Stephanie M de Boer

Margin and robustness settings for a library-of-plans IMPT strategy for locally advanced cervical cancer

Abstract Objective. This study aims to determine a margin and robustness setting for treating locally advanced cervical cancer (LACC) with a library-of-plans (LoP) based online-adaptive intensity-modulated proton therapy (IMPT). Approach. We analyzed 13 LACC patients with delineated planning and weekly repeat CT scans (reCTs). For each patient, 120 IMPT treatments of 25 fractions were simulated with a LoPs approach. Six different robustness settings (2–7 mm set-up robustness (SR) plus 3% range robustness (RR)) were used to create those 120 IMPT plans. Each fraction was simulated with a weekly reCT, combined with the sampling of inter- and intrafraction treatment uncertainties. The fraction doses were accumulated to obtain a treatment dose to the target volumes, distinguishing between the low-risk clinical target volume (CTV-T-LR) and the elective CTV (CTV-E). If one of the two targets obtained an adequate coverage for more than 90% of the treatments, different anisotropic margins were sampled on top of the robustness setting to the other target to obtain the Pareto-optimal margin in terms of adequate coverage versus increase in target volume. Main results. The percentage of treatments that reach the dose criterion V 42.75Gy > 95% for the CTV-T-LR was 22.3%, 28.5%, 51.2%, 73.1%, 85.3%, and 90.0% for 2, 3, 4, 5, 6, and 7 mm SR plus 3% RR and for the CTV-E, this percentage was 60.4%, 73.8%, 86.5%, 92.3%, 96.9%, and 98.5%. The Pareto-optimal margin combined with a 5 mm/3% robustness setting for the CTV-T-LR with an adequate coverage for >90% of the treatments was given by {0, 1, 0, 3, 3, 0} mm in the left, right, anterior, posterior, cranial, caudal direction. Significance. Our study evaluated combinations of robustness and anisotropic margin settings for IMPT for LACC. With 5 mm SR and 3% RR for CTV-E and CTV-T-LR plus a margin to the CTV-T-LR of {0, 1, 0, 3, 3, 0} mm in left, right, anterior, posterior, cranial, and caudal ensured an adequate coverage for >90% of the simulated IMPT treatments.

Predicting lymphocyte dose and surviving fraction for VMAT and IMPT treatments with a dynamic lymphocyte flow model for locally advanced cervical cancer

Abstract Objective. A dynamic model is developed to predict the impact of radiotherapy on circulating lymphocyte counts in women with locally advanced cervical cancer (LACC). This study aims to compare the effects of photon and proton therapy, as well as the influence of bone marrow sparing (BMS) techniques, on relative lymphocyte preservation over time. Approach. A dynamic lymphocyte flow model was developed to simulate the migration of lymphocytes based on seven compartments. Biological cell death and lymphocyte production were integrated across compartments. The lymphocyte flow model was applied to 19 LACC patients. Volumetric modulated arc therapy (VMAT) and intensity modulated proton therapy (IMPT) treatment plans were created for each patient without BMS and with BMS. The model calculated radiation dose to lymphocytes to estimate radiation-induced cell death over time. The output of the model was the relative lymphocyte count relative to baseline (RLC) over time and the RLC nadir in the blood and total body. Main results. According to the model, IMPT resulted in lower doses to lymphocyte and higher RLC nadirs compared to VMAT for all 19 patients. The total RLC nadir (mean ± SD) was 48.4% ± 4.0% for VMAT and 62.5% ± 5.1% for IMPT. In the blood compartment, the RLC nadir was 32.7% ± 3.5% for VMAT and 47.7% ± 5.9% for IMPT. The RLC nadir in the blood compartment improved with 3 Gy BMS from 32.7% ± 3.5% to 33.0% ± 3.5% , while it decreased for IMPT from 47.7% ± 5.9% to 46.6% ± 6.0%. Total RLC nadir decreased with BMS for VMAT from 48.4% ± 4.0% to 48.2% ± 3.9% and for IMPT from 62.5% ± 5.1% to 60.9% ± 5.3%. Significance. By incorporating a dynamic flow model, we predicted the RLC over time. The model predicted a substantial sparing effect IMPT has on the lymphocytes compared to VMAT. This sparing was both present in the blood and the total body. Sparing the bone marrow showed only a minimal effect on the RLC.