Publications by authors named "Hany Soliman"

167 Publications

Skull phantom-based methodology to validate MRI co-registration accuracy for Gamma Knife radiosurgery.

Med Phys 2022 Jul 17. Epub 2022 Jul 17.

Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.

Purpose: Target localization, for stereotactic radiosurgery (SRS) treatment with Gamma Knife, has become increasingly reliant on the co-registration between the planning MRI and the stereotactic cone-beam computed tomography (CBCT). Validating image registration between modalities would be particularly beneficial when considering the emergence of novel functional and metabolic MRI pulse sequences for target delineation. This study aimed to develop a phantom-based methodology to quantitatively compare the co-registration accuracy of the standard clinical imaging protocol to a representative MRI sequence that was likely to fail co-registration. The comparative methodology presented in this study may serve as a useful tool to evaluate the clinical translatability of novel MRI sequences.

Methods: A realistic human skull phantom with fiducial marker columns was designed and manufactured to fit into a typical MRI head coil and the Gamma Knife patient positioning system. A series of "optimized" 3D MRI sequences-T -weighted Dixon, T -weighted fast field echo (FFE), and T -weighted fluid-attenuated inversion recovery (FLAIR)-were acquired and co-registered to the CBCT. The same sequences were "compromised" by reconstructing without geometric distortion correction and re-collecting with lower signal-to-noise-ratio (SNR) to simulate a novel MRI sequence with poor co-registration accuracy. Image similarity metrics-structural similarity (SSIM) index, mean squared error (MSE), and peak SNR (PSNR)-were used to quantitatively compare the co-registration of the optimized and compromised MR images.

Results: The ground truth fiducial positions were compared to positions measured from each optimized image volume revealing a maximum median geometric uncertainty of 0.39 mm (LR), 0.92 mm (AP), and 0.13 mm (SI) between the CT and CBCT, 0.60 mm (LR), 0.36 mm (AP), and 0.07 mm (SI) between the CT and T -weighted Dixon, 0.42 mm (LR), 0.23 mm (AP), and 0.08 mm (SI) between the CT and T -weighted FFE, and 0.45 mm (LR), 0.19 mm (AP), and 1.04 mm (SI) between the CT and T -weighted FLAIR. Qualitatively, pairs of optimized and compromised image slices were compared using a fusion image where separable colors were used to differentiate between images. Quantitatively, MSE was the most predictive and SSIM the second most predictive metric for evaluating co-registration similarity. A clinically relevant threshold of MSE, SSIM, and/or PSNR may be defined beyond which point an MRI sequence should be rejected for target delineation based on its dissimilarity to an optimized sequence co-registration. All dissimilarity thresholds calculated using correlation coefficients with in-plane geometric uncertainty would need to be defined on a sequence-by-sequence basis and validated with patient data.

Conclusion: This study utilized a realistic skull phantom and image similarity metrics to develop a methodology capable of quantitatively assessing whether a modern research-based MRI sequence can be co-registered to the Gamma Knife CBCT with equal or less than equal accuracy when compared to a clinically accepted protocol.
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http://dx.doi.org/10.1002/mp.15851DOI Listing
July 2022

Outcomes of Definitive Spine Fusion Using All-pedicle-Screw Constructs in Skeletally Immature Patients Aged 8 to 10 Years With Severe Idiopathic Early-Onset Scoliosis.

J Pediatr Orthop 2022 Aug 10;42(7):e703-e708. Epub 2022 Mar 10.

Department of Orthopaedic Surgery, Al Zahraa University Hospital, Al-Azhar University, Cairo, Egypt.

Background: The choice between growth-sparing techniques or definitive spine fusion for severe idiopathic early-onset scoliosis (IEOS) in skeletally immature patients aged 8 to 10 years represents a challenging dilemma. Although growth-sparing techniques show high complication rates in severe IEOS, the outcomes of definitive fusion in borderline skeletally immature patients with severe IEOS have not been investigated. We aimed to investigate the outcomes of early definitive fusion using all-pedicle-screw constructs in skeletally immature patients aged 8 to 10 years with severe IEOS.

Methods: The inclusion criteria were as follows: IEOS, age 8 years or above, major coronal curve ≥90 degrees, thoracic height >18 cm, no history of previous spine surgery, no intraspinal anomalies and at least 3 years of postoperative follow-up. Patients underwent instrumented spinal fusion with all-pedicle-screw constructs and multiple Ponte osteotomies. All patients completed the Scoliosis Research Society 22 revision (Arabic version) questionnaire and Body Image Disturbance Questionnaire-Scoliosis version (BIDQ-S) preoperatively and at the last follow-up.

Results: Fifty-five patients (24 males, 31 females; mean age: 8.96 y; range: 8 to 10 y) with severe IEOS met the inclusion criteria (mean follow-up period: 4.1±0.6 y; range: 3 to 5 y). The mean major coronal Cobb angle improved significantly (P<0.001) from 107±12.5 degrees to 26.8±6.8 degrees. Mean thoracic kyphosis improved significantly (P<0.001) from 57.2±15.8 degrees to 31.2±4.4 degrees. The loss of correction at the latest follow-up was nonsignificant. The total Scoliosis Research Society 22 revision (SRS-22r) score improved significantly from 2.5±1 to 4.3±0.7. The mean BIDQ-S score improved significantly from 4.1±0.3 to 1.6±0.3. The immediate postoperative gains in the mean thoracic height (T1-T12) and spinal height (T1-S1) were 14.9% and 19.6%, respectively, and the overall height increase at the latest follow-up was 17.8% and 23.8%, respectively. One patient underwent revision for implant failure (rod breakage).

Conclusion: Early definitive fusion for skeletally immature patients with severe IEOS yielded excellent correction with major improvements in patient quality of life. Severe IEOS poses a significant risk, but definitive fusion can potentially mitigate that risk in patients aged 8 to 10 years.
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http://dx.doi.org/10.1097/BPO.0000000000002130DOI Listing
August 2022

Pattern of Recurrence of Glioblastoma Versus Grade 4 IDH-Mutant Astrocytoma Following Chemoradiation: A Retrospective Matched-Cohort Analysis.

Technol Cancer Res Treat 2022 Jan-Dec;21:15330338221109650

Department of Medical Imaging, 7938University of Toronto, 71545Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.

