Background: Quantitative image analysis using pre-operative magnetic resonance imaging (MRI) has ... more Background: Quantitative image analysis using pre-operative magnetic resonance imaging (MRI) has been able to predict survival in patients with glioblastoma (GBM). The study explored the role of postoperative radiation (RT) planning MRI-based radiomics to predict the outcomes, with features extracted from the gross tumor volume (GTV) and clinical target volume (CTV). Methods: Patients with IDH-wildtype GBM treated with adjuvant RT having MRI as a part of RT planning process were included in the study. 546 features were extracted from each GTV and CTV. A LASSO Cox model was applied, and internal validation was performed using leave-one-out cross-validation with overall survival as endpoint. Cross-validated time-dependent area under curve (AUC) was constructed to test the e cacy of the radiomics model, and clinical features were used to generate a combined model. Analysis was done for the entire group and in individual surgical groups-gross total excision (GTR), subtotal resection (STR), and biopsy. Results: 235 patients were included in the study with 57, 118, and 60 in the GTR, STR, and biopsy subgroup, respectively. Using the radiomics model, binary risk groups were feasible in the entire cohort (p<0.01) and biopsy group (p=0.04), but not in the other 2 surgical groups individually. The integrated AUC (iAUC) was 0.613 for radiomics-based classi cation in the biopsy subgroup, which improved to 0.632 with the inclusion of clinical features. Conclusion: Imaging features extracted from the GTV and CTV regions can lead to risk-strati cation of GBM undergoing biopsy, while it was redundant for patients with GTR and STR.
The standard clinical approach to assess the radiotherapy outcome in brain metastasis is through ... more The standard clinical approach to assess the radiotherapy outcome in brain metastasis is through monitoring the changes in tumour size on longitudinal MRI. This assessment requires contouring the tumour on many volumetric images acquired before and at several follow-up scans after the treatment that is routinely done manually by oncologists with a substantial burden on the clinical workflow. In this work, we introduce a novel system for automatic assessment of stereotactic radiation therapy (SRT) outcome in brain metastasis using standard serial MRI. At the heart of the proposed system is a deep learningbased segmentation framework to delineate tumours longitudinally on serial MRI with high precision. Longitudinal changes in tumour size are then analyzed automatically to assess the local response and detect possible adverse radiation effects (ARE) after SRT. The system was trained and optimized using the data acquired from 96 patients (130 tumours) and evaluated on an independent test set of 20 patients (22 tumours; 95 MRI scans). The comparison between automatic therapy outcome evaluation and manual assessments by expert oncologists demonstrates a good agreement with an accuracy, sensitivity, and specificity of 91%, 89%, and 92%, respectively, in detecting local control/failure and 91%, 100%, and 89% in detecting ARE on
PurposeThis study reports the workflow and initial clinical experience of high grade glioma (HGG)... more PurposeThis study reports the workflow and initial clinical experience of high grade glioma (HGG) radiotherapy on the 1.5 T MR-Linac (MRL), with a focus on the temporal variations of the tumor and feasibility of multi-parametric image (mpMRI) acquisition during routine treatment workflow.Materials and methodsTen HGG patients treated with radiation within the first year of the MRL’s clinical operation, between October 2019 and August 2020, were identified from a prospective database. Workflow timings were recorded and online adaptive plans were generated using the Adapt-To-Position (ATP) workflow. Temporal variation within the FLAIR hyperintense region (FHR) was assessed by the relative FHR volumes (n = 281 contours) and migration distances (maximum linear displacement of the volume). Research mpMRIs were acquired on the MRL during radiation and changes in selected functional parameters were investigated within the FHR.ResultsAll patients completed radiotherapy to a median dose of 60...
Magnetic Resonance Imaging (MRI)-Linear Accelerator (MR-Linac) radiotherapy is an innovative tech... more Magnetic Resonance Imaging (MRI)-Linear Accelerator (MR-Linac) 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. Thirty-seven consecutive glioma patients had treatment planning completed and approved prior to radiotherapy initiation using commercial treatment planning systems (TPS): a Monte Carlo-based or convolution-based TPS for MR-Linac or Cone Beam CT (CBCT)-guided Linac, respectively. In vivo skin dose was measured using an Optically Stimulated Luminescent Dosimeter (OSLD) and correlated with TPS skin dose. We found that Monte Carlo-based MR-Linac plans and convolution-based CBCT-Linac plans had similar dosimetric parameters for target volumes and organs-at-risk. However, MR-Linac plans had 1.52 Gy higher mean dose to air cavities (p<0.0001) and 1.10 Gy higher mean dose to skin (p<0.0001). In vivo skin dose was 14.5% greater f...
