Transformative Technology for FLASH Radiation Therapy.

The general concept of radiation therapy used in conventional cancer treatment is to increase the therapeutic index by creating a physical dose differential between tumors and normal tissues through precision dose targeting, image guidance, and radiation beams that deliver a radiation dose with high conformality, e.g., protons and ions. However, the treatment and cure are still limited by normal tissue radiation toxicity, with the corresponding side effects. A fundamentally different paradigm for increasing the therapeutic index of radiation therapy has emerged recently, supported by preclinical research, and based on the FLASH radiation effect. FLASH radiation therapy (FLASH-RT) is an ultra-high-dose-rate delivery of a therapeutic radiation dose within a fraction of a second. Experimental studies have shown that normal tissues seem to be universally spared at these high dose rates, whereas tumors are not. While dose delivery conditions to achieve a FLASH effect are not yet fully characterized, it is currently estimated that doses delivered in less than 200 ms produce normal-tissue-sparing effects, yet effectively kill tumor cells. Despite a great opportunity, there are many technical challenges for the accelerator community to create the required dose rates with novel compact accelerators to ensure the safe delivery of FLASH radiation beams.

Model-Based X-Ray-Induced Acoustic Computed Tomography.

X-ray-induced acoustic computed tomography (XACT) provides X-ray absorption-based contrast with acoustic detection. For its clinical translation, XACT imaging often has a limited field of view. This can result in image artifacts and overall loss of quantification accuracy. In this article, we aim to demonstrate model-based XACT image reconstruction to address these problems. An efficient matrix-free implementation of the regularized LSQR (MF-LSQR)-based minimization scheme and a noniterative model back-projection (MBP) scheme for computing XACT reconstructions have been demonstrated in this article. The proposed algorithms have been numerically validated and then used to perform reconstructions from experimental measurements obtained from an XACT setup. While the commonly used back-projection (BP) algorithm produces limited-view and noisy artifacts in the region of interest (ROI), model-based LSQR minimization overcomes these issues. The model-based algorithms also reduce the ring artifacts caused due to the nonuniformity response of the multichannel data acquisition. Using the model-based reconstruction algorithms, we are able to obtain reasonable XACT reconstructions for acoustic measurements of up to 120° view. Although the MBP is more efficient than the model-based LSQR algorithm, it provides only the structural information of the ROI. Overall, it has been demonstrated that the model-based image reconstruction yields better image quality for XACT than the standard BP. Moreover, the combination of model-based image reconstruction with different regularization methods can solve the limited-view problem for XACT imaging (in many realistic cases where the full-view dataset is unavailable), and hence pave the way for future clinical translation.

ROAD: ROtational direct Aperture optimization with a Decoupled ring-collimator for FLASH radiotherapy.

Ultra-high dose rate in radiotherapy (FLASH) has been shown to increase the therapeutic index with markedly reduced normal tissue toxicity and the same or better tumor cell killing. The challenge to achieve FLASH using x-rays, besides developing a high output linac, is to intensity-modulate the high-dose-rate x-rays so that the biological gain is not offset by the lack of physical dose conformity. In this study, we develop the ROtational direct Aperture optimization with a Decoupled ring-collimator (ROAD) to achieve simultaneous ultrafast delivery and complex dose modulation. The ROAD design includes a fast-rotating slip-ring linac and a decoupled collimator-ring with 75 pre-shaped multi-leaf-collimator (MLC) modules. The ring-source rotates at 1 rotation per second (rps) clockwise while the ring-collimator is either static or rotating at 1 rps counterclockwise, achieving 75 (ROAD-75) or 150 (ROAD-150) equal-angular beams for one full arc. The Direct Aperture Optimization (DAO) for ROAD was formulated to include a least-square dose fidelity, an anisotropic total variation term, and a single segment term. The FLASH dose (FD) and FLASH biological equivalent dose (FBED) were computed voxelwise, with the latter using a spatiotemporal model accounting for radiolytic oxygen depletion. ROAD was compared with clinical volumetric modulated arc therapy (VMAT) on a brain, a lung, a prostate, and a head and neck cancer patient. The mean dose rate of ROAD-75 and ROAD-150 are 76.2 Gy s-1 and 112 Gy s-1 respectively to deliver 25 Gy single-fraction dose in 1 s. With improved PTV homogeneity, ROAD-150 reduced (max, mean) OAR physical dose by (4.8 Gy, 6.3 Gy). The average R50 and integral dose of (VMAT, ROAD-75, ROAD-150) are (4.8, 3.2, 3.2) and (89, 57, 56) Gy×Liter, respectively. The FD and FBED showed model dependent FLASH effects. The novel ROAD design achieves ultrafast dose delivery and improves physical dosimetry compared with clinical VMAT, providing a potentially viable engineering solution for x-ray FLASH radiotherapy.

Many-isocenter optimization for robotic radiotherapy.

