MRI-guided adaptive radiotherapy for prostate cancer: When do we need to account for intra-fraction motion?

A shift of the daily plan can mitigate target position changes that occur between daily MR acquisition and treatment for MR-linac radiotherapy, but increases the session time. We demonstrated that our workflow strategy and decision-making process, to determine whether a subsequent shift is necessary, is appropriate

Feasibility of tumour-focused adaptive radiotherapy for bladder cancer on the MR-linac.

Bladder tumour-focused magnetic resonance image-guided adaptive radiotherapy using a 1.5 Tesla MR-linac is feasible. A full online workflow adapting to anatomy at each fraction is achievable in approximately 30 min. Intra-fraction bladder filling did not compromise target coverage with the class solution employed

Magnetic resonance imaging sequence evaluation of an MR Linac system; early clinical experience.

Objectives:To systematically identify the preferred magnetic resonance imaging (MRI) sequences following volunteer imaging on a 1.5 Tesla (T) MR-Linear Accelerator (MR Linac) for future protocol development. Methods:Non-patient volunteers were recruited to a Research and Ethics committee approved prospective MR-only imaging study on a 1.5T MR Linac system. Volunteers attended 1-3 imaging sessions that included a combination of mDixon, T1w, T2w sequences using 2-dimensional (2D) and 3-dimensional (3D) acquisitions. Each sequence was acquired over 2-7 minutes and reviewed by a panel of 3 observers to evaluate image quality using a visual grading analysis based on a 4-point Likert scale. Sequences were acquired and modified iteratively until deemed fit for purpose (online image matching or re-planning) and all observers agreed they were suitable in 3 volunteers. Results:26 volunteers underwent 31 imaging sessions of six general anatomical regions. Images were acquired in one or two of six general anatomical regions: male pelvis (n = 9), female pelvis (n = 4), chestwall/breast (n = 5), lung/oesophagus (n = 5), abdomen (n = 3) and head and neck (n = 5). Images were acquired using a pre-defined exam-card that on average, included six sequences (range 2-10), with a maximum scan time of approximately one hour. The majority of observers preferred T2-weighted sequences. The thorax teams were the only groups to prefer T1-weighted imaging. Conclusions:An iterative process identified sequence agreement in all anatomical regions. These sequences will now be evaluated in patient volunteers. Advances in knowledge:This manuscript is the first publication sharing the results of the first systematic selection of MRI sequences for use in on-board MRI-guided radiotherapy by end-users (therapeutic radiographers and clinical oncologists) in healthy volunteers

Interim Toxicity Analysis From the Randomized HERMES Trial of 2- and 5-Fraction Magnetic Resonance Imaging-Guided Adaptive Prostate Radiation Therapy.

PURPOSE: Ultrahypofractionated radiation therapy (UHRT) is an effective treatment for localized prostate cancer with an acceptable toxicity profile; boosting the visible intraprostatic tumor has been shown to improve biochemical disease-free survival with no significant effect on genitourinary (GU) and gastrointestinal (GI) toxicity. METHODS AND MATERIALS: HERMES is a single-center noncomparative randomized phase 2 trial in men with intermediate or lower high risk prostate cancer. Patients were allocated (1:1) to 36.25 Gy in 5 fractions over 2 weeks or 24 Gy in 2 fractions over 8 days with an integrated boost to the magnetic resonance imaging (MRI) visible tumor of 27 Gy in 2 fractions. A minimization algorithm with a random element with risk group as a balancing factor was used for participant randomization. Treatment was delivered on the Unity MR-Linac (Elekta AB) with daily online adaption. The primary endpoint was acute GU Common Terminology Criteria for Adverse Events version 5.0 toxicity with the aim of excluding a doubling of the rate of acute grade 2+ GU toxicity seen in PACE. Analysis was by treatment received and included all participants who received at least 1 fraction of study treatment. This interim analysis was prespecified (stage 1 of a 2-stage Simon design) for when 10 participants in each treatment group had completed the acute toxicity monitoring period (12 weeks after radiation therapy). RESULTS: Acute grade 2 GU toxicity was reported in 1 (10%) patient in the 5-fraction group and 2 (20%) patients in the 2-fraction group. No grade 3+ GU toxicities were reported. CONCLUSIONS: At this interim analysis, the rate of GU toxicity in the 2-fraction and 5-fraction treatment groups was found to be below the prespecified threshold (5/10 grade 2+) and continuation of the study to complete recruitment of 23 participants per group was recommended

Understanding the Benefit of Magnetic Resonance-guided Adaptive Radiotherapy in Rectal Cancer Patients: a Single-centre Study.

AIMS: Neoadjuvant chemoradiotherapy followed by surgery is the mainstay of treatment for patients with rectal cancer. Standard clinical target volume (CTV) to planning target volume (PTV) margins of 10 mm are used to accommodate inter- and intrafraction motion of target. Treating on magnetic resonance-integrated linear accelerators (MR-linacs) allows for online manual recontouring and adaptation (MRgART) enabling the reduction of PTV margins. The aim of this study was to investigate motion of the primary CTV (CTVA; gross tumour volume and macroscopic nodes with 10 mm expansion to cover microscopic disease) in order to develop a simultaneous integrated boost protocol for use on MR-linacs. MATERIALS AND METHODS: Patients suitable for neoadjuvant chemoradiotherapy were recruited for treatment on MR-linac using a two-phase technique; only the five phase 1 fractions on MR-linac were used for analysis. Intrafraction motion of CTVA was measured between pre-treatment and post-treatment MRI scans. In MRgART, isotropically expanded pre-treatment PTV margins from 1 to 10 mm were rigidly propagated to post-treatment MRI to determine overlap with 95% of CTVA. The PTV margin was considered acceptable if overlap was >95% in 90% of fractions. To understand the benefit of MRgART, the same methodology was repeated using a reference computed tomography planning scan for pre-treatment imaging. RESULTS: In total, nine patients were recruited between January 2018 and December 2020 with T3a-T4, N0-N2, M0 disease. Forty-five fractions were analysed in total. The median motion across all planes was 0 mm, demonstrating minimal intrafraction motion. A PTV margin of 3 and 5mm was found to be acceptable in 96 and 98% of fractions, respectively. When comparing to the computed tomography reference scan, the analysis found that PTV margins to 5 and 10 mm only acceptably covered 51 and 76% of fractions, respectively. CONCLUSION: PTV margins can be reduced to 3-5 mm in MRgART for rectal cancer treatment on MR-linac within an simultaneous integrated boost protocol

