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

Author ORCID Identifier


Date of Graduation


Document Type

Thesis (MS)

Program Affiliation

Medical Physics

Degree Name

Doctor of Philosophy (PhD)

Advisor/Committee Chair

Radhe Mohan

Committee Member

Xiaochun Wang

Committee Member

Narayan Sahoo

Committee Member

Steven J. Frank

Committee Member

Jing Wang


A major challenge in the application of intensity-modulated proton therapy (IMPT) for lung cancer patients is the mitigation and consideration of uncertainties associated with breathing motion in treatment planning. The primary objective of this research was to develop a novel four-dimensional robust optimization (4DRO) method and find an appropriate optimization strategy to make IMPT dose distributions less sensitive to both respiratory motion as well as to setup and range uncertainties simultaneously.

For full 4DRO, the effect of respiratory motion, characterized by different phases of 4D computed tomography (CT), was incorporated into a 4DRO algorithm. Dose distributions from multiple setup and range uncertainty scenarios were calculated for each of the 10 phases of CT datasets. Dose differences caused by respiratory organ motion and deformation were accounted for by the 4D CT datasets. The 4DRO algorithm optimizes dose distributions to achieve target dose coverage and normal tissue sparing for multiple setup and range uncertainty scenarios and for all 10 respiratory phases simultaneously. IMPT dose distributions of ten lung cancer patients with differing tumor sizes and motion magnitudes were optimized to illustrate and evaluate our method. Compared with treatment plans generated by 3D Robust optimization (3DRO) and the conventional planning target volume (PTV)-based IMPT optimization, 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 respiratory motion.

However, contouring GTV on every phase of respiratory process is a very time-consuming process. And 4D dose calculation, especially 4D influence matrix calculation, is time consuming and memory demanding. We also conducted a study to investigate if we can reduce the number of phases to be-included in the 4DRO process without affecting the IMPT plan quality and plan robustness of full 4DRO with all ten phases.

Compared to plans produced by full 4D RO strategies, reducing the phases included in robust optimization process improve computational efficiency, at the same time, decreases target coverage and plan robustness, increases dose heterogeneity and increases normal tissue sparing. But the reduction of target coverage and plan robustness is very small. The plans produced by 4D RO strategy including only two extreme phases, phase T0 and phase T50, achieve very good plan quality and plan robustness for lung cancer patients with tumor motion size less than 10mm. While for lung cancer patients with large tumor motion and diaphragm intruding into proton beam path, 5 phases 4D robust optimization or full 4D robust optimization is necessary.


intensity modulated proton therapy, 4-dimensional robust optimization, motion management, uncertainties, lung cancer

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