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Reports of stereotactic arrhythmia radioablation (STAR) in patients with refractory ventricular tachycardia after catheter ablation are limited to small series. Here, we carried out a systematic review and meta-analysis of studies to better determine the efficacy and toxicity of STAR for ventricular tachycardia. Following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) and the Meta-analyses Of Observational Studies in Epidemiology (MOOSE) guidelines, eligible studies were identified on Medline, Embase, Cochrane Library and the proceedings of annual meetings to 10 February 2023. Efficacy was defined as a ventricular tachycardia burden reduction >70% at 6 months; safety was defined as <10% of any grade ≥3 toxicity. Seven observational studies with a total of 61 patients treated were included. At 6 months, the ventricular tachycardia burden reduction was 92% (95% confidence interval 85–100%) and use of fewer than two anti-arrhythmic drugs was seen in 85% (95% confidence interval 50–100). Six months after STAR, an 86% reduction (95% confidence interval 80–93) in the number of implantable cardioverter-defibrillator shocks was observed. The rates for improved, unchanged and decreased cardiac ejection fraction were 10%, 84% and 6%, respectively. Overall survival at 6 and 12 months was 89% (95% confidence interval 81–97) and 82% (95% confidence interval 65–98). The cardiac-specific survival at 6 months was 87%. Late grade 3 toxicity occurred in 2% (95% confidence interval 0–5%) with no grade 4–5 toxicity. STAR demonstrated both satisfactory efficacy and safety for the management of refractory ventricular tachycardia and was also associated with a significant decline in anti-arrhythmic drugs consumption. These findings support the continued development of STAR as a treatment option. • Six months after STAR, the ventricular tachycardia burden reduction was 92%. • The use of <2 AAD was observed in 85% of the patients. • There was no report of grade 4–5 toxicity after STAR. [ABSTRACT FROM AUTHOR]

Ultrahypofractionated or stereotactic body radiotherapy (SBRT) is an established treatment option in intact prostate cancer, however, limited data exists on outcomes in the post-prostatectomy patient. We report toxicity and health-related quality of life (HRQOL) outcomes with SBRT in the post-prostatectomy setting in a single institutional prospective trial. Post-prostatectomy men with histologically confirmed prostate adenocarcinoma were eligible if they had pathologic stage T3/T4, NX-0, M0 disease without gross residual, and/or a rising serum prostate specific-antigen (PSA) on at least 2 consecutive measurements. Treatment consisted of 30 Gy to the prostate bed, with optional elective nodal irradiation (ENI) to a dose of 25 Gy in 5 weekly fractions. Up to 24 months of androgen deprivation therapy (ADT) was permitted with SBRT. The primary endpoint was acute (≤ 3 months) genitourinary (GU) and gastrointestinal (GI) toxicities based on CTCAE v5.0. Secondary endpoints included late (≥ 6 months) GU and GI toxicities, as well as acute and late HRQOL assessed using the Expanded Prostate Cancer Index Composite (EPIC) questionnaire. Mild, moderate, and severe minimal clinically important change (MCIC) in HRQOL was defined as an EPIC score decrease of > 0.5, > 1.0, and > 2.0 standard deviation, respectively, from the baseline for each domain. Thirty patients (median age 64) were enrolled between November 2019 and March 2021. Median follow-up was 37.7 months (range, 35.0 – 42.6 months). Median PSA prior to radiation was 0.20 (IQR 0.10 – 0.38). Only 1 patient was treated adjuvantly and the remainder was treated with salvage intent. Thirteen (43.3%), 7 (23.3%), and 10 (33.3%) patients had pT2, pT3a, and pT3b disease, respectively, where 14 (46.7%) had a positive margin. Sixteen (53.3%), 8 (26.7%), 4 (13.3%), and 2 (6.7%) patients had ISUP Grade Group 2, 3, 4, and 5 disease, respectively. A total of 12 (40.0%) patients received ADT for a median duration of 6.5 months (range, 2.9 – 24.4 months) and 16 (53.3%) received ENI. There were no grade ≥ 3 acute toxicities. The cumulative incidence of worst acute grade 2 GU & GI toxicities were 3.3% and 30.0%, respectively. Four late grade 3 toxicities were observed (1 urinary incontinence, 3 erectile dysfunction). Eight (26.7%), 16 (53.3%), and 3 (10.0%) patients reported acute moderate/severe MCIC in urinary, bowel, and sexual domains, respectively, while 2 (6.7%), 3 (10.0%), and 3 (10.0%) patients reported late moderate/severe MCIC in urinary, bowel, and sexual domains, respectively. Post-prostatectomy SBRT to the prostate bed, with or without ENI, is well tolerated with no grade ≥ 3 acute toxicities and minimal impact on late HRQOL. Further follow-up is warranted to better evaluate long-term toxicity and biochemical disease-free survival. [ABSTRACT FROM AUTHOR]

