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 ... -  《-》

Robust optimization for intensity-modulated proton therapy with soft spot sensitivity regularization.

Proton dose distribution is sensitive to uncertainties in range estimation and patient positioning. Currently, the proton robustness is managed by worst-case scenario optimization methods, which are computationally inefficient. To overcome these challenges, we develop a novel intensity-modulated proton therapy (IMPT) optimization method that integrates dose fidelity with a sensitivity term that describes dose perturbation as the result of range and positioning uncertainties. In the integrated optimization framework, the optimization cost function is formulated to include two terms: a dose fidelity term and a robustness term penalizing the inner product of the scanning spot sensitivity and intensity. The sensitivity of an IMPT scanning spot to perturbations is defined as the dose distribution variation induced by range and positioning errors. To evaluate the sensitivity, the spatial gradient of the dose distribution of a specific spot is first calculated. The spot sensitivity is then determined by the total absolute value of the directional gradients of all affected voxels. The fast iterative shrinkage-thresholding algorithm is used to solve the optimization problem. This method was tested on three skull base tumor (SBT) patients and three bilateral head-and-neck (H&N) patients. The proposed sensitivity-regularized method (SenR) was implemented on both clinic target volume (CTV) and planning target volume (PTV). They were compared with conventional PTV-based optimization method (Conv) and CTV-based voxel-wise worst-case scenario optimization approach (WC). Under the nominal condition without uncertainties, the three methods achieved similar CTV dose coverage, while the CTV-based SenR approach better spared organs at risks (OARs) compared with the WC approach, with an average reduction of [Dmean, Dmax] of [4.72, 3.38]  GyRBE for the SBT cases and [2.54, 3.33] GyRBE for the H&N cases. The OAR sparing of the PTV-based SenR method was comparable with the WC method. The WC method, and SenR approaches all improved the plan robustness from the conventional PTV-based method. On average, under range uncertainties, the lowest [D95%, V95%, V100%] of CTV were increased from [93.75%, 88.47%, 47.37%] in the Conv method, to [99.28%, 99.51%, 86.64%] in the WC method, [97.71%, 97.85%, 81.65%] in the SenR-CTV method and [98.77%, 99.30%, 85.12%] in the SenR-PTV method, respectively. Under setup uncertainties, the average lowest [D95%, V95%, V100%] of CTV were increased from [95.35%, 94.92%, 65.12%] in the Conv method, to [99.43%, 99.63%, 87.12%] in the WC method, [96.97%, 97.13%, 77.86%] in the SenR-CTV method, and [98.21%, 98.34%, 83.88%] in the SenR-PTV method, respectively. The runtime of the SenR optimization is eight times shorter than that of the voxel-wise worst-case method. We developed a novel computationally efficient robust optimization method for IMPT. The robustness is calculated as the spot sensitivity to both range and shift perturbations. The dose fidelity term is then regularized by the sensitivity term for the flexibility and trade-off between the dosimetry and the robustness. In the stress test, SenR is more resilient to unexpected uncertainties. These advantages in combination with its fast computation time make it a viable candidate for clinical IMPT planning.

Gu W ，Ruan D ，O'Connor D ，Zou W ，Dong L ，Tsai MY ，Jia X ，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 ... -  《-》

Reformulated McNamara RBE-weighted beam orientation optimization for intensity modulated proton therapy.

Empirical relative biological effectiveness (RBE) models have been used to estimate the biological dose in proton therapy but do not adequately capture the factors influencing RBE values for treatment planning. We reformulate the McNamara RBE model such that it can be added as a linear biological dose fidelity term within our previously developed sensitivity-regularized and heterogeneity-weighted beam orientation optimization (SHBOO) framework. Based on our SHBOO framework, we formulated the biological optimization problem to minimize total McNamara RBE dose to OARs. We solve this problem using two optimization algorithms: FISTA (McNam-FISTA) and Chambolle-Pock (McNam-CP). We compare their performances with a physical dose optimizer assuming RBE = 1.1 in all structures (PHYS-FISTA) and an LET-weighted dose model (LET-FISTA). Three head and neck patients were planned with the four techniques and compared on dosimetry and robustness. Compared to Phys-FISTA, McNam-CP was able to match CTV [HI, Dmax, D95%, D98%] by [0.00, 0.05%, 1.4%, 0.8%]. McNam-FISTA and McNam-CP were able to significantly improve overall OAR [Dmean, Dmax] by an average of [36.1%,26.4%] and [29.6%, 20.3%], respectively. Regarding CTV robustness, worst [Dmax, V95%, D95%, D98%] improvement of [-6.6%, 6.2%, 6.0%, 4.8%] was reported for McNam-FISTA and [2.7%, 2.7%, 5.3%, -4.3%] for McNam-CP under combinations of range and setup uncertainties. For OARs, worst [Dmax, Dmean] were improved by McNam-FISTA and McNam-CP by an average of [25.0%, 19.2%] and [29.5%, 36.5%], respectively. McNam-FISTA considerably improved dosimetry and CTV robustness compared to LET-FISTA, which achieved better worst-case OAR doses. The four optimization techniques deliver comparable biological doses for the head and neck cases. Besides modest CTV coverage and robustness improvement, OAR biological dose and robustness were substantially improved with both McNam-FISTA and McNam-CP, showing potential benefit for directly incorporating McNamara RBE in proton treatment planning.

Ramesh P ，Lyu Q ，Gu W ，Ruan D ，Sheng K ... -  《-》

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 ... -  《-》