Dose Escalation for Pancreas SBRT: Potential and Limitations of using Daily Online Adaptive Radiation Therapy and an Iterative Isotoxicity Automated Planning Approach

Purpose: To determine the dosimetric limitations of daily online adaptive pancreas stereotactic body radiation treatment by using an automated dose escalation approach. Methods and Materials: We collected 108 planning and daily computed tomography (CT) scans from 18 patients (18 patients × 6 CT scans) who received 5-fraction pancreas stereotactic body radiation treatment at MD Anderson Cancer Center. Dose metrics from the original non-dose-escalated clinical plan (non-DE), the dose-escalated plan created on the original planning CT (DE-ORI), and the dose-escalated plan created on daily adaptive radiation therapy CT (DE-ART) were analyzed. We developed a dose-escalation planning algorithm within the radiation treatment planning system to automate the dose-escalation planning process for efficiency and consistency. In this algorithm, the prescription dose of the dose-escalation plan was escalated before violating any organ-at-risk (OAR) dose constraint. Dose metrics for 3 targets (gross target volume [GTV], tumor vessel interface [TVI], and dose-escalated planning target volume [DE-PTV]) and 9 OARs (duodenum, large bowel, small bowel, stomach, spinal cord, kidneys, liver, and skin) for the 3 plans were compared. Furthermore, we evaluated the effectiveness of the online adaptive dose-escalation planning process by quantifying the effect of the interfractional dose distribution variations among the DE-ART plans. Results: The median D_95% dose to the GTV/TVI/DE-PTV was 33.1/36.2/32.4 Gy, 48.5/50.9/40.4 Gy, and 53.7/58.2/44.8 Gy for non-DE, DE-ORI, and DE-ART, respectively. Most OAR dose constraints were not violated for the non-DE and DE-ART plans, while OAR constraints were violated for the majority of the DE-ORI patients due to interfractional motion and lack of adaptation. The maximum difference per fraction in D_95%, due to interfractional motion, was 2.5 ± 2.7 Gy, 3.0 ± 2.9 Gy, and 2.0 ± 1.8 Gy for the TVI, GTV, and DE-PTV, respectively. Conclusions: Most patients require daily adaptation of the radiation planning process to maximally escalate delivered dose to the pancreatic tumor without exceeding OAR constraints. Using our automated approach, patients can receive higher target dose than standard of care without violating OAR constraints.