To quantitatively compare the recurrence patterns of glioblastoma (isocitrate dehydrogenase-wild type) versus grade 4 isocitrate dehydrogenase-mutant astrocytoma (wild type isocitrate dehydrogenase and mutant isocitrate dehydrogenase, respectively) following primary chemoradiation. A retrospective matched cohort of 22 wild type isocitrate dehydrogenase and 22 mutant isocitrate dehydrogenase patients were matched by sex, extent of resection, and corpus callosum involvement. The recurrent gross tumor volume was compared to the original gross tumor volume and clinical target volume contours from radiotherapy planning. Failure patterns were quantified by the incidence and volume of the recurrent gross tumor volume outside the gross tumor volume and clinical target volume, and positional differences of the recurrent gross tumor volume centroid from the gross tumor volume and clinical target volume. The gross tumor volume was smaller for wild type isocitrate dehydrogenase patients compared to the mutant isocitrate dehydrogenase cohort (mean ± SD: 46.5 ± 26.0 cm vs 72.2 ± 45.4 cm,  = .026). The recurrent gross tumor volume was 10.7 ± 26.9 cm and 46.9 ± 55.0 cm smaller than the gross tumor volume for the same groups ( = .018). The recurrent gross tumor volume extended outside the gross tumor volume in 22 (100%) and 15 (68%) (= .009) of wild type isocitrate dehydrogenase and mutant isocitrate dehydrogenase patients, respectively; however, the volume of recurrent gross tumor volume outside the gross tumor volume was not significantly different (12.4 ± 16.1 cm vs 8.4 ± 14.2 cm,  = .443). The recurrent gross tumor volume centroid was within 5.7 mm of the closest gross tumor volume edge for 21 (95%) and 22 (100%) of wild type isocitrate dehydrogenase and mutant isocitrate dehydrogenase patients, respectively. The recurrent gross tumor volume extended beyond the gross tumor volume less often in mutant isocitrate dehydrogenase patients possibly implying a differential response to chemoradiotherapy and suggesting isocitrate dehydrogenase status might be used to personalize radiotherapy. The results require validation in prospective randomized trials.
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http://dx.doi.org/10.1177/15330338221109650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9247382PMC
June 2022

Radiation myelopathy following stereotactic body radiation therapy for spine metastases.

J Neurooncol 2022 Aug 23;159(1):23-31. Epub 2022 Jun 23.

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

Purpose: Stereotactic body radiation therapy (SBRT) is now considered a standard of care treatment option in the management of spine metastases. One of the most feared complications of spine SBRT is radiation myelopathy (RM).

Methods: We provided a narrative review of RM following spine SBRT based on review of the published literature, including data on spinal cord dose constraints associated with the risk of RM, strategies to mitigate the risk, and management options for RM.

Results: There are limited published data of cases of RM following spine SBRT with detailed spinal cord dosimetry. The HyTEC report provided recommendations for the point maximal dose (Dmax) for the spinal cord that is associated with a < 5% risk of RM for 1-5 fractions spine SBRT. In the setting of spine SBRT reirradiation after previous conventional external beam radiation therapy (cEBRT), factors associated with RM are: SBRT spinal cord Dmax, cumulative spinal cord Dmax, and the time interval between previous RT and SBRT reirradiation. There are various strategies to mitigate the risk of RM, including accurate delineation of the spinal cord (or thecal sac), strict adherence to the recommended spinal cord dose constraints, and robust treatment immobilisation set-up and delivery. Limited effective treatment options are available for patients who develop RM, and these include corticosteroids, hyperbaric oxygen, and bevacizumab; however, none have been supported by high quality evidence.

Conclusion: RM is a rare but devastating complication following SBRT for spine metastases. There are strategies to minimise the risk of RM to ensure safe delivery of spine SBRT.
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http://dx.doi.org/10.1007/s11060-022-04037-0DOI Listing
August 2022

Predicting the outcome of radiotherapy in brain metastasis by integrating the clinical and MRI-based deep learning features.

Med Phys 2022 Jun 21. Epub 2022 Jun 21.

Department of Electrical Engineering and Computer Science, Lassonde School of Engineering, York University, Toronto, Ontario, Canada.

Background: A considerable proportion of metastatic brain tumors progress locally despite stereotactic radiation treatment, and it can take months before such local progression is evident on follow-up imaging. Prediction of radiotherapy outcome in terms of tumor local failure is crucial for these patients and can facilitate treatment adjustments or allow for early salvage therapies.

Purpose: In this work, a novel deep learning architecture is introduced to predict the outcome of local control/failure in brain metastasis treated with stereotactic radiation therapy using treatment-planning magnetic resonance imaging (MRI) and standard clinical attributes.

Methods: At the core of the proposed architecture is an InceptionResentV2 network to extract distinct features from each MRI slice for local outcome prediction. A recurrent or transformer network is integrated into the architecture to incorporate spatial dependencies between MRI slices into the predictive modeling. A visualization method based on prediction difference analysis is coupled with the deep learning model to illustrate how different regions of each lesion on MRI contribute to the model's prediction. The model was trained and optimized using the data acquired from 99 patients (116 lesions) and evaluated on an independent test set of 25 patients (40 lesions).

Results: The results demonstrate the promising potential of the MRI deep learning features for outcome prediction, outperforming standard clinical variables. The prediction model with only clinical variables demonstrated an area under the receiver operating characteristic curve (AUC) of 0.68. The MRI deep learning models resulted in AUCs in the range of 0.72 to 0.83 depending on the mechanism to integrate information from MRI slices of each lesion. The best prediction performance (AUC = 0.86) was associated with the model that combined the MRI deep learning features with clinical variables and incorporated the inter-slice dependencies using a long short-term memory recurrent network. The visualization results highlighted the importance of tumor/lesion margins in local outcome prediction for brain metastasis.

Conclusions: The promising results of this study show the possibility of early prediction of radiotherapy outcome for brain metastasis via deep learning of MRI and clinical attributes at pre-treatment and encourage future studies on larger groups of patients treated with other radiotherapy modalities.
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http://dx.doi.org/10.1002/mp.15814DOI Listing
June 2022

Trastuzumab emtansine increases the risk of stereotactic radiosurgery-induced radionecrosis in HER2 + breast cancer.

J Neurooncol 2022 Aug 17;159(1):177-183. Epub 2022 Jun 17.

Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Science Centre, 2075 Bayview Ave., T2 181, Toronto, ON, M4N 3M5, Canada.

Introduction: In this study, we investigate factors associated with radionecrosis (RN) in HER2 + (human epidermal growth factor receptor 2) patients with brain metastases (BrM) treated with stereotactic radiosurgery (SRS).

Methods: Patients with HER2 + breast cancer BrM treated with SRS (2010-2020) were identified from an institutional database. The incidence of RN was determined per treated BrM according to serial imaging and/or histology. Factors associated with RN such as age, RT dose, BrM volume, and initiation of Trastuzumab Emtansine (T-DM1) were investigated with univariate and multivariable analyses (MVA).

Results: 67 HER2 + patients with 223 BrM were identified. 21 patients (31.3%) were treated with T-DM1 post-SRS, including 14 patients (20.9%) who received T-DM1 within 12 months of SRS. The median follow-up was 15.6 (interquartile range (IQR) 5.4-35.3) months. The overall probability of RN post-SRS was 21.6% (95% confidence interval (CI) 2.7-10.7), and the 1 and 2 year risk was 6.7% (95% CI 2.7-10.7) and 15.2% (95% CI 9.2-21.3). MVA identified T-DM1 treatment post-SRS (hazard ratio (HR) 2.5, 95% CI 1.2-5.3, p = 0.02) and equivalent dose in 2 Gy fractions (EQD2) > 90 Gy (HR 2.4, 95% CI 1.1-5.1, p = 0.02) as predictors of RN. Patients treated with T-DM1 and SRS had a 29.9% (95% CI 15.3-44.6%) probability of RN, with a 25.2% (95% CI 12.8-37.6%) risk at 1- and 2 years post-T-DM1. The majority of RN were symptomatic (71%), with a median time to RN of 4.8 months.

