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Purpose: Stereotactic body radiation therapy (SBRT) is increasingly being used to treat spine metastases. Current post-SBRT imaging surveillance strategies in this patient population may benefit from a more data-driven and personalized approach. The objective of this study was to develop risk-stratified post-SBRT magnetic resonance imaging (MRI) surveillance strategies using quantitative methods., Methods and Materials: Adult patients with bony spine metastases treated with SBRT between 2008 and 2021 and who had at least 2 follow-up spine MRIs were reviewed retrospectively. A recursive partitioning analysis model was developed to separate patients into different risk categories for post-SBRT progression anywhere within the spine. Imaging intervals were derived for each risk category using parametric survival regression based on multiple expected spine progression rates per scan., Results: A total of 446 patients and 1039 vertebral segments were included. Cumulative incidence of spine progression was 19.2% at 1 year, 26.7% at 2 years, and 35.3% at 4 years. The internally validated risk stratification model was able to divide patients into 3 risk categories based on epidural disease, paraspinal disease, and Spinal Instability Neoplastic Score category. The 4-year risk of spine progression was 23.4%, 39.0%, and 51.8%, respectively, for the low-, intermediate-, and high-risk groups. Using an expected per-scan spine progression rate of 3.75%, the low-risk group would require follow-up scans every 6.0 months (95% CI, 4.9-7.6) and the intermediate-risk group would require surveillance every 3.1 months (95% CI, 2.6-3.7). At an expected spine progression rate of 5%, the high-risk group would require surveillance every 1.3 months (95% CI, 1.1-1.6) during the first 13.2 months after SBRT and every 5.9 months thereafter (95% CI, 2.8-12.3)., Conclusions: Data-driven follow-up MRI surveillance intervals at a range of expected spine progression rates have been determined for patients at different risks of spine progression based on an internally validated, single-institution risk stratification model., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: We present the final analyses of tumor dynamics and their prognostic significance during a 6-week course of concurrent chemoradiotherapy for glioblastoma in the Glioblastoma Longitudinal Imaging Observational study., Methods and Materials: This is a prospective serial magnetic resonance imaging study in 129 patients with glioblastoma who had magnetic resonance imaging obtained at radiation therapy (RT) planning (F0), fraction 10 (F10), fraction 20 (F20), and 1-month post-RT. Tumor dynamics assessed included gross tumor volume relative to F0 (V rel ) and tumor migration distance (d migration ). Covariables evaluated included: corpus callosum involvement, extent of surgery, O 6 -methylguanine-DNA-methyltransferase methylation, and isocitrate dehydrogenase mutation status., Results: The median V rel were 0.85 (range, 0.25-2.29) at F10, 0.79 (range, 0.09-2.22) at F20, and 0.78 (range, 0.13-4.27) at 1 month after completion of RT. The median d migration were 4.7 mm (range, 1.1-20.4 mm) at F10, 4.7 mm (range, 0.8-20.7 mm) at F20, and 6.1 mm (range, 0.0-45.5 mm) at 1 month after completion of RT. Compared with patients who had corpus callosum involvement (n = 26), those without corpus callosum involvement (n = 103) had significant V rel reduction at F20 (P = .03) and smaller d migration at F20 (P = .007). Compared with patients who had biopsy alone (n = 19) and subtotal resection (n = 71), those who had gross total resection (n = 38) had significant V rel reduction at F10 (P = .001) and F20 (P = .001) and a smaller d migration at F10 (P = .03) and F20 (P = .002). O 6 -Methylguanine-DNA-methyltransferase methylation and isocitrate dehydrogenase mutation status were not significantly associated with tumor dynamics. The median progression-free survival and overall survival (OS) were 8.5 months (95% CI, 6.9-9.9) and 20.4 months (95% CI, 17.6-25.2). In multivariable analyses, patients with V rel ≥ 1.33 at F10 had worse OS (hazard ratio [HR], 4.6; 95% CI, 1.8-11.4; P = .001), and patients with d migration ≥ 5 mm at 1-month post-RT had worse progression-free survival (HR, 1.76; 95% CI, 1.08-2.87) and OS (HR, 2.2; 95% CI, 1.2-4.0; P = .007)., Conclusions: Corpus callosum involvement and extent of surgery are independent predictors of tumor dynamics during RT and can enable patient selection for adaptive RT strategies. Significant tumor enlargement at F10 and tumor migration 1-month post-RT were associated with poorer OS., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose/objective(s): This study examined changes in the clinical target volume (CTV) and associated clinical implications on a magnetic resonance imaging linear accelerator (MR LINAC) during hypofractionated stereotactic radiotherapy (HSRT) to resected brain metastases. In addition, the suitability of using T2/FLAIR (T2f) sequence to define CTV was explored by assessing contouring variability between gadolinium-enhanced T1 (T1c) and T2f sequences., Materials/methods: Fifteen patients treated to either 27.5 or 30 Gy with five fraction HSRT were imaged with T1c and T2f sequences during treatment; T1c was acquired at planning (FxSim), and fraction 3 (Fx3), and T2f was acquired at FxSim and all five fractions. The CTV were contoured on all acquired images. Inter-fraction cavity dynamics and CTV contouring variability were quantified using absolute volume, Dice similarity coefficient (DSC), and Hausdorff distance (HD) metrics., Results: The median CTV on T1c and T2f sequences at FxSim were 12.0cm 3 (range, 1.2-30.1) and 10.2cm 3 (range, 2.9-27.9), respectively. At Fx3, the median CTV decreased in both sequences to 9.3cm 3 (range, 3.7-25.9) and 8.6cm 3 (range, 3.3-22.5), translating to a median % relative reduction of - 11.4% on T1c (p = 0.009) and - 8.4% on T2f (p = 0.032). We observed a median % relative reduction in CTV between T1c and T2f at FxSim of - 6.0% (p = 0.040). The mean DSC was 0.85 ± 0.10, and the mean HD was 5.3 ± 2.7 mm when comparing CTV on T1c and T2f at FxSim., Conclusion: Statistically significant reductions in cavity CTV was observed during HSRT, supporting the use of MR image guided radiation therapy and treatment adaptation to mitigate toxicity. Significant CTV contouring variability was seen between T1c and T2f sequences. Trial registration NCT04075305 - August 30, 2019., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The peritumoral region (PTR) of glioblastoma (GBM) appears as a T2W-hyperintensity and is composed of microscopic tumor and edema. Infiltrative low grade glioma (LGG) comprises tumor cells that seem similar to GBM PTR on MRI. The work here explored if a radiomics-based approach can distinguish between the two groups (tumor and edema versus tumor alone)., Methods: Patients with GBM and LGG imaged using a 1.5 T MRI were included in the study. Image data from cases of GBM PTR, and LGG were manually segmented guided by T2W hyperintensity. A set of 91 first-order and texture features were determined from each of T1W-contrast, and T2W-FLAIR, diffusion-weighted imaging sequences. Applying filtration techniques, a total of 3822 features were obtained. Different feature reduction techniques were employed, and a subsequent model was constructed using four machine learning classifiers. Leave-one-out cross-validation was used to assess classifier performance., Results: The analysis included 42 GBM and 36 LGG. The best performance was obtained using AdaBoost classifier using all the features with a sensitivity, specificity, accuracy, and area of curve (AUC) of 91%, 86%, 89%, and 0.96, respectively. Amongst the feature selection techniques, the recursive feature elimination technique had the best results, with an AUC ranging from 0.87 to 0.92. Evaluation with the F-test resulted in the most consistent feature selection with 3 T1W-contrast texture features chosen in over 90% of instances., Conclusions: Quantitative analysis of conventional MRI sequences can effectively demarcate GBM PTR from LGG, which is otherwise indistinguishable on visual estimation., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Magnetic resonance image (MRI) guided radiation therapy has the potential to improve outcomes for glioblastoma by adapting to tumor changes during radiation therapy. This study quantifies interfraction dynamics (tumor size, position, and geometry) based on sequential magnetic resonance imaging scans obtained during standard 6-week chemoradiation., Methods and Materials: Sixty-one patients were prospectively imaged with gadolinium-enhanced T1 (T1c) and T2/FLAIR axial sequences at planning (Fx0), fraction 10 (Fx10), fraction 20 (Fx20), and 1 month after the final fraction of chemoradiation therapy (P1M). Gross tumor volumes (GTVs) and clinical target volumes (CTVs) were contoured at all time points. Target dynamics were quantified by absolute volume (V), volume relative to Fx0 (V rel ), and the migration distance (d migrate ; the linear displacement of the GTV or CTV relative to Fx0). Temporal changes were assessed using a linear mixed-effects model., Results: Median volumes at Fx0, Fx10, Fx20, and P1M for the GTV were 18.4 cm 3 (range, 1.1-110.5 cm 3 ), 14.7 cm 3 (range, 0.9-115.1 cm 3 ), 13.7 cm 3 (range, 0.6-174.2 cm 3 ), and 13.0 cm 3 (range, 0.9-76.3 cm 3 ), respectively, with corresponding median V rel of 0.88 at Fx10, 0.77 at Fx20, and 0.71 at P1M relative to Fx0 (P < .001 for all). The GTV (CTV) migration distances were greater than 5 mm in 46% (54%) of patients at Fx10, 50% (58%) of patients at Fx20, and 52% (57%) of patients at P1M. Dynamic tumor morphologic changes were observed, with 40% of patients exhibiting a decreased GTV (V rel ≤1) with a d migrate >5 mm during chemoradiation therapy., Conclusions: Clinically meaningful tumor dynamics were observed during chemoradiation therapy for glioblastoma, supporting evaluation of daily MRI guided radiation therapy and treatment plan adaptation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: This study proposes contouring recommendations for radiation treatment planning target volumes and organs-at-risk (OARs) for both low grade and high grade gliomas., Methods: Ten cases consisting of 5 glioblastomas and 5 grade II or III gliomas, including their respective gross tumor volume (GTV), clinical target volume (CTV), and OARs were each contoured by 6 experienced neuro-radiation oncologists from 5 international institutions. Each case was first contoured using only MRI sequences (MRI-only), and then re-contoured with the addition of a fused planning CT (CT-MRI). The level of agreement among all contours was assessed using simultaneous truth and performance level estimation (STAPLE) with the kappa statistic and Dice similarity coefficient., Results: A high level of agreement was observed between the GTV and CTV contours in the MRI-only workflow with a mean kappa of 0.88 and 0.89, respectively, with no statistically significant differences compared to the CT-MRI workflow (p = 0.88 and p = 0.82 for GTV and CTV, respectively). Agreement in cochlea contours improved from a mean kappa of 0.39 to 0.41, to 0.69 to 0.71 with the addition of CT information (p < 0.0001 for both cochleae). Substantial to near perfect level of agreement was observed in all other contoured OARs with a mean kappa range of 0.60 to 0.90 in both MRI-only and CT-MRI workflows., Conclusions: Consensus contouring recommendations for low grade and high grade gliomas were established using the results from the consensus STAPLE contours, which will serve as a basis for further study and clinical trials by the MR-Linac Consortium.

