Potential for Improvements in Robustness and Optimality of Intensity-Modulated Proton Therapy for Lung Cancer with 4-Dimensional Robust Optimization

Abstract

Major challenges in the application of intensity-modulated proton therapy (IMPT) for lung cancer patients include the uncertainties associated with breathing motion, its mitigation and its consideration in IMPT optimization. The primary objective of this research was to evaluate the potential of four-dimensional robust optimization (4DRO) methodology to make IMPT dose distributions resilient to respiratory motion as well as to setup and range uncertainties; Methods: The effect of respiratory motion, characterized by different phases of 4D computed tomography (4DCT), was incorporated into an in-house 4DRO system. Dose distributions from multiple setup and range uncertainty scenarios were calculated for each of the ten phases of CT datasets. The 4DRO algorithm optimizes dose distributions to achieve target dose coverage and normal tissue sparing for multiple setup and range uncertainty scenarios as well as for all ten respiratory phases simultaneously. IMPT dose distributions of ten lung cancer patients with different tumor sizes and motion magnitudes were optimized to illustrate our approach and its potential; Results: Compared with treatment plans generated using the conventional planning target volume (PTV)-based optimization and 3D robust optimization (3DRO), plans generated by 4DRO were found to have superior clinical target volume coverage and dose robustness in the face of setup and range uncertainties as well as for respiratory motion. In most of the cases we studied, 4DRO also resulted in more homogeneous target dose distributions. Interestingly, such improvements were found even for cases in which moving diaphragms intruded into the proton beam paths; Conclusion: The incorporation of respiratory motion, along with setup and range uncertainties, into robust optimization, has the potential to improve the resilience of target and normal tissue dose distributions in IMPT plans in the face of the uncertainties considered. Moreover, it improves the optimality of plans compared to PTV-based optimization as well as 3DRO.

Keywords: 4-dimensional robust optimization; lung cancer; motion management; proton therapy; uncertainties.

Figure 1

Bands of 90 DVHs corresponding to ten respiratory phases for each of nine uncertainty scenarios for the CTV (a,b), esophagus (c), heart (d), spinal cord (e) and total lung (f) for treatment plans resulting from 4DRO, 3DRO and the PTV-based optimization for patient E (ITV = 633 cc, motion = 5.7 mm). The solid lines highlight the boundaries of the DVH bands. Panel (b) shows the same CTV data as in panel (a) but on an expanded dose scale.

Figure 2

(a) Worst-case CTV coverage at prescription dose and (b) plan robustness in terms of DVH band widths at 95% of the CTV as a function of GTV motion for 4DRO, 3DRO and PTV-based optimization approaches. Diaphragm intrudes in one or more proton beams for patient E, G, I, J. Panels (c,d) show the range and median value of heterogeneity and conformity indices respectively.

Figure 3

Dose-volume indices of interest for organs at risk. Range and median value of (a) mean lung dose, (b) lung V20, (c) lung V5, (d) spinal cord D_max1%, (e) mean heart dose, (f) heart V30, (g) mean esophagus dose, and (h) esophagus V50 of 90 dose distributions for plans produced with 4DRO, 3DRO and PTV-based optimization vs. GTV motion magnitude.

Figure 4

DVHs of CTV, heart and total lung for plans produced by three optimization methods for patient J. Panel (A,C,E) shows the DVH bands of 90 dose distributions of nine setup and range uncertainty scenarios for each of the 10 respiratory phases for CTV, heart and total lung respectively. Panel (B,D,F) shows the DVH bands of dose distributions accumulated over all the respiratory phases for each of the 9 setup and range uncertainty scenarios for CTV, heart and total lung respectively.