Daily adaptive radiotherapy for patients with prostate cancer using a high field MR-linac: Initial clinical experiences and assessment of delivered doses compared to a C-arm linac.

Introduction:MR-guided adapted radiotherapy (MRgART) using a high field MR-linac has recently become available. We report the estimated delivered fractional dose of the first five prostate cancer patients treated at our centre using MRgART and compare this to C-Arm linac daily Image Guided Radiotherapy (IGRT). Methods:Patients were treated using adapted treatment plans shaped to their daily anatomy. The treatments were recalculated on an MR image acquired immediately prior to treatment delivery in order to estimate the delivered fractional dose. C-arm linac non-adapted VMAT treatment plans were recalculated on the same MR images to estimate the fractional dose that would have been delivered using conventional radiotherapy techniques using a daily IGRT protocol. Results:95% and 93% of mandatory target coverage objectives and organ at risk dose constraints were achieved by MRgART and C-arm linac delivered dose estimates, respectively. Both delivery techniques were estimated to have achieved 98% of mandatory Organ At Risk (OAR) dose constraints whereas for the target clinical goals, 86% and 80% were achieved by MRgART and C-arm linac delivered dose estimates. Conclusions:Prostate MRgART can be delivered using the a high field MR-linac. Radiotherapy performed on a C-arm linac offers a good solution for prostate cancer patients who present with favourable anatomy at the time of reference imaging and demonstrate stable anatomy throughout the course of their treatment. For patients with critical OARs abutting target volumes on their reference image we have demonstrated the potential for a target dose coverage improvement for MRgART compared to C-arm linac treatment

On the effects of the final state interaction in the electro-disintegration of the deuteron at intermediate and high energies

The role of the final state interactions (FSI) in the inclusive quasi-elastic disintegration of the deuteron is investigated treating the two-nucleon final state within the exact continuum solutions of the non-relativistic Schroedinger equation, as well as within the Glauber multiple scattering approach. It is shown that for values of the Bjorken scaling variable $x_{Bj}\simeq 1$ both approaches provide similar results, unless the case $x_{Bj}\gtrsim 1$, where they appreciably disagree. It is demonstrated that present experimental data, which are mostly limited to a region of four-momentum transfer ($Q^2 \lesssim 4 (GeV/c)^2$) where the Center-of-Mass energy of the final state is below the pion threshold production, can be satisfactorily reproduced by the approach based on the exact solution of the Schroedinger equation and not by the Glauber approach. It is also pointed out that the latter, unlike the former, does not satisfy the inelastic Coulomb sum rule, the violation being of the order of about 20%.Comment: 16 LaTeX pages, 10 eps-figures, 1 tabl

Deep Inelastic Scattering from off-Shell Nucleons

We derive the general structure of the hadronic tensor required to describe deep-inelastic scattering from an off-shell nucleon within a covariant formalism. Of the large number of possible off-shell structure functions we find that only three contribute in the Bjorken limit. In our approach the usual ambiguities encountered when discussing problems related to off-shellness in deep-inelastic scattering are not present. The formulation therefore provides a clear framework within which one can discuss the various approximations and assumptions which have been used in earlier work. As examples, we investigate scattering from the deuteron, nuclear matter and dressed nucleons. The results of the full calculation are compared with those where various aspects of the off-shell structure are neglected, as well as with those of the convolution model.Comment: 36 pages RevTeX, 9 figures (available upon request), ADP-93-210/T128, PSI-PR-93-13, accepted for publication in Physical Review

Efficient online 4D magnetic resonance imaging

Magnetic Resonance (MR)-guided online Adaptive RadioTherapy (MRgoART) utilises the excellent soft-tissue contrast of MR images taken just before the patient's treatment to quickly update and personalise radiotherapy treatment plans. Four-dimensional (4D) MR Imaging (MRI) can resolve variations in respiratory motion patterns. 4D MRI data can be used to adapt the radiation beams to maximally target the tumour while sparing as much healthy tissue as possible. 4D MRI reconstruction, however, is computationally challenging and current state-of-the-art implementations are unable to meet MRgoART time requirements. This study bridges the gap between high-performance computing and medical applications by developing and implementing a parallel, heterogeneous architecture for the XD-GRASP algorithm capable of meeting the MRgoART time requirements. Our architecture exploits long-vector instructions and utilises all available resources, while minimising and hiding the communication overhead when external GPUs are used. As a result, the reconstruction time was reduced from 994 seconds to just 90 seconds with a speedup of more than 11x. In addition, we evaluated the impact of the emerging Processing-in-Memory (PIM) technology. Our simulation results show that 16 low power, in-order PIM cores with no SIMD unit are 2.7x faster than an Intel Core™ i7-9700 8-core CPU equipped with AVX512 SIMD units. Additionally, 40 PIM cores match the performance of two AMD EPYC 7551 CPUs, with 32 cores each and just 87 PIM cores will match the performance of an NVIDIA Tesla V100 GPU equipped with 5,120 CUDA core