Purpose: The current magnetic resonance imaging-computed tomography (MRI-CT) fusion-based workflow for postimplant dosimetry of low-dose-rate (LDR) prostate brachytherapy takes advantage of the superior soft tissue contrast of MRI, but still relies on CT for seed visualization and detection. Recently an MR-only workflow has been proposed that employs standard MR sequences and visualizes conventional implanted seed with positive contrast solely through MR postprocessing. In this work, the novel MR-only based workflow is compared with the clinical CT-MRI fusion approach., Methods and Materials: Twenty-four prostate patients with a total of 1775 implanted LDR seeds were scanned using a 3-dimensional multiecho gradient echo sequence on a 3 Tesla MR scanner within 30 days after implantation. Quantitative susceptibility mapping was used for seed visualization. Seeds were automatically segmented and localized on the quantitative susceptibility mapping using convolutional neural network and k-means clustering, respectively. To assess the MR-only seed localization error, CT and MR-derived seed positions were coregistered, and ultimately, the resulting dose-volume histograms were compared., Results: The MR-based seed visualization, segmentation, and localization generated comparable results to the CT-MR registration approach. The accuracy of the MRI-only based seed identification was 99.1%. After a rigid registration between the MR and CT-derived seed centroids, the average localization error was 0.8 ± 0.8 mm. The average prostate D 90 , V 100 , V 150 , and V 200 for MRI-only and CT-MR fusion based dosimetry were 114.3 ± 12.5% versus 113.9 ± 11.9%, 95.1 ± 3.7% versus 95.3 ± 3.8%, 54.5 ± 14.5% versus 55.0 ± 13.2% and 22.9 ± 6.8% versus 23.2 ± 6.7%, respectively. No significant differences were observed in 3-dimensional seed positions and dosimetric parameters between MR-only and CT-MR fusion-based workflows (P > 0.2)., Conclusions: The MRI-only LDR postimplant dosimetry is feasible and has very good potential to eliminate the need for CT-based seed identification., (Copyright © 2019 Elsevier Inc. All rights reserved.)