Conclusion: T-DM1 exposure post-SRS was associated with a higher risk of RN among patients with HER2 + BrM.
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http://dx.doi.org/10.1007/s11060-022-04055-yDOI Listing
August 2022

Mature Local Control and Reirradiation Rates Comparing Spine Stereotactic Body Radiation Therapy With Conventional Palliative External Beam Radiation Therapy.

Int J Radiat Oncol Biol Phys 2022 Jun 5. Epub 2022 Jun 5.

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

Purpose: Stereotactic body radiation therapy (SBRT) improves complete pain response for painful spinal metastases compared with conventional external beam radiation therapy (cEBRT). We report mature local control and reirradiation rates in a large cohort of patients treated with SBRT versus cEBRT enrolled previously in the Canadian Clinical Trials Group Symptom Control 24 phase 2/3 trial.

Methods And Materials: One hundred thirty-seven of 229 (60%) patients randomized to 24 Gy in 2 SBRT fractions or 20 Gy in 5 cEBRT fractions were retrospectively reviewed. By including all treated spinal segments, we report on 66 patients (119 spine segments) treated with SBRT and 71 patients (169 segments) treated with cEBRT. The primary outcomes were magnetic resonance-based local control and reirradiation rates for each treated spine segment.

Results: The median follow-up was 11.3 months (interquartile range, 5.3-27.7 months), and median overall survival in the SBRT and cEBRT cohorts were 21.6 (95% confidence interval [CI], 11.3, upper bound not reached) and 18.9 (95% CI, 12.2-29.1) months (P = .428), respectively. The cohorts were balanced with respect to radioresistant histology and presence of mass (paraspinal and/or epidural disease extension). Risk of local failure after SBRT versus cEBRT at 6, 12, and 24 months were 2.8% (95% CI, 0.8%-7.4%) versus 11.2% (95% CI, 6.9%-16.6%), 6.1% (95% CI, 2.5%-12.1%) versus 28.4% (95% CI, 21.3%-35.9%), and 14.8% (95% CI, 8.2-23.1%) versus 35.6% (95% CI, 27.8%-43.6%), respectively (P < .001). cEBRT (hazard ratio [HR], 3.48; 95% CI, 1.94-6.25; P < .001) and presence of mass (HR, 2.07; 95% CI, 1.29-3.31; P = .002) independently predicted local failure on multivariable analysis. The 1-year reirradiation rates and median times to reirradiation after SBRT versus cEBRT were 2.2% (95% CI, 0.4-7.0%) versus 15.8% (95% CI, 10.4%-22.3%) (P = .002) and 22.9 months versus 9.5 months, respectively. cEBRT (HR, 2.60; 95% CI, 1.27-5.30; P = .009) and radioresistant histology (HR, 2.00; 95% CI, 1.12-3.60; P = .020) independently predicted for reirradiation. Eight of 12 iatrogenic vertebral compression fractures were after SBRT and 4 of 12 after cEBRT; grade 3 adverse fracture effects were isolated to the SBRT cohort (5 of 12).

Conclusions: Risk of local failure and reirradiation is lower with SBRT compared with cEBRT for spinal metastases. Although the iatrogenic vertebral compression fracture rates were within expectations, grade 3 vertebral compression fractures were isolated to the SBRT cohort.
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http://dx.doi.org/10.1016/j.ijrobp.2022.05.043DOI Listing
June 2022

The modern management of untreated large (>2 cm) brain metastases: a narrative review.

Chin Clin Oncol 2022 Apr;11(2):16

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

Objective: Our objective was to identify contemporary management options for large brain metastases reported in literature, specifically evaluating local control and risk of toxicity.

Background: Large brain metastases are typically defined as lesions >2 cm in diameter, and historically conferred poor outcomes due to the high rates of radiation necrosis and less local control in comparison to smaller brain metastases.

Methods: A literature search examining modern management of large brain metastases was performed using ovid-MEDLINE. A total of 18 articles met criteria for review, evaluating single fraction radiosurgery [stereotactic radiosurgery (SRS)] and multi-fraction stereotactic radiation therapy (MFSRT) in both the definitive and post-operative cavity setting, as well as targeted therapies.

Conclusions: Multi-fractionated radiosurgery represents a modern and attractive treatment approach in the definitive management of patients with large brain metastases, with equivalent local control and reduced rates of radionecrosis less than 13% in comparison to single fraction SRS. In cases where surgery is indicated, fractionated cavity radiation should be considered for large tumor bed volumes. More research is needed for the optimal dose and fractionation regimen for optimal tumor control with reduced risk of radiation toxicity, but common regimens include 3-5 fractions while meeting appropriate biologically effective dose (BED) goals. Future areas of interest include targeted therapies in the initial management of brain metastases as well as pre-operative radiation therapy to reduce risk of leptomeningeal disease (LMD).
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http://dx.doi.org/10.21037/cco-21-136DOI Listing
April 2022

Spine Stereotactic Body Radiotherapy for Prostate Cancer Metastases and the Impact of Hormone Sensitivity Status on Local Control.

Neurosurgery 2022 06 30;90(6):743-749. Epub 2022 Mar 30.

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

Background: Stereotactic body radiotherapy (SBRT) is used to deliver ablative dose of radiation to spinal metastases.

Objective: To report the first dedicated series of spine SBRT specific to prostate cancer (PCa) metastases with outcomes reported according to hormone sensitivity status.

Methods: A prospective database was reviewed identifying patients with PCa treated with spine SBRT. This included those with hormone-sensitive PCa (HSPC) and castrate-resistant PCa (CRPC). The primary end point was MRI-based local control (LC).

Results: A total of 183 spine segments in 93 patients were identified; 146 segments had no prior radiation and 37 had been previously radiated; 27 segments were postoperative. The median follow-up was 31 months. At the time of SBRT, 50 patients had HSPC and the remaining 43 had CRPC. The most common fractionation scheme was 24-28 Gy in 2 SBRT fractions (76%). LC rates at 1 and 2 years were 99% and 95% and 94% and 78% for the HSPC and CRPC cohorts, respectively. For patients treated with de novo SBRT, a higher risk of local failure was observed in patients with CRPC (P = .0425). The 1-year and 2-year overall survival rates were significantly longer at 98% and 95% in the HSPC cohort compared with 79% and 65% in the CRPC cohort (P = .0005). The cumulative risk of vertebral compression fracture at 2 years was 10%.

Conclusion: Favorable LC rates were observed after spine SBRT for PCa metastases; strategies to improve long-term LC in patients with CRPC require further investigation.
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http://dx.doi.org/10.1227/neu.0000000000001909DOI Listing
June 2022

Graded Prognostic Assessment (GPA) for Patients With Lung Cancer and Brain Metastases: Initial Report of the Small Cell Lung Cancer GPA and Update of the Non-Small Cell Lung Cancer GPA Including the Effect of Programmed Death Ligand 1 and Other Prognostic Factors.

Int J Radiat Oncol Biol Phys 2022 Mar 21. Epub 2022 Mar 21.

University of Niigata, Niigata, Japan.

Purpose: Patients with lung cancer and brain metastases represent a markedly heterogeneous population. Accurate prognosis is essential to optimally individualize care. In prior publications, we described the graded prognostic assessment (GPA), but a GPA for patients with small cell lung cancer (SCLC) has never been reported, and in non-small cell lung cancer (NSCLC), the effect of programmed death ligand 1 (PD-L1) was unknown. The 3-fold purpose of this work is to provide the initial report of an SCLC GPA, to evaluate the effect of PD-L1 on survival in patients with NSCLC, and to update the Lung GPA accordingly.