The relationship between spine SBRT outcomes and the extent of malignant epidural disease (MED) compression of the cauda equina has yet to be reported. Our objective was to determine clinical, anatomic and dosimetric predictive factors for local failure (LF) and overall survival (OS) in a cohort of patients with spine metastases and epidural disease at the level of the cauda equina. Consecutive patients with cauda equina MED treated with SBRT, between January 1, 2008 and July 1, 2023, were identified and retrospectively reviewed from a prospectively maintained institutional database. MED parameters including linear dimensions, surface area, and volume ratios relative to the spinal canal, lumbar stenosis grading systems, clock position and various dosimetric factors were analyzed for their predictive value for LF post-SBRT and OS. Covariates with a P value ≤ 0.20 on univariate analysis were selected for multivariable analysis (MVA), and those statistically significant (P <0.05) were included in the final model. Ninety-five individual spinal segments (79 patients) with cauda equina MED were identified, of which 69 (73%) were intact and 26 (27%) post-op. Forty-one (43.2%) received 24 Gy in 2 fractions (fr), 27 (28.4%) received 30 Gy in 4 fr, 22 (23.2%) received 28 Gy in 2 fr and 5 (5.2%) received 30 Gy in 5 fr. Median follow-up and median time to LF were 16.3 (IQR 6.7-32.0) months and 4.7 (IQR 2.2-12.1) months, respectively. The cumulative incidence of LF at 6, 12, and 24 months was 12.7%, 12.7% and 17.4% respectively. OS at 6, 12, and 24 months was 79.6%, 58.4% and 40.7% respectively. In the intact cohort only (69/95), factors predictive of a higher risk of LF on MVA were chemotherapy naive (HR = 8.197, 95% CI = 2.198-30.303, P = 0.0017), MED greater than one third of the circumference of the spinal canal (HR = 9.632, 95% CI = 1.863-49.806, P = 0.0069), and lower V50Gy Equivalent Dose in 2Gy Fractions (EQD2) to the MED volume (HR = 1.049, 95% CI = 1.018-1.081, P = 0.0014). These factors retained significance on MVA for LF when combined with the post-op (26/95) cohort (P = 0.0047, 0.0272, 0.0024, respectively). In the intact cohort only, MVA identified oligometastatic disease (HR = 0.381, 95% CI = 0.190-0.764, P = 0.0065) and MED limited to a single spinal level (HR = 0.405, 95% CI = 0.182-0.902, P = 0.0269) as prognostic for OS. Oligometastatic disease and MED limited to a single spinal level also retained significance as predictors for OS on MVA when combined with the post-op (26/95) cohort (P <0.0001, 0.0182, respectively). We identified chemotherapy naive, MED encompassing more than one third of the circumference of the spinal canal, and lower V50Gy EQD2 to the epidural disease volume, as novel predictive factors for higher LF post-SBRT for MED at the cauda equina. Consideration for more aggressive management with decompressive surgery in those with MED spanning greater than a third of the spinal canal circumference and dose escalation to the thecal sac organ-at-risk may improve outcomes. [ABSTRACT FROM AUTHOR]

The most common complication following spine stereotactic body radiotherapy (SBRT) is vertebral compression fracture (VCF). The purpose of this analyses was to determine if predictors of VCF vary according to presence or absence of a pre-existing (baseline) VCF. A retrospective review of a prospectively maintained institutional database of patients treated with SBRT for spinal metastases performed. The primary outcome was VCF. Clinical, dosimetric and radiographic factors were reported with descriptive statistics. The cumulative incidence of VCF was estimated using a competing risk analysis method. The impact of covariates was estimated with Cox proportional hazards model and hazard ratios (HR) generated. From 2008 – 2022, 744 patients with 1813 spinal segments were treated with spine SBRT. The median age was 64.9 years, and 19.1% had a baseline VCF. The majority of segments were treated with 24Gy (42.8%) or 28Gy (27.4%) in 2 fractions, the median dose-per fraction was 12Gy (range = 5-24), 68% were de novo (no prior radiation exposure) and 235 (13.0%) had prior surgical stabilization. 254 VCF event were observed (14%), 179 were iatrogenic and 75 associated with concurrent tumor progression. The 1-, 2- and 5-year VCF rates were 8.3%, 12%, and 15.2%, respectively. 