Abstract
Background
Target volume definition for curative radiochemotherapy in head and neck cancer is crucial since the predominant recurrence pattern is local. Additional diagnostic imaging like ...MRI is increasingly used, yet it is usually hampered by different patient positioning compared to radiotherapy. In this study, we investigated the impact of diagnostic MRI in treatment position for target volume delineation.
Methods
We prospectively analyzed patients who were suitable and agreed to undergo an MRI in treatment position with immobilization devices prior to radiotherapy planning from 2017 to 2019. Target volume delineation for the primary tumor was first performed using all available information except for the MRI and subsequently with additional consideration of the co-registered MRI. The derived volumes were compared by subjective visual judgment and by quantitative mathematical methods.
Results
Sixteen patients were included and underwent the planning CT, MRI and subsequent definitive radiochemotherapy. In 69% of the patients, there were visually relevant changes to the gross tumor volume (GTV) by use of the MRI. In 44%, the GTV_MRI would not have been covered completely by the planning target volume (PTV) of the CT-only contour. Yet, median Hausdorff und DSI values did not reflect these differences. The 3-year local control rate was 94%.
Conclusions
Adding a diagnostic MRI in RT treatment position is feasible and results in relevant changes in target volumes in the majority of patients.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
MR-guided radiotherapy (MRgRT) online plan adaptation accounts for tumor volume changes, interfraction motion and thus allows daily sparing of relevant organs at risk. Due to the high interfraction ...variability of bladder and rectum, patients with tumors in the pelvic region may strongly benefit from adaptive MRgRT. Currently, fast automatic annotation of anatomical structures is not available within the online MRgRT workflow. Therefore, the aim of this study was to train and validate a fast, accurate deep learning model for automatic MRI segmentation at the MR-Linac for future implementation in a clinical MRgRT workflow.
For a total of 47 patients, T2w MRI data were acquired on a 1.5 T MR-Linac (Unity, Elekta) on five different days. Prostate, seminal vesicles, rectum, anal canal, bladder, penile bulb, body and bony structures were manually annotated. These training data consisting of 232 data sets in total was used for the generation of a deep learning based autocontouring model and validated on 20 unseen T2w-MRIs. For quantitative evaluation the validation set was contoured by a radiation oncologist as gold standard contours (GSC) and compared in MATLAB to the automatic contours (AIC). For the evaluation, dice similarity coefficients (DSC), and 95% Hausdorff distances (95% HD), added path length (APL) and surface DSC (sDSC) were calculated in a caudal-cranial window of ± 4 cm with respect to the prostate ends. For qualitative evaluation, five radiation oncologists scored the AIC on the possible usage within an online adaptive workflow as follows: (1) no modifications needed, (2) minor adjustments needed, (3) major adjustments/ multiple minor adjustments needed, (4) not usable.
The quantitative evaluation revealed a maximum median 95% HD of 6.9 mm for the rectum and minimum median 95% HD of 2.7 mm for the bladder. Maximal and minimal median DSC were detected for bladder with 0.97 and for penile bulb with 0.73, respectively. Using a tolerance level of 3 mm, the highest and lowest sDSC were determined for rectum (0.94) and anal canal (0.68), respectively.
Qualitative evaluation resulted in a mean score of 1.2 for AICs over all organs and patients across all expert ratings. For the different autocontoured structures, the highest mean score of 1.0 was observed for anal canal, sacrum, femur left and right, and pelvis left, whereas for prostate the lowest mean score of 2.0 was detected. In total, 80% of the contours were rated be clinically acceptable, 16% to require minor and 4% major adjustments for online adaptive MRgRT.
In this study, an AI-based autocontouring was successfully trained for online adaptive MR-guided radiotherapy on the 1.5 T MR-Linac system. The developed model can automatically generate contours accepted by physicians (80%) or only with the need of minor corrections (16%) for the irradiation of primary prostate on the clinically employed sequences.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Many preclinical and clinical observations support that functional magnetic resonance imaging (MRI), such as diffusion weighted (DW) and dynamic contrast enhanced (DCE) MRI, might have a predictive ...value for radiotherapy. The aim of this review was to assess the current status of quantitative MRI on hybrid MR-Linacs. In a literature research, four publications were identified, investigating technical feasibility, accuracy, repeatability and reproducibility of DW and DCE-MRI in phantoms and first patients. Accuracy and short term repeatability was < 5% for DW-MRI in current MR-Linac systems. Consequently, quantitative imaging providing accurate and reproducible functional information seems possible in MR-Linacs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•First implementation of an independent 3D-secondary dose calculation (3D-SDC).•Validation of the 3D-SDC solution using patient plans and experimental plan QA.•Online SDC of central targets is ...feasible with a median calculation time of 1:23 min.•Peripheral targets with small beam numbers need alternative validation strategies.
