Publications by authors named "Pejman Maralani"

42 Publications

Chemical exchange saturation transfer MRI in central nervous system tumours on a 1.5 T MR-Linac.

Radiother Oncol 2021 Jul 17;162:140-149. Epub 2021 Jul 17.

Physical Sciences Platform, Sunnybrook Research Institute, Toronto, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Canada.

Purpose: 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.

Methods: 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), nuclear Overhauser effect (NOE) MTR (MTR) 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.

Results: The gross tumour volume (GTV) exhibited lower MTR and MTR 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.

Conclusion: 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.
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http://dx.doi.org/10.1016/j.radonc.2021.07.010DOI Listing
July 2021

Stereotactic body radiotherapy versus conventional external beam radiotherapy in patients with painful spinal metastases: an open-label, multicentre, randomised, controlled, phase 2/3 trial.

Lancet Oncol 2021 07 11;22(7):1023-1033. Epub 2021 Jun 11.

Canadian Clinical Trials Group, Queens's University, Kingston, ON, Canada.

Background: Conventional external beam radiotherapy is the standard palliative treatment for spinal metastases; however, complete response rates for pain are as low as 10-20%. Stereotactic body radiotherapy delivers high-dose, ablative radiotherapy. We aimed to compare complete response rates for pain after stereotactic body radiotherapy or conventional external beam radiotherapy in patients with painful spinal metastasis.

Methods: This open-label, multicentre, randomised, controlled, phase 2/3 trial was done at 13 hospitals in Canada and five hospitals in Australia. Patients were eligible if they were aged 18 years and older, and had painful (defined as ≥2 points with the Brief Pain Inventory) MRI-confirmed spinal metastasis, no more than three consecutive vertebral segments to be included in the treatment volume, an Eastern Cooperative Oncology Group performance status of 0-2, a Spinal Instability Neoplasia Score of less than 12, and no neurologically symptomatic spinal cord or cauda equina compression. Patients were randomly assigned (1:1) with a web-based, computer-generated allocation sequence to receive either stereotactic body radiotherapy at a dose of 24 Gy in two daily fractions or conventional external beam radiotherapy at a dose of 20 Gy in five daily fractions using standard techniques. Treatment assignment was done centrally by use of a minimisation method to achieve balance for the stratification factors of radiosensitivity, the presence or absence of mass-type tumour (extraosseous or epidural disease extension, or both) on imaging, and centre. The primary endpoint was the proportion of patients with a complete response for pain at 3 months after radiotherapy. The primary endpoint was analysed in the intention-to-treat population and all safety and quality assurance analyses were done in the as-treated population (ie, all patients who received at least one fraction of radiotherapy). The trial is registered with ClinicalTrials.gov, NCT02512965.

Findings: Between Jan 4, 2016, and Sept 27, 2019, 229 patients were enrolled and randomly assigned to receive conventional external beam radiotherapy (n=115) or stereotactic body radiotherapy (n=114). All 229 patients were included in the intention-to-treat analysis. The median follow-up was 6·7 months (IQR 6·3-6·9). At 3 months, 40 (35%) of 114 patients in the stereotactic body radiotherapy group, and 16 (14%) of 115 patients in the conventional external beam radiotherapy group had a complete response for pain (risk ratio 1·33, 95% CI 1·14-1·55; p=0·0002). This significant difference was maintained in multivariable-adjusted analyses (odds ratio 3·47, 95% CI 1·77-6·80; p=0·0003). The most common grade 3-4 adverse event was grade 3 pain (five [4%] of 115 patients in the conventional external beam radiotherapy group vs five (5%) of 110 patients in the stereotactic body radiotherapy group). No treatment-related deaths were observed.

Interpretation: Stereotactic body radiotherapy at a dose of 24 Gy in two daily fractions was superior to conventional external beam radiotherapy at a dose of 20 Gy in five daily fractions in improving the complete response rate for pain. These results suggest that use of conformal, image-guided, stereotactically dose-escalated radiotherapy is appropriate in the palliative setting for symptom control for selected patients with painful spinal metastases, and an increased awareness of the need for specialised and multidisciplinary involvement in the delivery of end-of-life care is needed.

Funding: Canadian Cancer Society and the Australian National Health and Medical Research Council.
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http://dx.doi.org/10.1016/S1470-2045(21)00196-0DOI Listing
July 2021

Quantitative mapping of individual voxels in the peritumoral region of IDH-wildtype glioblastoma to distinguish between tumor infiltration and edema.

J Neurooncol 2021 Jun 27;153(2):251-261. Epub 2021 Apr 27.

Department of Radiation Oncology, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, T2, Toronto, Ontario, M4N3M5, Canada.

Purpose: The peritumoral region (PTR) in glioblastoma (GBM) represents a combination of infiltrative tumor and vasogenic edema, which are indistinguishable on magnetic resonance imaging (MRI). We developed a radiomic signature by using imaging data from low grade glioma (LGG) (marker of tumor) and PTR of brain metastasis (BM) (marker of edema) and applied it on the GBM PTR to generate probabilistic maps.

Methods: 270 features were extracted from T1-weighted, T2-weighted, and apparent diffusion coefficient maps in over 3.5 million voxels of LGG (36 segments) and BM (45 segments) scanned in a 1.5T MRI. A support vector machine classifier was used to develop the radiomics model from approximately 50% voxels (downsampled to 10%) and validated with the remaining. The model was applied to over 575,000 voxels of the PTR of 10 patients with GBM to generate a quantitative map using Platt scaling (infiltrative tumor vs. edema).

Results: The radiomics model had an accuracy of 0.92 and 0.79 in the training and test set, respectively (LGG vs. BM). When extrapolated on the GBM PTR, 9 of 10 patients had a higher percentage of voxels with a tumor-like signature over radiological recurrence areas. In 7 of 10 patients, the areas under curves (AUC) were > 0.50 confirming a positive correlation. Including all the voxels from the GBM patients, the infiltration signature had an AUC of 0.61 to predict recurrence.

Conclusion: A radiomic signature can demarcate areas of microscopic tumors from edema in the PTR of GBM, which correlates with areas of future recurrence.
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http://dx.doi.org/10.1007/s11060-021-03762-2DOI Listing
June 2021

ADC, D, f dataset calculated through the simplified IVIM model, with MGMT promoter methylation, age, and ECOG, in 38 patients with wildtype IDH glioblastoma.

Data Brief 2021 Apr 15;35:106950. Epub 2021 Mar 15.