Background: Quantitative image analysis using pre-operative magnetic resonance imaging (MRI) has ... more Background: Quantitative image analysis using pre-operative magnetic resonance imaging (MRI) has been able to predict survival in patients with glioblastoma (GBM). The study explored the role of postoperative radiation (RT) planning MRI-based radiomics to predict the outcomes, with features extracted from the gross tumor volume (GTV) and clinical target volume (CTV). Methods: Patients with IDH-wildtype GBM treated with adjuvant RT having MRI as a part of RT planning process were included in the study. 546 features were extracted from each GTV and CTV. A LASSO Cox model was applied, and internal validation was performed using leave-one-out cross-validation with overall survival as endpoint. Cross-validated time-dependent area under curve (AUC) was constructed to test the efficacy of the radiomics model, and clinical features were used to generate a combined model. Analysis was done for the entire group and in individual surgical groups-gross total excision (GTR), subtotal resection (...
This study investigated the effectiveness of pre-treatment quantitative MRI and clinical features... more This study investigated the effectiveness of pre-treatment quantitative MRI and clinical features along with machine learning techniques to predict local failure in patients with brain metastasis treated with hypo-fractionated stereotactic radiation therapy (SRT). The predictive models were developed using the data from 100 patients (141 lesions) and evaluated on an independent test set with data from 20 patients (30 lesions). Quantitative MRI radiomic features were derived from the treatment-planning contrast-enhanced T1w and T2-FLAIR images. A multi-phase feature reduction and selection procedure was applied to construct an optimal quantitative MRI biomarker for predicting therapy outcome. The performance of standard clinical features in therapy outcome prediction was evaluated using a similar procedure. Survival analyses were conducted to compare the long-term outcome of the two patient cohorts (local control/failure) identified based on prediction at pre-treatment, and standard ...
Background The peritumoral region (PTR) of glioblastoma (GBM) appears as a T2W-hyperintensity and... more Background The peritumoral region (PTR) of glioblastoma (GBM) appears as a T2W-hyperintensity and is characterized by microscopic tumor and edema. In ltrative 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 LGG and GBM PTR, which can have future implications on existing treatment paradigms. 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 rst-order and texture features were determined from each of T1W-contrast, and T2W-FLAIR, diffusion-weighted imaging sequences. Applying ltration techniques, a total of 3822 features were obtained. Different feature reduction techniques were employed, and a subsequent model was constructed using four machine learning classi ers. Leave-one-out cross-validation was used to assess classi er performance. Results The analysis included 42 GBM and 36 LGG. The best performance was obtained using AdaBoost classi er using all the features with a sensitivity, speci city, 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 Ftest 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.
Background Stereotactic radiosurgery (SRS) is used to manage intracranial metastases in a signifi... more Background Stereotactic radiosurgery (SRS) is used to manage intracranial metastases in a significant fraction of patients. Local progression after SRS can often only be detected with increased volume of enhancement on serial MRI scans which may lag true progression by weeks or months. Methods Patients with intracranial metastases (N = 11) were scanned using hyperpolarized $$^{13}$$ 13 C MRI prior to treatment with stereotactic radiosurgery (SRS). The status of each lesion was then recorded at six months post-treatment follow-up (or at the time of death). Results The positive predictive value of $$^{13}$$ 13 C-lactate signal, measured pre-treatment, for prediction of progression of intracranial metastases at six months post-treatment with SRS was 0.8 $$p < 0.05$$ p < 0.05 , and the AUC from an ROC analysis was 0.77 $$p < 0.05$$ p < 0.05 . The distribution of $$^{13}$$ 13 C-lactate z-scores was different for intracranial metastases from different primary cancer types (F =...
Introduction This study proposes contouring recommendations for radiation treatment planning targ... more 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 workf...
Quantitative magnetization transfer (qMT) was used as a biomarker to monitor glioblastoma (GBM) r... more Quantitative magnetization transfer (qMT) was used as a biomarker to monitor glioblastoma (GBM) response to chemo-radiation and identify the earliest time-point qMT could differentiate progressors from non-progressors. Nineteen GBM patients were recruited and MRI-scanned before (Day), two weeks (Day), and four weeks (Day) into the treatment, and one month after the end of the treatment (Day). Comprehensive qMT data was acquired, and a two-pool MT model was fit to the data. Response was determined at 3-8 months following the end of chemo-radiation. The amount of magnetization transfer ([Formula: see text]) was significantly lower in GBM compared to normal appearing white matter (p < 0.001). Statistically significant difference was observed in [Formula: see text] at Day between non-progressors (1.06 ± 0.24) and progressors (1.64 ± 0.48), with p = 0.006. Changes in several qMT parameters between Day and Day were able to differentiate the two cohorts with [Formula: see text] providin...
International Journal of Radiation Oncology*Biology*Physics, 2016
were (1) construction of a prototype high-speed proton residual range detector, (2) analysis of t... more were (1) construction of a prototype high-speed proton residual range detector, (2) analysis of the range detector test beam and simulation data, and (3) construction and testing of a high-speed proton tracking detector prototype. Results: We have built a prototype residual range detector with all the features required. The prototype meets our requirements of high-speed operation and optimal resolution. The performance in test proton beams agrees very well with detailed Geant4 simulations. (Detailed graphs, figures, and data will be presented at the meeting). Conclusion: The combination of high performance, simple monolithic construction, and reduced electronics channel count will enable us to design a low-cost system, which will allow us to start testing strategies to optimize PBT treatments and maintain patient throughput. Use of a proton beam for imaging and range determination appears feasible, practical, and economical. This "apples to apples" comparison could prove superior to the use of X rays for imaging and range determination in certain aspects. Tests are now underway using our prototype.