About 20-40% of cancer patients develop brain metastases, causing significant morbidity and mortality. Stereotactic radiation treatment is an established option that delivers high dose radiation to the target while sparing the surrounding normal tissue. However, up to 20% of metastatic brain tumours progress despite stereotactic treatment, and it can take months before it is evident on follow-up imaging. An early predictor of radiation therapy outcome in terms of tumour local failure (LF) is crucial, and can facilitate treatment adjustments or allow for early salvage treatment. In this study, an MR-based radiomics framework was proposed to derive and investigate quantitative MRI (qMRI) biomarkers for the outcome of LF in brain metastasis patients treated with hypo-fractionated stereotactic radiation therapy (SRT). The qMRI biomarkers were constructed through a multi-step feature extraction/reduction/selection framework using the conventional MR imaging data acquired from 100 patients (133 lesions), and were applied in conjunction with machine learning techniques for outcome prediction and risk assessment. The results indicated that the majority of the features in the optimal qMRI biomarkers characterize the heterogeneity in the surrounding regions of tumour including edema and tumour/lesion margins. The optimal qMRI biomarker consisted of five features that predict the outcome of LF with an area under the curve (AUC) of 0.79, and a cross-validated sensitivity and specificity of 81% and 79%, respectively. The Kaplan-Meier analyses showed a statistically significant difference in local control (p-value < 0.0001) and overall survival (p = 0.01). Findings from this study are a step towards using qMRI for early prediction of local failure in brain metastasis patients treated with SRT. This may facilitate early adjustments in treatment, such as surgical resection or salvage radiation, that can potentially improve treatment outcomes. Investigations on larger cohorts of patients are, however, required for further validation of the technique.

Background: We study the changes in organs-at-risk (OARs) morphology as contoured on serial MRIs during chemoradiation therapy (CRT) of glioblastoma (GBM). The dosimetric implication of assuming non-deformable OAR changes and the accuracy and feasibility of semi-automatic OAR contour propagation are investigated., Methods: Fourteen GBM patients who were treated with adjuvant CRT for GBM prospectively underwent MRIs on fractions 0 (i.e., planning), 10, 20, and 1 month post last fraction of CRT. Three sets of OAR contours - (a) manual, (b) rigidly registered (static), and (c) semi-automatically propagated - were compared using Dice similarity coefficient (DSC) and Hausdorff distance (HD). Dosimetric impact was determined by comparing the minimum dose to the 0.03 cc receiving the highest dose (D0.03 cc) on a clinically approved reference, non-adapted radiation therapy plan., Results: The DSC between the manual contours and the static contours decreased significantly over time (fraction 10: [mean ± 1 SD] 0.78 ± 0.17, post 1 month: 0.76 ± 0.17, P = 0.02) while the HD (P = 0.74) and the difference in D0.03cc did not change significantly (P = 0.51). Using the manual contours as reference, compared to static contours, propagated contours have a significantly higher DSC (propagated: [mean ± 1 SD] 0.81 ± 0.15, static: 0.77 ± 0.17, P < 0.001), lower HD (propagated: 3.77 ± 1.8 mm, static: 3.96 ± 1.6 mm, P = 0.002), and a significantly lower absolute difference in D0.03cc (propagated: 101 ± 159 cGy, static: 136 ± 243 cGy, P = 0.019)., Conclusions: Nonrigid changes in OARs over time lead to different maximum doses than planned. By using semi-automatic OAR contour propagation, OARs are more accurately delineated on subsequent fractions, with corresponding improved accuracy of the reported dose to the OARs., (© 2019 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Background: On a new dedicated radiosurgery unit enabling frameless treatments, a cone-beam computed tomography (CBCT) can be used for stereotactic definition. Since magnetic resonance imaging (MRI) is used to delineate target, reproducible MRI-to-CBCT coregistration is vital for accurate target localization., Objective: To evaluate reproducibility of image coregistration in patient images., Methods: Three types of coregistration (source-to-target) were analyzed: (1) MRI-to-CT; (2) MRI-to-CBCT; and (3) CT-to-CBCT. For each patient (n = 15), each coregistration type was independently performed 5 to 30 times (total: 465 coregistrations). Each coregistration yielded a transformation matrix, which was subsequently applied to transform every point in the source image to stereotactic coordinates. Two metrics were measured: (1) target registration error (TRE): mean distance between the registered position of each target point and the average registration position of that point; (2) compound registration error (CRE): mean spatial difference between stereotactic coordinates using (A) MRI-to-CT-to-CBCT and (B) MRI-to-CBCT., Results: The median (range) of TRE was 0.11 mm (0.06-0.22 mm), 0.17 mm (0.10-0.36 mm), and 0.12 mm (0.08-0.21 mm) for MRI-to-CT, MRI-to-CBCT, and CT-to-CBCT, respectively. The TRE for MRI-to-CBCT was statistically higher than the other 2 methods (P < .01). The median (range) of CRE was 0.44 mm (0.22-0.59 mm). The maximum point CRE between patients ranged from 0.37-1.15 mm when considering all MRI points, but reduced to 0.31-0.90 mm within the central 16 cm. The CRE varied across the image volume, and typically was minimized near the center., Conclusion: The variation in image coregistration is within 0.2 mm, indicating a high degree of reproducibility. The CRE varies throughout the head but is submillimeter in the central 16 cm region., (Copyright © 2018 by the Congress of Neurological Surgeons.)

