To enable magnetic resonance (MR)-only radiotherapy and facilitate modelling of radiation attenuation in humans, synthetic CT (sCT) images need to be generated. Considering the application of ...MR-guided radiotherapy and online adaptive replanning, sCT generation should occur within minutes. This work aims at assessing whether an existing deep learning network can rapidly generate sCT images for accurate MR-based dose calculations in the entire pelvis. A study was conducted on data of 91 patients with prostate (59), rectal (18) and cervical (14) cancer who underwent external beam radiotherapy acquiring both CT and MRI for patients' simulation. Dixon reconstructed water, fat and in-phase images obtained from a conventional dual gradient-recalled echo sequence were used to generate sCT images. A conditional generative adversarial network (cGAN) was trained in a paired fashion on 2D transverse slices of 32 prostate cancer patients. The trained network was tested on the remaining patients to generate sCT images. For 30 patients in the test set, dose recalculations of the clinical plan were performed on sCT images. Dose distributions were evaluated comparing voxel-based dose differences, gamma and dose-volume histogram (DVH) analysis. The sCT generation required 5.6 s and 21 s for a single patient volume on a GPU and CPU, respectively. On average, sCT images resulted in a higher dose to the target of maximum 0.3%. The average gamma pass rates using the 3%, 3 mm and 2%, 2 mm criteria were above 97 and 91%, respectively, for all volumes of interests considered. All DVH points calculated on sCT differed less than ±2.5% from the corresponding points on CT. Results suggest that accurate MR-based dose calculation using sCT images generated with a cGAN trained on prostate cancer patients is feasible for the entire pelvis. The sCT generation was sufficiently fast for integration in an MR-guided radiotherapy workflow.
Purpose
To study the influence of gradient echo–based contrasts as input channels to a 3D patch‐based neural network trained for synthetic CT (sCT) generation in canine and human populations.
Methods
...Magnetic resonance images and CT scans of human and canine pelvic regions were acquired and paired using nonrigid registration. Magnitude MR images and Dixon reconstructed water, fat, in‐phase and opposed‐phase images were obtained from a single T1‐weighted multi‐echo gradient‐echo acquisition. From this set, 6 input configurations were defined, each containing 1 to 4 MR images regarded as input channels. For each configuration, a UNet‐derived deep learning model was trained for synthetic CT generation. Reconstructed Hounsfield unit maps were evaluated with peak SNR, mean absolute error, and mean error. Dice similarity coefficient and surface distance maps assessed the geometric fidelity of bones. Repeatability was estimated by replicating the training up to 10 times.
Results
Seventeen canines and 23 human subjects were included in the study. Performance and repeatability of single‐channel models were dependent on the TE‐related water–fat interference with variations of up to 17% in mean absolute error, and variations of up to 28% specifically in bones. Repeatability, Dice similarity coefficient, and mean absolute error were statistically significantly better in multichannel models with mean absolute error ranging from 33 to 40 Hounsfield units in humans and from 35 to 47 Hounsfield units in canines.
Conclusion
Significant differences in performance and robustness of deep learning models for synthetic CT generation were observed depending on the input. In‐phase images outperformed opposed‐phase images, and Dixon reconstructed multichannel inputs outperformed single‐channel inputs.
This study investigates whether focal boosting of the macroscopic visible tumor with external beam radiotherapy increases biochemical disease-free survival (bDFS) in patients with localized prostate ...cancer.
In the phase III, multicenter, randomized controlled Focal Lesion Ablative Microboost in Prostate Cancer trial, 571 patients with intermediate- and high-risk prostate cancer were enrolled between 2009 and 2015. Patients assigned to standard treatment received 77 Gy (fractions of 2.2 Gy) to the entire prostate. The focal boost arm received an additional simultaneous integrated focal boost up to 95 Gy (fractions up to 2.7 Gy) to the intraprostatic lesion visible on multiparametric magnetic resonance imaging. Organ at risk constraints were prioritized over the focal boost dose. The primary end point was 5-year bDFS. Secondary end points were disease-free survival (DFS), distant metastases-free survival, prostate cancer-specific survival, overall survival, toxicity, and health-related quality of life.