International Journal of Radiation Oncology*Biology*Physics, 2017
To use contours automatically generated on the pre-treatment cone-beam CT (CBCT) to improve the r... more To use contours automatically generated on the pre-treatment cone-beam CT (CBCT) to improve the registration with the plan CT for prostate image-guided radiation therapy (IGRT). Materials/Methods: 10 patients, each with 10 to 28 daily kV-CBCTs, had their prostate manually contoured on the plan CT and daily CBCTs. Prostate contours were also automatically generated on the CBCTs. Auto-contours are produced by deformably registering prior CBCTs (atlases) to the current CBCT and deforming the prior contours with the resulting deformation field. This set of deformed prostate contours on the current CBCT is then combined using the STAPLE algorithm. The optimal IGRT shift is determined by comparing the centroid of the manual prostate contour in the CBCT and plan CT. This shift is compared both to the clinical shift that was based on qualitative alignment of the images, and to a centroid shift based on auto-contours. The dosimetric impact of the different shift methods is estimated by overlaying the plan prescription isodose line on the CBCT according to the shifts, and then determining the coverage of the manual prostate and PTV contours. Results: On average there is a 2.3AE1.5 mm difference in the superior/ inferior (SI) direction between the clinical and centroid shifts. The difference is 0.9AE0.7 mm in the left/right (LR) and 1.8AE1.5 mm in the anterior/posterior (AP) directions. Using the clinical shifts gave on average 98.7AE2.6% coverage of the prostate, and 89.6AE3.8% coverage of the PTV by the prescription dose. Centroid based shifts gave significantly better coverage of 99.5AE1.1% (PZ0.0013) and 92.7AE2.4% (P<0.00001) for the prostate and PTV respectively. The reduction in standard deviation also implies more consistent coverage day to day with the centroid shifts. The average dice similarity coefficient of prostate auto-contours to manual contours is 0.91, which equals our intra-observer error. The average time for auto-contouring was 90 seconds on a Tesla K20c GPU. Using auto-contours to determine the centroid produces equivalent shifts to the manual contour centroid shifts, with average differences of 0.8AE0.6, 0.4AE0.3 and 0.8AE0.7 mm in SI, LR and AP directions, respectively. This is to be expected given the consistency of the manual and auto-contours. Conclusion: There are >2 mm differences between our new centroid based shifts and the current clinical, image based shifts, with centroid based shifts providing significantly higher prostate coverage. Autocontouring provides equivalent shifts to manual centroid based shifts. IGRT can thus be fully automated, resulting in improved prostate coverage.
Clinical cancer research : an official journal of the American Association for Cancer Research, Jan 17, 2017
Stereotactic radiosurgery (SRS) is a common treatment used in patients with brain metastases and ... more Stereotactic radiosurgery (SRS) is a common treatment used in patients with brain metastases and is associated with high rates of local control, however, at the risk of radiation necrosis. It is difficult to differentiate radiation necrosis from tumor progression using conventional MRI making it a major diagnostic dilemma for practitioners. This prospective study investigated whether chemical exchange saturation transfer (CEST) was able to differentiate these two conditions. Sixteen patients with brain metastases who had been previously treated with SRS were included. Average time between SRS and evaluation was 12.6 months. Lesion type was determined by pathology in nine patients and the other seven were clinically followed. CEST imaging was performed on a 3T Philips scanner and the following CEST metrics were measured: Amide Proton Transfer (APT), Magnetization transfer (MT), magnetization transfer ratio (MTR) and area under the curve for CEST peaks corresponding to amide and Nucle...
Technology in cancer research & treatment, Apr 1, 2017
The aim of this study is to determine whether stereotactic body radiotherapy for multiple vertebr... more The aim of this study is to determine whether stereotactic body radiotherapy for multiple vertebral metastases treated with a single isocenter results in greater intrafraction errors than stereotactic body radiotherapy for single vertebral metastases and to determine whether the currently used spinal cord planning organ at risk volume and planning target volume margins are appropriate. Intrafraction errors were assessed for 65 stereotactic body radiotherapy treatments for vertebral metastases. Cone beam computed tomography images were acquired before, during, and after treatment for each fraction. Residual translational and rotational errors in patient positioning were recorded and planning organ at risk volume and planning target volume margins were calculated in each direction using this information. The mean translational residual errors were smaller for single (0.4 (0.4) mm) than for multiple vertebral metastases (0.5 (0.7) mm; P = .0019). The mean rotational residual errors wer...