85/254 (33.5%) occurred in those with a baseline VCF and 169/254 (66.5%) in those without. On multivariable analysis (MVA), tumor progression (HR = 2.24, 95% CI = 1.66-3.04, P <0.01), baseline VCF (HR = 1.91, 95% CI = 1.35-2.71, P <0.01), mechanical pain (HR = 2.01, 1.31-3.08, P <0.01), increasing age (HR = 1.015, 95% CI = 1.002-1.03, P <0.02), fewer consecutive segments treated (HR = 0.80, 95% CI = 0.65-0.98, P <0.03), increasing dose to 90% (D90) of the clinical target volume (CTV) as equivalent dose in 2-Gy fractions (EQD2) (CTV D90 EQD2, HR = 1.007, 95% CI = 1.002-1.01, P <0.02) predicted for VCF. Predictors common to segments treated with or without a baseline VCF included concurrent tumor progression and an increasing CTVD90 EQD2. No prior stabilization surgery, involvement of the posterior elements, fewer consecutive segments treated were unique to the baseline VCF cohort, while histology, mechanical pain and higher dose per fraction were unique predictors in the no prior VCF cohort. We report predictive factors for VCF following spine SBRT and observe distinct risk factors according to presence or absence of a baseline VCF that can guide treatment decisions. [ABSTRACT FROM AUTHOR]

Diffusion-weighted imaging (DWI) enables in vivo diffusivity measurement through the ADC. Aggressive hypercellular tumors exhibit restricted water diffusion and low-ADC values. We hypothesized that areas of glioblastoma that have a high likelihood of recurrence would exhibit smaller ADC change during concurrent CRT than those areas responsive to treatment. Our study aims to compare ADC changes within the areas of the gross tumor volume (GTV) that developed recurrence versus those that remained recurrence-free. We reviewed a prospectively collected cohort of patients with glioblastoma imaged between Dec 2017 and Apr 2021 with DWI at planning (Fx0), fraction 10 (Fx10), fraction 20 (Fx20), and 1 month after a standard 6-week course of concurrent CRT (P1M). The GTV was contoured at all time points and included the surgical cavity and any residual enhancing tumor. The contrast-enhancing recurrence was contoured at the first magnetic resonance imaging (MR) timepoint showing progression per RANO 2.0 criteria. The intersection of the GTV and the recurrence volume was labelled resistant-GTV (R-GTV), while the GTV that did not intersect with the recurrence was labelled sensitive-GTV (S-GTV). Patients who did not experience failure within the GTV and had a minimum follow-up of 36 months were included in the analysis, and the entire GTV was labelled S-GTV. The interior of the surgical cavity was contoured at each time point and excluded from measurement of ADC values to avoid bias. Absolute ADC values and ADC changes (%) at each time point relative to Fx0 were compared between R-GTV and S-GTV using one-sided Wilcoxon rank-sum tests. Temporal changes were assessed using a linear mixed-effects model (fixed effects: region, time; random effects: subject). A total of 51 patients were included (median age 56y, range 20-69). The median absolute ADC values for R-GTV and S-GTV were 0.91 (IQR = 0.84-1.08) vs 0.94 (IQR = 0.87-1.10) at Fx0 (P = 0.358), 1.02 (IQR = 0.88-1.18) vs 1.17 (IQR = 0.96-1.35) at Fx10 (P = 0.011), 1.09 (IQR = 0.95-1.22) vs 1.16 (IQR = 1.00-1.44) at Fx20 (P = 0.058), and 1.19 (IQR = 1.07-1.33) vs 1.37 (IQR = 1.17-1.52) at P1M (P = 0.008), respectively. The median relative ADC change for R-GTV and S-GTV was 0.9% (IQR = -2.3-20.4) vs 15.3% (IQR = 7.5-28.5) at Fx10 (P = 0.006), 11.2% (IQR = 2.7-27.4) vs 23.1% (IQR = 11.8-27.8) at Fx20 (P = 0.048), and 22.5% (IQR = 10.1-39.0) vs 33.3% (IQR = 21.1-50.2) at P1M (P = 0.034), respectively. The linear mixed-effects model revealed a significant difference in relative ADC changes between R-GTV and S-GTV (P <0.001). Early ADC change during CRT is an imaging biomarker for treatment response and recurrence prediction in glioblastoma. Regions exhibiting smaller ADC changes during CRT indicate potential sites of recurrence, suggesting utility for MR-guided biologically adapted radiation clinical trials. [ABSTRACT FROM AUTHOR]

The most common complication following spine stereotactic body radiotherapy (SBRT) is vertebral compression fracture (VCF). Iatrogenic VCF has been widely reported, but it has not yet been reported in the context of tumor progression. We hypothesized that predictors of VCF vary with cause, whether iatrogenic or in conjunction with local failure. A prospectively maintained institutional database of patients treated with SBRT for spinal metastases was retrospectively reviewed. The primary outcome was VCF, with or without local failure. Clinical, dosimetric and radiographic factors were reported with descriptive statistics. The cumulative incidence of iatrogenic VCF and VCF with tumor progression was estimated using a competing risk analysis method. The impact of covariates was estimated with Cox proportional hazards model and hazard ratios (HR) generated. From 2008 – 2022, 744 patients with 1813 spinal segments were treated with spine SBRT. The median age was 64.9 years and median follow up