Hybrid magnetic resonance linear accelerator (MR-Linac) systems represent a novel technology for online adaptive radiotherapy. 3D secondary dose calculation (SDC) of online adapted plans is required to assure patient safety. Currently, no 3D-SDC solution is available for 1.5T MR-Linac systems. Therefore, the aim of this project was to develop and validate a method for online automatic 3D-SDC for adaptive MR-Linac treatments.
An accelerator head model was designed for an 1.5T MR-Linac system, neglecting the magnetic field. The use of this model for online 3D-SDC of MR-Linac plans was validated in a three-step process: (1) comparison to measured beam data, (2) investigation of performance and limitations in a planning phantom and (3) clinical validation using n = 100 patient plans from different tumor entities, comparing the developed 3D-SDC with experimental plan QA.
The developed model showed median gamma passing rates compared to MR-Linac base data of 84.7%, 100% and 99.1% for crossplane, inplane and depth-dose-profiles, respectively. Comparison of 3D-SDC and full dose calculation in a planning phantom revealed that with ⩾5 beams gamma passing rates >95% can be achieved for central target locations. With a median calculation time of 1:23 min, 3D-SDC of online adapted clinical MR-Linac plans demonstrated a median gamma passing rate of 98.9% compared to full dose calculation, whereas experimental plan QA reached 99.5%.
Here, we describe the first technical 3D-SDC solution for online adaptive MR-guided radiotherapy. For clinical situations with peripheral targets and a small number of beams additional verification appears necessary. Further improvement may include 3D-SDC with consideration of the magnetic field.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Stereotactic radiosurgery (SRS) has been increasingly used to treat intracranial pathologies in elderly patients. The treatment efficiency of SRS has been demonstrated in meningiomas, with excellent ...local control. We aimed to analyze the safety of robotic SRS in elderly patients with meningiomas.
We searched for patients with suspected WHO °I meningioma ≥ 60 years old, who underwent CyberKnife (CK) SRS from January 2011 to December 2021. Tumor localization was categorized using the "CLASS" algorithmic scale. Tumor response was evaluated using the Response Assessment in Neuro-Oncology (RANO) criteria for meningiomas. Adverse effects were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and a cox regression was performed to investigate possible predictors.
We identified 82 patients with 102 CK-treated lesions that matched the criteria for the first SRS. The median age was 70 IQR 64-75 years, and 24.3% of the patients were aged > 75 years. Multiple lesions (up to six) were treated in 14.1% of the SRS-sessions. A previous surgery was performed in 57.3% of lesions, with a median time interval of 41 IQR 10 - 58 months between the initial surgical procedure and the SRS treatment. In 47.9% of cases, CLASS 3 meningiomas at high-risk locations were irradiated. Single fraction radiosurgery was applied to 62.5% of the lesions, while in the remaining cases multi-session SRS with three to five fractions was used. During the median follow-up period of 15.9 months, lesion size progression was observed in 3 cases. Karnofsky Performance Status (KPS) declined by ≥ 20 points in four patients. Adverse effects occurred in 13 patients, while only four patients had CTCAE ≥2 toxicities. Hereby only one of these toxicities was persistent. The occurrence of complications was independent of age, planned target volume (PTV), high-risk localization, and surgery before SRS.
The data indicates that SRS is a safe, efficient, and convenient treatment modality for elderly patients with meningioma, even at high-risk locations.
Stereotactic body radiotherapy (SBRT) is used to treat liver metastases with the intention of ablation. High local control rates were shown. Magnetic resonance imaging guided radiotherapy (MRgRT) ...provides the opportunity of a marker-less liver SBRT treatment due to the high soft tissue contrast. We report herein on one of the largest cohorts of patients treated with online MRgRT of liver metastases focusing on oncological outcome, toxicity, patient reported outcome measures (PROMs), quality of life.
Patients treated for liver metastases with online MR-guided SBRT at a 1,5 T MR-Linac (Unity, Elekta, Crawley, UK) between March 2019 and December 2021 were included in this prospective study. UK SABR guidelines were used for organs at risk constraints. Oncological endpoints such as survival parameters (overall survival, progression-free survival) and local control as well as patient reported acceptance and quality of life data (EORTC QLQ-C30 questionnaire) were assessed. For toxicity scoring the Common Toxicity Criteria Version 5 were used.