International journal of radiation oncology, biology, physics, 2017
To determine a threshold of vertebral body (VB) osteolytic or osteoblastic tumor involvement that... more To determine a threshold of vertebral body (VB) osteolytic or osteoblastic tumor involvement that would predict vertebral compression fracture (VCF) risk after stereotactic body radiation therapy (SBRT), using volumetric image-segmentation software. A computational semiautomated skeletal metastasis segmentation process refined in our laboratory was applied to the pretreatment planning CT scan of 100 vertebral segments in 55 patients treated with spine SBRT. Each VB was segmented and the percentage of lytic and/or blastic disease by volume determined. The cumulative incidence of VCF at 3 and 12 months was 14.1% and 17.3%, respectively. The median follow-up was 7.3 months (range, 0.6-67.6 months). In all, 56% of segments were determined lytic, 23% blastic, and 21% mixed, according to clinical radiologic determination. Within these 3 clinical cohorts, the segmentation-determined mean percentages of lytic and blastic tumor were 8.9% and 6.0%, 0.2% and 26.9%, and 3.4% and 15.8% by volume...
International Journal of Radiation Oncology*Biology*Physics, 2017
Disclosures: Drs. Redmond, Sahgal, and Lo are members of an oligometastasis research consortium f... more Disclosures: Drs. Redmond, Sahgal, and Lo are members of an oligometastasis research consortium funded through a grant from Elekta AB. Dr. Redmond has received an honorarium for an educational seminar from AstraZeneca. Dr. Lo has received travel expenses and honorarium for past educational seminars from Varian Medical Systems and Accuray. Dr. Sahgal has research grants from Elekta AB and received honorarium for past educational seminars from Elekta AB, Medtronic and Varian Medical Systems. Dr. Chang has received Elekta users group meeting honorarium. Dr. Soltys has received consultant fees from Nektar Therapeutics. Dr. Chao reports past travel expenses and honorarium from Varian. Dr. Yamada has received consultant fees from Varian medical systems.
CARO 2016 S31 ___________________________________________________________________________________... more CARO 2016 S31 _________________________________________________________________________________________________________ using the NanoString platform. Patients were classified into lowversus high-risk groups based on pathological stage (≤ T2 versus ≥ T3), Gleason Score (GS) (≤ 7 versus ≥ 8), post-operative PSA level (≤0.2 versus > 0.2), margin status (positive versus negative) and nodal status (positive versus negative). Results: Seventy patients were recruited prospectively from 2015 to 2016 (median age = 64.5 years; range 48-77), and 30 patients were used as a discovery cohort. Five hundred and eighty-eight miRNAs were differentially expressed in serum exosomes (301 overexpressed and 287 underexpressed). Of these, three miRNAs (miR-122, miR-4421, and miR-92a) and 2 miRNAs (miR-145 and miR-630) were significantly overexpressed and underexpressed (> 2 fold difference, p < 0.05) in patients with high pathological stage and GS, respectively. miR-630 was found to be the only miRNA significantly downregulated in patients harboring all three high-risk features of GS, pathological stage and post-operative PSA. Pathway analysis was performed and indicated that these differentially expressed miRNAs were highly related to PCa carcinogenesis, progression, and angiogenesis. Preclinical studies were carried out to investigate the biological role of selected miRNAs in PCa proliferation, invasion and response to radiation and chemotherapy. Conclusions: This is the first report to our knowledge, detailing the discovery of a unique signature of exosomal miRNA obtained from PCa patient sera post-RP, with direct comparison to clinicopathological factors. This exosomal miRNA signature will be assessed in a validation cohort to assess its predictive value for biochemical recurrence post-RP.
Stereotactic body radiation therapy (SBRT) has the ability to deliver significantly higher biolog... more Stereotactic body radiation therapy (SBRT) has the ability to deliver significantly higher biologically equivalent doses (BED) compared to conventional radiation treatment. The main goal of SBRT is to improve local tumor control while reducing pain. The side effects however may be greater than those of conventional treatment. A review of the literature was conducted and articles pertaining to studies of SBRT in non-spine bone metastases were included. Data on outcomes and toxicities were collected in addition to inclusion and exclusion criteria for each study. A total of 14 studies were included in this review. Very rarely were grade 3 and 4 toxicities reported. Endpoints for the studies varied significantly, which made conclusions of overall local control and progression free survival near impossible. In studies that reported local control rates, these rates were all greater than 85%. Progression free survival varied significantly between studies. Due to the lack of consistency in ...
Purpose. Quantitative PET response assessment during therapy requires regions of interest (ROI). ... more Purpose. Quantitative PET response assessment during therapy requires regions of interest (ROI). Commonly, a fixed-size ROI is placed at the maximum uptake point in the pretreatment study. For intratreatment, the ROI is placed either at the maximum uptake point (ROIpeak) or at the same location as the pretreatment ROI (ROIsame). We have evaluated the effects of the ROI placement on response assessment. Methods. PET scans of 15 head and neck cancer patients were used to evaluate the effects of the two ROI methods on response assessment. Results. The average intratreatment ROIpeak uptake was 13.4% higher than the ROIsame uptake (range −14% to 38%). The average relative change in ROIpeak uptake was 7.9% lower than ROIsame uptake (range −5% to 36%), resulting in ambiguous tumour classification in 19% of the tumours. Conclusion. Quantitative PET response assessment using a fixed-size ROI is sensitive the ROI placement. The difference between ROIpeak and ROIsame could be substantial resul...