was 19.9 months. Of the 254 VCF events (14%), 179 (70.5%) were iatrogenic and 75 (29.5%) associated with concurrent tumor progression. Median time to iatrogenic VCF was 10.1 months and 9.0 months in those with tumor progression. The majority of segments that had an iatrogenic VCF or with tumor progression were treated with 24Gy in 2 fractions (41.8% and 41.3%, respectively) and the median dose per fraction was 12Gy in both (range = 5-24). The 1- and 2-year iatrogenic VCF rates were 6.8% and 9.9%, respectively, and 15.6% and 22.0% in those concurrent with tumor progression, respectively. On multivariable analysis (MVA), spinal level and increasing dose to 90% (D90) of the clinical target volume (CTV) as equivalent dose in 2-Gy fractions (EQD2) were the only predictors common to both iatrogenic VCF and those secondary to tumor progression. Risk factors that uniquely increased the risk of iatrogenic VCF were presence of a baseline VCF (HR = 1.85, 95% CI = 1.25-2.74, P = 0.002), increasing consecutive segments treated (HR = 0.76, 95% CI = 0.64-0.90, P <0.01), and older age (HR = 1.02, 95% CI = 1.002-1.03, P = 0.03). Meanwhile, epidural disease (HR = 2.84, 95% CI = 1.68-4.79, P <0.001), mechanical pain (HR = 3.33, 95% CI = 1.53-7.25, P <0.01) and fewer SBRT fractions (HR = 0.65, 95% CI = 0.45-0.93, P <0.02) were predictive of VCF in those concurrent with tumor recurrence. This first report of predictive factors for VCF following spine SBRT, according to an iatrogenic cause or concurrent with tumor progression, may improve clinical decision making in VCF management. [ABSTRACT FROM AUTHOR]

We report outcomes after spine stereotactic body radiotherapy (SBRT) in patients with metastatic non-small cell lung cancer (NSCLC), to determine the significance of programmed death-ligand 1 (PD-L1) status and epidermal growth factor (EGFR) mutation on local failure (LF) rate. A total of 165 patients and 389 spinal segments were retrospectively reviewed from 2009 to 2021. Baseline patient characteristics, treatment and outcomes were abstracted. Primary endpoint was LF and secondary outcomes included overall survival (OS) and vertebral compression fracture (VCF) rates. OS was estimated using the Kaplan-Meier method. Cumulative LF and VCF rates were calculated using competing risk analysis method. Multivariable analysis (MVA) evaluated factors predictive of LF and VCF. Median follow-up was 13 months (range, 0.5-95 months). Median OS was 18.4 months (95% CI 11.4-24.6). Median age was 67 years (range, 28.2-89.9). 52% were female, 76% had an adenocarcinoma histology and 61% had a smoking history. 49/165 (29%) had an EGFR mutation. PD-L1 status was analyzed in 109/165 (66%) patients with 16% PD-L1 ≥ 50%, 20% PD-L1 1-49% and 35% PD-L1 <1%. Of 389 segments, 79% were de novo and 21% were previously radiated. At baseline, 35% had a VCF, 27% had epidural disease, 27% had paraspinal extension, and 49% were Spinal Instability in Neoplasia Score (SINS) stable. 239/389 (61%) were treated with either 24 or 28 Gy in 2 SBRT fractions. Within 1 month of SBRT, 39/165 (24%) had a tyrosine kinase inhibitor, 27/165 (16%) immunotherapy (IO) with or without chemotherapy, and 31/165 (19%) chemotherapy alone. LF cumulative incidence at 1- and 2-years was 16.3% (95% CI 12.8-20.3%) and 25.4% (95% CI 20.9%-30%), respectively. EGFR positivity (p<0.0001), PD-L1≥50% (p = 0.013) and treatment with IO within 1 month of SBRT (p = 0.004) predicted for improved local control on MVA. The 1- and 2-year LF rate in EGFR-positive vs. negative patients were 12.9% vs. 16.6% and 17.7% vs. 28.8%, respectively, and in those PD-L1 ≥50% vs PD-L1<50% were 7.8% vs. 19.6% and 7.8% vs. 38.1% respectively. Cumulative incidence of VCF at 1- and 2-years were 6.6% (95% CI 4.4-9.4%) and 8.8% (95% CI 6.1-12.0%). MVA identified prior SBRT to the same treated segment (P<0.0001) and a baseline VCF (p<0.0001) as significant predictors. 18/389 (4.6%) had radiation-induced radiculopathy and no radiation myelopathy events detected. We identify the predictive utility of EGFR mutation and PD-L1 ≥50% status on local control in NSCLC patients with spinal metastases treated with spine SBRT, and a therapeutic benefit with peri-SBRT IO. [ABSTRACT FROM AUTHOR]

