Fig. 4.

Clinical case showing the impact of anatomic changes during proton radiotherapy in clinical target volume (CTV) coverage and critical tissue toxicity in a proton dose-escalated clinical trial. (A) Isodose distribution showed increased normal tissue doses after 5 weeks of proton therapy because of tumor shrinkage and adapted proton plan. (a) Original plan based on simulation four-dimensional computed tomography (4D-CT). (b) Original plan recalculated on basis of 4DCT after 5 weeks of treatment. (c) Re-plan based on CT after 5 weeks of treatment. (B) Dose–volume histograms showing increased normal tissue doses after 5 weeks of proton therapy because of tumor shrinkage and reduced doses resulting from the adaptive proton therapy plan. Dashed line indicates original plan; solid line indicates original plan recalculated based on CT taken after 5 weeks of proton therapy; dot-dashed line indicates re-plan. The dose increased to the brachial plexus (7% over 60 Gy) and esophagus (14% over 55 Gy) at 5 weeks if no re-planning was conducted. However, the adaptive plan reduced the dose to the brachial plexus (<1% over 50 Gy) and the esophagus (<3% over 55 Gy).