Background: Quantitative image analysis using pre-operative magnetic resonance imaging (MRI) has ... more Background: Quantitative image analysis using pre-operative magnetic resonance imaging (MRI) has been able to predict survival in patients with glioblastoma (GBM). The study explored the role of postoperative radiation (RT) planning MRI-based radiomics to predict the outcomes, with features extracted from the gross tumor volume (GTV) and clinical target volume (CTV). Methods: Patients with IDH-wildtype GBM treated with adjuvant RT having MRI as a part of RT planning process were included in the study. 546 features were extracted from each GTV and CTV. A LASSO Cox model was applied, and internal validation was performed using leave-one-out cross-validation with overall survival as endpoint. Cross-validated time-dependent area under curve (AUC) was constructed to test the e cacy of the radiomics model, and clinical features were used to generate a combined model. Analysis was done for the entire group and in individual surgical groups-gross total excision (GTR), subtotal resection (STR), and biopsy. Results: 235 patients were included in the study with 57, 118, and 60 in the GTR, STR, and biopsy subgroup, respectively. Using the radiomics model, binary risk groups were feasible in the entire cohort (p<0.01) and biopsy group (p=0.04), but not in the other 2 surgical groups individually. The integrated AUC (iAUC) was 0.613 for radiomics-based classi cation in the biopsy subgroup, which improved to 0.632 with the inclusion of clinical features. Conclusion: Imaging features extracted from the GTV and CTV regions can lead to risk-strati cation of GBM undergoing biopsy, while it was redundant for patients with GTR and STR.
The standard clinical approach to assess the radiotherapy outcome in brain metastasis is through ... more The standard clinical approach to assess the radiotherapy outcome in brain metastasis is through monitoring the changes in tumour size on longitudinal MRI. This assessment requires contouring the tumour on many volumetric images acquired before and at several follow-up scans after the treatment that is routinely done manually by oncologists with a substantial burden on the clinical workflow. In this work, we introduce a novel system for automatic assessment of stereotactic radiation therapy (SRT) outcome in brain metastasis using standard serial MRI. At the heart of the proposed system is a deep learningbased segmentation framework to delineate tumours longitudinally on serial MRI with high precision. Longitudinal changes in tumour size are then analyzed automatically to assess the local response and detect possible adverse radiation effects (ARE) after SRT. The system was trained and optimized using the data acquired from 96 patients (130 tumours) and evaluated on an independent test set of 20 patients (22 tumours; 95 MRI scans). The comparison between automatic therapy outcome evaluation and manual assessments by expert oncologists demonstrates a good agreement with an accuracy, sensitivity, and specificity of 91%, 89%, and 92%, respectively, in detecting local control/failure and 91%, 100%, and 89% in detecting ARE on
PurposeThis study reports the workflow and initial clinical experience of high grade glioma (HGG)... more PurposeThis study reports the workflow and initial clinical experience of high grade glioma (HGG) radiotherapy on the 1.5 T MR-Linac (MRL), with a focus on the temporal variations of the tumor and feasibility of multi-parametric image (mpMRI) acquisition during routine treatment workflow.Materials and methodsTen HGG patients treated with radiation within the first year of the MRL’s clinical operation, between October 2019 and August 2020, were identified from a prospective database. Workflow timings were recorded and online adaptive plans were generated using the Adapt-To-Position (ATP) workflow. Temporal variation within the FLAIR hyperintense region (FHR) was assessed by the relative FHR volumes (n = 281 contours) and migration distances (maximum linear displacement of the volume). Research mpMRIs were acquired on the MRL during radiation and changes in selected functional parameters were investigated within the FHR.ResultsAll patients completed radiotherapy to a median dose of 60...
Magnetic Resonance Imaging (MRI)-Linear Accelerator (MR-Linac) radiotherapy is an innovative tech... more Magnetic Resonance Imaging (MRI)-Linear Accelerator (MR-Linac) 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. Thirty-seven consecutive glioma patients had treatment planning completed and approved prior to radiotherapy initiation using commercial treatment planning systems (TPS): a Monte Carlo-based or convolution-based TPS for MR-Linac or Cone Beam CT (CBCT)-guided Linac, respectively. In vivo skin dose was measured using an Optically Stimulated Luminescent Dosimeter (OSLD) and correlated with TPS skin dose. We found that Monte Carlo-based MR-Linac plans and convolution-based CBCT-Linac plans had similar dosimetric parameters for target volumes and organs-at-risk. However, MR-Linac plans had 1.52 Gy higher mean dose to air cavities (p<0.0001) and 1.10 Gy higher mean dose to skin (p<0.0001). In vivo skin dose was 14.5% greater f...