Methods And Materials: A multivariable analysis of prognostic factors and treatments associated with survival was performed on 4183 patients with lung cancer (3002 adenocarcinoma, 611 nonadenocarcinoma, 570 SCLC) with newly diagnosed brain metastases between January 1, 2015, and December 31, 2020, using a multi-institutional retrospective database. Significant variables were used to update the Lung GPA.

Results: Overall median survival for lung adenocarcinoma, SCLC, and nonadenocarcinoma was 17, 10, and 8 months, respectively, but varied widely by GPA from 2 to 52 months. In SCLC, the significant prognostic factors were age, performance status, extracranial metastases, and number of brain metastases. In NSCLC, the distribution of molecular markers among patients with lung adenocarcinoma and known primary tumor molecular status revealed alterations/expression in PD-L1 50% to 100%, PD-L1 1% to 49%, epidermal growth factor receptor, and anaplastic lymphoma kinase in 32%, 31%, 30%, and 7%, respectively. Median survival of patients with lung adenocarcinoma and brain metastases with 0, 1% to 49%, and ≥50% PD-L1 expression was 17, 19, and 24 months, respectively (P < .01), confirming PD-L1 is a prognostic factor. Previously identified prognostic factors for NSCLC (epidermal growth factor receptor and anaplastic lymphoma kinase status, performance status, age, number of brain metastases, and extracranial metastases) were reaffirmed. These factors were incorporated into the updated Lung GPA with robust separation between subgroups for all histologies.

Conclusions: Survival for patients with lung cancer and brain metastases has improved but varies widely. The initial report of a GPA for SCLC is presented. For patients with NSCLC-adenocarcinoma and brain metastases, PD-L1 is a newly identified significant prognostic factor, and the previously identified factors were reaffirmed. The updated indices establish unique criteria for SCLC, NSCLC-nonadenocarcinoma, and NSCLC-adenocarcinoma (incorporating PD-L1). The updated Lung GPA, available for free at brainmetgpa.com, provides an accurate tool to estimate survival, individualize treatment, and stratify clinical trials.
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http://dx.doi.org/10.1016/j.ijrobp.2022.03.020DOI Listing
March 2022

Comparison of latissimus dorsi tendon transfer with subscapularis release versus sliding of internal rotation contracture in obstetrical brachial plexus paralysis sequela.

J Orthop Surg Res 2022 Mar 15;17(1):163. Epub 2022 Mar 15.

Alzhraa University Hospital, Faculty of Medicine for Girls, Al-Azhar University, Cairo, 11517, Egypt.

Background: The purpose of this study was to compare the functional results of latissimus dorsi (LD) tendon transfer with those of subscapularis (SS) muscle release versus sliding.

Methods: Fifty-six patients with internal rotation contracture and external rotation (ER) weakness as sequelae of Erb's palsy were included in the study. Of the patients, 24 were included in group 1 (11 boys and 13 girls), with a mean age of 2 years 8 months (range 1.5-5 years) and a follow-up period of 62 months (range 38-68 months). The patients in group 1 underwent LD tendon transfer, with internal rotation contracture and SS release procedures. Thirty-two patients were included in group 2 (18 boys and 14 girls), with a mean age of 2 years 6 months (range 1.5-4.8 years) and a follow-up period of 58 months (range 38-68 months). The patients in group 2 underwent LD tendon transfer with SS sliding.

Results: A significant improvement in preoperative passive ER from - 3.6° to 67.3° after operation was observed in group 1. In group 2, preoperative passive ER in adduction improved from 0° to 72.3°. We found no significant difference (P = 0.1) in postoperative improvement in active ER in both groups (group 1 vs. group 2: 75° vs. 77.3°). Similarly, no significant difference (P = 0.7) in postoperative improvement in passive ER was found between the groups (group 1 vs. group 2: 71° vs. 72.3°).

Conclusions: LD tendon transfer with SS release or sliding is an effective procedure to improve shoulder ER in patients with OBPP, with no inferiority of SS muscle release or sliding for internal rotation contractures and increased passive range of shoulder motion.

Level Of Evidence: Level III; Retrospective Cohort Comparison; Treatment Study.
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http://dx.doi.org/10.1186/s13018-022-03065-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8922728PMC
March 2022

Predicting survival in patients with glioblastoma using MRI radiomic features extracted from radiation planning volumes.

J Neurooncol 2022 Feb 3;156(3):579-588. Epub 2022 Jan 3.

Department of Radiation Oncology, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada.

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 (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 two surgical groups individually. The integrated AUC (iAUC) was 0.613 for radiomics-based classification 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-stratification of GBM undergoing biopsy, while the utility in other individual subgroups needs to be further explored.
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http://dx.doi.org/10.1007/s11060-021-03939-9DOI Listing
February 2022

Inter-fraction dynamics during post-operative 5 fraction cavity hypofractionated stereotactic radiotherapy with a MR LINAC: a prospective serial imaging study.

J Neurooncol 2022 Feb 3;156(3):569-577. Epub 2022 Jan 3.

Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada.

Purpose/objective(s): This study examined changes in the clinical target volume (CTV) and associated clinical implications on a magnetic resonance imaging linear accelerator (MR LINAC) during hypofractionated stereotactic radiotherapy (HSRT) to resected brain metastases. In addition, the suitability of using T2/FLAIR (T2f) sequence to define CTV was explored by assessing contouring variability between gadolinium-enhanced T1 (T1c) and T2f sequences.

Materials/methods: Fifteen patients treated to either 27.5 or 30 Gy with five fraction HSRT were imaged with T1c and T2f sequences during treatment; T1c was acquired at planning (FxSim), and fraction 3 (Fx3), and T2f was acquired at FxSim and all five fractions. The CTV were contoured on all acquired images. Inter-fraction cavity dynamics and CTV contouring variability were quantified using absolute volume, Dice similarity coefficient (DSC), and Hausdorff distance (HD) metrics.

Results: The median CTV on T1c and T2f sequences at FxSim were 12.0cm (range, 1.2-30.1) and 10.2cm (range, 2.9-27.9), respectively. At Fx3, the median CTV decreased in both sequences to 9.3cm (range, 3.7-25.9) and 8.6cm (range, 3.3-22.5), translating to a median % relative reduction of - 11.4% on T1c (p = 0.009) and - 8.4% on T2f (p = 0.032). We observed a median % relative reduction in CTV between T1c and T2f at FxSim of - 6.0% (p = 0.040). The mean DSC was 0.85 ± 0.10, and the mean HD was 5.3 ± 2.7 mm when comparing CTV on T1c and T2f at FxSim.

Conclusion: Statistically significant reductions in cavity CTV was observed during HSRT, supporting the use of MR image guided radiation therapy and treatment adaptation to mitigate toxicity. Significant CTV contouring variability was seen between T1c and T2f sequences. Trial registration NCT04075305 - August 30, 2019.
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http://dx.doi.org/10.1007/s11060-021-03938-wDOI Listing
February 2022

Case series of radiation pneumonitis in breast cancer.

J Med Imaging Radiat Sci 2022 03 9;53(1):167-174. Epub 2021 Dec 9.