Purpose: This study investigates the inter-observer variability of contouring non-spine bone metastases using the planning CT alone vs. the addition of MRI T1 and T2 imaging sequences., Methods and Materials: 10 cases of non-spine bone metastases treated with SBRT at our institution were selected. The gross tumor volume (GTV) for each case was delineated by six SBRT radiation oncologists (RO) and one diagnostic radiologist (DR) on the treatment planning CT. After a minimum of three months, each case was re-contoured on the CT fused with a MRI T1 sequence followed by a MRI T2 sequence. STAPLE consensus contours were created from the RO volumes and inter-observer variability was measured using both κ agreement and the Dice coefficient (DSC)., Results: In total, 180 RO contours were analyzed within three datasets (CT, CT + MRI T1 and CT + MRI T1 + MRI T2). The mean GTV was 16.95 cm 3 (range, 0.12-269.6 cm 3 ). The RO κ agreement was 0.6129 based on CT alone, and significantly increased to 0.7045 in the CT + MRI T1 (P = .042) dataset and 0.7017 in the CT + MRI T1 + MRI T2 dataset (P = .048). The mean DSC in the CT alone dataset was 0.7047, and significantly increased to 0.7628 in the CT + MRI T1 dataset (P < .001) and 0.7544 in the CT + MRI T1 + MRI T2 dataset (P = .001). There were no statistical differences in RO κ agreement (P = .948) or mean DSC (P = .573) when comparing the CT + MRI T1 and CT + MRI T1 + MRI T2 datasets. The DSC agreement between DR and RO volumes was lowest (0.6887) in the CT alone dataset and significantly increased to 0.7398 in the CT + MRI T1 dataset (P = .003) and 0.7342 in the CT + MRI T1 + MRI T2 dataset (P = .008)., Conclusions: The fusion of MRI T1 images to CT significantly reduced inter-observer variability amongst RO's in delineating non-spine bone metastases, and improved agreement between GTVs delineated by the RO to the DR., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To quantify the dosimetric impact of using virtual couch shift (VCS) for correcting setup errors in glioblastoma multiforme (GBM) patients treated on a magnetic resonance imaging (MRI)-linac., Methods and Materials: Six GBM patients treated with 60 Gy (30 fractions) were selected for this simulation study. For each case, 2 reference plans were generated in the MRL treatment planning system: With (WIB) and with no (NOB) MRI B field present. Subsequently, 2-mm, 4-mm, and 6-mm translational errors were simulated and corrected for using a VCS method based on shift-only, warm start segment weight (SWO), and segment weight and shape (SSO) optimization. The resulting distributions were compared with the reference plan using planning target volume (PTV) homogeneity index (HI), conformity index (CI), organs at risk (OAR) maximum dose (D 0.01cc ), and OAR median dose (D50). A simulated 30-fraction treatment was constructed to evaluate the cumulative effect of daily corrections. Feasibility and workflow for correcting rotations were also assessed., Results: All reference plans were deemed clinically acceptable with respect to PTV and OAR objectives. The difference in HI (ΔHI) between corrected and reference was not statistically significant between WIB and NOB (P=.89). The average ΔHI was +0.8%, -0.1%, and -1.0% for shift-only, SWO, and SSO, respectively, with a statistically significant difference (P<.001) for shift-only versus SWO and SSO. The CI remained unchanged (mean ΔCI = -0.01) between the corrected and reference plans, with no statistically significant dependence on magnetic field presence, correction method, or shift magnitude or orientation. The brainstem D50 on average decreased with SWO and SSO; however, D 0.01cc increased by a median value of 1.2%, 1.9%, and 2.0% for shift-only, SWO, and SSO, respectively. For other OARs, D 0.01cc decreased using SWO or SSO. For the simulated treatment and rotational corrections, similar trends were measured., Conclusion: For translational errors in brain MRI-linac radiation therapy, the VCS method is an acceptable correction strategy, but caution must be used in particular for serial organs where maximum doses are most relevant. The effect of the magnetic field on relative changes between corrected versus reference plans is not clinically relevant., (Copyright © 2017 Elsevier Inc. All rights reserved.)

