Search

OBJECTIVE With the incorporation of real-time image guidance on the Gamma Knife system allowing for mask-based immobilization (Gamma Knife Icon [GKI]), conventionally fully fractionated (1.8–3.0 Gy/day) GKI radiation can now be delivered to take advantage of an inherently minimal margin for delivery uncertainty, sharp dose falloff, and inhomogeneous dose distribution. This case series details the authors’ preliminary experience in re-irradiating 7 complex primary intracranial tumors, which were considered to have been previously maximally radiated and situated adjacent to critical organs at risk. METHODS The authors retrospectively reviewed all patients who received fractionated re-irradiation using GKI at the Sunnybrook Health Sciences Centre, University of Toronto, Ontario, Canada, between 2016 and 2021. Patients with brain metastases, and those who received radiotherapy courses in 5 or fewer fractions, were excluded. All radiotherapy doses were converted to the equivalent total dose in 2-Gy fractions (EQD2), with the assumption of an α/β ratio of 2 for late normal tissue toxicity and 10 for the tumor. RESULTS A total of 7 patients were included in this case series. Three patients had recurrent meningiomas, as well as 1 patient each with ependymoma, intracranial sarcoma, pituitary macroadenoma, and papillary pineal tumor. Six patients had undergone prior linear accelerator–based conventional fractionated radiotherapy and 1 patient had undergone prior proton therapy. Patients were re-irradiated with a median (range) total dose of 50.4 (30–63.4) Gy delivered in a median (range) of 28 (10–38) fractions with GKI. The median (range) target volume was 6.58 (0.2–46.3) cm3. The median (range) cumulative mean EQD2 administered to the tumor was 121.1 (107.9–181.3) Gy, and the median (range) maximum point EQD2 administered to the brainstem, optic nerves, and optic chiasm were 91.6 (74.0–111.5) Gy, 58.9 (6.3–102.9) Gy, and 59.9 (36.7–127.3) Gy, respectively. At a median (range) follow-up of 15 (6–42) months, 6 of 7 patients were alive with 4 having locally controlled disease. Only 3 patients experienced treatment-related toxicities, which were self-limited. CONCLUSIONS Fractionated radiotherapy using GKI may be a safe and effective method for the re-irradiation of complex progressive primary intracranial tumors, where the aim is to minimize the potential for serious late effects.

To provide a summary of the diagnostic performance ofMEDLINE, EMBASE, and Cochrane Database of Systematic Reviews databases were searched for studies that reported on diagnostic test parameters in radiotherapy planning, response assessment, and tumour recurrence/treatment-related changes differentiation. Radiomic studies were excluded. Quality assessment was performed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool and the GRADE approach. A bivariate, random-effects model was used to produce summary estimates of sensitivity and specificity.Twenty-six studies with a total of 1206 patients/lesions were included in the analysis. For radiotherapy planning of glioma, the pooled proportion of patients from 3 studies withWhile

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.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.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).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.

Gamma Knife Icon-based hypofractionated stereotactic radiosurgery (GKI-HSRS) is a novel technical paradigm in the treatment of brain metastases that allows for both the dosimetric benefits of the GKI stereotactic radiosurgery (SRS) platform as well as the biologic benefits of fractionation. We report mature local control and adverse radiation effect (ARE) outcomes following 5 fraction GKI-HSRS for intact brain metastases.Patients with intact brain metastases treated with 5-fraction GKI-HSRS were retrospectively reviewed. Survival, local control, and adverse radiation effect rates were determined. Univariable and multivariable regression (MVA) were performed on potential predictive factors.Two hundred and ninety-nine metastases in 146 patients were identified. The median clinical follow-up was 10.7 months (range 0.5-47.6). The median total dose and prescription isodose was 27.5 Gy (range, 20-27.5) in 5 daily fractions and 52% (range, 45-93), respectively. The median overall survival (OS) was 12.7 months, and the 1-year local failure rate was 15.2%. MVA identified a total dose of 27.5 Gy vs. ≤ 25 Gy (hazard ratio [HR] 0.59, p = 0.042), and prior chemotherapy exposure (HR 1.99, p = 0.015), as significant predictors of LC. The 1-year ARE rate was 10.8% and the symptomatic ARE rate was 1.8%. MVA identified a gross tumor volume of ≥ 4.5 cc (HR 7.29, p 0.001) as a significant predictor of symptomatic ARE.Moderate total doses in 5 daily fractions of GKI-HSRS were associated with high rates of LC and a low incidence of symptomatic ARE.

