A fast and robust constraint-based online re-optimization approach for automated online adaptive intensity modulated proton therapy in head and neck cancer.

Objective - In head-and-neck cancer intensity modulated proton therapy (IMPT), adaptive radiotherapy is currently restricted to offline re-planning, mitigating the effect of slow changes in patient anatomies. Daily online adaptations can potentially improve dosimetry. Here, a new, fully automated online re-optimization strategy is presented. In a retrospective study, this online re-optimization approach was compared to our trigger-based offline re-planning (offlineTB re-planning) schedule, including extensive robustness analyses.&#xD;&#xD;Approach - The online re-optimization method employs automated multi-criterial re-optimization, using robust optimization with 1 mm setup-robustness settings (in contrast to 3 mm for offlineTB re-planning). Hard planning constraints and spot addition are used to enforce adequate target coverage, avoid prohibitively large maximum doses and minimize organ-at-risk doses. For 67 repeat-CTs from 15 patients, fraction doses of the two strategies were compared for the CTVs and organs-at-risk. Per repeat-CT, 10.000 fractions with different setup and range robustness settings were simulated using Polynomial Chaos Expansion for fast and accurate dose calculations. &#xD;&#xD;Main results - For 14/67 repeat-CTs, offlineTB re-planning resulted in <50% probability of D98%≥95% of the prescribed dose (Dpres) in one or both CTVs, which never happened with online re-optimization. With offlineTB re-planning, eight repeat-CTs had zero probability of obtaining D98%≥95%Dpres for CTV7000, while the minimum probability with online re-optimization was 81%. Risks of xerostomia and dysphagia grade ≥ II were reduced by 3.5 ± 1.7 and 3.9 ± 2.8 percentage point [mean ± SD] (p<10-5 for both). In online re-optimization, adjustment of spot configuration followed by spot-intensity re-optimization took 3.4 minutes on average. &#xD;&#xD;Significance - The fast online re-optimization strategy always prevented substantial losses of target coverage caused by day-to-day anatomical variations, as opposed to the clinical trigger-based offline re-planning schedule. On top of this, online re-optimization could be performed with smaller setup robustness settings, contributing to improved organs-at-risk sparing.&#xD;&#xD.

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