Department of Radiation Oncology, Sunnybrook Health Sciences Center, University of Toronto, Toronto, ON, Canada.

Patients undergoing standard chemoradiation post-resection had MRIs at radiation planning and fractions 10 and 20 of chemoradiation. MRIs were 1.5T and 3D T2-FLAIR, pre- and post-contrast 3D T1-weighted (T1) and echo planar DWI with three b-values (0, 500, and 1000s/mm) were acquired. T2-FLAIR was coregistered to T1C images. Non-overlapping T1 contrast-enhancing (T1C) and nonenhancing T2-FLAIR hyperintense regions were segmented, with necrotic/cystic regions, the surgical cavity, and large vessels excluded. The simplified IVIM model was used to calculate voxelwise diffusion coefficient () and perfusion fraction () maps; ADC was calculated using the natural logarithm of  = 1000 over  = 0 images. T1C and T2-FLAIR segmentations were brought into this space, and medians calculated. MGMT promoter methylation status (MGMT), age at diagnosis, and Eastern Cooperative Oncology Group (ECOG) performance status were extracted from electronic medical records. The data were presented, analyzed, and described in the article, "Intravoxel incoherent motion (IVIM) modeling of diffusion MRI during chemoradiation predicts therapeutic response in IDH wildtype Glioblastoma", published in Radiotherapy and Oncology [1].
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http://dx.doi.org/10.1016/j.dib.2021.106950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039816PMC
April 2021

In vivo detection of beta-amyloid at the nasal cavity and other skull-base sites: a retrospective evaluation of ADNI1/GO.

Ann Nucl Med 2021 Jun 12;35(6):728-734. Epub 2021 Apr 12.

Department of Medical Imaging, Sunnybrook Health Sciences Centre, Toronto, M4N 3M5, Canada.

Introduction: Amyloid beta (Aβ) is partially cleared from the CSF via skull base perivascular and perineural lymphatic pathways, particularly at the nasal cavity. In vivo differences in Aβ level at the nasal cavity between patients with Alzheimer's disease (AD), subjects with mild cognitive impairment (MCI) and cognitively normal (CN) individuals have not been previously assessed.

Methods: This is a retrospective evaluation of subject level data from the ADNI-1/GO database. Standardized uptake value ratio (SUVR) maximum on C-Pittsburgh compound-B (PiB)-PET was assessed at the nasal cavity on 223 scans. Exploratory ROI analysis was also performed at other skull base sites. SUVR maximum values and their differences between groups (CN, MCI, AD) were assessed. CSF Aβ levels and CSF Aβ 42/40 ratios were correlated with SUVR maximum values.

Results: 103 subjects with 223 PiB-PET scans (47 CN, 32 AD and 144 MCI) were included in the study. The SUVR maxima at the nasal cavity were significantly lower in subjects with AD [1.35 (± 0.31)] compared to CN [1.54 (± 0.30); p = 0.024] and MCI [1.49 (± 0.33); p = 0.049]. At very low CSF Aβ, less than 132 pg/ml, there was significant correlation with nasal cavity SUVR maximum. The summed averaged SUVR maximum values were significantly lower in subjects with AD [1.35 (± 0.16)] compared to CN [1.49 (± 0.17); p = 0.003] and MCI [1.40 (± 0.17); p = 0.017].

Conclusion: Patients with AD demonstrate reduced nasal cavity PiB-PET radiotracer uptake compared to MCI and CN, possibly representing reduced Aβ clearance via perineural/perivascular lymphatic pathway. Further work is necessary to elucidate the true nature of this finding.
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http://dx.doi.org/10.1007/s12149-021-01614-7DOI Listing
June 2021

Is there an optimal MRI surveillance schedule for patients with high-grade glioma after standard-of-care-therapy?

Neuro Oncol 2021 05;23(5):711-712

Department of Medical Imaging, Sunnybrook Health Sciences Centre, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.

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http://dx.doi.org/10.1093/neuonc/noab053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099464PMC
May 2021

Prognostic Factors Associated With Surviving Less Than 3 Months vs Greater Than 3 Years Specific to Spine Stereotactic Body Radiotherapy and Late Adverse Events.

Neurosurgery 2021 04;88(5):971-979

Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.

Background: Patient selection is critical for spine stereotactic body radiotherapy (SBRT) given potential for serious adverse effects and the associated costs.

Objective: To identify prognostic factors associated with dying within 3 mo, or living greater than 3 yr, following spine SBRT, to better inform patient selection.

Methods: Patients living ≤3 mo after spine SBRT and >3 yr after spine SBRT were identified, and multivariable regression analyses were performed. We report serious late toxicities observed, including vertebral compression fractures (VCF) and plexopathy.

Results: A total of 605 patients (1406 spine segments) were treated from 2009 to 2018. A total of 51 patients (8.4%) lived ≤3 mo, and 79 patients (13%) survived >3 yr. Significant differences in baseline features were observed. On multivariable analysis, nonbreast/prostate primaries (odds ratio [ORs]: 28.8-104.2, P = .0004), eastern cooperative oncology group (ECOG) ≥2 (OR: 23.7, 95% CI: 3.2-177, P = .0020), polymetastatic disease (OR: 6.715, 95% CI: 1.89-23.85, P = .0032), painful lesions (OR: 3.833-8.898, P = .0118), and paraspinal disease (OR: 2.874, 95% CI: 1.118-7.393, P = .0288) were prognostic for ≤3 mo survival. The 3- and 5-yr rates of VCF were 10.4% and 14.4%, respectively, and 3- and 5-yr rates of plexopathy were 2.2% and 5.1%, respectively. A single duodenal perforation was observed, and there was no radiation myelopathy events.

Conclusion: Shorter survival after spine SBRT was seen in patients with less radiosensitive histologies (ie, not breast or prostate), ECOG ≥2, and polymetastatic disease. Pain and paraspinal disease were also associated with poor survival. Fractionated spine SBRT confers a low risk of late serious adverse events.
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http://dx.doi.org/10.1093/neuros/nyaa583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223248PMC
April 2021

Diagnostic Neuroradiology Subspecialty Training: 1 Versus 2 Years; the Canadian Perspective.

Can Assoc Radiol J 2021 Jan 18:846537120982984. Epub 2021 Jan 18.

Department of Diagnostic Radiology, Dalhousie University, Halifax, Nova Scotia, Canada.

Background: Canada began a national reform of its post-graduate medical education training programs to a Competence By Design (CBD) model. Trends from accredited neuroradiology programs from the past 10 years were investigated to inform educators and stakeholders for this process.