This review article describes advancement of magnetic resonance imaging technologies in radiation therapy planning, guidance, and adaptation of brain tumors. The potential for MR-guided radiation therapy to improve outcomes and the challenges in its adoption are discussed., (© The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To assess motion of the spinal cord and cauda equina, which are critical neural tissues (CNT), which is important when evaluating the planning organ-at-risk margin required for stereotactic body radiation therapy., Methods and Materials: We analyzed CNT motion in 65 patients with spinal metastases (11 cervical, 39 thoracic, and 24 lumbar spinal segments) in the supine position using dynamic axial and sagittal magnetic resonance imaging (dMRI, 3T Verio, Siemens) over a 137-second interval. Motion was segregated according to physiologic cardiorespiratory oscillatory motion (characterized by the average root mean square deviation) and random bulk shifts associated with gross patient motion (characterized by the range). Displacement was evaluated in the anteroposterior (AP), lateral (LR), and superior-inferior (SI) directions by use of a correlation coefficient template matching algorithm, with quantification of random motion measure error over 3 separate trials. Statistical significance was defined according to P<.05., Results: In the AP, LR, and SI directions, significant oscillatory motion was observed in 39.2%, 35.1%, and 10.8% of spinal segments, respectively, and significant bulk motions in all cases. The median oscillatory CNT motions in the AP, LR, and SI directions were 0.16 mm, 0.17 mm, and 0.44 mm, respectively, and the maximal statistically significant oscillatory motions were 0.39 mm, 0.41 mm, and 0.77 mm, respectively. The median bulk displacements in the AP, LR, and SI directions were 0.51 mm, 0.59 mm, and 0.66 mm, and the maximal statistically significant displacements were 2.21 mm, 2.87 mm, and 3.90 mm, respectively. In the AP, LR, and SI directions, bulk displacements were greater than 1.5 mm in 5.4%, 9.0%, and 14.9% of spinal segments, respectively. No significant differences in axial motion were observed according to cord level or cauda equina., Conclusions: Oscillatory CNT motion was observed to be relatively minor. Our results support the importance of controlling bulk patient motion and the practice of applying a planning organ-at-risk margin., (Copyright © 2015 Elsevier Inc. All rights reserved.)

BackgroundPrediction of early progression in glioblastoma may provide an opportunity to personalize treatment. Simplified intravoxel incoherent motion (IVIM) MRI offers quantitative estimates of diffusion and perfusion metrics. We investigated whether these metrics, during chemoradiation, could predict treatment outcome.Methods38 patients with newly diagnosed IDH-wildtype glioblastoma undergoing 6-week/30-fraction chemoradiation had standardized post-operative MRIs at baseline (radiation planning), and at the 10th and 20th fractions. Non-overlapping T1-enhancing (T1C) and non-enhancing T2-FLAIR hyperintense regions were independently segmented. Apparent diffusion coefficient (ADCT1C, ADCT2-FLAIR) and perfusion fraction (fT1C, fT2-FLAIR) maps were generated with simplified IVIM modelling. Parameters associated with progression before or after 6.9 months (early vs late progression, respectively), overall survival (OS) and progression-free survival (PFS) were investigated.ResultsHigher ADCT2-FLAIR at baseline [Odds Ratio (OR) = 1.06, 95% CI 1.01-1.15, p = 0.025], lower fT2-FLAIR at fraction 10 (OR = 2.11, 95% CI 1.04-4.27, p = 0.018), and lack of increase in ADCT2-FLAIR at fraction 20 compared to baseline (OR = 1.12, 95% CI 1.02-1.22, p = 0.02) were associated with early progression. Combining ADCT2-FLAIR at baseline, fT2-FLAIR at fraction 10, ECOG and MGMT promoter methylation status significantly improved AUC to 90.3% compared to a model with only ECOG and MGMT promoter methylation status (p = 0.001). Using multivariable analysis, neither IVIM metrics were associated with OS but higher fT2-FLAIR at fraction 10 (HR = 0.72, 95% CI 0.56-0.95, p = 0.018) was associated with longer PFS.ConclusionADCT2-FLAIR at baseline, its lack of increase from baseline to fraction 20, or fT2-FLAIR at fraction 10 significantly predicted early progression. fT2-FLAIR at fraction 10 was associated with PFS.

Background: The radiotherapy process relies on several metrics in determining a notion of "distance" from one three‐dimensional region‐of‐interest (ROI) to another. The majority are symmetric (or commutative) and do not contain information pertaining to directionality. Growth versus regression, for example, is not inherently distinguished by these metrics. Purpose: The purpose of this work was to formalize a unidirectional distance metric, motivated by radiotherapy margin concepts, which we term the migration distance. Informally, the migration distance from ROI X$X$ to Y$Y$ is the minimum isotropic expansion of X$X$ such that Y$Y$ is completely encompassed by the expansion. If Y$Y$ is contained within X$X$, the migration distance is negative with magnitude equal to the maximum isotropic contraction of X$X$ such that Y$Y$ remains contained within contraction. The metric is demonstrated by quantifying glioblastoma interfraction target changes. Methods: An explicit mathematical formulation of the migration distance is presented and contrasted with the related Hausdorff distance. The results are demonstrated for the gross tumor volume (GTV) dynamics of a glioblastoma cohort consisting of 111 patients that underwent standard chemoradiotherapy with offline MR imaging at planning, fraction 10, fraction 20, and 1‐month post radiotherapy. Results: The mean ± SD of the GTV migration distance relative to planning was 5.9 ± 3.9 mm at fraction 10, 6.2 ± 4.4 mm at fraction 20, and 7.9 ± 7.1 mm at 1‐month post radiotherapy. The maximum GTV migration distance across all patients at the same timepoints was 20.4, 20.7, and 45.5 mm, respectively. Conclusions: We have proposed and demonstrated a unidirectional distance metric. The migration distance may have applications in the quantification of anatomical changes, planning target volume designs, and dosimetric radiotherapy plan assessment. [ABSTRACT FROM AUTHOR]