We report outcomes specific to a novel 3 fraction (frx) staged stereotactic radiosurgery (St-SRS) regimen designed to salvage metastases previously irradiated and considered to be at high risk of radiation necrosis (RN). A total of 24 patients with 55 metastases treated with our 3 frx St-SRS approach were reviewed. Prior to each frx, patients were re-simulated and planned with a new MRI to allow for treatment adaption. The primary endpoint was the cumulative incidence of local failure (LF) and secondary endpoints included tumor dynamics and RN rates. The median follow up was 9.0 months (range: 2.7-40.1 months) and median age was 59-years (range: 32-84). Primary cancers were of breast (44%), lung (33%), melanoma (22%), and gastro-intestinal (1%) origin. Individual metastases treated with St-SRS had initially failed surgery and post-op cavity hypofractionated SRS (HSRS) for 2/55 (4%), SRS alone for 19/55 (34%), whole brain radiation (WBRT) alone for 6/55 (11%), HSRS for 2/55 (4%), and prior SRS and WBRT exposure for 28/55 (51%). 46/55 (84%) were prescribed 8 Gy, 8 Gy, 4 Gy; 8/55 (14%) had 6 Gy, 6 Gy, 4 Gy and 1/55 (2%) had 8 Gy, 8 Gy, 6 Gy. The median number of weeks between frx was 2.6 (range: 1.0-6.8). The median of the mean and maximum target doses were 9.7 Gy (range: 5.4-11.7 Gy) and 12.4 Gy (range, 7.5-16.0 Gy) respectively. The median prescription isodose line was 62% (range: 50-85%). The mean lesion volume and diameter was 3.8cc (range: 0.05-24.8cc) and 1.6cm (range: 0.2-4.4cm), respectively. The mean percent target volume coverage, Paddick Conformality Index and Gradient Index were 100% (range: 97-100%), 0.7 (range: 0.1-0.9), and 3.2 (range: 2.5-6.7), respectively. The mean volume change between staged frxs was -4.2% (range: -69.3 to +63.1%), and based on the first and last St-SRS MRI was -10.8% (range: -86.6% to +68.7%). The crude LF rate was 27%. The median time to LF was 3.4 months (range: 1.2-7.4 months). Amongst those with a LF, 7/15 (46%) were melanoma, 6/15 (40%) HER2 positive breast cancer, 1/15 (7%) gastrointestinal and 1/15 (7%) non-small cell lung carcinoma. 8/15 (53%) had prior WBRT and SRS exposure, 1/16 (7%) surgery and cavity HSRS, 5/15 (33%) SRS alone and 1/15 (7%) WBRT alone. Only asymptomatic RN events were observed in 4/55 (7%). St-SRS is a promising approach to salvage previously irradiated brain metastases, including prior SRS, with a favorable rate of RN. Tumor volume dynamics between stages can be significant warranting adaptive replanning. [ABSTRACT FROM AUTHOR]

Our prior imaging studies have shown geometrically meaningful inter-fraction tumor dynamics specific to glioblastoma (GBM). We aim to identify predictors associated with tumor dynamics during a 6-week course of concurrent chemoradiotherapy (CRT) for GBM. Patients enrolled in a prospective serial magnetic resonance imaging (MRI) study were reviewed. All patients were treated with 54-60 Gy in 30 fractions. The gross tumor volume (GTV) included the surgical cavity and T1c enhanced residual tumor; clinical tumor volume (CTV) included GTV with a 15mm isotropic expansion, respecting anatomical boundaries; planning target volume (PTV) was 4mm expansion. MRIs were obtained at RT planning (F0), fraction 10 (F10), and fraction 20 (F20). Tumor dynamic metrics (relative to F0) assessed included the GTV volume (Vrel), Hausdorff distance (dH) and migration distance (dM). dH is the average distance between two datasets in metric space. dM is the maximum linear displacement of the GTV in any direction. Factors to be determined associated with tumor dynamics included: age, sex, corpus callosum (CC) involvement, extent of surgery (gross total resection (GTR), subtotal resection (STR) or biopsy alone (Bx)), MGMT methylation and IDH mutation status. A total of 129 patients were reviewed. Median GTV was 20.9cc at F0, 17.6cc at F10 (Vrel 0.85), and 16.1cc at F20 (Vrel 0.78). Patients without CC involvement had more marked GTV volume reduction: Vrel 0.82 vs 1.02 with CC involvement at F10 (P = 0.05), and Vrel 0.77 vs 0.88 with CC involvement at F20 (P = 0.03). Patients with GTR (vs STR vs Bx) had more marked GTV volume reduction across all time points: Vrel 0.78, 0.85 and 1.07 respectively at F10 (P = 0.001), and Vrel 0.69, 0.80, 1.04 respectively at F20 (P = 0.001). The median dH was 8.1mm at F10 and 9.2mm at F20. Patients with CC involvement (vs without CC involvement) had a larger dH: 54% vs 25% had dH>10mm respectively at F10 (P = 0.03), and 73% vs 28% had dH>10mm respectively at F20 (P<0.005). Patients with a GTR had smaller dH at both F10 (P = 0.02) and F20 (P = 0.006). At F20, 20%, 47% and 37% of patients with GTR, STR and Bx had dH>10mm (P = 0.04). The median dM were 4.7mm at F10 and 4.7mm at F20. Patients with CC involvement (vs without CC involvement) had larger dM: 41% vs 12% had dM >10mm respectively at F10 (P = 0.01), and 45% vs 9% had dM >10mm respectively at F20 (P<0.001). Patients with GTR had smaller dM at F10 (P = 0.03) and F20 (P0.002). At F20, 0%, 25% and 19% of patients with GTR, STR and Bx had dM>10mm (P = 0.002). Age, sex, MGMT methylation and IDH mutation status were not associated with Vrel, dH and dM at F10 and F20. We identified CC involvement and extent of surgery to be associated with tumor dynamics at F10 and F20 over the course of CRT for GBM. This offers opportunities to better select patients who may benefit from earlier/ more frequent RT replan/ adaptation to ensure adequate tumor coverage, or to reduce RT toxicities. [ABSTRACT FROM AUTHOR]