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

Background: Radiation pneumonitis (RP) is a potentially severe inflammatory reaction that occurs in approximately 1-16% of breast cancer patients treated with radiation (RT).

Methods: Case histories and patient demographics were collected from 4 patients who received either hypofractionated (42.56 Gy in 16 fractions) or conventionally fractionated (50 Gy in 25 fractions) RT for breast cancer at a cancer centre from 2018-2020 and experienced clinically symptomatic RP. Lung dose parameters including mean lung dose, V5, and V20 were collected from institutional planning software and compared to institutional guidelines.

Results: The 4 cases were all female, aged 42-73 years old and received 2- or 4-field RT with wide or high tangent techniques. The most common symptoms in patients who developed RP were exertional dyspnea and dry cough. Corticosteroid doses in the daily range of 40-60 mg were the primary treatment followed by a highly variable tapering schedule. Two patients experienced a recurrence of symptoms after initial treatment and were restarted on corticosteroids. Patients had several predisposing risk factors including administration of wide tangents, chemotherapy with cyclophosphamide and/or taxanes, age>65 years, and comorbidities such as diabetes.

Discussion: Identification of RP is difficult as evidenced by the large gap in time between the appearance of RP symptoms to treatment with corticosteroids in several patients. Irregular tapering schedules may contribute to symptom recurrence. Three of the four patients treated with 4-field wide tangents exceeded the 35% dose constraint for ipsilateral lung V20 or V17.5.

Conclusion: Careful radiation planning and review of lung dose constraints is essential to reduce risk of RP. Greater standardization of steroid tapering practices is recommended.
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http://dx.doi.org/10.1016/j.jmir.2021.11.008DOI Listing
March 2022

Intraoperative and postoperative outcomes of Harmonic Focus versus monopolar electrocautery after neoadjuvant chemotherapy in breast conservative surgery: a comparative study.

World J Surg Oncol 2021 Nov 15;19(1):325. Epub 2021 Nov 15.

Department of Surgery, Faculty of Medicine, Surgical Oncology Unit, Suez Canal University, Kilo 4.5, Ring Road, Ismailia, Egypt.

Background: Surgical devices are commonly used during breast conservative surgery (BCS) to provide better hemostasis. The Harmonic scalpel has recently gained momentum as an effective tool for intraoperative bleeding reduction. This comparative study was designed to determine the efficacy of Harmonic Focus in reducing postoperative complications of BCS after neoadjuvant chemotherapy (CTH) compared to the conventional method using monopolar diathermy.

Results: A prospective, nonrandomized, comparative study was conducted on patients scheduled to undergo BCS with axillary dissection after neoadjuvant CTH. Patients in the Harmonic Focus group had significantly shorter operative times than the monopolar electrocautery group (101.32 ± 27.3 vs. 139.3 ± 31.9 min, respectively; p < 0.001). Besides, blood loss was significantly lower in the Harmonic Focus group (117.14 ± 35.6 vs. 187 ± 49.8 mL, respectively; p < 0.001). Postoperatively, patients in the Harmonic Focus group had a significantly lower volume of chest wall drain (p < 0.001) and shorter time until drain removal (p < 0.001). Likewise, patients in the Harmonic Focus group had a significantly lower volume of axillary drain and shorter time until drain removal than monopolar electrocautery (p < 0.001). The incidence of postoperative complications was comparable between both groups (p = 0.128).

Conclusions: This study confirmed the superiority of Harmonic Focus compared to monopolar electrocautery among patients receiving neoadjuvant CTH before BCS.
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http://dx.doi.org/10.1186/s12957-021-02435-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8591841PMC
November 2021

Characterization of the SARS-CoV-2 genomes in Egypt in first and second waves of infection.

Sci Rep 2021 11 3;11(1):21632. Epub 2021 Nov 3.

Systems and Biomedical Engineering Department, Faculty of Engineering, Cairo University, Cairo, 12613, Egypt.

At Wuhan, in December 2019, the SRAS-CoV-2 outbreak was detected and it has been the pandemic worldwide. This study aims to investigate the mutations in sequence of the SARS-CoV-2 genome and characterize the mutation patterns in Egyptian COVID-19 patients during different waves of infection. The samples were collected from 250 COVID-19 patients and the whole genome sequencing was conducted using Next Generation Sequencing. The viral sequence analysis showed 1115 different genome from all Egyptian samples in the second wave mutations including 613 missense mutations, 431 synonymous mutations, 25 upstream gene mutations, 24 downstream gene mutations, 10 frame-shift deletions, and 6 stop gained mutation. The Egyptian genomic strains sequenced in second wave of infection are different to that of the first wave. We observe a shift of lineage prevalence from the strain B.1 to B.1.1.1. Only one case was of the new English B.1.1.7. Few samples have one or two mutations of interest from the Brazil and South Africa isolates. New clade 20B appear by March 2020 and 20D appear by May 2020 till January 2021.
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http://dx.doi.org/10.1038/s41598-021-99014-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8566477PMC
November 2021

A priori prediction of local failure in brain metastasis after hypo-fractionated stereotactic radiotherapy using quantitative MRI and machine learning.

Sci Rep 2021 11 3;11(1):21620. Epub 2021 Nov 3.

Department of Electrical Engineering and Computer Science, Lassonde School of Engineering, York University, Toronto, ON, Canada.

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 clinical criteria at last patient follow-up after SRT. The developed quantitative MRI biomarker consists of four features with two features quantifying heterogeneity in the edema region, one feature characterizing intra-tumour heterogeneity, and one feature describing tumour morphology. The predictive models with the radiomic and clinical feature sets yielded an AUC of 0.87 and 0.62, respectively on the independent test set. Incorporating radiomic features into the clinical predictive model improved the AUC of the model by up to 16%, relatively. A statistically significant difference was observed in survival of the two patient cohorts identified at pre-treatment using the radiomics-based predictive model, and at post-treatment using the the RANO-BM criteria. Results of this study revealed a good potential for quantitative MRI radiomic features at pre-treatment in predicting local failure in relatively large brain metastases undergoing SRT, and is a step forward towards a precision oncology paradigm for brain metastasis.
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http://dx.doi.org/10.1038/s41598-021-01024-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8566533PMC
November 2021

Technical note: Personalized treatment gating thresholds in frameless stereotactic radiosurgery using predictions of dosimetric fidelity and treatment interruption.

Med Phys 2021 Dec 16;48(12):8045-8051. Epub 2021 Nov 16.

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

Purpose: Gamma Knife Icon (GKI) enables a user-defined gating threshold for intrafraction motion during stereotactic radiosurgery (SRS). An optimal threshold would ensure dosimetric fidelity of the planned distribution and minimize treatment time extension by gating. A prediction of motion characteristics for a patient based on a retrospective database of motion traces could be beneficial to evaluating the choice of gating threshold. A short acquisition of motion may help to define a personalized threshold that balances dosimetric accuracy and treatment length. This study aims to evaluate the performance of a prediction of motion and the resultant dosimetric consequences for a range of motion gating thresholds.