Background: High radiation doses of stereotactic radiosurgery (SRS) for brain metastases (BM) can increase the likelihood of radiation necrosis (RN). Advanced MRI sequences can improve the differentiation between RN and tumor progression (TP). Purpose: To use saturation transfer MRI methods including chemical exchange saturation transfer (CEST) and magnetization transfer (MT) to distinguish RN from TP. Study Type: Prospective cohort study. Subjects: Seventy patients (median age 60; 73% females) with BM (75 lesions) post‐SRS. Field Strength/Sequence: 3‐T, CEST imaging using low/high‐power (saturation B1 = 0.52 and 2.0 μT), quantitative MT imaging using B1 = 1.5, 3.0, and 5.0 μT, WAter Saturation Shift Referencing (WASSR), WAter Shift And B1 (WASABI), T1, and T2 mapping. All used gradient echoes except T2 mapping (gradient and spin echo). Assessment: Voxel‐wise metrics included: magnetization transfer ratio (MTR); apparent exchange‐dependent relaxation (AREX); MTR asymmetry; normalized MT exchange rate and pool size product; direct water saturation peak width; and the observed T1 and T2. Regions of interests (ROIs) were manually contoured on the post‐Gd T1w. The mean (of median ROI values) was compared between groups. Clinical outcomes were determined by clinical and radiologic follow‐up or histopathology. Statistical Tests: t‐Test, univariable and multivariable logistic regression, receiver operating characteristic, and area under the curve (AUC) with sensitivity/specificity values with the optimal cut point using the Youden index, Akaike information criterion (AIC), Cohen's d. P < 0.05 with Bonferroni correction was considered significant. Results: Seven metrics showed significant differences between RN and TP. The high‐power MTR showed the highest AUC of 0.88, followed by low‐power MTR (AUC = 0.87). The combination of low‐power CEST scans improved the separation compared to individual parameters (with an AIC of 70.3 for low‐power MTR/AREX). Cohen's d effect size showed that the MTR provided the largest effect sizes among all metrics. Data Conclusion: Significant differences between RN and TP were observed based on saturation transfer MRI. Evidence Level: 3 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

Purpose: Target localization, for stereotactic radiosurgery (SRS) treatment with Gamma Knife, has become increasingly reliant on the co‐registration between the planning MRI and the stereotactic cone‐beam computed tomography (CBCT). Validating image registration between modalities would be particularly beneficial when considering the emergence of novel functional and metabolic MRI pulse sequences for target delineation. This study aimed to develop a phantom‐based methodology to quantitatively compare the co‐registration accuracy of the standard clinical imaging protocol to a representative MRI sequence that was likely to fail co‐registration. The comparative methodology presented in this study may serve as a useful tool to evaluate the clinical translatability of novel MRI sequences. Methods: A realistic human skull phantom with fiducial marker columns was designed and manufactured to fit into a typical MRI head coil and the Gamma Knife patient positioning system. A series of "optimized" 3D MRI sequences—T1‐weighted Dixon, T1‐weighted fast field echo (FFE), and T2‐weighted fluid‐attenuated inversion recovery (FLAIR)—were acquired and co‐registered to the CBCT. The same sequences were "compromised" by reconstructing without geometric distortion correction and re‐collecting with lower signal‐to‐noise‐ratio (SNR) to simulate a novel MRI sequence with poor co‐registration accuracy. Image similarity metrics—structural similarity (SSIM) index, mean squared error (MSE), and peak SNR (PSNR)—were used to quantitatively compare the co‐registration of the optimized and compromised MR images. Results: The ground truth fiducial positions were compared to positions measured from each optimized image volume revealing a maximum median geometric uncertainty of 0.39 mm (LR), 0.92 mm (AP), and 0.13 mm (SI) between the CT and CBCT, 0.60 mm (LR), 0.36 mm (AP), and 0.07 mm (SI) between the CT and T1‐weighted Dixon, 0.42 mm (LR), 0.23 mm (AP), and 0.08 mm (SI) between the CT and T1‐weighted FFE, and 0.45 mm (LR), 0.19 mm (AP), and 1.04 mm (SI) between the CT and T2‐weighted FLAIR. Qualitatively, pairs of optimized and compromised image slices were compared using a fusion image where separable colors were used to differentiate between images. Quantitatively, MSE was the most predictive and SSIM the second most predictive metric for evaluating co‐registration similarity. A clinically relevant threshold of MSE, SSIM, and/or PSNR may be defined beyond which point an MRI sequence should be rejected for target delineation based on its dissimilarity to an optimized sequence co‐registration. All dissimilarity thresholds calculated using correlation coefficients with in‐plane geometric uncertainty would need to be defined on a sequence‐by‐sequence basis and validated with patient data. Conclusion: This study utilized a realistic skull phantom and image similarity metrics to develop a methodology capable of quantitatively assessing whether a modern research‐based MRI sequence can be co‐registered to the Gamma Knife CBCT with equal or less than equal accuracy when compared to a clinically accepted protocol. [ABSTRACT FROM AUTHOR]

Introduction: Magnetic resonance imaging-linear accelerator radiotherapy is an innovative technology that requires special consideration for secondary electron interactions within the magnetic field, which can alter dose deposition at air–tissue interfaces. As part of ongoing quality assurance and quality improvement of new radiotherapy technologies, the purpose of this study was to evaluate skin dose modelled from the treatment planning systems of a magnetic resonance imaging-linear accelerator and a conventional linear accelerator, and then correlate with in vivo measurements of delivered skin dose from each linear accelerator. Methods: In this prospective cohort study, 37 consecutive glioma patients had treatment planning completed and approved prior to radiotherapy initiation using commercial treatment planning systems: a Monte Carlo-based algorithm for magnetic resonance imaging-linear accelerator or a convolution-based algorithm for conventional linear accelerator. In vivo skin dose was measured using an optically stimulated luminescent dosimeter. Results: Monte Carlo-based magnetic resonance imaging-linear accelerator plans and convolution-based conventional linear accelerator plans had similar dosimetric parameters for target volumes and organs-at-risk. However, magnetic resonance imaging-linear accelerator plans had 1.52 Gy higher mean dose to air cavities (P <.0001) and 1.10 Gy higher mean dose to skin (P <.0001). In vivo skin dose was 14.5% greater for magnetic resonance imaging-linear accelerator treatments (P =.0027), and was more accurately predicted by Monte Carlo-based calculation (ρ = 0.95, P <.0001) versus convolution-based (ρ = 0.80, P =.0096). Conclusion: This is the first prospective dosimetric comparison of glioma patients clinically treated on both magnetic resonance imaging-linear accelerator and conventional linear accelerator. Our findings suggest that skin doses were significantly greater with magnetic resonance imaging-linear accelerator plans but correlated better with in vivo measurements of actual skin dose from delivered treatments. Future magnetic resonance imaging-linear accelerator planning processes are being designed to account for skin dosimetry and treatment delivery. [ABSTRACT FROM AUTHOR]