To analyze the predictors of survival and radiation necrosis in adult patients (pts) with recurrent high-grade gliomas (rHGG) who have undergone re-irradiation (ReRT). All adult pts with rHGG who had ReRT from 2009 to 2020 at one institution were retrospectively reviewed. Demographic, clinical, dosimetric, and radiological data were obtained from the electronic medical records. The primary outcome was to identify predictors of overall survival (OS) and radiation necrosis (RN). The secondary outcome was to identify patterns of failure after ReRT, which was defined as in-field, marginal or distant if >95% of the recurrence volume was in the 80% isodose line (IDL), between 80%-20% IDL, or outside 20% IDL, respectively. OS, progression-free survival (PFS), and RN were estimated by the Kaplan-Meier method. Toxicity was recorded according to CTCAE V5.0. Were included 79 pts with a median age of 52 yrs (range, 19-79), 62% were male, 85% had grade 4 glioma at presentation and 98% at ReRT. IDH was wildtype/mutated/unknown in 73%/11%/15% of pts. 92% had concurrent/adjuvant temozolamide at the primary treatment. 34% had re-resection prior to ReRT. 16% had concurrent bevacizumab at ReRT. The most common fractionation schedules at the primary treatment were 40 Gy/15Fx (9%) and 50-60 Gy/28-33Fx (91%), and at ReRT were 17-24 Gy/1Fx (9%), 20-35 Gy/5Fx (38%), 25-35 Gy/10Fx (48%) and 36-54 Gy/18-30Fx (5%). The median cumulative equivalent dose in 2 Gy fractions (EQD2, a/b=2) was 103 Gy (range, 81-216). The median OS and PFS were 9.9 (95% CI 8.3-11.6) and 4.1 mos (95% CI 3.6-5.4), respectively. The OS and PFS rate at 6/12 months were 69.6%/34.2% and 29.1%/7.5%, respectively. The prognostic factors for OS on multivariate analyses (MVA) were interval from initial treatment to first progression ≥16.3mos (HR=0.35, 95% CI 0.20-0.59, p<0.001), re-resection prior ReRT (HR=0.43, 95% CI 0.25-0.73, p=0.002), ECOG ≥1 at ReRT (HR=1.90, 95% CI 1.10-3.30, p=0.022) and PTV volume at ReRT ≥112cc (HR=2.63, 95% CI 1.55-4.44, p≤0.001). Toxicities G2 and G3 were 22% (8.8% RN) and 5% (2.5% RN), respectively. Concurrent use of bevacizumab (p<0.001) and EQD2 ≤98 Gy (p<0.001) were predictors for lower incidence of RN on MVA. Exploratory analysis suggested three risk groups for RNs based on cumulative EQD2: ≤100 Gy (RN = 4%), 100-111 Gy (RN = 13%), and ≥111 Gy (RN = 20%). The failures after ReRT were in-field, marginal or distant in 67%, 6%, and 27% of pts who had follow-up MRI, respectively. Re-irradiation is a safe and effective treatment for GBM. We describe predictive factors for OS and RN to guide patient section. Focus on pts with the most favorable OS may aid in identifying pts most likely to benefit from ReRT. [ABSTRACT FROM AUTHOR]

Frameless, gated, image-guided, Cobalt60-based hypofractionated stereotactic radiosurgery (Co60-HSRS) is a novel technical paradigm in the treatment of brain metastases that allows for both the dosimetric benefits of the Co60 based stereotactic radiosurgery (SRS) platform as well as the biologic benefits of fractionation. We report mature local control (LC) and adverse radiation effects (ARE) outcomes following 5 fraction Co60-HSRS for intact brain metastases. All patients with intact brain metastases treated with 5-fraction Co60-HSRS between 2017-2020 were retrospectively reviewed. Patients were typically selected for HSRS as opposed to single fraction SRS if the metastases were larger (>2cm diameter), were in eloquent areas, or were in proximity to another lesion receiving HSRS. Survival estimates were determined per patient using Kaplan Meier methods, and LC as well as symptomatic ARE rates were determined per lesion using competing risk methods. Univariable competing risk regression using Fine and Gray's methods were performed, and subsequent multivariable (MVA) regression using a backwards step-wise selection technique generated the final adjusted models. In total 299 metastases in 146 patients were identified. The median clinical and radiologic follow-up was 10.6 (range 0.5-49.9) and 10.7 months (range 0.5-47.6), respectively. The median maximum tumor diameter and volume were 1.7 cm (range, 0.2-3.9 cm) and 2.38 cc (range, 0.004-24.92 cc), respectively. The median total dose and prescription isodose was 27.5 Gy (range, 20-27.5 Gy) in 5 daily fractions and 52% (range, 45%-93%), respectively. The median overall survival (OS) was 12.7 months and the 1-year LC rate was 85%. 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 ≥4.5cc (HR 7.29, p < 0.001) and a mean intra-tumoral dose of ≥39 Gy (HR 3.17, p = 0.034) as significant predictors of symptomatic ARE. Moderate total doses in 5 daily fractions of Co60-HSRS were associated with high rates of LC and a low incidence of symptomatic ARE. A prescription dose of 27.5 Gy was superior with respect to local control versus ≤25 Gy in 5 daily fractions. Target volumes of 4.5cc or larger as well as mean dose >39 Gy, were associated with higher rates of symptomatic necrosis. Further study will help refine the optimal dosimetric constraints for Co60-HSRS. [ABSTRACT FROM AUTHOR]