Despite significant dosimetric gains, clinical implementation of the 4π non-coplanar radiotherapy on the widely available C-arm gantry system is hindered by limited clearance, and the need to perform complex coordinated gantry and couch motion. A robotic radiotherapy platform would be conducive to such treatment but a new conflict between field size and MLC modulation resolution needs to be managed for versatile applications. This study investigates the dosimetry and delivery efficiency of purposefully creating many isocenters to achieve simultaneously high MLC modulation resolution and large tumor coverage. An integrated optimization framework was proposed for simultaneous beam orientation optimization (BOO), isocenter selection, and fluence map optimization (FMO). The framework includes a least-square dose fidelity objective, a total variation term for regularizing the fluence smoothness, and a group sparsity term for beam selection. A minimal number of isocenters were identified for efficient target coverage. Colliding beams excluded, high-resolution small-field 4π intensity-modulated radiotherapy (IMRT) treatment plans with 50 cm source-to-isocenter distance (SID-50) on 10 Head and Neck (H&N) cancer patients were compared with low-resolution large-field plans with 100 cm SID (SID-100). With the same or better target coverage, the average reduction of [Dmean, Dmax] of 20-beam SID-50 plans from 20-beam SID-100 plans were [2.09 Gy, 1.19 Gy] for organs at risk (OARs) overall, [3.05 Gy, 0.04 Gy] for parotid gland, [3.62 Gy, 5.19 Gy] for larynx, and [3.27 Gy, 1.10 Gy] for mandible. R50 and integral dose were reduced by 5.3% and 9.6%, respectively. Wilcoxon signed-rank test showed significant difference (p  < 0.05) in planning target volume (PTV) homogeneity, PTV Dmax, R50, Integral dose, and OAR Dmean and Dmax. The estimated delivery time of 20-beam [SID-50, SID-100] plans were [19, 18] min and [14, 9] min, assuming 5 fractions and 30 fractions, respectively. With clinically acceptable delivery efficiency, many-isocenter optimization is dosimetrically desirable for treating large targets with high modulation resolution on the robotic platform.

A novel software and conceptual design of the hardware platform for intensity modulated radiation therapy.

PURPOSE: To deliver high quality intensity modulated radiotherapy (IMRT) using a novel generalized sparse orthogonal collimators (SOCs), the authors introduce a novel direct aperture optimization (DAO) approach based on discrete rectangular representation. METHODS: A total of seven patients-two glioblastoma multiforme, three head & neck (including one with three prescription doses), and two lung-were included. 20 noncoplanar beams were selected using a column generation and pricing optimization method. The SOC is a generalized conventional orthogonal collimators with N leaves in each collimator bank, where N = 1, 2, or 4. SOC degenerates to conventional jaws when N = 1. For SOC-based IMRT, rectangular aperture optimization (RAO) was performed to optimize the fluence maps using rectangular representation, producing fluence maps that can be directly converted into a set of deliverable rectangular apertures. In order to optimize the dose distribution and minimize the number of apertures used, the overall objective was formulated to incorporate an L2 penalty reflecting the difference between the prescription and the projected doses, and an L1 sparsity regularization term to encourage a low number of nonzero rectangular basis coefficients. The optimization problem was solved using the Chambolle-Pock algorithm, a first-order primal-dual algorithm. Performance of RAO was compared to conventional two-step IMRT optimization including fluence map optimization and direct stratification for multileaf collimator (MLC) segmentation (DMS) using the same number of segments. For the RAO plans, segment travel time for SOC delivery was evaluated for the N = 1, N = 2, and N = 4 SOC designs to characterize the improvement in delivery efficiency as a function of N. RESULTS: Comparable PTV dose homogeneity and coverage were observed between the RAO and the DMS plans. The RAO plans were slightly superior to the DMS plans in sparing critical structures. On average, the maximum and mean critical organ doses were reduced by 1.94% and 1.44% of the prescription dose. The average number of delivery segments was 12.68 segments per beam for both the RAO and DMS plans. The N = 2 and N = 4 SOC designs were, on average, 1.56 and 1.80 times more efficient than the N = 1 SOC design to deliver. The mean aperture size produced by the RAO plans was 3.9 times larger than that of the DMS plans. CONCLUSIONS: The DAO and dose domain optimization approach enabled high quality IMRT plans using a low-complexity collimator setup. The dosimetric quality is comparable or slightly superior to conventional MLC-based IMRT plans using the same number of delivery segments. The SOC IMRT delivery efficiency can be significantly improved by increasing the leaf numbers, but the number is still significantly lower than the number of leaves in a typical MLC.

Feasibility of using intermediate x-ray energies for highly conformal extracranial radiotherapy.

PURPOSE: To investigate the feasibility of using intermediate energy 2 MV x-rays for extracranial robotic intensity modulated radiation therapy. METHODS: Two megavolts flattening filter free x-rays were simulated using the Monte Carlo code MCNP (v4c). A convolution/superposition dose calculation program was tuned to match the Monte Carlo calculation. The modeled 2 MV x-rays and actual 6 MV flattened x-rays from existing Varian Linacs were used in integrated beam orientation and fluence optimization for a head and neck, a liver, a lung, and a partial breast treatment. A column generation algorithm was used for the intensity modulation and beam orientation optimization. Identical optimization parameters were applied in three different planning modes for each site: 2, 6 MV, and dual energy 2/6 MV. RESULTS: Excellent agreement was observed between the convolution/superposition and the Monte Carlo calculated percent depth dose profiles. For the patient plans, overall, the 2/6 MV x-ray plans had the best dosimetry followed by 2 MV only and 6 MV only plans. Between the two single energy plans, the PTV coverage was equivalent but 2 MV x-rays improved organs-at-risk sparing. For the head and neck case, the 2 MV plan reduced lips, mandible, tongue, oral cavity, brain, larynx, left and right parotid gland mean doses by 14%, 8%, 4%, 14%, 24%, 6%, 30% and 16%, respectively. For the liver case, the 2 MV plan reduced the liver and body mean doses by 17% and 18%, respectively. For the lung case, lung V 20, V 10, and V5 were reduced by 13%, 25%, and 30%, respectively. V 10 of heart with 2 MV plan was reduced by 59%. For the partial breast treatment, the 2 MV plan reduced the mean dose to the ipsilateral and contralateral lungs by 27% and 47%, respectively. The mean body dose was reduced by 16%. CONCLUSIONS: The authors showed the feasibility of using flattening filter free 2 MV x-rays for extracranial treatments as evidenced by equivalent or superior dosimetry compared to 6 MV plans using the same inverse noncoplanar intensity modulated planning method.