Background: Quantitative image analysis using pre-operative magnetic resonance imaging (MRI) has ... more Background: Quantitative image analysis using pre-operative magnetic resonance imaging (MRI) has been able to predict survival in patients with glioblastoma (GBM). The study explored the role of postoperative radiation (RT) planning MRI-based radiomics to predict the outcomes, with features extracted from the gross tumor volume (GTV) and clinical target volume (CTV). Methods: Patients with IDH-wildtype GBM treated with adjuvant RT having MRI as a part of RT planning process were included in the study. 546 features were extracted from each GTV and CTV. A LASSO Cox model was applied, and internal validation was performed using leave-one-out cross-validation with overall survival as endpoint. Cross-validated time-dependent area under curve (AUC) was constructed to test the efficacy of the radiomics model, and clinical features were used to generate a combined model. Analysis was done for the entire group and in individual surgical groups-gross total excision (GTR), subtotal resection (...
This study investigated the effectiveness of pre-treatment quantitative MRI and clinical features... more This study investigated the effectiveness of pre-treatment quantitative MRI and clinical features along with machine learning techniques to predict local failure in patients with brain metastasis treated with hypo-fractionated stereotactic radiation therapy (SRT). The predictive models were developed using the data from 100 patients (141 lesions) and evaluated on an independent test set with data from 20 patients (30 lesions). Quantitative MRI radiomic features were derived from the treatment-planning contrast-enhanced T1w and T2-FLAIR images. A multi-phase feature reduction and selection procedure was applied to construct an optimal quantitative MRI biomarker for predicting therapy outcome. The performance of standard clinical features in therapy outcome prediction was evaluated using a similar procedure. Survival analyses were conducted to compare the long-term outcome of the two patient cohorts (local control/failure) identified based on prediction at pre-treatment, and standard ...
Background The peritumoral region (PTR) of glioblastoma (GBM) appears as a T2W-hyperintensity and... more Background The peritumoral region (PTR) of glioblastoma (GBM) appears as a T2W-hyperintensity and is characterized by microscopic tumor and edema. In ltrative 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 LGG and GBM PTR, which can have future implications on existing treatment paradigms. 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 rst-order and texture features were determined from each of T1W-contrast, and T2W-FLAIR, diffusion-weighted imaging sequences. Applying ltration techniques, a total of 3822 features were obtained. Different feature reduction techniques were employed, and a subsequent model was constructed using four machine learning classi ers. Leave-one-out cross-validation was used to assess classi er performance. Results The analysis included 42 GBM and 36 LGG. The best performance was obtained using AdaBoost classi er using all the features with a sensitivity, speci city, 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 Ftest 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.
Background Stereotactic radiosurgery (SRS) is used to manage intracranial metastases in a signifi... more Background Stereotactic radiosurgery (SRS) is used to manage intracranial metastases in a significant fraction of patients. Local progression after SRS can often only be detected with increased volume of enhancement on serial MRI scans which may lag true progression by weeks or months. Methods Patients with intracranial metastases (N = 11) were scanned using hyperpolarized $$^{13}$$ 13 C MRI prior to treatment with stereotactic radiosurgery (SRS). The status of each lesion was then recorded at six months post-treatment follow-up (or at the time of death). Results The positive predictive value of $$^{13}$$ 13 C-lactate signal, measured pre-treatment, for prediction of progression of intracranial metastases at six months post-treatment with SRS was 0.8 $$p < 0.05$$ p < 0.05 , and the AUC from an ROC analysis was 0.77 $$p < 0.05$$ p < 0.05 . The distribution of $$^{13}$$ 13 C-lactate z-scores was different for intracranial metastases from different primary cancer types (F =...
Introduction This study proposes contouring recommendations for radiation treatment planning targ... more 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 workf...
Quantitative magnetization transfer (qMT) was used as a biomarker to monitor glioblastoma (GBM) r... more Quantitative magnetization transfer (qMT) was used as a biomarker to monitor glioblastoma (GBM) response to chemo-radiation and identify the earliest time-point qMT could differentiate progressors from non-progressors. Nineteen GBM patients were recruited and MRI-scanned before (Day), two weeks (Day), and four weeks (Day) into the treatment, and one month after the end of the treatment (Day). Comprehensive qMT data was acquired, and a two-pool MT model was fit to the data. Response was determined at 3-8 months following the end of chemo-radiation. The amount of magnetization transfer ([Formula: see text]) was significantly lower in GBM compared to normal appearing white matter (p < 0.001). Statistically significant difference was observed in [Formula: see text] at Day between non-progressors (1.06 ± 0.24) and progressors (1.64 ± 0.48), with p = 0.006. Changes in several qMT parameters between Day and Day were able to differentiate the two cohorts with [Formula: see text] providin...
International Journal of Radiation Oncology*Biology*Physics, 2016
were (1) construction of a prototype high-speed proton residual range detector, (2) analysis of t... more were (1) construction of a prototype high-speed proton residual range detector, (2) analysis of the range detector test beam and simulation data, and (3) construction and testing of a high-speed proton tracking detector prototype. Results: We have built a prototype residual range detector with all the features required. The prototype meets our requirements of high-speed operation and optimal resolution. The performance in test proton beams agrees very well with detailed Geant4 simulations. (Detailed graphs, figures, and data will be presented at the meeting). Conclusion: The combination of high performance, simple monolithic construction, and reduced electronics channel count will enable us to design a low-cost system, which will allow us to start testing strategies to optimize PBT treatments and maintain patient throughput. Use of a proton beam for imaging and range determination appears feasible, practical, and economical. This "apples to apples" comparison could prove superior to the use of X rays for imaging and range determination in certain aspects. Tests are now underway using our prototype.