Methods: A 13-question electronic survey was sent to program directors of all 8 accredited neuroradiology training programs in Canada. Data was requested for each year on the 2008-2019 graduating classes. Questions pertained to program enrolment; program completion; post-training employment; and the sufficiency of 1-year training programs.

Results: Response rate was 100%. Over the timeframe studied, the 2-year programs increased in size ( = 0.007), while the 1-year programs remained steady ( = 0.27). 12.2% of trainees enrolled in the 2-year program dropped out after 1 year, and were considered 1-year trainees thereafter. A higher proportion of 2-year trainees obtain positions within academic institutions (89.5 vs 67.2%, = 0.0007), whereas a higher proportion of 1-year trainees obtain positions within non-academic institutions (29.3 vs 8.1%, = 0.0007). A higher proportion of those with Canadian board certification in diagnostic radiology who completed a 2-year program obtained a position within a Canadian academic institution compared to non-certified 2-year trainees ( < 0.001). 71.4% of program directors agreed that a 1-year program was sufficient for non-academic staff positions.

Conclusion: The length of the training program has significant impact on employment in academic vs non-academic institutions. This information can be used to guide the upcoming CBD initiative for neuroradiology programs.
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http://dx.doi.org/10.1177/0846537120982984DOI Listing
January 2021

Local control and patterns of failure for "Radioresistant" spinal metastases following stereotactic body radiotherapy compared to a "Radiosensitive" reference.

J Neurooncol 2021 Mar 16;152(1):173-182. Epub 2021 Jan 16.

Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Avenue, Toronto, ON, M4N3M5, Canada.

Purpose: The concept of a radioresistant (RR) phenotype has been challenged with use of stereotactic body radiotherapy (SBRT). We compared outcomes following SBRT to RR spinal metastases to a radiosensitive cohort.

Methods: Renal cell, melanoma, sarcoma, gastro-intestinal, and thyroid spinal metastases were identified as RR and prostate cancer (PCA) as radiosensitive. The primary endpoint was MRI-based local failure (LF). Secondary endpoints included overall survival (OS) and vertebral compression fracture (VCF).

Results: From a prospectively maintained database of 1394 spinal segments in 605 patients treated with spine SBRT, 173 patients/395 RR spinal segments were compared to 94 patients/185 PCA segments. Most received 24-28 Gy in 2 fractions (68.9%) and median follow-up was 15.5 months (range, 1.4-84.2 months). 1- and 2-year LF rates were 19.2% and 22.4% for RR metastases, respectively, which were significantly greater (p < 0.001) than PCA (3.2% and 8.4%, respectively). Epidural disease (HR: 2.47, 95% CI 1.65-3.71, p < 0.001) and RR histology (HR: 2.41, 95% CI 1.45-3.99, p < 0.001) predicted for greater LF. Median OS was 17.4 and 61.0 months for RR and PCA cohorts, respectively. Lung/liver metastases, polymetastatic disease and epidural disease predicted for worse OS. 2-year VCF rates were ~ 13% in both cohorts. Coverage of the CTV V90 (clinical target volume receiving 90% of prescription dose) by ≥ 87% (HR: 2.32, 95% CI 1.29-4.18, p = 0.005), no prior spine radiotherapy (HR: 1.96, 95% CI 1.09-3.55, p = 0.025), and a greater Spinal Instability Neoplasia Score (p = 0.013) predicted for VCF.

Conclusions: Higher rates of LF were observed after spine SBRT in RR metastases. Optimization strategies include dose escalation and aggressive management of epidural disease.
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http://dx.doi.org/10.1007/s11060-020-03691-6DOI Listing
March 2021

Quantitative CEST and MT at 1.5T for monitoring treatment response in glioblastoma: early and late tumor progression during chemoradiation.

J Neurooncol 2021 Jan 16;151(2):267-278. Epub 2020 Nov 16.

Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada.

Purpose: Quantitative MRI (qMRI) was performed using a 1.5T protocol that includes a novel chemical exchange saturation transfer/magnetization transfer (CEST/MT) approach. The purpose of this prospective study was to determine if qMRI metrics at baseline, at the 10th and 20th fraction during a 30 fraction/6 week standard chemoradiation (CRT) schedule, and at 1 month following treatment could be an early indicator of response for glioblastoma (GBM).

Methods: The study included 51 newly diagnosed GBM patients. Four regions-of-interest (ROI) were analyzed: (i) the radiation defined clinical target volume (CTV), (ii) radiation defined gross tumor volume (GTV), (iii) enhancing-tumor regions, and (iv) FLAIR-hyperintense regions. Quantitative CEST, MT, T and T parameters were compared between those patients progressing within 6.9 months (early), and those progressing after CRT (late), using mixed modelling. Exploratory predictive modelling was performed to identify significant predictors of early progression using a multivariable LASSO model.

Results: Results were dependent on the specific tumor ROI analyzed and the imaging time point. The baseline CEST asymmetry within the CTV was significantly higher in the early progression cohort. Other significant predictors included the T of the MT pools (for semi-solid at fraction 20 and water at 1 month after CRT), the exchange rate (at fraction 20) and the MGMT methylation status.

Conclusions: We observe the potential for multiparametric qMRI, including a novel pulsed CEST/MT approach, to show potential in distinguishing early from late progression GBM cohorts. Ultimately, the goal is to personalize therapeutic decisions and treatment adaptation based on non-invasive imaging-based biomarkers.
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http://dx.doi.org/10.1007/s11060-020-03661-yDOI Listing
January 2021

Quantitating Interfraction Target Dynamics During Concurrent Chemoradiation for Glioblastoma: A Prospective Serial Imaging Study.

Int J Radiat Oncol Biol Phys 2021 03 14;109(3):736-746. Epub 2020 Oct 14.

Department of Radiation Oncology, Sunnybrook Odette Cancer Centre, Toronto, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Canada. Electronic address:

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), and the migration distance (d; 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 (range, 1.1-110.5 cm), 14.7 cm (range, 0.9-115.1 cm), 13.7 cm (range, 0.6-174.2 cm), and 13.0 cm (range, 0.9-76.3 cm), respectively, with corresponding median V 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 ≤1) with a d >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.
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http://dx.doi.org/10.1016/j.ijrobp.2020.10.002DOI Listing
March 2021

Congenital Herniation of the Gyrus Rectus Resulting in Compressive Optic Neuropathy.