A total of 51 patients with 74 metastases were treated with a median of five fractions. The median applied BED GTV D98 was 84,1 Gy. Median follow-up was 15 months. Local control of the irradiated liver metastasis after 12 months was 89,6%, local control of the liver was 40,3%. Overall survival (OS) after 12 months was 85.1%. Progression free survival (PFS) after 12 months was 22,4%. Local control of the irradiated liver lesion was 100% after three years when a BED ≥100 Gy was reached. The number of treated lesions did not impact local control neither of the treated or of the hepatic control. Patient acceptance of online MRgSBRT was high. There were no acute grade ≥ 3 toxicities. Quality of life data showed no significant difference comparing baseline and follow-up data.
Online MR guided radiotherapy is a noninvasive, well-tolerated and effective treatment for liver metastases. Further prospective trials with the goal to define patients who actually benefit most from an online adaptive workflow are currently ongoing.
Neoadjuvant stereotactic radiosurgery (NaSRS) of brain metastases has gained importance, but it is not routinely performed. While awaiting the results of prospective studies, we aimed to analyze the ...changes in the volume of brain metastases irradiated pre- and postoperatively and the resulting dosimetric effects on normal brain tissue (NBT).
We identified patients treated with SRS at our institution to compare hypothetical preoperative gross tumor and planning target volumes (pre-GTV and pre-PTV) with original postoperative resection cavity volumes (post-GTV and post-PTV) as well as with a standardized-hypothetical PTV with 2.0 mm margin. We used Pearson correlation to assess the association between the GTV and PTV changes with the pre-GTV. A multiple linear regression analysis was established to predict the GTV change. Hypothetical planning for the selected cases was created to assess the volume effect on the NBT exposure. We performed a literature review on NaSRS and searched for ongoing prospective trials.
We included 30 patients in the analysis. The pre-/post-GTV and pre-/post-PTV did not differ significantly. We observed a negative correlation between pre-GTV and GTV-change, which was also a predictor of volume change in the regression analysis, in terms of a larger volume change for a smaller pre-GTV. In total, 62.5% of cases with an enlargement greater than 5.0 cm
were smaller tumors (pre-GTV < 15.0 cm
), whereas larger tumors greater than 25.0 cm
showed only a decrease in post-GTV. Hypothetical planning for the selected cases to evaluate the volume effect resulted in a median NBT exposure of only 67.6% (range: 33.2-84.5%) relative to the dose received by the NBT in the postoperative SRS setting. Nine published studies and twenty ongoing studies are listed as an overview.
Patients with smaller brain metastases may have a higher risk of volume increase when irradiated postoperatively. Target volume delineation is of great importance because the PTV directly affects the exposure of NBT, but it is a challenge when contouring resection cavities. Further studies should identify patients at risk of relevant volume increase to be preferably treated with NaSRS in routine practice. Ongoing clinical trials will evaluate additional benefits of NaSRS.
The objective of this study is to conduct a qualitative and a quantitative image quality and lesion evaluation in patients undergoing MR-guided radiation therapy (MRgRT) for prostate cancer on a ...hybrid magnetic resonance imaging and linear accelerator system (MR-Linac or MRL) at 1.5 Tesla. This prospective study was approved by the institutional review board. A total of 13 consecutive patients with biopsy-confirmed prostate cancer and an indication for MRgRT were included. Prior to radiation therapy, each patient underwent an MR-examination on an MRL and on a standard MRI scanner at 3 Tesla (MRI
). Three readers (two radiologists and a radiation oncologist) conducted an independent qualitative and quantitative analysis of T2-weighted (T2w) and diffusion-weighted images (DWI). Qualitative outcome measures were as follows: zonal anatomy, capsule demarcation, resolution, visibility of the seminal vesicles, geometric distortion, artifacts, overall image quality, lesion conspicuity, and diagnostic confidence. All ratings were performed on an ordinal 4-point Likert scale. Lesion conspicuity and diagnostic confidence were firstly analyzed only on MRL. Afterwards, these outcome parameters were analyzed in consensus with the MRI
. Quantitative outcome measures were as follows: anteroposterior and right left diameter of the prostate, lesion size, PI-RADS score (Prostate Imaging-Reporting and Data System) and apparent diffusion coefficient (ADC) of the lesions. Intergroup comparisons were computed using the Wilcoxon-sign rank test and
tests. A post-hoc regression analysis was computed for lesion evaluation. Finally, inter-/intra-reader agreement was analyzed using the Fleiss kappa and intraclass correlation coefficient. For T2w images, the MRL showed good results across all quality criteria (median 3 and 4). Furthermore, there were no significant differences between MRL and MRI