Median follow-up was 72 months. Biochemical DFS was significantly higher in the focal boost compared with the standard arm (hazard ratio 0.45, 95% CI, 0.28 to 0.71,
< .001). At 5-year follow-up bDFS was 92% and 85%, respectively. We did not observe differences in prostate cancer-specific survival (
= .49) and overall survival (
= .50). The cumulative incidence of late genitourinary and GI toxicity grade ≥ 2 was 23% and 12% in the standard arm versus 28% and 13% in the focal boost arm, respectively. Both for late toxicity as health-related quality of life, differences were small and not statistically significant.
The addition of a focal boost to the intraprostatic lesion improved bDFS for patients with localized intermediate- and high-risk prostate cancer without impacting toxicity and quality of life. The Focal Lesion Ablative Microboost in Prostate Cancer study shows that a high focal boost strategy to improve tumor control while respecting organ at risk dose constraints is effective and safe.
External beam radiotherapy remains the primary treatment modality for localized prostate cancer. The radiobiology of prostate carcinoma lends itself to hypofractionation, with recent studies showing ...good outcomes with shorter treatment schedules. However, the ability to accurately deliver hypofractionated treatment is limited by current image-guided techniques. Magnetic resonance imaging is the main diagnostic tool for localized prostate cancer and its use in the therapeutic setting offers anatomical information to improve organ delineation. MR-guided radiotherapy, with daily re-planning, has shown early promise in the accurate delivery of radiotherapy. In this article, we discuss the shortcomings of current image-guidance strategies and the potential benefits and limitations of MR-guided treatment for prostate cancer. We also recount present experiences of MR-linac workflow and the opportunities afforded by this technology.
•The Elekta Unity MR-linac adaptive radiotherapy concept is explained.•The adapt to shape and adapt to position workflows are compared.•Different methods for dose re-calculation and optimization are ...discussed.•Full online re-planning is the most robust adaptive planning method for the Unity.•Faster methods are available, but should be dosimetrically explored per use case.
The promise of the MR-linac is that one can visualize all anatomical changes during the course of radiotherapy and hence adapt the treatment plan in order to always have the optimal treatment. Yet, there is a trade-off to be made between the time spent for adapting the treatment plan against the dosimetric gain. In this work, the various daily plan adaptation methods will be presented and applied on a variety of tumour sites. The aim is to provide an insight in the behavior of the state-of-the-art 1.5 T MRI guided on-line adaptive radiotherapy methods.
To explore the different available plan adaptation workflows and methods, we have simulated online plan adaptation for five cases with varying levels of inter-fraction motion, regions of interest and target sizes: prostate, rectum, esophagus and lymph node oligometastases (single and multiple target). The plans were evaluated based on the clinical dose constraints and the optimization time was measured.
The time needed for plan adaptation ranged between 17 and 485 s. More advanced plan adaptation methods generally resulted in more plans that met the clinical dose criteria. Violations were often caused by insufficient PTV coverage or, for the multiple lymph node case, a too high dose to OAR in the vicinity of the PTV. With full online replanning it was possible to create plans that met all clinical dose constraints for all cases.
Daily full online replanning is the most robust adaptive planning method for Unity. It is feasible for specific sites in clinically acceptable times. Faster methods are available, but before applying these, the specific use cases should be explored dosimetrically.
An international research consortium has been formed to facilitate evidence-based introduction of MR-guided radiotherapy (MR-linac) and to address how the MR-linac could be used to achieve an ...optimized radiation treatment approach to improve patients' survival, local, and regional tumor control and quality of life. The present paper describes the organizational structure of the clinical part of the MR-linac consortium. Furthermore, it elucidates why collaboration on this large project is necessary, and how a central data registry program will be implemented.
•Focal intraprostatic lesion SBRT boosting is associated with low acute toxicity.•No acute grade ≥3 toxicity was reported in the phase II hypo-FLAME trial.•SBRT for PCa is attractive to both patients ...and radiation oncology departments.