Stereotactic body radiation therapy (SBRT) for spine metastases improves pain response rates compared with conventional external beam radiation therapy; however, the optimal fractionation schedule is unclear. We report local control and toxicity outcomes after dose-escalated 2-fraction spine SBRT. A prospectively maintained institutional database of over 600 patients and 1400 vertebral segments treated with spine SBRT was reviewed to identify those prescribed 28 or 24 Gy in 2 daily fractions. The primary endpoint was magnetic resonance imaging based local failure (LF), and secondary endpoints included overall survival and vertebral compression fracture (VCF). A total of 947 treated vertebral segments in 482 patients were identified, of which 301 segments in 159 patients received 28 Gy, and 646 segments in 323 patients received 24 Gy in 2 fractions. Median follow-up per patient was 23.5 months, and median overall survival was 49.1 months. In the 28 Gy cohort, the 6-, 12-, and 24-month cumulative incidences of LF were 3.5%, 5.4%, and 11.1%, respectively, versus 6.0%, 12.5%, and 17.6% in the 24 Gy cohort, respectively (P =.008). On multivariable analysis, 24 Gy (hazard ratio [HR], 1.525; 95% confidence interval, 1.039-2.238; P =.031), paraspinal disease extension (HR, 1.422; 95% confidence interval, 1.010-2.002; P =.044), and epidural extension in either radioresistant or radiosensitive histologies (HR, 2.117 and 1.227, respectively; P =.003) were prognostic for higher rates of LF. Risk of VCF was 5.5%, 7.6%, and 10.7% at 6, 12, and 24 months, respectively, and was similar between cohorts (P =.573). Spinal malalignment (P <.001), baseline VCF (P =.003), junctional spine location (P =.030), and greater minimum dose to 90% of planning target volume were prognostic for higher rates of VCF. Dose escalation to 28 Gy in 2 daily fractions was associated with improved local control without increasing the risk of VCF. The 2-year local control rates are consistent with those predicted by the Hypofractionated Treatment Effects in the Clinic spine tumor control probability model, and these data will inform a proposed dose escalation randomized trial. [ABSTRACT FROM AUTHOR]

Purpose: Despite the increasing use of stereotactic body radiation therapy for non-spine bone metastases (NSBM), there is no established standard for target delineation. The objective of this study was to provide consensus recommendations on clinical target volume (CTV) delineation based on international expert contours.Methods and Materials: Eleven cases of NSBM were contoured by 9 international radiation oncologists. For each case, the gross tumor volume was provided on the simulation computed tomography scans with accompanying magnetic resonance imaging. Participants contoured the CTV and completed a clinical survey. Agreement between CTV contours were analyzed with simultaneous truth and performance level estimation using the kappa coefficient and the Dice similarity coefficient (DSC) and summarized to establish contouring recommendations. A direction-dependent analysis was applied to the consensus contours to quantify margins.Results: All CTV contours were completed. Six participants used a single-dose level, whereas 3 used a 2-dose level simultaneous integrated boost (SIB) technique. For the SIB cases, the largest volume receiving a stereotactic body radiation therapy (SBRT) dose was used for contour analysis. There was substantial agreement between contours across cases with a mean kappa of 0.72 (mean sensitivity 0.85, mean specificity 0.97). The mean DSC value was 0.77 (range, 0.67-0.87). Consensus CTV contouring recommendations were (1) an intraosseous CTV margin of 5 to 10 mm should be strongly considered within contiguous bone; (2) an extraosseous margin of 5 to 10 mm should be strongly considered where there is soft tissue disease or cortical bone disruption; (3) CTVs should be manually cropped to respect anatomic barriers to spread (eg, peritoneal cavity, pleura, uninvolved joint space and cortical bone).Conclusions: CTV contouring recommendations for NSBM-SBRT were established based on analysis of international expert consensus contours with a high level of agreement. These principles may provide guidance to treating physicians and inform future study until prospective clinical data can provide further refinement. [ABSTRACT FROM AUTHOR]

Purpose: Multileaf collimator (MLC) linear accelerator (Linac)-based hypofractionated stereotactic radiation therapy (HSRT) is increasingly used not only for large brain metastases or those adjacent to critical structures but also for those metastases that would otherwise be considered for single-fraction radiosurgery (SRS). However, data on outcomes in general are limited, and there is a lack of understanding regarding optimal dosing. Our aim was to report mature image-based outcomes for MLC-Linac HSRT with a focus on clinical and dosimetric factors associated with local failure (LF).Methods and Materials: A total of 220 patients with 334 brain metastases treated with HSRT were identified. All patients were treated using a 5-fraction daily regimen and were followed with clinical evaluation and volumetric magnetic resonance imaging every 2 to 3 months. Overall survival and progression-free survival were calculated using the Kaplan-Meier method, with LF determined using Fine and Gray's competing risk method. Predictive factors were identified using Cox regression multivariate analysis.Results: Median follow-up was 10.8 months. Median size of treated metastasis was 1.9 cm; 60% of metastases were <2 cm in size. The median total dose was 30 Gy in 5 fractions; 36% of the cohort received <30 Gy. The median time to LF and 12-month cumulative incidence of LF was 8.5 months and 23.8%, respectively. Median time to death and 12-month overall survival rates were 11.8 months and 48.2%, respectively. Fifty-two metastases (15.6%) had an adverse radiation effect, of which 32 (9.5%) were symptomatic necrosis. Multivariable analysis identified worse LF in patients who received a total dose of <30 Gy (hazard ratio, 1.62; P = .03), with LF at 6 and 12 months of 13% and 33% for patients treated with <30 Gy versus 5% and 19% for patients treated with >30 Gy. Exploratory analysis demonstrated a dose-response effect observed in all histologic types, including among breast cancer subtypes.Conclusion: Optimal local control is achieved with HSRT of ≥30 Gy in 5 daily fractions, independent of tumor volume and histology, with an acceptable risk of radiation necrosis. [ABSTRACT FROM AUTHOR]

