Fraction-variant beam orientation optimization for intensity-modulated proton therapy.

To achieve a superior balance between dosimetry and the delivery efficiency of intensity-modulated proton therapy (IMPT) using as few beams as possible in a single fraction, we optimally vary beams in different fractions. In the optimization, 400~800 feasible noncoplanar beams were included in the candidate pool. For each beam, the doses of all scanning spots covering the target volume and a margin were calculated. The fraction-variant beam orientation optimization (FVBOO) problem was formulated to include three terms: two quadratic dose fidelity terms to penalize the deviation of planning target volume fractional dose and organs at risk (OAR) cumulative doses from prescription, respectively; an L2,1/2-norm group sparsity term to control the number of active beams per fraction to between 1 and 4. The Fast Iterative Shrinkage-Thresholding Algorithm (FISTA) was applied to solve this problem. FVBOO was tested on a patient with base-of-skull (BOS) tumor of 5 fractions (5f) and 30 fractions (30f) with an average number of active beams per fraction varying between 4 and 1. In addition, one bilateral head-and-neck (H&N) patient, and one esophageal cancer (ESG) patient of 30f were tested with about three active beams per fraction. The results were compared with IMPT plans that use fixed beams in each fraction. The fixed beams were selected using the group sparsity term with a fraction-invariant BOO (FIBOO) constraint. Varying beams were chosen in either the 5f or 30f FVBOO plans. While similar number of beams per fraction was selected as the FIBOO plan, the FVBOO plans were able to spare the OARs better, with an average reduction of [Dmean, Dmax] from the FIBOO plans by [0.85, 2.08] Relative Biological Effective Gy (GyRBE) in the 5f plan and [1.87, 4.06] GyRBE in the 30f plans. While reducing the number of beams per fraction in the BOS patient, a three-beam/fraction 5f FVBOO plan performs comparably as the four-beam FIBOO plan and a two-beam/fraction 30f FVBOO plan still provides superior dosimetry. Fraction-variant beam orientation optimization allows the utilization of a larger beam solution space for superior dose distribution in IMPT while maintaining a practical number of beams in each fraction.

Gu W ，O'Connor D ，Ruan D ，Zou W ，Dong L ，Sheng K ... -  《-》

Integrated beam orientation and scanning-spot optimization in intensity-modulated proton therapy for brain and unilateral head and neck tumors.

Intensity-Modulated Proton Therapy (IMPT) is the state-of-the-art method of delivering proton radiotherapy. Previous research has been mainly focused on optimization of scanning spots with manually selected beam angles. Due to the computational complexity, the potential benefit of simultaneously optimizing beam orientations and spot pattern could not be realized. In this study, we developed a novel integrated beam orientation optimization (BOO) and scanning-spot optimization algorithm for intensity-modulated proton therapy (IMPT). A brain chordoma and three unilateral head-and-neck patients with a maximal target size of 112.49 cm3 were included in this study. A total number of 1162 noncoplanar candidate beams evenly distributed across 4π steradians were included in the optimization. For each candidate beam, the pencil-beam doses of all scanning spots covering the PTV and a margin were calculated. The beam angle selection and spot intensity optimization problem was formulated to include three terms: a dose fidelity term to penalize the deviation of PTV and OAR doses from ideal dose distribution; an L1-norm sparsity term to reduce the number of active spots and improve delivery efficiency; a group sparsity term to control the number of active beams between 2 and 4. For the group sparsity term, convex L2,1-norm and nonconvex L2,1/2-norm were tested. For the dose fidelity term, both quadratic function and linearized equivalent uniform dose (LEUD) cost function were implemented. The optimization problem was solved using the Fast Iterative Shrinkage-Thresholding Algorithm (FISTA). The IMPT BOO method was tested on three head-and-neck patients and one skull base chordoma patient. The results were compared with IMPT plans created using column generation selected beams or manually selected beams. The L2,1-norm plan selected spatially aggregated beams, indicating potential degeneracy using this norm. L2,1/2-norm was able to select spatially separated beams and achieve smaller deviation from the ideal dose. In the L2,1/2-norm plans, the [mean dose, maximum dose] of OAR were reduced by an average of [2.38%, 4.24%] and[2.32%, 3.76%] of the prescription dose for the quadratic and LEUD cost function, respectively, compared with the IMPT plan using manual beam selection while maintaining the same PTV coverage. The L2,1/2 group sparsity plans were dosimetrically superior to the column generation plans as well. Besides beam orientation selection, spot sparsification was observed. Generally, with the quadratic cost function, 30%~60% spots in the selected beams remained active. With the LEUD cost function, the percentages of active spots were in the range of 35%~85%.The BOO-IMPT run time was approximately 20 min. This work shows the first IMPT approach integrating noncoplanar BOO and scanning-spot optimization in a single mathematical framework. This method is computationally efficient, dosimetrically superior and produces delivery-friendly IMPT plans.