Can J Neurol Sci 2020 11 6;47(6):820-821. Epub 2020 Jul 6.

Department of Medicine, Division of Neurology, University of Toronto, Toronto, Ontario, Canada.

We report a 34-year-old male with a previously uninvestigated lifelong blindness of the right eye from compressive optic neuropathy secondary to congenital herniation of the gyrus rectus (HGR). His past medical history was otherwise unremarkable, with no history of prior head or ocular trauma. On examination, he had no light perception in the right eye, right relative afferent pupillary defect (RAPD), and primary optic atrophy. His left eye had normal visual acuity, color vision, and a healthy optic disc. There was a sensory exotropia in the right eye; however, extraocular movements were intact and the remainder of his neurological exam was normal. MRI revealed compression of the prechiasmatic right optic nerve from HGR and atrophy of the right optic nerve and optic chiasm (Figures 1 and 2), without any parenchymal mass lesions. There were no signal abnormalities in the optic nerves or the chiasm.
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http://dx.doi.org/10.1017/cjn.2020.136DOI Listing
November 2020

Adverse Events to the Gadolinium-based Contrast Agent Gadoxetic Acid: Systematic Review and Meta-Analysis.

Radiology 2020 12 26;297(3):565-572. Epub 2020 May 26.

From the Department of Medical Imaging, The Ottawa Hospital, 1053 Carling Ave, Room C159, Ottawa, ON, Canada K1Y 4E9 (N.S., D.W.); Department of Diagnostic Imaging, Juravinski Cancer Centre, Hamilton, Canada (C.B.v.d.P.); Clinical Research Unit, Children's Hospital of Eastern Ontario, Ottawa, Canada (A.K.T.); Department of Radiology, Sunnybrook Health Sciences Centre, Toronto, Canada (P.J.M.); Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY (S.W.); and Department of Radiology, University of Michigan Medical Center, Ann Arbor, Mich (M.S.D.).

Background Gadoxetic acid is classified by the American College of Radiology as a group III gadolinium-based contrast agent (GBCA), which indicates that there are limited data regarding nephrogenic systemic fibrosis (NSF) risk, but there are few if any unconfounded cases of NSF. Purpose To perform a systematic review and meta-analysis of gadoxetic acid adverse events, including immediate hypersensitivity reactions, NSF, and intracranial gadolinium retention. Materials and Methods Original research studies, case series, and case reports that reported adverse events in patients undergoing gadoxetic acid-enhanced MRI were searched in MEDLINE (1946-2019), Embase (1947-2019), CENTRAL (March 2019), and Scopus (1946-2019). The study protocol was registered at Prospero (number 162811). Risk of bias was evaluated by using Quality Assessment of Diagnostic Accuracy Studies-2, or QUADAS-2. Meta-analysis of proportions was performed by using random-effects modeling. Upper bound of 95% confidence interval (CI) for risk of NSF was determined. Results Seventy-one studies underwent full-text review. From 17 studies reporting 14 850 administrations, hypersensitivity reactions occurred in 0.3% (31 of 14 850; 95% CI: 0.2%, 0.4%) with zero deaths. From four studies reporting 106 administrations in patients with stage 4 or 5 chronic kidney disease or undergoing dialysis, the upper bound 95% CI for the risk of NSF was 2.8%. Five studies evaluating intracranial retention of gadolinium after gadoxetic acid administration were at high risk of bias. Conclusion Gadoxetic acid had a similar safety profile to American College of Radiology group 2 gadolinium-based contrast agents for hypersensitivity reactions and nephrogenic systemic fibrosis (NSF) but had lower confidence for risk of NSF because of fewer administrations in patients with severe kidney impairment. There is incomplete information documenting intracranial gadolinium retention in patients administered gadoxetic acid. © RSNA, 2020
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http://dx.doi.org/10.1148/radiol.2020200073DOI Listing
December 2020

Mature Imaging-Based Outcomes Supporting Local Control for Complex Reirradiation Salvage Spine Stereotactic Body Radiotherapy.

Neurosurgery 2020 09;87(4):816-822

Department of Radiation Oncology, Odette Cancer Center, Sunnybrook Health Sciences Centre, Toronto, Ontario.

Background: Upon progression after upfront radiotherapy to spinal metastases, low-dose re-irradiation conventional external beam radiation (cEBRT) provides limited clinical benefit. Spine stereotactic body radiotherapy (SBRT) allows for dose escalation in the salvage setting with the potential for improved local control.

Objective: To report mature clinical and imaging-based outcomes for salvage SBRT.

Methods: A retrospective review was undertaken of consecutive patients with spinal metastases treated with re-irradiation spine SBRT having failed either cEBRT (n = 60 with 1 prior course and n = 17 with 2 or more prior cEBRT courses), or prior SBRT (n = 6) to the same spinal segment. The primary outcome was local failure (LF), and secondary outcomes included overall survival (OS) and the rate of vertebral compression fracture (VCF).

Results: A total of 43 patients with 83 spinal segments treated with salvage SBRT were reviewed. The crude risk of LF was 18%, and actuarial LF rates at 6, 12, and 24 mo were 7%, 14%, and 19%, respectively. The presence of extensive paraspinal disease (hazard ratio [HR] = 7.1, 95% CI 1.5-34) significantly predicted for LF. The median OS was 13.2 (95% CI 6.1-16.3) mo, and the presence of neurological deficits (HR = 4.7, 95% CI 1.8-12.1) and brain metastases (HR = 2.6, 95% CI 1.1-6.3) were significant prognostic factors. The crude risk of VCF was 4%, and radiation myelopathy was not observed.

Conclusion: These data support the safety and efficacy of spinal re-irradiation with SBRT including patients with prior SBRT and multiple courses of prior cEBRT.
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http://dx.doi.org/10.1093/neuros/nyaa109DOI Listing
September 2020

Adverse Radiation Effect After Hypofractionated Stereotactic Radiosurgery in 5 Daily Fractions for Surgical Cavities and Intact Brain Metastases.

Int J Radiat Oncol Biol Phys 2020 03 9;106(4):772-779. Epub 2020 Jan 9.

Department of Radiation Oncology, University of Toronto, Sunnybrook Odette Cancer Centre, Toronto, Ontario, Canada.

Purpose: Limited data exist quantifying the risk of adverse radiation effect (ARE) specific to hypofractionated stereotactic radiosurgery (HSRS). We present our analyses of the risk of ARE after 5 daily fractions of HSRS to surgical cavities and intact metastases.