Methods: A database of 2552 motion traces (776 patients) was analyzed using previously published methods to characterize patient intrafraction motion on the GKI. For a selection of six fractionated SRS patient cases (two patients with single brain metastasis, four vestibular schwannomas), a 10-min sample of motion was used to classify motion and identify traces in the database with similar metrics. The similar motion traces were used to perform a predictive reconstruction of the selected patient's delivered dose for a range of motion thresholds. The remaining fractions were reconstructed and compared to that predicted. From the six cases, 26 fractions were used to predict the number of interruptions (n = 26), change in target coverage (n = 26), and change in brainstem maximum dose (vestibular cases only, n = 20). The difference between mean predicted and reconstructed values was compared for accuracy.

Results: The difference between mean prediction and reconstructed values was 0.32 ± 0.38% in target coverage, 2.36 ± 5.06 interruptions, and 0.15 ± 0.24 Gy for the brainstem maximum dose. Sixty-seven of the 72 predictions (26 coverage, 26 interruptions, and 20 brainstem maximum dose) were within one standard deviation of the predicted mean.

Conclusions: Large databases of motion traces were used to characterize patient performance and predict motion performance. Dosimetric deterioration due to motion and extension of treatment duration can be predicted in some cases using only a short acquisition of motion and the treatment plan. This reconstruction may provide benefit in generating a patient-specific motion threshold.
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http://dx.doi.org/10.1002/mp.15331DOI Listing
December 2021

MRI radiomics to differentiate between low grade glioma and glioblastoma peritumoral region.

J Neurooncol 2021 Nov 25;155(2):181-191. Epub 2021 Oct 25.

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

Background: The peritumoral region (PTR) of glioblastoma (GBM) appears as a T2W-hyperintensity and is composed of microscopic tumor and edema. Infiltrative low grade glioma (LGG) comprises tumor cells that seem similar to GBM PTR on MRI. The work here explored if a radiomics-based approach can distinguish between the two groups (tumor and edema versus tumor alone).

Methods: Patients with GBM and LGG imaged using a 1.5 T MRI were included in the study. Image data from cases of GBM PTR, and LGG were manually segmented guided by T2W hyperintensity. A set of 91 first-order and texture features were determined from each of T1W-contrast, and T2W-FLAIR, diffusion-weighted imaging sequences. Applying filtration techniques, a total of 3822 features were obtained. Different feature reduction techniques were employed, and a subsequent model was constructed using four machine learning classifiers. Leave-one-out cross-validation was used to assess classifier performance.

Results: The analysis included 42 GBM and 36 LGG. The best performance was obtained using AdaBoost classifier using all the features with a sensitivity, specificity, accuracy, and area of curve (AUC) of 91%, 86%, 89%, and 0.96, respectively. Amongst the feature selection techniques, the recursive feature elimination technique had the best results, with an AUC ranging from 0.87 to 0.92. Evaluation with the F-test resulted in the most consistent feature selection with 3 T1W-contrast texture features chosen in over 90% of instances.

Conclusions: Quantitative analysis of conventional MRI sequences can effectively demarcate GBM PTR from LGG, which is otherwise indistinguishable on visual estimation.
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http://dx.doi.org/10.1007/s11060-021-03866-9DOI Listing
November 2021

Hypofractionated Stereotactic Radiation Therapy for Intact Brain Metastases in 5 Daily Fractions: Effect of Dose on Treatment Response.

Int J Radiat Oncol Biol Phys 2022 02 17;112(2):342-350. Epub 2021 Sep 17.

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

Purpose: Multileaf collimator (MLC) linear accelerator (Linac)-based hypofractionated stereotactic radiation therapy (HSRT) is increasingly used not only for large brain metastases or those adjacent to critical structures but also for those metastases that would otherwise be considered for single-fraction radiosurgery (SRS). However, data on outcomes in general are limited, and there is a lack of understanding regarding optimal dosing. Our aim was to report mature image-based outcomes for MLC-Linac HSRT with a focus on clinical and dosimetric factors associated with local failure (LF).

Methods And Materials: A total of 220 patients with 334 brain metastases treated with HSRT were identified. All patients were treated using a 5-fraction daily regimen and were followed with clinical evaluation and volumetric magnetic resonance imaging every 2 to 3 months. Overall survival and progression-free survival were calculated using the Kaplan-Meier method, with LF determined using Fine and Gray's competing risk method. Predictive factors were identified using Cox regression multivariate analysis.

Results: Median follow-up was 10.8 months. Median size of treated metastasis was 1.9 cm; 60% of metastases were <2 cm in size. The median total dose was 30 Gy in 5 fractions; 36% of the cohort received <30 Gy. The median time to LF and 12-month cumulative incidence of LF was 8.5 months and 23.8%, respectively. Median time to death and 12-month overall survival rates were 11.8 months and 48.2%, respectively. Fifty-two metastases (15.6%) had an adverse radiation effect, of which 32 (9.5%) were symptomatic necrosis. Multivariable analysis identified worse LF in patients who received a total dose of <30 Gy (hazard ratio, 1.62; P = .03), with LF at 6 and 12 months of 13% and 33% for patients treated with <30 Gy versus 5% and 19% for patients treated with >30 Gy. Exploratory analysis demonstrated a dose-response effect observed in all histologic types, including among breast cancer subtypes.

Conclusion: Optimal local control is achieved with HSRT of ≥30 Gy in 5 daily fractions, independent of tumor volume and histology, with an acceptable risk of radiation necrosis.
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http://dx.doi.org/10.1016/j.ijrobp.2021.09.003DOI Listing
February 2022

Treatment Patterns and Outcomes of Women with Symptomatic and Asymptomatic Breast Cancer Brain Metastases: A Single-Center Retrospective Study.

Oncologist 2021 11 21;26(11):e1951-e1961. Epub 2021 Sep 21.

Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.

Background: Breast cancer is the most common cancer among women worldwide and the second leading cause of brain metastases (BrM). We assessed the treatment patterns and outcomes of women treated for breast cancer BrM at our institution in the modern era of stereotactic radiosurgery (SRS).

Materials And Methods: We conducted a retrospective analysis of women (≥18 years of age) with metastatic breast cancer who were treated with surgery, whole brain radiotherapy (WBRT), or SRS to the brain at the Sunnybrook Odette Cancer Centre, Toronto, Canada, between 2008 and 2018. Patients with a history of other malignancies and those with an uncertain date of diagnosis of BrM were excluded. Descriptive statistics were generated and survival analyses were performed with subgroup analyses by breast cancer subtype.

Results: Among 683 eligible patients, 153 (22.4%) had triple-negative breast cancer, 188 (27.5%) had HER2+, 246 (36.0%) had hormone receptor (HR)+/HER2-, and 61 (13.3%) had breast cancer of an unknown subtype. The majority of patients received first-line WBRT (n = 459, 67.2%) or SRS (n = 126, 18.4%). The median brain-specific progression-free survival and median overall survival (OS) were 4.1 months (interquartile range [IQR] 1.0-9.6 months) and 5.1 months (IQR 2.0-11.7 months) in the overall patent population, respectively. Age >60 years, presence of neurological symptoms at BrM diagnosis, first-line WBRT, and HER2- subtype were independently prognostic for shorter OS.

Conclusion: Despite the use of SRS, outcomes among patients with breast cancer BrM remain poor. Strategies for early detection of BrM and central nervous system-active systemic therapies warrant further investigation.