Purpose:Vertebroplasty (VP) and balloon kyphoplasty (KP) are minimally invasive stabilization procedures for pathologic vertebral compression fractures (VCF). Concurrent administration of photodynamic therapy (PDT) as a tumor-ablative modality has yet to be studied in humans as a potential complement to improved mechanical stability that is afforded by vertebral cement augmentation (VCA).Patients and Methods:This first-in-human trial used a single 6 mg/m2 dose of the clinical photosensitizer Visudyne with escalating laser light doses. Following a cohort of light-only controls (n = 6), the drug and light treatment groups (n = 6 each) were 50, 100, 150, and 200 J/cm. VCA was performed within 15 minutes following PDT. Patients were clinically reviewed at 1 and 6 weeks. The primary outcome measure was safety from a neurologic perspective.Results:Thirty patients comprising a variety of primary tumors were treated with PDT and either KP or VP. Vertebral PDT was technically feasible and delivered in all study patients. No dose groups showed significant increases in pain as defined by the generic SF-36 as well as disease-specific EORTC-QLQ-BM22 and EORTC-QLQ-C15-PAL questionnaires. The 50 and 100 J/cm groups showed the most significant pain reduction (P < 0.05). Twelve (40%) patients experienced complications during the study including 3 patients with further vertebral fracture progression by 6 weeks despite VCA. No complications were directly attributed to PDT.Conclusions:Using the parameters described, vertebral PDT as an adjunct to VCA is safe from a pharmaceutical and neurologic perspective. The results of this trial motivate scale-up study evaluating potential PDT efficacy in vertebral metastatic treatment.

Table S1 highlights the inclusion/exclusion criteria for the PDT clinical trial in table format.

Figure S1 shows an overview of the PDT fiber set-up and placement for a kyphoplasty case.

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 (pConclusion: Imaging features extracted from the GTV and CTV regions can lead to risk-stratification of GBM undergoing biopsy, while it was redundant for patients with GTR and STR.

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.

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 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.

High radiation doses of stereotactic radiosurgery (SRS) for brain metastases (BM) can increase the likelihood of radiation necrosis (RN). Advanced MRI sequences can improve the differentiation between RN and tumor progression (TP).To use saturation transfer MRI methods including chemical exchange saturation transfer (CEST) and magnetization transfer (MT) to distinguish RN from TP.Prospective cohort study.Seventy patients (median age 60; 73% females) with BM (75 lesions) post-SRS.3-T, CEST imaging using low/high-power (saturation BVoxel-wise metrics included: magnetization transfer ratio (MTR); apparent exchange-dependent relaxation (AREX); MTR asymmetry; normalized MT exchange rate and pool size product; direct water saturation peak width; and the observed Tt-Test, univariable and multivariable logistic regression, receiver operating characteristic, and area under the curve (AUC) with sensitivity/specificity values with the optimal cut point using the Youden index, Akaike information criterion (AIC), Cohen's d. P 0.05 with Bonferroni correction was considered significant.Seven metrics showed significant differences between RN and TP. The high-power MTR showed the highest AUC of 0.88, followed by low-power MTR (AUC = 0.87). The combination of low-power CEST scans improved the separation compared to individual parameters (with an AIC of 70.3 for low-power MTR/AREX). Cohen's d effect size showed that the MTR provided the largest effect sizes among all metrics.Significant differences between RN and TP were observed based on saturation transfer MRI.3 Technical Efficacy: Stage 2.

To provide evidence towards a quantitative response assessment framework incorporating MRI-based linear measurements for spinal metastasis that predicts outcome following stereotactic body radiation therapy (SBRT).Adult patients with de novo spinal metastases treated with SBRT between 2008 and 2018 were retrospectively assessed. The metastatic lesions involving the pedicles, articular processes, lamina, transverse process, spinous process and vertebral body at leach level were measured separately using linear measurements on pre- and all post-SBRT MRIs. The outcome was segment-specific progression (SSP) using SPINO guidelines which was dated to the first clinical documentation of progression, or the date of the associated MRI if imaging was the reason for progression. Random forest analysis for variable selection and recursive partitioning analysis for SSP probability prediction were used.Five Hundred Ninety-three spinal levels (323 patients) from 4081 MRIs were evaluated. The appearance of new T1 hypointensity and increase in Bilsky grade had an odds ratio (OR) of 33.5 and 15.5 for SSP, respectively. Compared to baseline, an increase of 3 mm in any lesion dimension, combined with a 1.67-fold increase in area, had an OR of 4.6 for SSP. The sensitivity, specificity, positive predictive value, negative predictive value, balanced accuracy and area under the curve of the training model were 96.7%, 89.6%, 28.6%, 99.8%, 93.2% and 0.905 and of the test model were 91.3%, 89.3%, 27.1% 99.6%, 90.3% and 0.933, respectively.With further refinement and validation in prospective multicentre studies, MRI-based linear measurements can help predict response assessment in SBRT-treated spinal metastases.