Gu W ，O'Connor D ，Nguyen D ，Yu VY ，Ruan D ，Dong L ，Sheng K ... -  《-》

Robust beam orientation optimization for intensity-modulated proton therapy.

Dose conformality and robustness are equally important in intensity modulated proton therapy (IMPT). Despite the obvious implication of beam orientation on both dosimetry and robustness, an automated, robust beam orientation optimization algorithm has not been incorporated due to the problem complexity and paramount computational challenge. In this study, we developed a novel IMPT framework that integrates robust beam orientation optimization (BOO) and robust fluence map optimization (FMO) in a unified framework. The unified framework is formulated to include a dose fidelity term, a heterogeneity-weighted group sparsity term, and a sensitivity regularization term. The L2, 1/2-norm group sparsity is used to reduce the number of active beams from the initial 1162 evenly distributed noncoplanar candidate beams, to between two and four. A heterogeneity index, which evaluates the lateral tissue heterogeneity of a beam, is used to weigh the group sparsity term. With this index, beams more resilient to setup uncertainties are encouraged. There is a symbiotic relationship between the heterogeneity index and the sensitivity regularization; the integrated optimization framework further improves beam robustness against both range and setup uncertainties. This Sensitivity regularization and Heterogeneity weighting based BOO and FMO framework (SHBOO-FMO) was tested on two skull-base tumor (SBT) patients and two bilateral head-and-neck (H&N) patients. The conventional CTV-based optimized plans (Conv) with SHBOO-FMO beams (SHBOO-Conv) and manual beams (MAN-Conv) were compared to investigate the beam robustness of the proposed method. The dosimetry and robustness of SHBOO-FMO plan were compared against the manual beam plan with CTV-based voxel-wise worst-case scenario approach (MAN-WC). With SHBOO-FMO method, the beams with superior range robustness over manual beams were selected while the setup robustness was maintained or improved. On average, the lowest [D95%, V95%, V100%] of CTV were increased from [93.85%, 91.06%, 70.64%] in MAN-Conv plans, to [98.62%, 98.61%, 96.17%] in SHBOO-Conv plans with range uncertainties. With setup uncertainties, the average lowest [D98%, D95%, V95%, V100%] of CTV were increased from [92.06%, 94.83%, 94.31%, 78.93%] in MAN-Conv plans, to [93.54%, 96.61%, 97.01%, 91.98%] in SHBOO-Conv plans. Compared with the MAN-WC plans, the final SHBOO-FMO plans achieved comparable plan robustness and better OAR sparing, with an average reduction of [Dmean, Dmax] of [6.31, 6.55] GyRBE for the SBT cases and [1.89, 5.08] GyRBE for the H&N cases from the MAN-WC plans. We developed a novel method to integrate robust BOO and robust FMO into IMPT optimization for a unified solution of both BOO and FMO, generating plans with superior dosimetry and good robustness.

Gu W ，Neph R ，Ruan D ，Zou W ，Dong L ，Sheng K ... -  《-》

Linear energy transfer weighted beam orientation optimization for intensity-modulated proton therapy.