International Journal of Radiation Oncology*Biology*Physics, 2017
To use contours automatically generated on the pre-treatment cone-beam CT (CBCT) to improve the r... more To use contours automatically generated on the pre-treatment cone-beam CT (CBCT) to improve the registration with the plan CT for prostate image-guided radiation therapy (IGRT). Materials/Methods: 10 patients, each with 10 to 28 daily kV-CBCTs, had their prostate manually contoured on the plan CT and daily CBCTs. Prostate contours were also automatically generated on the CBCTs. Auto-contours are produced by deformably registering prior CBCTs (atlases) to the current CBCT and deforming the prior contours with the resulting deformation field. This set of deformed prostate contours on the current CBCT is then combined using the STAPLE algorithm. The optimal IGRT shift is determined by comparing the centroid of the manual prostate contour in the CBCT and plan CT. This shift is compared both to the clinical shift that was based on qualitative alignment of the images, and to a centroid shift based on auto-contours. The dosimetric impact of the different shift methods is estimated by overlaying the plan prescription isodose line on the CBCT according to the shifts, and then determining the coverage of the manual prostate and PTV contours. Results: On average there is a 2.3AE1.5 mm difference in the superior/ inferior (SI) direction between the clinical and centroid shifts. The difference is 0.9AE0.7 mm in the left/right (LR) and 1.8AE1.5 mm in the anterior/posterior (AP) directions. Using the clinical shifts gave on average 98.7AE2.6% coverage of the prostate, and 89.6AE3.8% coverage of the PTV by the prescription dose. Centroid based shifts gave significantly better coverage of 99.5AE1.1% (PZ0.0013) and 92.7AE2.4% (P<0.00001) for the prostate and PTV respectively. The reduction in standard deviation also implies more consistent coverage day to day with the centroid shifts. The average dice similarity coefficient of prostate auto-contours to manual contours is 0.91, which equals our intra-observer error. The average time for auto-contouring was 90 seconds on a Tesla K20c GPU. Using auto-contours to determine the centroid produces equivalent shifts to the manual contour centroid shifts, with average differences of 0.8AE0.6, 0.4AE0.3 and 0.8AE0.7 mm in SI, LR and AP directions, respectively. This is to be expected given the consistency of the manual and auto-contours. Conclusion: There are >2 mm differences between our new centroid based shifts and the current clinical, image based shifts, with centroid based shifts providing significantly higher prostate coverage. Autocontouring provides equivalent shifts to manual centroid based shifts. IGRT can thus be fully automated, resulting in improved prostate coverage.
Clinical cancer research : an official journal of the American Association for Cancer Research, Jan 17, 2017
Stereotactic radiosurgery (SRS) is a common treatment used in patients with brain metastases and ... more Stereotactic radiosurgery (SRS) is a common treatment used in patients with brain metastases and is associated with high rates of local control, however, at the risk of radiation necrosis. It is difficult to differentiate radiation necrosis from tumor progression using conventional MRI making it a major diagnostic dilemma for practitioners. This prospective study investigated whether chemical exchange saturation transfer (CEST) was able to differentiate these two conditions. Sixteen patients with brain metastases who had been previously treated with SRS were included. Average time between SRS and evaluation was 12.6 months. Lesion type was determined by pathology in nine patients and the other seven were clinically followed. CEST imaging was performed on a 3T Philips scanner and the following CEST metrics were measured: Amide Proton Transfer (APT), Magnetization transfer (MT), magnetization transfer ratio (MTR) and area under the curve for CEST peaks corresponding to amide and Nucle...
Technology in cancer research & treatment, Apr 1, 2017
The aim of this study is to determine whether stereotactic body radiotherapy for multiple vertebr... more The aim of this study is to determine whether stereotactic body radiotherapy for multiple vertebral metastases treated with a single isocenter results in greater intrafraction errors than stereotactic body radiotherapy for single vertebral metastases and to determine whether the currently used spinal cord planning organ at risk volume and planning target volume margins are appropriate. Intrafraction errors were assessed for 65 stereotactic body radiotherapy treatments for vertebral metastases. Cone beam computed tomography images were acquired before, during, and after treatment for each fraction. Residual translational and rotational errors in patient positioning were recorded and planning organ at risk volume and planning target volume margins were calculated in each direction using this information. The mean translational residual errors were smaller for single (0.4 (0.4) mm) than for multiple vertebral metastases (0.5 (0.7) mm; P = .0019). The mean rotational residual errors wer...