Adaptive MRI-guided radiotherapy (RT) on a 1.5T MR-Linac using a reduced clinical target volume (CTV) of 5mm instead of the 15mm standard for glioblastoma (GBM) is currently being evaluated on the UNITED clinical trial (NCT04726397). We present a preliminary comparison of morphological changes during a course of adaptive RT with concurrent temozolomide between tumors with MGMT promotor methylation (MGMT-m) and those that are MGMT promoter unmethylated (MGMT-um). The first 30 patients with GBM (all IDH wildtype) enrolled on the UNITED trial were analyzed. RT consisted of 60 Gy in 30 fractions (n=12) or 40 Gy in 15 fractions (n=18) (Fx). Expansions on the gross tumor volume (GTV) consisted of a 5 mm CTV with the provision to include FLAIR hyperintense areas at-risk and a 3 mm planning target volume (PTV). A pre-treatment reference plan was developed from a standard planning MRI (FxRef) followed by weekly on-line fully adaptive re-planning at Fx1, Fx6, Fx11, etc., based on a gadolinium contrast-enhanced MRI acquired on the MR-Linac. Remaining fractions were image-guided by pre-beam-on onboard non-contrast MRI, to ensure stability of the treatment volumes. The GTV and CTV were quantified by their absolute volumes, volumes relative to the FxRef and the maximum linear distance from the edges of the reference contour at FxRef to the weekly adapted contours (migration distance, d mig). MGMT promoter methylation status was explored as a fixed effect in a linear mixed statistical model. The median changes in GTV relative to FxRef at Fx1, Fx6, Fx11, Fx16, Fx21, and Fx25 in MGMT-um tumors (n=12) were 10.3%, 9.2%, 10.6%, 14.5%, 18.0% and 17.3%, respectively, while for MGMT-m (n=18) were 3.4%, 0.0%, -8.6%, -11.3%, -11.3% and -5.6% (p=0.021). A similar significant trend was observed with the CTV. With a median time interval of 6 days (range, 1-18 days) between FxRef and Fx1, the GTV increased by over 10% in 58% of MGMT-um tumors compared to only 33% of MGMT-m tumors. MGMT-um tumors had significantly larger maximum d mig compared to tumors with MGMT-m, with a median d mig of 9.6 mm vs. 5.8 mm, respectively (p=0.018). The maximum GTV migration distance was greater than 5, 10 and 15 mm in 83%, 50% and 17% of MGMT-um tumors but only 56%, 11% and 0% for MGMT-m tumors, respectively. MGMT-um GBM exhibited significant changes in morphology and migration distance between the time of treatment planning to the first treatment fraction, as well as throughout a course of RT. In this population, our results support a greater frequency of imaging and plan adaptation when applying personalized reduced CTV margins. [ABSTRACT FROM AUTHOR]

Stereotactic body radiotherapy (SBRT) improves complete pain response for painful spinal metastases compared to conventional external beam radiotherapy (cEBRT). We report mature local control and reirradiation rates in a large cohort of patients treated with SBRT vs. cEBRT enrolled previously in the Canadian Clinical Trials Group Symptom Control (SC).24 phase II/III trial. 137/229 (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 MR-based local control and reirradiation rates for each treated spine segment. The median follow-up was 11.3 months (IQR:5.3-27.7 months), and median OS in the SBRT and cEBRT cohorts were 21.6 and 18.9 months (p=0.428), 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 vs. cEBRT at 6, 12 and 24 months were 2.8% vs. 11.2%, 6.1% vs. 28.4% and 14.8% vs. 35.6%, respectively (p<0.001). cEBRT (HR:3.48, 95%CI:1.94-6.25, p<0.001) and presence of "Mass" (HR:2.07, 95%CI:1.29-3.31, p=0.002) independently predicted local failure on multivariable analysis. The 1-year reirradiation rates and median times to reirradiation after SBRT vs. cEBRT, were 2.2% vs 15.8% (p=0.002) and 22.9 months vs. 9.5 months respectively. Radioresistant histology (HR:2.66, 95%CI:1.43-4.94, p=0.002) and cEBRT (HR:2.34, 95%CI:1.14-4.78, p=0.002) independently predicted for reirradiation. 8/12 iatrogenic vertebral compression fractures (VCFs) were after SBRT and 4/12 after cEBRT; Grade 3 toxicities were isolated to the SBRT cohort (5/12). Risk of local failure and reirradiation is lower with SBRT compared to cEBRT for spinal metastases. Although the iatrogenic VCF rates were within expectations, Grade 3 VCF were isolated to the SBRT cohort. [ABSTRACT FROM AUTHOR]

