanned IMPT_3D was found to be suitable to treat thoracic tumours in free breathing for motion up to 16 mm, in both pre-clinical 4DREM and clinical 4DREAL. Our comprehensive 4DREM was able to accurately estimate the clinical delivery. Therefore, this method can be safely used as a pre-clinical treatment course quality control tool for IMPT planning protocols.