International journal of radiation oncology, biology, physics, 2017
To determine a threshold of vertebral body (VB) osteolytic or osteoblastic tumor involvement that... more To determine a threshold of vertebral body (VB) osteolytic or osteoblastic tumor involvement that would predict vertebral compression fracture (VCF) risk after stereotactic body radiation therapy (SBRT), using volumetric image-segmentation software. A computational semiautomated skeletal metastasis segmentation process refined in our laboratory was applied to the pretreatment planning CT scan of 100 vertebral segments in 55 patients treated with spine SBRT. Each VB was segmented and the percentage of lytic and/or blastic disease by volume determined. The cumulative incidence of VCF at 3 and 12 months was 14.1% and 17.3%, respectively. The median follow-up was 7.3 months (range, 0.6-67.6 months). In all, 56% of segments were determined lytic, 23% blastic, and 21% mixed, according to clinical radiologic determination. Within these 3 clinical cohorts, the segmentation-determined mean percentages of lytic and blastic tumor were 8.9% and 6.0%, 0.2% and 26.9%, and 3.4% and 15.8% by volume...
International Journal of Radiation Oncology*Biology*Physics, 2017
Disclosures: Drs. Redmond, Sahgal, and Lo are members of an oligometastasis research consortium f... more Disclosures: Drs. Redmond, Sahgal, and Lo are members of an oligometastasis research consortium funded through a grant from Elekta AB. Dr. Redmond has received an honorarium for an educational seminar from AstraZeneca. Dr. Lo has received travel expenses and honorarium for past educational seminars from Varian Medical Systems and Accuray. Dr. Sahgal has research grants from Elekta AB and received honorarium for past educational seminars from Elekta AB, Medtronic and Varian Medical Systems. Dr. Chang has received Elekta users group meeting honorarium. Dr. Soltys has received consultant fees from Nektar Therapeutics. Dr. Chao reports past travel expenses and honorarium from Varian. Dr. Yamada has received consultant fees from Varian medical systems.
CARO 2016 S31 ___________________________________________________________________________________... more CARO 2016 S31 _________________________________________________________________________________________________________ using the NanoString platform. Patients were classified into lowversus high-risk groups based on pathological stage (≤ T2 versus ≥ T3), Gleason Score (GS) (≤ 7 versus ≥ 8), post-operative PSA level (≤0.2 versus > 0.2), margin status (positive versus negative) and nodal status (positive versus negative). Results: Seventy patients were recruited prospectively from 2015 to 2016 (median age = 64.5 years; range 48-77), and 30 patients were used as a discovery cohort. Five hundred and eighty-eight miRNAs were differentially expressed in serum exosomes (301 overexpressed and 287 underexpressed). Of these, three miRNAs (miR-122, miR-4421, and miR-92a) and 2 miRNAs (miR-145 and miR-630) were significantly overexpressed and underexpressed (> 2 fold difference, p < 0.05) in patients with high pathological stage and GS, respectively. miR-630 was found to be the only miRNA significantly downregulated in patients harboring all three high-risk features of GS, pathological stage and post-operative PSA. Pathway analysis was performed and indicated that these differentially expressed miRNAs were highly related to PCa carcinogenesis, progression, and angiogenesis. Preclinical studies were carried out to investigate the biological role of selected miRNAs in PCa proliferation, invasion and response to radiation and chemotherapy. Conclusions: This is the first report to our knowledge, detailing the discovery of a unique signature of exosomal miRNA obtained from PCa patient sera post-RP, with direct comparison to clinicopathological factors. This exosomal miRNA signature will be assessed in a validation cohort to assess its predictive value for biochemical recurrence post-RP.
Stereotactic body radiation therapy (SBRT) has the ability to deliver significantly higher biolog... more Stereotactic body radiation therapy (SBRT) has the ability to deliver significantly higher biologically equivalent doses (BED) compared to conventional radiation treatment. The main goal of SBRT is to improve local tumor control while reducing pain. The side effects however may be greater than those of conventional treatment. A review of the literature was conducted and articles pertaining to studies of SBRT in non-spine bone metastases were included. Data on outcomes and toxicities were collected in addition to inclusion and exclusion criteria for each study. A total of 14 studies were included in this review. Very rarely were grade 3 and 4 toxicities reported. Endpoints for the studies varied significantly, which made conclusions of overall local control and progression free survival near impossible. In studies that reported local control rates, these rates were all greater than 85%. Progression free survival varied significantly between studies. Due to the lack of consistency in ...
Purpose. Quantitative PET response assessment during therapy requires regions of interest (ROI). ... more Purpose. Quantitative PET response assessment during therapy requires regions of interest (ROI). Commonly, a fixed-size ROI is placed at the maximum uptake point in the pretreatment study. For intratreatment, the ROI is placed either at the maximum uptake point (ROIpeak) or at the same location as the pretreatment ROI (ROIsame). We have evaluated the effects of the ROI placement on response assessment. Methods. PET scans of 15 head and neck cancer patients were used to evaluate the effects of the two ROI methods on response assessment. Results. The average intratreatment ROIpeak uptake was 13.4% higher than the ROIsame uptake (range −14% to 38%). The average relative change in ROIpeak uptake was 7.9% lower than ROIsame uptake (range −5% to 36%), resulting in ambiguous tumour classification in 19% of the tumours. Conclusion. Quantitative PET response assessment using a fixed-size ROI is sensitive the ROI placement. The difference between ROIpeak and ROIsame could be substantial resul...
Uploads
Papers by Hany Soliman