Comparison of 3D and 4D robustly optimized proton treatment plans for non-small cell lung cancer patients with tumour motion amplitudes larger than 5 mm

Abstract

Background and purpose: There is no consensus about an ideal robust optimization (RO) strategy for proton therapy of targets with large intrafractional motion. We investigated the plan robustness of 3D and different 4D RO strategies.

Materials and methods: For eight non-small cell lung cancer patients with clinical target volume (CTV) motion >5 mm, different RO approaches were investigated: 3DRO considering the average CT (AvgCT) with a target density override, 4DRO considering three/all 4DCT phases, and 4DRO considering the AvgCT and three/all 4DCT phases. Robustness against setup/range errors, interplay effects based on breathing and machine log file data for deliveries with/without rescanning, and interfractional anatomical changes were analyzed for target coverage and OAR sparing.

Results: All nominal plans fulfilled the clinical requirements with individual CTV coverage differences <2pp; 4DRO without AvgCT generated the most conformal dose distributions. Robustness against setup/range errors was best for 4DRO with AvgCT (18% more passed error scenarios than 3DRO). Interplay effects caused fraction-wise median CTV coverage loss of 3pp and missed maximum dose constraints for heart and esophagus in 18% of scenarios. CTV coverage and OAR sparing fulfilled requirements in all cases when accumulating four interplay scenarios. Interfractional changes caused less target misses for RO with AvgCT compared to 4DRO without AvgCT (≤42%/33% vs. ≥56%/44% failed single/accumulated scenarios).

Conclusions: All RO strategies provided acceptable plans with equally low robustness against interplay effects demanding other mitigation than rescanning to ensure fraction-wise target coverage. 4DRO considering three phases and the AvgCT provided best compromise on planning effort and robustness.

Keywords: Interfraction changes; Large intrafraction motion; Lung cancer; Proton therapy; Robust optimization.

Fig. 1

Coronal fusion view of the end-exhale (blue) and end-inhale (orange) 4DCT phase and a transversal view of the end-exhale phase with indicated beam directions (yellow lines) for all patients (P1-P8). Primary and nodal target (if depicted on the same slice) are delineated in pink and orange, respectively. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 2

Coverage robustness against setup and range errors for both primary (CTVp; red) and nodal (CTVn; blue) clinical target volumes, represented by (a) the ratio of scenarios that passed/failed the criterion D_98% >95% and (b) the coverage (D_98%) of voxel-wise worst-case scenarios (VWWC). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 3

Target coverage (D_98%) of the primary (CTVp; red) and nodal clinical target volume (CTVn; blue) in the planning CTs (a) and the control CTs (b) for interplay-affected dose distributions considering plan deliveries with/without (right/left) layered rescanning in single scenarios (cohort mean: open circle, cohort median: thick tick) and the four accumulated scenario per patient (cohort mean: solid circle, cohort median: thick tick). Target coverage is clinically acceptable when fulfilling D_98%>95% (dashed line). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 4

Organ at risk DVH parameters extracted from interplay-affected dose distributions on the planning CTs from the different robust optimization strategies and considering plan deliveries with/without (right/left) layered rescanning in single scenarios (4 per patient, cohort mean: open circle) and the four accumulated scenario per patient (cohort mean: solid circle, cohort median: thick tick). The DVH parameters for spinal cord and lungs are well below the constraints for all patients while the maximum dose constraints in the heart and esophagus (70 Gy, horizontal line) are violated in several single scenarios.