Purpose: Proton therapy has been proposed as an alternative to conventional photon therapy for the treatment of locally advanced cervical cancer (LACC) since these patients experience toxicities. Proton therapy may allow for significant sparing of the organs at risk, reducing the incidence of treatment-related morbidities. The aim of this study is to develop a treatment strategy that is robust to motion and uncertainties in intensity-modulated proton therapy (IMPT) for the treatment of LACC.
Materials and methods: Data from 14 LACC patients was included in this study. For each patient, a full and empty bladder planning CT (pCT) scan before treatment and four weekly repeat CT (reCT) scans after daily fraction were available. The full and empty pCT scans were used to create the patient-specific motion model of the cervix-uterus. An anisotropic CTV-to-ITV margin to expand this motion model was explored to account for uterine interfraction target motion. Subsequently, the motion model was divided into subranges to create a library of 1 to 4 plans, depending on the uterine motion due to bladder filling. Range and geometric uncertainties in the treatment of LACC are accounted for by robust optimization and evaluation. For each plan in the plan library, a treatment plan is created using the Erasmus-iCycle treatment planning system, taking into account EMBRACE-II constraints. To investigate whether the combination of margins, plan library, and robustness recipe is safe considering geometric and range uncertainties, ten treatments for each of the fourteen patients were simulated. These simulations were performed by recalculating the optimized treatment plans on the reCT scans with added uncertainties. We assumed that the target coverage was sufficient if the D95 of the target volumes was greater than or equal to 95% in at least 90% of the patients.
Results: Of the 3430 margin recipes that were tested, the margin recipe with 95% cervix-uterus overlap and the smallest target volume was 1, 5, 7, 3, and 3 mm in the left/right, posterior, anterior, cranial, and caudal directions, respectively. The subranges of the motion model were expanded with the anisotropic margin recipe, after which robust optimization (setup robustness 5 mm, range robustness 3%) and evaluation (32 scenarios) of the treatment plans were performed. The treatment simulations showed that the D95 was greater than 42.75 for 99% and 92% of the patients for the cervix-uterus target volume and nodal target volume, respectively.
Conclusion: The anisotropic margin and robustness recipe was robust to motion, geometric uncertainties, and range uncertainties when treating LACC patients with IMPT. Both values comfortably met the delivered dose criterion, indicating the strategy can be further improved.