Methods And Materials: One hundred and eighty-seven consecutively treated patients with 118 surgical cavities and 132 intact metastases were retrospectively reviewed. All patients were treated with 5 daily fractions with a 2 mm planning target volume applied. Clinical and dosimetric variables were assessed to identify predictors of ARE.

Results: The median total prescribed dose was 30 Gy (range, 20-35 Gy) and median follow-up was 12 months. One hundred forty-four patients (77%) received treatment to a single target. Median planning target volumes for resection cavity and intact metastases were 24.9 cm and 7.7 cm, respectively. ARE and symptomatic ARE were observed 21.2% and 10.8% of targets, respectively, and the median time to ARE was 8 months. Time to ARE was <6 months for 38%, 6 to 12 months for 43%, and >12 months for 19% of targets. Multivariable analysis identified intact metastases versus cavities (odds ratio [OR], 3.65; 95% confidence interval [CI], 1.33-10) as a significant predictor of symptomatic ARE. Specific to cavity HSRS, prior whole brain radiation therapy (OR 7.73; 95% CI, 1.67-35.69) and prior stereotactic radiosurgery (OR 8.66; 95% CI, 1.14-65.7) were significant predictors of symptomatic ARE. For intact metastases, the total brain minus gross tumor volume (GTV) receiving 30 Gy (BMC30) was a significant predictor of symptomatic ARE (OR, 1.21; 95% CI, 1.02-1.43), and a volume-based BMC30 threshold of 10.5 cm was significant with an OR of 7.21 (95% CI, 1.31-39.45).

Conclusions: The risk of ARE was greater for intact metastases compared with cavities after HSRS. For intact lesions, the BMC30 was predictive for symptomatic necrosis, and a threshold of 10.5 cm may guide treatment planning.
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http://dx.doi.org/10.1016/j.ijrobp.2019.12.002DOI Listing
March 2020

Acute orbital myositis preceding vesicular rash eruption in herpes zoster ophthalmicus.

Can J Ophthalmol 2020 06 24;55(3):e107-e109. Epub 2019 Dec 24.

University of Toronto, Toronto, Ont.. Electronic address:

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http://dx.doi.org/10.1016/j.jcjo.2019.09.005DOI Listing
June 2020

Predictors of leptomeningeal disease following hypofractionated stereotactic radiotherapy for intact and resected brain metastases.

Neuro Oncol 2020 01;22(1):84-93

Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.

Background: The objective was to evaluate the risk and predictors of developing leptomeningeal disease (LMD) in patients with brain metastases treated with 5-fraction hypofractionated stereotactic radiotherapy (HSRT).

Methods: Patients treated with HSRT for intact brain metastases and/or surgical cavities were reviewed from a prospectively maintained database. Radiographic patterns of LMD were classified as focal classical, diffuse classical, focal nodular, and diffuse nodular.

Results: HSRT was delivered, most commonly 30 Gy in 5 fractions, to 320 intracranial lesions (57% intact and 43% surgical cavities) in 235 patients. The median follow-up was 13.4 months (range, 0.8 to 60 mo). LMD developed in 19% of patients with a 1-year LMD rate of 12%. From the diagnosis of LMD, the median overall survival (OS) was 3.8 months (range, 2-20.8 mo). The most common LMD pattern was diffuse nodular (44%). No difference in OS was observed between LMD patterns (P = 0.203). Multivariable analysis identified surgical cavities at significantly higher risk of LMD compared with intact lesions (odds ratio [OR] = 2.30, 95% CI: 1.24, 4.29, P = 0.008). For cavities, radiosensitive tumors (OR = 2.35, 95% CI: 1.04, 5.35, P = 0.041) predicted for LMD, while, for intact metastases, patients receiving treatment with targeted agents or immunotherapy (TA/I) were at lower risk (OR = 0.178, 95% CI: 0.04, 0.79, P = 0.023).

Conclusions: Patients who had a brain metastasis resected were at an increased risk of LMD. OS was poor despite treatment of LMD, and no differences in OS based on the pattern of LMD was observed. Treatment with TA/I was observed to be protective against LMD and requires further study.
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http://dx.doi.org/10.1093/neuonc/noz144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954436PMC
January 2020

Updated Clinical Practice Guideline on Use of Gadolinium-Based Contrast Agents in Kidney Disease Issued by the Canadian Association of Radiologists.

Can Assoc Radiol J 2019 Aug 27;70(3):226-232. Epub 2019 Jun 27.

Division of Nephrology, Department of Medicine and Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.

In 2017, the Canadian Association of Radiologists issued a clinical practice guideline (CPG) regarding the use of gadolinium-based contrast agents (GBCAs) in patients with acute kidney injury (AKI), chronic kidney disease (CKD), or on dialysis due to mounting evidence indicating that nephrogenic systemic fibrosis (NSF) occurs with extreme rarity or not at all when using Group II GBCAs or the Group III GBCA gadoxetic acid (compared to first generation Group I linear GBCAs). One of the goals of the work group was to re-evaluate the CPG after 24 months to determine the effect of more liberal use of GBCA on reported cases of NSF in patients with AKI, CKD Stage 4 or 5 (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m), or those that are dialysis-dependent. A comprehensive review of the literature was conducted by a subcommittee of the initial CPG panel between the dates of January 1, 2017-December 31, 2018 to identify new unconfounded cases of NSF linked to Group II or Group III GBCAs and an updated CPG developed. To our knowledge, when using a Group II or Group III GBCA between 2017-2018, only a single unconfounded case report of a fibrosing dermopathy has been reported in a patient who received gadobenate dimeglumine with Stage 2 CKD. No other unconfounded cases of NSF have been reported with Group II or III agents in during this timeframe. The subcommittee concluded that the main recommendations from the 2017 CPG should remain unaltered, but agreed that screening for renal disease in the outpatient setting is no longer justifiable, cost-effective or recommended. Patients on hemodialysis (HD) should, however, be identified prior to GBCA administration to arrange timely HD to optimize gadolinium clearance, although there remains no evidence that HD reduces the risk of NSF. When administering Group II or III GBCAs to patients with AKI, on dialysis or with severe CKD, informed consent relating to NSF is also no longer explicitly recommended.
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http://dx.doi.org/10.1016/j.carj.2019.04.001DOI Listing
August 2019

Image-Guided, Linac-Based, Surgical Cavity-Hypofractionated Stereotactic Radiotherapy in 5 Daily Fractions for Brain Metastases.