Implications For Practice: Although triple-negative breast cancer and HER2+ breast cancer have a predilection for metastasis to the central nervous system (CNS), patients with hormone receptor-positive/HER2- breast cancer represent a high proportion of patients with breast cancer brain metastases (BrM). Hence, clinical trials should include patients with BrM and evaluate CNS-specific activity of novel systemic therapies when feasible, irrespective of breast cancer subtype. In addition, given that symptomatic BrM are associated with shorter survival, this study suggests that screening programs for the early detection and treatment of breast cancer BrM warrant further investigation in an era of minimally toxic stereotactic radiosurgery.
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http://dx.doi.org/10.1002/onco.13965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571756PMC
November 2021

Stereotactic Radiotherapy for Oligoprogression in Metastatic Renal Cell Cancer Patients Receiving Tyrosine Kinase Inhibitor Therapy: A Phase 2 Prospective Multicenter Study.

Eur Urol 2021 Dec 13;80(6):693-700. Epub 2021 Aug 13.

Division of Medical Oncology, Department of Medicine, Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada. Electronic address:

Background: Despite the paucity of prospective evidence, stereotactic radiotherapy (SRT) is increasingly being considered in the setting of oligoprogression to delay the need to change systemic therapy.

Objective: To determine the local control (LC), progression-free survival (PFS), cumulative incidence of changing systemic therapy, and overall survival (OS) after SRT to oligoprogressive metastatic renal cell carcinoma (mRCC) lesions in patients who are on tyrosine kinase inhibitor (TKI) therapy.

Design, Setting, And Participants: A prospective multicenter study was performed to evaluate the use of SRT in oligoprogressive mRCC patients. Patients with mRCC who had previous stability or response after ≥3 mo of TKI therapy were eligible if they developed progression of five of fewer metastases. Thirty-seven patients with 57 oligoprogressive tumors were enrolled.

Intervention: Oligoprogressive tumors were treated with SRT, and the same TKI therapy was continued afterward.

Outcome Measurements And Statistical Analysis: Competing risk analyses and the Kaplan-Meir methodology were used to report the outcomes of interest.

Results And Limitations: The median duration of TKI therapy prior to study entry was 18.6 mo; 1-yr LC of the irradiated tumors was 93% (95% confidence interval [CI] 71-98%). The median PFS after SRT was 9.3 mo (95% CI 7.5-15.7 mo). The cumulative incidence of changing systemic therapy was 47% (95% CI 32-68%) at 1 yr, with a median time to change in systemic therapy of 12.6 mo (95% CI 9.6-17.4 mo). One-year OS was 92% (95% CI 82-100%). There were no grade 3-5 SRT-related toxicities.

Conclusions: LC of irradiated oligoprogressive mRCC tumors was high, and the need to change systemic therapy was delayed for a median of >1 yr.

Patient Summary: The use of stereotactic radiotherapy in metastatic kidney cancer patients, who develop growth of a few tumors while on oral targeted therapy, can significantly delay the need to change to the next line of drug therapy.
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http://dx.doi.org/10.1016/j.eururo.2021.07.026DOI Listing
December 2021

The Initial Step Towards Establishing a Quantitative, Magnetic Resonance Imaging-Based Framework for Response Assessment of Spinal Metastases After Stereotactic Body Radiation Therapy.

Neurosurgery 2021 10;89(5):884-891

Department of Radiation Oncology, University of Toronto, Toronto, Canada.

Background: There are no established threshold values regarding the degree of growth on imaging when assessing response of spinal metastases treated with stereotactic body radiation therapy (SBRT).

Objective: To determine a magnetic resonance imaging-based minimum detectable difference (MDD) in gross tumor volume (GTV) and its association with 1-yr radiation site-specific (RSS) progression-free survival (PFS).

Methods: GTVs at baseline and first 2 post-SBRT scans (Post1 and Post2, respectively) for 142 spinal segments were contoured, and percentage volume change between scans calculated. One-year RSS PFS was acquired from medical records. The MDD was determined. The MDD was compared against optimal thresholds of GTV changes associated with 1-yr RSS PFS using Youden's J index, and receiver operating characteristic curves between timepoints compared to determine which timeframe had the best association.

Results: A total of 17 of the 142 segments demonstrated progression. The MDD was 10.9%. Baseline-Post2 demonstrated the best performance (area under the curve [AUC] 0.90). Only Baseline-Post2 had an optimal threshold > MDD at 14.7%. Due to large distribution of GTVs, volumes were split into tertiles. Small tumors (GTV < 2 cc) had optimal thresholds of 42.0%, 71.3%, and 37.2% at Baseline-Post1 (AUC 0.81), Baseline-Post2 (AUC 0.89), and Post1-Post2 (AUC 0.77), respectively. Medium tumors (2 ≤ GTV ≤ 8.3 cc) all demonstrated optimal thresholds < MDD, with AUCs ranging from 0.65 to 0.84. Large tumors (GTV > 8.3 cc) had 2 timepoints where optimal thresholds > MDD: Baseline-Post2 (13.3%; AUC 0.97) and Post1-Post2 (11.8%; AUC 0.66). Baseline-Post2 had the best association with RSS PFS for all tertiles.

Conclusion: Given a MDD of 10.9%, for small GTVs, larger (>37%) changes were required before local failure could be determined, compared to 11% to 13% for medium/large tumors.
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http://dx.doi.org/10.1093/neuros/nyab310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8645191PMC
October 2021

Oncological outcomes of laparoscopic versus open gastrectomy after neoadjuvant chemotherapy for locally advanced gastric cancer: a retrospective multicenter study.

World J Surg Oncol 2021 Jul 9;19(1):206. Epub 2021 Jul 9.

Surgical Oncology Department, National Cancer Institute, Cairo University, Cairo, Egypt.

Background: The oncological outcomes of laparoscopic gastrectomy (LG) and open gastrectomy (OG) following neoadjuvant chemotherapy have been investigated in a few studies. Our purpose was to evaluate the oncological outcomes of LG and OG after neoadjuvant chemotherapy in patients with locally advanced gastric cancer (GC) and to determine the advantages, preferences, and ease of use of the two techniques after chemotherapy.

Methods: We conducted a retrospective chart review of all patients who underwent either OG (n = 43) or LG (n = 41). The neoadjuvant treatment regimen consisted of capecitabine plus oxaliplatin for three cycles, which was then repeated 6 to 12 weeks after the operation for four cycles.

Results: The hospital stay time and intraoperative blood loss in the LG group were significantly lower than those in the OG group. The mortality rate and the 3-year survival rate for patients in the LG group were comparable to those of patients in the OG group (4.6% vs. 9.7% and 68.3% vs. 58.1%, respectively). Similar trends were observed regarding the 3-year recurrence rate and metastasis. The mean survival time was 52.9 months (95% confidence interval [CI], 44.2-61.6) in the OG group compared with 43.3 (95% CI, 36.6-49.8) in the LG group. Likewise, the mean disease-free survival was 56.1 months (95% CI, 46.36-65.8) in the LG group compared with 50.9 months (95% CI, 44.6-57.2) in the OG group.

Conclusion: LG is a feasible and safe alternative to OG for patients with locally advanced GC receiving neoadjuvant chemotherapy.
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http://dx.doi.org/10.1186/s12957-021-02322-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8272390PMC
July 2021

Outcomes of extra-cranial stereotactic body radiotherapy for metastatic breast cancer: Treatment indication matters.