Brain metastases (BM) are perceived as a rare complication of prostate cancer associated with poor outcome. Due to limited published data, we conducted a literature review regarding incidence, clinical characteristics, treatment options, and outcomes of patients with prostate cancer BM. A literature analysis of the PubMed, MEDLINE, and EMBASE databases was performed for full-text published articles on patients diagnosed with BM from prostate cancer. Eligible studies included four or more patients. Twenty-seven publications were selected and analyzed. The sources of published patient cohorts were retrospective chart reviews, administrative healthcare databases, autopsy records, and case series. BM are rare, with an incidence of 1.14% across publications that mainly focus on intraparenchymal metastases. Synchronous visceral metastasis and rare histological prostate cancer subtypes are associated with an increased rate of BM. Many patients do not receive brain metastasis-directed local therapy and the median survival after BM diagnosis is poor, notably in patients with multiple BM, dural-based metastases, or leptomeningeal dissemination. Overall, prostate cancer BM are rare and associated with poor prognosis. Future research is needed to study the impact of novel prostate cancer therapeutics on BM incidence, to identify patients at risk of BM, and to characterize molecular treatment targets.

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.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-TThe 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 TThis 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.

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).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).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 GyT-DM1 exposure post-SRS was associated with a higher risk of RN among patients with HER2 + BrM.

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. 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). 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. A radiomic signature can demarcate areas of microscopic tumors from edema in the PTR of GBM, which correlates with areas of future recurrence.

Background Stereotactic radiosurgery (SRS) is used to manage intracranial metastases in a significant fraction of patients. Local progression after SRS can often only be detected with increased volume of enhancement on serial MRI scans which may lag true progression by weeks or months. Methods Patients with intracranial metastases (N = 11) were scanned using hyperpolarized $$^{13}$$ 13 C MRI prior to treatment with stereotactic radiosurgery (SRS). The status of each lesion was then recorded at six months post-treatment follow-up (or at the time of death). Results The positive predictive value of $$^{13}$$ 13 C-lactate signal, measured pre-treatment, for prediction of progression of intracranial metastases at six months post-treatment with SRS was 0.8 $$p < 0.05$$ p < 0.05 , and the AUC from an ROC analysis was 0.77 $$p < 0.05$$ p < 0.05 . The distribution of $$^{13}$$ 13 C-lactate z-scores was different for intracranial metastases from different primary cancer types (F = 2.46, $$p = 0.1$$ p = 0.1 ). Conclusions Hyperpolarized $$^{13}$$ 13 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.

Background Prediction of early progression in glioblastoma may provide an opportunity to personalize treatment. Simplified intravoxel incoherent motion (IVIM) MRI offers quantitative estimates of diffusion and perfusion metrics. We investigated whether these metrics, during chemoradiation, could predict treatment outcome. Methods 38 patients with newly diagnosed IDH-wildtype glioblastoma undergoing 6-week/30-fraction chemoradiation had standardized post-operative MRIs at baseline (radiation planning), and at the 10th and 20th fractions. Non-overlapping T1-enhancing (T1C) and non-enhancing T2-FLAIR hyperintense regions were independently segmented. Apparent diffusion coefficient (ADCT1C, ADCT2-FLAIR) and perfusion fraction (fT1C, fT2-FLAIR) maps were generated with simplified IVIM modelling. Parameters associated with progression before or after 6.9 months (early vs late progression, respectively), overall survival (OS) and progression-free survival (PFS) were investigated. Results Higher ADCT2-FLAIR at baseline [Odds Ratio (OR) = 1.06, 95% CI 1.01–1.15, p = 0.025], lower fT2-FLAIR at fraction 10 (OR = 2.11, 95% CI 1.04–4.27, p = 0.018), and lack of increase in ADCT2-FLAIR at fraction 20 compared to baseline (OR = 1.12, 95% CI 1.02–1.22, p = 0.02) were associated with early progression. Combining ADCT2-FLAIR at baseline, fT2-FLAIR at fraction 10, ECOG and MGMT promoter methylation status significantly improved AUC to 90.3% compared to a model with only ECOG and MGMT promoter methylation status (p = 0.001). Using multivariable analysis, neither IVIM metrics were associated with OS but higher fT2-FLAIR at fraction 10 (HR = 0.72, 95% CI 0.56–0.95, p = 0.018) was associated with longer PFS. Conclusion ADCT2-FLAIR at baseline, its lack of increase from baseline to fraction 20, or fT2-FLAIR at fraction 10 significantly predicted early progression. fT2-FLAIR at fraction 10 was associated with PFS.