Local recurrences after radiotherapy for prostate cancer (PCa) often originate at the location of the macroscopic tumour(s). Since PCa cells are known to be sensitive to high fraction doses, hypofractionated whole gland stereotactic body radiotherapy (SBRT) in conjunction with a simultaneous ablative microboost to the macroscopic tumour(s) within the prostate could be a way to reduce the risk of local failure. We investigated the safety of this treatment strategy.
Patients with intermediate or high risk PCa were enrolled in a prospective phase II trial, called hypo-FLAME. All patients were treated with extreme hypofractionated doses of 35 Gy in 5 weekly fractions to the whole prostate gland with an integrated boost up to 50 Gy to the multiparametric (mp) MRI-defined tumour(s). Treatment-related toxicity was measured using the CTCAE v4.0. The primary endpoint of the trial was treatment-related acute toxicity.
Between April 2016 and December 2018, 100 men were treated in 4 academic centres. All patients were followed up for a minimum of 6 months. The median mean dose delivered to the visible tumour nodule(s) on mpMRI was 44.7 Gy in this trial. No grade ≥3 acute genitourinary (GU) or gastrointestinal (GI) toxicity was observed. Furthermore, 90 days after start of treatment, the cumulative acute grade 2 GU and GI toxicity rates were 34.0% and 5.0%, respectively.
Simultaneous focal boosting to the macroscopic tumour(s) in addition to whole gland prostate SBRT is associated with acceptable acute GU and GI toxicity.
Radiation therapy to the prostate involves increasingly sophisticated delivery techniques and changing fractionation schedules. With a low estimated α/β ratio, a larger dose per fraction would be ...beneficial, with moderate fractionation schedules rapidly becoming a standard of care. The integration of a magnetic resonance imaging (MRI) scanner and linear accelerator allows for accurate soft tissue tracking with the capacity to replan for the anatomy of the day. Extreme hypofractionation schedules become a possibility using the potentially automated steps of autosegmentation, MRI-only workflow, and real-time adaptive planning. The present report reviews the steps involved in hypofractionated adaptive MRI-guided prostate radiation therapy and addresses the challenges for implementation.
To compare toxicity rates in patients with localized prostate cancer treated with standard fractionated external beam radiotherapy (EBRT) with or without an additional integrated boost to the ...macroscopically visible tumour.
FLAME is a phase 3 multicentre RCT (NCT01168479) of patients with pathologically confirmed localized intermediate or high-risk prostate cancer. The standard treatment arm (n = 287) received a dose to the entire prostate of 77 Gy in 35 fractions. The dose-escalated treatment arm (n = 284) received 77 Gy in 35 fractions to the entire prostate, with an integrated boost up to 95 Gy to the multi-parametric MRI-defined (macroscopic) tumour within the prostate. Treatment related toxicity was measured using the CTCAE version 3.0. Grade 2 or worse GU or GI events up to two years were compared between groups by presenting proportions and by Generalized Estimating Equations (GEE) analyses for repeated measures.
Ninety percent of the 571 men randomly assigned between September 2009 and January 2015 had high-risk disease (Ash 2000), of whom nearly 66% were prescribed hormonal therapy up to three years. Median follow-up was 55 months at the time of this analysis. Toxicity prevalence rates for both GI and GU increased until the end of treatment and regressed thereafter, with no obvious differences across treatment groups. Late cumulative GI toxicity rates were 11.1% and 10.2% for the standard and dose-escalated group, respectively. These rates were 22.6% and 27.1% for GU toxicity. GEE analyses showed that both GU toxicity and GI toxicity (≥grade 2) up to two years after treatment were similar between arms (OR 1.02 95%CI 0.78–1.33p = 0.81 and (OR 1.19 95%CI 0.82–1.73p = 0.38), respectively.
In intermediate- and high-risk prostate cancer patients, focal dose escalation integrated with standard EBRT did not result in an increase in GU and GI toxicity when compared to the standard treatment up to two years after treatment. This suggests that the described focal dose escalation technique is safe and feasible.
Magnetic resonance imaging (MRI)-guided radiotherapy allows for online adaptation of the radiation plan on the basis of anatomical and functional changes during treatment. MRI-guided radiotherapy ...holds significant promise for broadening the therapeutic window for multiple urological cancers.
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