Radiother Oncol 2021 08 10;161:159-165. Epub 2021 Jun 10.

Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Canada. Electronic address:

Background And Purpose: To summarize the clinical outcomes of stereotactic body radiotherapy (SBRT) for metastatic breast cancer (mBC) from a large institution.

Materials And Methods: Patients with mBC who received extra-cranial SBRT to metastatic lesions from 2011 to 2017 were identified. Treatment indications were: oligometastases, oligoprogression, and local control of dominant tumor (CDT). Endpoints included overall survival (OS), progression-free survival (PFS), local control (LC) and cumulative incidence of starting/changing chemo or hormonal therapy (SCT). Univariate and multivariate analyses were used to identify predictive factors.

Results: We analyzed 120 patients (193 treated metastatic lesions) with a median follow up of 15.25 months. 1-and 2-year LC rates were 89% and 86.6%, respectively. 1-and 2-year OS rates were 83.5% and 70%, respectively, with treatment indication and molecular subtype being the predictive factors on MVA. 1-year OS was 91.0%, 78.5% and 63.9% for oligometastases, oligoprogression and CDT, respectively (p = 0.003). The worst OS was seen in basal subtype with 1-and 2-year OS rates of 59.2% and 39.5% (p = 0.01). Treatment indication was found to be predictive for PFS and lower rates of SCT on MVA. 1-and 2-year PFS rates were 45% and 32%, respectively. The 1-year PFS for oligometastases, oligoprogression, and CDT was 66%, 19.6%, and 14.3%, respectively (p < 0.001). The cumulative incidence of SCT at 1-year was 12% for oligometastases, 39.7% for oligoprogression and 53.3% for CDT (p < 0.001).

Conclusion: Patients treated for oligometastases have better OS and PFS than those treated for oligoprogression or CDT. SBRT may delay SCT in mBC patients, particularly those with oligometastases. SBRT provided an excellent LC in mBC patients.
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http://dx.doi.org/10.1016/j.radonc.2021.06.012DOI Listing
August 2021

Genome sequencing of SARS-CoV-2 in a cohort of Egyptian patients revealed mutation hotspots that are related to clinical outcomes.

Biochim Biophys Acta Mol Basis Dis 2021 08 28;1867(8):166154. Epub 2021 Apr 28.

Cancer Biology Department, Virology and Immunology Unit, National Cancer Institute, Cairo University, 11796, Egypt.

Background: Severe acute respiratory syndrome-2 (SARS-CoV-2) exhibits a broad spectrum of clinical manifestations. Despite the fact that SARS-CoV-2 has slower evolutionary rate than other coronaviruses, different mutational hotspots have been identified along the SARS-CoV-2 genome.

Methods: We performed whole-genome high throughput sequencing on isolates from 50 Egyptian patients to see if the variation in clinical symptoms was related to mutations in the SARS-CoV-2 genome. Then, we investigated the relationship between the observed mutations and the clinical characteristics of the patients.

Results: Among the 36 most common mutations, we found two frameshift deletions linked to an increased risk of shortness of breath, a V6 deletion in the spike glycoprotein's signal peptide region linked to an increased risk of fever, longer fever duration and nasal congestion, and L3606-nsp6 deletion linked to a higher prevalence of cough and conjunctival congestion. S5398L nsp13-helicase was linked to an increased risk of fever duration and progression. The most common mutations (241, 3037, 14,408, and 23,403) were not linked to clinical variability. However, the E3909G-nsp7 variant was more common in children (2-13 years old) and was associated with a shorter duration of symptoms. The duration of fever was significantly reduced with E1363D-nsp3 and E3073A-nsp4.

Conclusions: The most common mutations, D614G/spike-glycoprotein and P4715L/RNA-dependent-RNA-polymerase, were linked to transmissibility regardless of symptom variability. E3909G-nsp7 could explain why children recover so quickly. Nsp6-L3606fs, spike-glycoprotein-V6fs, and nsp13-S5398L variants may be linked to clinical symptom worsening. These variations related to host-virus interactions might open new therapeutic avenues for symptom relief and disease containment.
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http://dx.doi.org/10.1016/j.bbadis.2021.166154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079944PMC
August 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

DUCHESS: an evaluation of the ductal carcinoma in situ score for decisions on radiotherapy in patients with low/intermediate-risk DCIS.

Breast Cancer Res Treat 2021 Jul 8;188(1):133-139. Epub 2021 Apr 8.

Juravinski Cancer Centre, McMaster University, 699 Concession Street, Hamilton, ON, Canada.

Background: Identification of women with DCIS who have a very low risk of local recurrence risk (LRR) after breast-conserving surgery (BCS) is needed to de-escalate therapy. We evaluated the impact of 10-year LRR estimates after BCS, calculated by the integration of a 12-gene molecular expression assay (Oncotype Breast DCIS Score) and clinicopathological features (CPFs), on its ability to change radiation oncologists' recommendations for RT after BCS for DCIS.

Methods: Prospective cohort study of women with DCIS treated with BCS. Eligibility criteria were as follows: age > 45 years, tumor ≤ 2.5 cm, and margins ≥ 1 mm. Radiation oncologists provided 10-year LRR estimates without RT and recommendation for RT pre- and post-assay. Primary outcome was change in RT recommendation.

Results: 217 patients were evaluable, with mean age = 63 years, mean tumor size = 1.1 cm, and mean DCIS Score = 32; 140 (64%) were in the low-risk (<39), 32 (15%) were in the intermediate-risk (39-54), and 45 (21%) were in the high-risk groups (≥55). The assay led to a change in treatment recommendation in 76 (35.2%) (95%CI 29.1-41.8%) patients. RT recommendations decreased from 79% pre-assay to 50% post-assay (difference = 29%; 95%CI 22-35%) due to a significant increase in the proportion of patients with a predicted low LRR (< 10%) post-assay and recommendations to omit RT for those with a low predicted risk. The assay was associated with improved patient satisfaction and reduced decisional conflict.

Conclusion: The DCIS Score assay combined with CPFs identified more women with an estimated low (<10%) 10-yr LR risk after BCS, leading to a significant decrease in recommendations for RT compared to estimates based on CPFs alone.
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http://dx.doi.org/10.1007/s10549-021-06187-7DOI Listing
July 2021

Predicting response to radiotherapy of intracranial metastases with hyperpolarized [Formula: see text]C MRI.

J Neurooncol 2021 May 19;152(3):551-557. Epub 2021 Mar 19.

Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.

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 [Formula: see text]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 [Formula: see text]C-lactate signal, measured pre-treatment, for prediction of progression of intracranial metastases at six months post-treatment with SRS was 0.8 [Formula: see text], and the AUC from an ROC analysis was 0.77 [Formula: see text]. The distribution of [Formula: see text]C-lactate z-scores was different for intracranial metastases from different primary cancer types (F = 2.46, [Formula: see text]).

Conclusions: Hyperpolarized [Formula: see text]C imaging has potential as a method for improving outcomes for patients with intracranial metastases, by identifying patients at high risk of treatment failure with SRS and considering other therapeutic options such as surgery.
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http://dx.doi.org/10.1007/s11060-021-03725-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084843PMC
May 2021
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