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 (Vrel), and the migration distance (dmigrate; 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 cm3 (range, 1.1–110.5 cm3), 14.7 cm3 (range, 0.9–115.1 cm3), 13.7 cm3 (range, 0.6–174.2 cm3), and 13.0 cm3 (range, 0.9–76.3 cm3), respectively, with corresponding median Vrel of 0.88 at Fx10, 0.77 at Fx20, and 0.71 at P1M relative to Fx0 (P 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.

349 Background: Prostate stereotactic ablative radiotherapy (SABR) for localised prostate cancer is commonly delivered over 5 fractions. Focal boost to the dominant intraprostatic lesion (DIL) seen on multiparametric magnetic resonance imaging (mpMRI) is an approach for dose-escalation in prostate SABR. This is the first report of the outcomes of the 2SMART trial, a phase 2 single-arm study using 2-fraction prostate SABR with DIL boost. Methods: Men with low to intermediate risk prostate cancer were enrolled in the study. Three gold fiducial markers were inserted for image guidance. The clinical target volume (CTV) included the prostate gland, and the planning target volume (PTV) was a 2mm expansion antero-posterior and laterally, and 2.5mm supero-inferiorly. The DIL was contoured on fused mpMRI. The prescribed dose was 26Gy in 2 fractions (EQD2 110Gy, α/β of 1.4) to the CTV, and up to 32Gy in 2 fractions (EQD2 164Gy) to the DIL as long as the dose constraints for the organs at risks were not exceeded. Each fraction was delivered 1 week apart. Daily image guidance with cone-beam computed tomography was used pre- and post-treatment. The primary endpoint was acute (≤3 months) changes in quality of life (QOL), assessed using the EPIC questionnaire. Minimal clinically important change (MCIC) in QOL was defined as an EPIC score decrease of >0.5 standard deviation of the baseline EPIC score for each domain. Secondary endpoints were acute and late toxicities (assessed using CTCAEv4), and biochemical failure (based on Phoenix criteria). Results: 30 men were enrolled in the study, of which 2 (7%) had low risk and 28 (93%) had intermediate risk prostate cancer. The median follow-up was 44 months (range: 39-49 months). The median PSA nadir was 0.2ng/mL, with median time to nadir of 37 months. One patient (3%) had biochemical failure at 44 months post-treatment. 1 (3%) and 17 (57%) had acute Grade 2 GU and GI toxicities, while 3 (10%) and 15 (50%) had late (>6 months) Grade 2 GU and GI toxicities. No acute or late Grade ≥3 GU or GI was reported. 10 (33%), 6 (20%), and 3 (10%) men had acute MCIC in urinary, bowel and sexual domains respectively. 15 (50%), 9 (30%) and 13 (43%) had late MCIC in urinary, bowel and sexual domain respectively. Conclusions: Two-fraction prostate SABR with DIL boost is a safe approach for dose-escalation for localised prostate cancer, with minimal impact on acute QOL, and no grade 3-4 toxicities. Clinical trial information: NCT03588819 .

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. 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). 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

Glioblastoma in the elderly (>65 years of age) is associated with shorter overall survival (OS) than in younger patients. Best practice recommendations for elderly patients, especially those with borderline or poor performance status, remain a subject of debate amongst clinicians despite recent randomized trials. This review provides an updated evidence-based summary to inform the modern management of elderly patients with glioblastoma. Based on evidence from the CE.6 randomized controlled trial, hypofractionated radiation therapy administered over a three-week course (40 Gy in 15 fractions) concomitantly with temozolomide (TMZ) followed by adjuvant TMZ has been found to be superior to radiation therapy alone with mean OS of 9.3 vs. 7.6 months and progression-free survival (PFS) of 5.3 vs. 3.9 months. This regimen should be offered to newly-diagnosed elderly patients with glioblastoma with preserved functional status, and was not associated with a negative impact on health-related quality of life (QOL). Management of elderly patients with glioblastoma can be challenging and requires a patient-centered strategy. Personalized decisions accounting for clinical, psychosocial, molecular and treatment factors are critical for realistic decision making. The importance of discussing goals-of-care with patients and their caregivers early in the disease trajectory, and establishing capacity for decision-making and advanced care planning, is also reviewed.