Neurosurgery 2019 11;85(5):E860-E869

Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.

Background: Cavity stereotactic radiotherapy has emerged as a standard option following resection of brain metastases. However, the optimal approach with either single-fraction or hypofractionated stereotactic radiotherapy (HSRT) remains a significant question.

Objective: To report outcomes for 5-fraction HSRT to the surgical cavity, based on contouring according to a recently reported international consensus guideline.

Methods: Patients treated with cavity HSRT were identified from a prospective institutional database. Local brain control (LC), distant brain failure (DBF), leptomeningeal disease (LMD), and overall survival rates were determined. Univariate and multivariable analyses were performed on potential predictive factors.

Results: One hundred thirty-seven cavities in 122 patients were treated at a median total dose of 30 Gy (range, 25-35 Gy). The median follow-up was 16 mo (range, 1-60 mo). Nonsmall cell lung cancer was the most common histology (44%), followed by breast cancer (21%). In 57% of surgical cavities, the preoperative tumor diameter was >3 cm. One-year LC, DBF, LMD, and overall survival rates were 84%, 45%, 22%, and 62%, respectively. Multivariable analyses identified colorectal (hazard ratio [HR] 4.1, P = .0066) and melanoma (HR 2.4, P = .012) metastases as predictors of local recurrence; preoperative tumor diameter >2 cm (HR 8.9, P = .012) and absence of targeted therapy (HR 4.4, P = .03) as predictors of DBF; and breast cancer histology (HR 2.1, P = .05) and subtotal resection (HR 2.6, P = .009) as predictors of LMD. Symptomatic radiation necrosis was observed in 7 patients (6%).

Conclusion: High rates of LC were observed following this 5-fraction HSRT regimen. Superiority as compared to single-fraction SRS requires a randomized trial.
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http://dx.doi.org/10.1093/neuros/nyz162DOI Listing
November 2019

Rescue bevacizumab following symptomatic pseudoprogression of a tectal glioma post-radiotherapy: a case report and review of the literature.

J Neurooncol 2019 Jul 3;143(3):475-481. Epub 2019 May 3.

Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, T-Wing 2nd Floor, 2075 Bayview Avenue, Toronto, ON, M4N3M5, Canada.

Purpose: Radiation-induced pseudoprogression is a subacute clinical entity that is distinct from radiation necrosis and mimics tumor progression. Bevacizumab is a well-described treatment option for radiation necrosis, but its role in pseudoprogression is not clearly defined.

Methods: We report a case of radiation-induced pseudoprogression rescued with bevacizumab in a 20-year-old man with a biopsy-proven low-grade astrocytoma of the tectum. A review of the literature was also conducted specific to bevacizumab as a treatment for symptomatic pseudoprogression after radiotherapy for CNS tumors.

Results: This patient was treated with definitive intensity modulated stereotactic radiotherapy at a total dose of 54 Gy delivered in 30 daily fractions. Six weeks after radiotherapy the patient developed progressive headache, weakness and a documented deterioration in vision, which was accompanied by worsening of radiographic findings. A diagnosis of pseudoprogression was made and after limited benefit from a trial of dexamethasone, four cycles of bevacizumab were administered which resulted in rapid clinical and radiographic improvement.

Conclusions: Our findings support the potential use of bevacizumab as a rescue agent for symptomatic pseudoprogression.
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http://dx.doi.org/10.1007/s11060-019-03179-yDOI Listing
July 2019

Incidence of Dural Venous Sinus Thrombosis in Patients with Glioblastoma and Its Implications.

World Neurosurg 2019 05 24;125:e189-e197. Epub 2019 Jan 24.

Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Objective: Glioblastoma (GBM) is associated with increased risk of developing dural venous sinus thrombosis (DVST), which often goes undiagnosed as symptoms are readily attributed to tumor. The purpose of this study was to investigate the incidence of DVST, potential predictive features on imaging, complications, its effect on survival, and time of greatest risk for developing DVST.

Methods: A retrospective search of patients with GBM who had surgery followed by chemotherapy and/or radiation therapy between 2009 and 2015 at our institution was performed. Magnetic resonance imaging studies of the brain were reviewed on volumetric postgadolinium T1-weighted sequences for DVST. Tumors were characterized using the Visually Accessible REMBRANDT (Repository for Molecular Brain Neoplasia Data) Images classification, and identified thromboses were tracked for propagation, regression, or resolution. Statistical analyses were directed at identifying clinical predictors and survival differences between the DVST and no-DVST groups.

Results: In total, 163 cases totaling 1637 scans, were reviewed; 12 patients (7.4%) developed DVST, of whom 11 presented with thrombus before any treatment. Tumor invasion of dural sinuses and greater T1/fluid-attenuated inversion recovery ratios were significantly associated with thrombus development (P = 0.02 and P = 0.02, respectively). In patients who developed DVST, thrombosis was more likely to develop ipsilateral to tumor side (P = 0.01) and was associated with a greater likelihood of developing extracranial venous thromboembolism (P = 0.012). There were no venous infarcts and no significant difference in survival between groups (P = 0.83).

Conclusions: Patients with GBM have increased risk of developing DVST, independent of surgical treatment or chemoradiation. DVST presence does not affect survival. Tumor invasion of dural sinuses and greater T1/fluid-attenuated inversion recovery ratio on preoperative imaging were the most significant predictors of DVST development.
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http://dx.doi.org/10.1016/j.wneu.2019.01.039DOI Listing
May 2019

Gadolinium Deposition in the Brain: A Systematic Review of Existing Guidelines and Policy Statement Issued by the Canadian Association of Radiologists.

Can Assoc Radiol J 2018 Nov 22;69(4):373-382. Epub 2018 Sep 22.