regarding capsule demarcation or geometric distortion. For the DWI, the MRL performed significantly less than MRI
across most image quality criteria with a median ranging between 2 and 3. However, there were no significant differences between MRL and MRI
regarding geometric distortion. In terms of lesion conspicuity and diagnostic confidence, inter-reader agreement was fair for MRL alone (Kappa = 0.42) and good for MRL in consensus with MRI
(Kappa = 0.708). Thus, lesion conspicuity and diagnostic confidence could be significantly improved when reading MRL images in consensus with MRI
(Odds ratio: 9- to 11-fold for the T2w images and 5- to 8-fold for the DWI) (
< 0.001). For measures of lesion size, anterior-posterior and right-left prostate diameter, inter-reader and intersequence agreement were excellent (ICC > 0.90) and there were no significant differences between MRL and MRI
among all three readers. In terms of Prostate Imaging Reporting and Data System (PIRADS) scoring, no significant differences were observed between MRL and MRI
. Finally, there was a significant positive linear relationship between lesion ADC measurements (r = 0.76,
< 0.01) between the ADC values measured on both systems. In conclusion, image quality for T2w was comparable and diagnostic even without administration of spasmolytic- or contrast agents, while DWI images did not reach diagnostic level and need to be optimized for further exploitation in the setting of MRgRT. Diagnostic confidence and lesion conspicuity were significantly improved by reading MRL in consensus with MRI
which would be advisable for a safe planning and treatment workflow. Finally, ADC measurements of lesions on both systems were comparable indicating that, lesion ADC as measured on the MRL could be used as a biomarker for evaluation of treatment response, similar to examinations using MRI
.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Hybrid MRI linear accelerators (MR-Linac) might enable individualized online adaptation of radiotherapy using quantitative MRI sequences as diffusion-weighted imaging (DWI). The purpose of this study ...was to investigate the dynamics of lesion apparent diffusion coefficient (ADC) in patients with prostate cancer undergoing MR-guided radiation therapy (MRgRT) on a 1.5T MR-Linac. The ADC values at a diagnostic 3T MRI scanner were used as the reference standard.
In this prospective single-center study, patients with biopsy-confirmed prostate cancer who underwent both an MRI exam at a 3T scanner (MRI
) and an exam at a 1.5T MR-Linac (MRL) at baseline and during radiotherapy were included. Lesion ADC values were measured by a radiologist and a radiation oncologist on the slice with the largest lesion. ADC values were compared before
. during radiotherapy (during the second week) on both systems via paired t-tests. Furthermore, Pearson correlation coefficient and inter-reader agreement were computed.
A total of nine male patients aged 67 ± 6 years range 60 - 67 years were included. In seven patients, the cancerous lesion was in the peripheral zone, and in two patients the lesion was in the transition zone. Inter-reader reliability regarding lesion ADC measurement was excellent with an intraclass correlation coefficient of (ICC) > 0.90 both at baseline and during radiotherapy. Thus, the results of the first reader will be reported. In both systems, there was a statistically significant elevation of lesion ADC during radiotherapy (mean MRL-ADC at baseline was 0.97 ± 0.18 × 10
mm
/s
. mean MRL-ADC during radiotherapy 1.38 ± 0.3 × 10
mm
/s, yielding a mean lesion ADC elevation of 0.41 ± 0.20 × 10
mm
/s, p < 0.001). Mean MRI
-ADC at baseline was 0.78 ± 0.165 × 10
mm
/s
. mean MRI
-ADC during radiotherapy 0.99 ± 0.175 × 10
mm
/s, yielding a mean lesion ADC elevation of 0.21 ± 0.96 × 10
mm
/s p < 0.001). The absolute ADC values from MRL were consistently significantly higher than those from MRI
at baseline and during radiotherapy (p < = 0.001). However, there was a strong positive correlation between MRL-ADC and MRI
-ADC at baseline (
= 0.798, p = 0.01) and during radiotherapy (
= 0.863, p = 0.003).
Lesion ADC as measured on MRL increased significantly during radiotherapy and ADC measurements of lesions on both systems showed similar dynamics. This indicates that lesion ADC as measured on the MRL may be used as a biomarker for evaluation of treatment response. In contrast, absolute ADC values as calculated by the algorithm of the manufacturer of the MRL showed systematic deviations from values obtained on a diagnostic 3T MRI system. These preliminary findings are promising but need large-scale validation. Once validated, lesion ADC on MRL might be used for real-time assessment of tumor response in patients with prostate cancer undergoing MR-guided radiation therapy.
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