• CEST MRI is feasible on a 1.5 tesla MR-Linac for imaging CNS tumours. • Differences were found in CEST signals between tumour and white matter. • Detectable signal changes between treatment fractions were observed. • Differences in asymmetry were found between high- and low-grade tumours. To describe the implementation and initial results of using Chemical Exchange Saturation Transfer (CEST) for monitoring patients with central nervous system (CNS) tumours treated using a 1.5 tesla MR-guided radiotherapy system. CNS patients were treated with up to 30 fractions (total dose up to 60 Gy) using a 1.5 T Elekta Unity MR-Linac. CEST scans were obtained in 54 subjects at one or more time points during treatment. CEST metrics, including the amide magnetization transfer ratio (MTR Amide), nuclear Overhauser effect (NOE) MTR (MTR NOE) and asymmetry, were quantified in phantoms and CNS patients. The signal was investigated between tumour and white matter, across time, and across disease categories including high- and low-grade tumours. The gross tumour volume (GTV) exhibited lower MTR Amide and MTR NOE and higher asymmetry compared to contralateral normal appearing white matter. Signal changes in the GTV during fractionated radiotherapy were observed. There were differences between high- and low-grade tumours, with higher CEST asymmetry associated with higher grade disease. CEST MRI using a 1.5 T MR-Linac was demonstrated to be feasible for in vivo imaging of CNS tumours. CEST images showed tumour/white-matter contrast, temporal CEST signal changes, and associations with tumour grade. These results show promise for the eventual goal of using metabolic imaging to inform the design of adaptive radiotherapy protocols. [ABSTRACT FROM AUTHOR]

To explore the changes in T2-weighted (T2w) and apparent diffusion coefficient (ADC) magnetic resonance imaging -derived radiomic features of the gross tumor volume (GTV) from focal salvage high-dose-rate prostate brachytherapy (HDRB) and to correlate with clinical parameters. Eligible patients included those with biopsy-confirmed local recurrence that correlated with MRI (T2w, ADC). Patients received 27 Gy in 2 fractions separated by 1 week to a quadrant consisting of the GTV. The MRI was repeated 1 year after HDRB. GTVs, planning target volumes, and normal prostate tissue control volumes were identified on the pre- and post-HDRB MRIs. Radiomic features from each GTV were extracted, and principle component analysis identified features with the highest variance. Pre- and post-HDRB MRIs were obtained from 14 trial patients. Principle component analysis showed that 18 and 17 features contributed to 93% and 86% of the variance observed in the T2w and ADC data, respectively. Sixteen T2w features and 1 ADC GTV feature were different from the control volumes in the pre-HDRB images (p < 0.05). Ten T2w and 7 ADC GTV post-HDRB features were different from those of pre-HDRB (p < 0.05). Exploratory analysis reveals several radiomic features in the T2w and ADC image GTVs that distinguish the GTV from healthy prostate tissue and change significantly after salvage HDRB. [ABSTRACT FROM AUTHOR]

• Two-fraction prostate SABR with boost to MRI-defined DIL is technically feasible. • Overall changes in urinary, bowel and sexual QOL score met acceptability threshold. • No acute or late G3 toxicities were observed. • Early signals of efficacy (4yrPSARR, and BF) are encouraging. This is the first report of the 2SMART Phase II trial evaluating the safety of two-fraction stereotactic ablative radiotherapy (SABR) with focal boost to magnetic resonance imaging (MRI) defined dominant intra-prostatic lesion (DIL) for localised prostate cancer. Men with low or intermediate risk prostate cancer were eligible for the study. The gross tumour volume (GTV) was MRI-defined DIL, and the clinical target volume (CTV) was entire prostate gland. The planning target volume (PTV) was a 2 mm expansion anteroposterior and lateral, and 2.5 mm superoinferior. The prescribed dose was 32 Gy to GTV, and 26 Gy to CTV. Primary endpoint was minimal clinically important change (MCIC) in quality of life (QOL) within 3-months of SABR, assessed using the EPIC-26 questionnaire. Secondary endpoints were acute and late toxicities (assessed using CTCAEv4), PSA nadir, and biochemical failure (based on Phoenix criteria). Thirty men were enrolled in the study – 2 (7%) had low-risk and 28 (93%) had intermediate risk prostate cancer. The median follow-up was 44 months (range:39–49 months). The median PSA nadir was 0.25 ng/mL, with median time to nadir of 37 months. One patient (3%) had biochemical failure at 44 months post-treatment. Ten (33%), six (20%), and three (10%) men had acute MCIC in urinary, bowel, and sexual QOL domains respectively. No acute or late grade ≥ 3 urinary or bowel toxicities were observed. This novel protocol of two-fraction prostate SABR with MRI-defined DIL boost is a safe approach for dose-escalation, with minimal impact on acute QOL and no grade ≥ 3 toxicities. [ABSTRACT FROM AUTHOR]