Department of Radiology, The Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada. Electronic address:

Emerging evidence has confirmed that, following administration of a gadolinium-based contrast agent (GBCA), very small amounts of gadolinium will deposit in the brain of humans with intact blood-brain barriers. The literature is evolving rapidly and the degree to which gadolinium will deposit for a particular GBCA or class of GBCAs remains undetermined. Several studies suggest that linear GBCAs deposit more gadolinium in the brain compared with macrocyclic GBCAs; however, our understanding of the molecular composition of deposited gadolinium is preliminary, and the clinical significance of gadolinium deposition remains unknown. To date, there is no conclusive evidence linking gadolinium deposition in the brain with any adverse patient outcome. A panel of radiologists representing the Canadian Association of Radiologists was assembled to assist the Canadian medical imaging community in making informed decisions regarding the issue of gadolinium deposition in the brain. The objectives of the working group were: 1) to review the evidence from animal and human studies; 2) to systematically review existing guidelines and position statements issued by other organizations and health agencies; and 3) to formulate an evidence-based position statement on behalf of the Canadian Association of Radiologists. Based on our appraisal of the evidence and systematic review of 9 guidelines issued by other organizations, the working group established the following consensus statement. GBCA administration should be considered carefully with respect to potential risks and benefits, and only used when required. Standard dosing should be used and repeat administrations should be avoided unless necessary. Gadolinium deposition is one of several issues to consider when prescribing a particular GBCA. Currently there is insufficient evidence to recommend one class of GBCA over another. The panel considered it inappropriate to withhold a linear GBCA if a macrocyclic agent is unavailable, if hepatobiliary phase imaging is required, or if there is a history of severe allergic reaction to a macrocyclic GBCA. Further study in this area is required, and the evidence should be monitored regularly with policy statements updated accordingly.
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http://dx.doi.org/10.1016/j.carj.2018.04.002DOI Listing
November 2018

Optic nerve sheath meningocele.

Int Med Case Rep J 2018 10;11:213-215. Epub 2018 Sep 10.

Department of Ophthalmology and Vision Sciences, Sunnybrook Health Sciences Center, University of Toronto, Toronto, ON, Canada,

Optic nerve sheath meningocele, also called dural ectasia of the optic nerve, is a benign dilation of the optic nerve sheath. We report two interesting cases of primary optic nerve sheath meningocele. Etiology, clinical features, and management options are discussed.
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http://dx.doi.org/10.2147/IMCRJ.S166655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6136404PMC
September 2018

Stereotactic Body Radiotherapy for Spinal Metastases at the Extreme Ends of the Spine: Imaging-Based Outcomes for Cervical and Sacral Metastases.

Neurosurgery 2019 11;85(5):605-612

Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.

Background: The unique anatomy and biomechanical features of the cervical spine and sacrum may impact treatment outcomes following spine stereotactic body radiotherapy (SBRT). Current data for spine metastases are not specific for these locations.

Objective: To report imaging-based SBRT outcomes to cervical and sacral metastases.

Methods: We retrospectively reviewed our prospective spine SBRT database for cervical and sacral metastases. Patients were followed at 2- to 3-mo intervals with a clinical visit and full spine magnetic resonance imaging (MRI) and we report overall survival (OS), vertebral compression fracture (VCF), and MR imaging-based local control (LC) rates.

Results: Fifty-two patients and 93 treated spinal segments were identified. Fifty-six segments were within the cervical spine and 37 within the sacrum, the median follow-up was 14.4 and 19.5 mo, and the median total dose/number of fractions was 24 Gy/2, respectively. Cumulative LC at 1 and 2 yr were 94.5% and 92.7% for the cervical cohort, and 86.5% and 78.7% in the sacral cohort, respectively. Lack of posterior spinal element involvement in the cervical spine (P < .0001) and absence of epidural disease (hazard ratio 0.275, 95% confidence interval 0.076-0.989, P = .048) in the sacral cohort predicted LC. Median OS was 16.3 and 28.5 mo in the cervical spine and sacrum cohorts, respectively. Two cases of sacral VCF, 1 brachial plexopathy, and 1 lumbar-sacral plexopathy were observed.

Conclusion: Although high rates of LC were observed, strategies specific to the sacrum may require further optimization.
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http://dx.doi.org/10.1093/neuros/nyy393DOI Listing
November 2019

Imaging-Based Outcomes for 24 Gy in 2 Daily Fractions for Patients with de Novo Spinal Metastases Treated With Spine Stereotactic Body Radiation Therapy (SBRT).

Int J Radiat Oncol Biol Phys 2018 11 10;102(3):499-507. Epub 2018 Jul 10.

Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.

Purpose: We report mature outcomes for a cohort of patients with no prior radiation (de novo) to the spine treated with 24 Gy in 2 daily fractions for metastases, which represents the same stereotactic body radiation therapy (SBRT) regimen under evaluation in the current Symptom Control-24 phase 3 randomized trial (NCT02512965).

Methods And Materials: The cohort consisted of 279 de novo spinal metastases in 145 consecutive patients treated with 24 Gy in 2 SBRT fractions, identified from a prospective single-institution database. The endpoints were overall survival (OS), imaging-based local failure (LF), and cumulative risk of vertebral compression fractures (VCF).

Results: The median follow-up per treated metastasis was 15.0 months (range, 0.1-71.6). The 1-year and 2-year OS rates were 73.1% and 60.7%, respectively. Presence of epidural disease (P < .0001), lung (P = .0415), and renal cell (P < .0001) primary histologies and baseline diffuse metastases (P = .0034) were significant prognostic factors for OS. The 1-year and 2-year LF rates were 9.7% and 17.6%, respectively, and the median time to LF was 9.2 month (range, 0.4-31.3 months). Only the presence of epidural disease predicted for LF (P < .0001). The cumulative risk of VCF at 1 and 2 years was 8.5% and 13.8%, respectively. Lytic (P = .0143) or mixed lytic/blastic (P = .0214) lesions, spinal malalignment (P = .0121), and the dose to 90% of the planning target volume (P = .0085) were significant predictors for VCF.

Conclusions: Twenty-four Gray in 2 daily fractions is safe and effective in achieving high tumor control rates for de novo spinal metastases. These outcomes will serve as a benchmark for the ongoing Symptom Control-24 randomized trial comparing 24 Gy in 2 SBRT fractions to 20 Gy delivered in 5 daily conventional fractions.
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http://dx.doi.org/10.1016/j.ijrobp.2018.06.047DOI Listing
November 2018

Hypoxia Detection in Infiltrative Astrocytoma: Ferumoxytol-based Quantitative BOLD MRI with Intraoperative and Histologic Validation.

Radiology 2018 09 26;288(3):821-829. Epub 2018 Jun 26.

From the Department of Medical Imaging (P.J.M., A.B., S.S., Z.F.D., A.C., P.A.L., O.S., D.M.), Division of Neurosurgery (S.D., T.M., R.J.), Department of Laboratory Medicine and Pathobiology (J.K., D.G.M.), Department of Radiation Oncology (A.S.), Division of Neurology (S.I.), and Department of Biostatistics (E.G.A.), University of Toronto, 263 McCaul St, 4th Floor, Toronto, ON, Canada M5T 1W7; Department of Neurosurgery, Joan C. Edwards School of Medicine, Huntington, WV (N.P.); Department of Mechanical Engineering, Australian College of Kuwait, Kuwait City, Kuwait (A.E.); Department of Physics, Ryerson University, Toronto, Canada (R.J.); and Department of Radiology, Stanford University School of Medicine, Stanford, Calif (G.Z.).