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., Graphical Abstract Graphical Abstract

Active surveillance for prostate cancer relies on regular prostate specific antigen tests and surveillance biopsies. Compliance rates with biopsies vary but the subsequent impact on oncologic outcomes is not known. The objective of this study was to determine whether noncompliance with the confirmatory biopsy negatively impacts prostate cancer specific outcomes.A retrospective analysis was performed on a prospective single-arm cohort of men enrolled in active surveillance for prostate cancer between 1995 and 2018 with a median followup of 9.1 years. A total of 1,275 patients were enrolled and 1,043 had a minimum of 3 years of followup and were included in the analysis. Patients were stratified by compliance with a confirmatory biopsy within 24 months of enrollment in active surveillance. The primary outcome was recurrence-free survival. Secondary outcomes included metastatic-free survival and cause specific survival.A total of 1,275 patients were enrolled, and 1,043 had a minimum of 3 years of followup and were included in the analysis, of whom 425 were treated for localized prostate cancer. Patients noncompliant with the confirmatory biopsy had higher rates of recurrence after treatment (19% vs 12%, HR 1.64, 95% CI 1.19-2.26, p=0.003) and metastases (7% vs 2%, HR 3.56, 95% CI 1.8-7.0, p=0.0003) even after accounting for age, prostate specific antigen and Grade Group. Cause specific survival was not significantly different between the 2 groups. The results were consistent even in the subset of patients with Grade Group 1 disease at study entry.Noncompliance with a confirmatory biopsy compromises the control of prostate cancer in men followed on active surveillance. Patients and physicians should be aware of the importance of adhering to protocol for men on active surveillance.

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).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.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.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.

Stereotactic body radiotherapy (SBRT) for spine metastases improves pain response rates compared to conventional external beam radiotherapy, however, the optimal fractionation schedule is unclear. We report local control and toxicity outcomes after dose-escalated two-fraction spine SBRT.A prospectively maintained institutional database of over 600 patients and 1400 vertebral segments treated with spine SBRT was reviewed to identify those prescribed 28 Gy or 24 Gy in two daily fractions. The primary endpoint was MRI-based local failure (LF), and secondary endpoints included overall survival (OS) and vertebral compression fracture (VCF).A total of 947 treated vertebral segments in 482 patients were identified, of which 301 segments in 159 patients received 28 Gy, and 646 segments in 323 patients received 24 Gy, in 2 fractions. Median follow-up per patient was 23.5 months and median OS was 49.1 months. In the 28 Gy cohort, the 6-, 12-, and 24-month cumulative incidences of LF were 3.5%, 5.4% and 11.1%, respectively, vs. 6.0%, 12.5% and 17.6% in the 24 Gy cohort, respectively (p=0.008). On multivariable analysis, 24 Gy (HR:1.525, 95%CI: 1.039-2.238, p=0.031), paraspinal disease extension (HR:1.422, 95%CI: 1.010-2.002, p=0.044), and epidural extension in either radioresistant or radiosensitive histologies (HR 2.117 and 1.227, respectively, p=0.003) were prognostic for higher rates of LF. Risk of VCF was 5.5%, 7.6% and 10.7% at 6-, 12- and 24-months, respectively, and similar between cohorts (p=0.573). Spinal malalignment (p0.001), baseline VCF (p=0.003), junctional spine location (p=0.030), and greater PTV_D90 (minimum dose to 90% of planning target volume) were prognostic for higher rates of VCF.Dose escalation to 28 Gy in 2 daily fractions was associated with improved local control without increasing the risk of VCF. The 2-year local control rates are consistent with those predicted by the HYTEC spine tumour control probability model and these data will inform a proposed dose escalation randomized trial.

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.

Magnetic Resonance Imaging (MRI)-Linear Accelerator (MR-Linac) radiotherapy is an innovative technology that requires special consideration for secondary electron interactions within the magnetic field, which can alter dose deposition at air-tissue interfaces. Thirty-seven consecutive glioma patients had treatment planning completed and approved prior to radiotherapy initiation using commercial treatment planning systems (TPS): a Monte Carlo-based or convolution-based TPS for MR-Linac or Cone Beam CT (CBCT)-guided Linac, respectively. In vivo skin dose was measured using an Optically Stimulated Luminescent Dosimeter (OSLD) and correlated with TPS skin dose. We found that Monte Carlo-based MR-Linac plans and convolution-based CBCT-Linac plans had similar dosimetric parameters for target volumes and organs-at-risk. However, MR-Linac plans had 1.52 Gy higher mean dose to air cavities (p