Sample size calculation
toxicities, DLT
ADVERSE EVENTS, EVENT, ADVERSE EVENT
The study is designed as a single arm, multi-center dose escalation trial employing the i3 + 3 design assuming that 15 patients will be treated and an event rate of 20% is acceptable (Fig. The ITV dose will be escalated from 27.0 Gy to an ITV prescription dose-equivalent level of maximum 35.1 Gy while keeping the PTV prescription dose constant at 25 Gy after each patient if no dose limiting toxicities (DLT) have occurred (E). If a DLT is observed within the first five patients, the dose will not be further increased unless 5 patients were treated at the same dose (S) without occurrence of another DLT in one of these remaining four patients (Fig. 
Simulation of the dose escalation according to the occurrence of adverse events. Unless an adverse event is registered, dose escalation until the target dose will follow with each patient