Purpose To validate ferumoxytol-based quantitative blood oxygenation level-dependent (BOLD) MRI for mapping oxygenation of human infiltrative astrocytomas by using intraoperative measurement of tissue oxygen tension and histologic staining. Materials and Methods Fifteen patients with infiltrative astrocytomas were recruited into this prospective multicenter study between July 2014 and December 2016. Prior to treatment, participants underwent preoperative quantitative BOLD MRI with ferumoxytol to generate tissue oxygen saturation (StO) maps. Two intratumoral sites were identified, one with low StO and one with high StO. Neuronavigation was used to locate sites intraoperatively for insertion of oxygen-sensing probes to measure local tissue oxygen tension (PtO). Biopsies from both sites were taken and stained for markers of hypoxia (hypoxia-inducible factor 1α, carbonic anhydrase IX) and neoangiogenesis (vascular endothelial growth factor, endoglin [CD105]). Spearman correlation and nonparametric sign-rank tests were used to analyze data. Results Ten patients with median age of 58.5 years (interquartile range, 25 years; four men and six women) completed the study. Because there is no linear relationship between StO and PtO, the ratios of low to high StO versus low to high PtO in each patient were compared and a significant correlation was found (r = 0.73; P = .01). Pathologic analyses revealed differences between carbonic anhydrase IX (P = .03) for sites of low StO versus high StO. CD105 displayed a similar trend but was not significant (P = .09). Conclusion Ferumoxytol-based quantitative blood oxygenation level-dependent MRI can potentially be used as a noninvasive surrogate for oxygenation mapping in infiltrative astrocytomas. This technique can potentially be integrated in treatment planning for aggressive targeting of hypoxic areas in tumors.
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http://dx.doi.org/10.1148/radiol.2018172601DOI Listing
September 2018

Population description and clinical response assessment for spinal metastases: part 2 of the SPIne response assessment in Neuro-Oncology (SPINO) group report.

Neuro Oncol 2018 08;20(9):1215-1224

Department of Radiation Oncology, University of Toronto, Sunnybrook Odette Cancer Centre, Toronto, Ontario, Canada.

Background: Approximately 40% of metastatic cancer patients will develop spinal metastases. The current report provides recommendations for standardization of metrics used for spinal oncology patient population description and outcome assessment beyond local control endpoints on behalf of the SPIne response assessment in Neuro-Oncology (SPINO) group.

Methods: The SPINO group survey was conducted in order to determine the preferences for utilization of clinician-based and patient-reported outcome measures for description of patients with spinal metastases. Subsequently, ClinicalTrials.gov registry was searched for spinal oncology clinical trials, and measures for patient description and outcome reporting were identified for each trial. These two searches were used to identify currently used descriptors and instruments. A literature search was performed focusing on the measures identified in the survey and clinical trial search in order to assess their validity in the metastatic spinal tumor patient population. References for this manuscript were identified through PubMed and Medline searches.

Results: Published literature, expert survey, and ongoing clinical trials were used to synthesize recommendations for instruments for reporting of spinal stability, epidural tumor extension, neurological and functional status, and symptom severity.

Conclusions: Accurate description of patient population and therapy effects requires a combination of clinician-based and patient-reported outcome measures. The current report provides international consensus recommendations for the systematic reporting of patient- and clinician-reported measures required to develop trials applicable to surgery for spinal metastases and postoperative spine stereotactic body radiotherapy (SBRT).
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http://dx.doi.org/10.1093/neuonc/noy047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6071663PMC
August 2018

Vertebral Compression Fracture After Spine Stereotactic Body Radiation Therapy: A Review of the Pathophysiology and Risk Factors.

Neurosurgery 2018 09;83(3):314-322

Department of Radiation Oncology, Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada.

Background: Vertebral compression fracture (VCF) is a challenging and not infrequent complication observed following spine stereotactic body radiation therapy (SBRT).

Objective: To summarize the data from the multiple studies that have been published, addressing the risk and predictive factors for VCF post-SBRT.

Methods: A systematic literature review was conducted. Studies were selected if they specifically addressed risk factors for post-SBRT VCF in their analyses.

Results: A total of 11 studies were identified, reporting both the risk of VCF post-SBRT and an analysis of risk factors based on univariate and multivariate analysis. A total of 2911 spinal segments were treated with a crude VCF rate of 13.9%. The most frequently identified risk factors on multivariate analysis were: lytic disease (hazard ratio [HR] range, 2.76-12.2), baseline VCF prior to SBRT (HR range, 1.69-9.25), higher dose per fraction SBRT (HR range, 5.03-6.82), spinal deformity (HR range, 2.99-11.1), older age (HR range, 2.15-5.67), and more than 40% to 50% of vertebral body involved by tumor (HR range, 3.9-4.46). In the 9 studies that specifically reported on the use of post-SBRT surgical procedures, 37% of VCF had undergone an intervention (range, 11%-60%).

Conclusion: VCF is an important adverse effect following SBRT. Risk factors have been identified to guide the selection of high-risk patients. Evidence-based algorithms with respect to patient selection and intervention are needed.
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http://dx.doi.org/10.1093/neuros/nyx493DOI Listing
September 2018

Postoperative stereotactic body radiotherapy for spinal metastases.

Chin Clin Oncol 2017 Sep;6(Suppl 2):S18

Department of Radiation Oncology, Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada.

Spine is a common site of metastases in cancer patients. Spine surgery is indicated for select patients, typically those with mechanical instability and/or malignant epidural spinal cord (or cauda equina) compression. Although post-operative conventional palliative external beam radiation therapy has been the standard of care, technical improvements in radiation planning and image-guided radiotherapy have allowed for the application of stereotactic body radiotherapy (SBRT) to the spine. Spine SBRT is intended to ablate residual tumor and optimize local control by delivering several fold greater biologically effective doses. Early clinical experience of postoperative spinal SBRT report encouraging results in terms of safety and efficacy. In this review, we summarize the clinical and technical aspects pertinent to a safe and effective practice of postoperative SBRT for spinal metastases.
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http://dx.doi.org/10.21037/cco.2017.06.27DOI Listing
September 2017
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