For the treatment of locally advanced cervical cancer (LACC), proton therapy has been proposed as an alternative to photon therapy to mitigate the treatment-induced morbidities. The large anatomic variations in the pelvis presents a challenge in achieving adequate target coverage and therefore plan-of-the-day (PotD) strategies have been proposed. However, appropriate robustness settings for a PotD strategy for LACC IMPT are currently lacking. The aim of this study is to determine these settings by evaluating the dose of simulated treatment courses. This study included thirteen patients treated for LACC. For each patient, a full and empty bladder planning CT scan (pCT) and three to five weekly repeat CT scans (reCTs) were available. ITVs were constructed by interpolating between the cervix-uteri on the pCTs. Depending on the range of motion, a library of 1 to 4 plans was created. Four-beam IMPT plans were created using our in-house automated treatment planning system. For optimization and evaluation, five set-up robustness (SR) settings were considered, namely 2, 3, 4, 5, or 7 mm set-up error. On top of that, a 3% range robustness (RR) was used. The evaluation was done on 28 error scenarios. The prescribed dose to the targets was V42.75 Gy > 95% on the voxelwise-min dose. Ten treatments per patient were simulated by recalculating the dose on the reCTs, with additional simulated treatment uncertainties. Adequate coverage was assumed when at least 90% of the treatments had a target coverage of V42.75 Gy > 95%. This was evaluated on the low-risk CTV (CTV-LR) and elective CTV (CTV-E) by accumulating the dose on the different reCTs. The volume that gets >40 Gy was also quantified for five different OAR. In total, 125 treatment plans were created. With these plans, 130 treatments were simulated on the reCTs. The table shows the percentage of the 130 treatments that reached the dose criterion for the five SR error scenarios. For a SR of 4 mm and larger, the dose criterion is fulfilled for the CTV-E in at least 90% of the treatments. For the CTV-LR, adequate coverage could not be reached for any of the five robustness settings. The table also shows the relative volume receiving >40 Gy for five OAR. All OAR V40 increase linearly with larger SR. Adequate CTV-E coverage with a PotD strategy was reached with modest robust optimization. For the CTV-LR, however, this could not be achieved, not even with an SR of 7 mm. Since the setup is a global parameter and a larger SR would greatly increase the dose for OAR, we advocate the addition of margins around the ITV to address the underdosages.
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