In intensity-modulated proton therapy (IMPT), unaccounted-for variation in biological effectiveness contributes to the discrepancy between the constant relative biological effectiveness (RBE) model prediction and experimental observation. It is desirable to incorporate biological doses in treatment planning to improve modeling accuracy and consequently achieve a higher therapeutic ratio. This study addresses this demand by developing a method to incorporate linear energy transfer (LET) into beam orientation optimization (BOO). Instead of RBE-weighted dose, this LET weighted BOO (LETwBOO) framework uses the dose and LET product (LET  ×  D) as the biological surrogate. The problem is formulated with a physical dose fidelity term, a LET  ×  D constraint term, and a group sparsity term. The LET  ×  D of organs at risks is penalized for minimizing the biological effect while maintaining the physical dose objectives. Group sparsity is used to reduce the number of active beams from 600-800 non-coplanar candidate beams to between 2 and 4. This LETwBOO method was tested on three skull base tumor (SBT) patients and three bilateral head-and-neck (H&N) patients. The LETwBOO plans were compared with IMPT plans using manually selected beams with only physical dose constraint (MAN) and the initial MAN plan reoptimized with additional LET  ×  D constraint (LETwMAN). The LETwBOO plans show superior physical dose and LET  ×  D sparing. On average, the [mean, maximal] doses of organs at risks (OARs) in LETwBOO are reduced by [2.85, 4.6] GyRBE from the MAN plans in the SBT cases and reduced by [0.9, 2.5] GyRBE in the H&N cases, while LETwMAN is comparable to MAN. cLET × Ds of PTVs are comparable in LETwBOO and LETwMAN, where c is a scaling factor of 0.04 μm/keV. On average, in the SBT cases, LETwBOO reduces the OAR [mean, maximal] cLET × D by [1.1, 2.9] Gy from the MAN plans, compared to the reduction by LETwMAN from MAN of [0.7, 1.7] Gy. In the H&N cases, LETwBOO reduces the OAR [mean, maximal] cLET × D by [0.8, 2.6] Gy from the MAN plans, compared to the reduction by LETwMAN from MAN of [0.3, 1.2] Gy. We developed a novel LET weighted BOO method for IMPT to generate plans with improved physical and biological OAR sparing compared with the plans unaccounted for biological effects from BOO.

Gu W ，Ruan D ，Zou W ，Dong L ，Sheng K ... -  《-》

A unified path seeking algorithm for IMRT and IMPT beam orientation optimization.

Objective. Fully automated beam orientation optimization (BOO) for intensity-modulated radiotherapy and intensity modulated proton therapy (IMPT) is gaining interest, since achieving optimal plan quality for an unknown number of fixed beam arrangements is tedious. Fast group sparsity-based optimization methods have been proposed to find the optimal orientation, but manual tuning is required to eliminate the exact number of beams from a large candidate set. Here, we introduce a fast, automated gradient descent-based path-seeking algorithm (PathGD), which performs fluence map optimization for sequentially added beams, to visualize the dosimetric benefit of one added field at a time.Approach. Several configurations of 2-4 proton and 5-15 photon beams were selected for three head-and-neck patients using PathGD, which was compared to group sparsity-regularized BOO solved with the fast iterative shrinkage-thresholding algorithm (GS-FISTA), and manually selected IMPT beams or one coplanar photon VMAT arc (MAN). Once beams were chosen, all plans were compared on computational efficiency, dosimetry, and for proton plans, robustness.Main results. With each added proton beam, Clinical Target Volume (CTV) and organs at risk (OAR) dosimetric cost improved on average across plans by [1.1%, 13.6%], and for photons, [0.6%, 2.0%]. Comparing algorithms, beam selection for PathGD was faster than GS-FISTA on average by 35%, and PathGD matched the CTV coverage of GS-FISTA plans while reducing OAR mean and maximum dose in all structures by an average of 13.6%. PathGD was able to improve CTV [Dmax, D95%] by [2.6%, 5.2%] and reduced worst-case [max, mean] dose in OARs by [11.1%, 13.1%].Significance. The benefit of a path-seeking algorithm is the beam-by-beam analysis of dosimetric cost. PathGD was shown to be most efficient and dosimetrically desirable amongst group sparsity and manual BOO methods, and highlights the sensitivity of beam addition for IMPT in particular.

Ramesh P ，Valdes G ，O'Connor D ，Sheng K ... -  《-》