At our institution, 30 Gy in 4 spine stereotactic body radiotherapy (SBRT) fractions is typically delivered for larger volume when multiple segments are included in the treatment volume and/or for the retreatment of spinal metastases. We report MRI-based local failure (LF) and vertebral compression fracture (VCF) rates for patients (pts) treated with 30 Gy/4Fx of spine SBRT. A retrospective analysis of all pts with spine metastases treated with 30 Gy/4Fx from 2010 to 2021 from an institutional registry was performed. Demographic, clinical, dosimetric, and radiological data were summarized, and the primary endpoint was the MRI-based LF rate. Secondary endpoints included the incidence of VCF and overall survival (OS). Kaplan Meier was used to calculate LF and VCF per segment and OS per patient. Were included 116 pts with 245 treated segments in this analysis. The median number of consecutive segments in the treatment volume was 3 (1-7), and the median clinical target volume (CTV) was 126 cc (range, 10-863). Kidney (25%), lung (20%), breast (19%), prostate (19%), and colon (10%) cancer were the most common primary histologic types. 38% of pts had oligometastatic disease and 24% spine metastases only. 15% (17/116) of the patients were treated with postoperative SBRT. 31% of segments were re-irradiated for conventional palliative radiation, and 26% prior SBRT, failures. 25% of segments had a baseline VCF, 46% epidural disease, and 53% paraspinal tumor extension. The median follow-up per patient was 18.5 (range, 0.1-61) and per segment 10.7 mos (range, 0.1-59). The LF rates at 12 and 24 mos were 10.7% (95% CI 7.1-15.2) and 16% (95% CI 11.5-21.2), and for VCF were 7.3% (95% CI 4.4-11.2) and 11.2% (95% CI 7.5-15.8), respectively. 60% of failures had an epidural, and 23% a paraspinal, component. Age <68y (HR=0.43, 95% CI 0.19-0.95, p=0.038), volume of CTV <72cc (HR=0.09, 95% CI 0.01-0.70, p=0.021), and prior surgical stabilization (HR=0.25, 95% CI 0.07-0.81, p=0.021) were protective predictors for VCF on multivariable analyses (MVA). In particular, the VCF rate at 24 mos was 1.8% for pts with CTV volume <72 vs 14.6% for ≥72cc. Median OS was 20.3 mos (95% CI 14.8-27.1). Low grade or no epidural disease (HR=0.42, 95% CI 0.21-0.84, p=0.014), paraspinal disease (HR=3.07, 95% CI 1.68-5.62, p<0.001) and kidney primary cancer (HR=2.43, 95% CI 1.08-5.44, p=0.031) were predictors for OS on MVA, with a trend for oligometastatic disease (HR=0.56, 95% CI 0.31-1.02, p=0.059). No radiation-induced myelopathy was observed. This first report for 30 Gy/4Fx as a novel fractionation for spine SBRT suggests high rates of local control and a low rate of VCF, particularly for those target volumes with a CTV<72 cc. However, our rate of VCF in very large treatment volumes (≥72cc) is comparable to the SBRT-induced VCF literature, where optimal management remains an active area of investigation. [ABSTRACT FROM AUTHOR]

The management of locally recurrent brain metastases is a clinical challenge. A second course of radiosurgery may be delivered as the primary salvage treatment or as postoperative radiosurgery to the surgical cavity if the recurrence resected. We report our institutional experience of repeat radiosurgery for locally recurrent brain metastases, with a focus on local control and radionecrosis (RN) outcomes. We report a single institution retrospective cohort study specific to patients with recurrent brain metastases treated with repeat radiosurgery. Clinical and dosimetric details were collected. Overall survival was estimated using the Kaplan Meier method. Local recurrence and RN rates were estimated using the Aalen-Johnson method, with death from any cause as the competing risk for both endpoints. Univariable competing risk regression using Fine and Gray's methods were performed, and subsequent multivariable (MVA) regression based on a priori variable selection generated final adjusted models. We identified 96 patients and 130 brain metastases re-treated with radiosurgery (either single fraction or hypofractionation between July 2010 to April 2020. The most common primary sites were lung (N = 44, 33.8%), breast, (N = 38, 29.2%), and melanoma (N = 26, 20%). More than half of the retreated lesions were postoperative cavities (N = 68, 52.3%). Re-treatment was most commonly delivered with 25 Gy in 5 fractions (N = 77, 59.2%) followed by 27.5 Gy in 5 fractions (N = 23, 17.7%). The mean BED 10 was 39.71 Gy (standard deviation [SD] 6.16) with a mean treatment volume of 14.94 cm3 (SD, 20.15). Nearly half (N = 64, 49.2%) of lesions were treated in the absence of systemic therapy, while 43.8% (N = 57) and 6.9% (N = 9) were treated while receiving targeted therapy/immunotherapy and chemotherapy, respectively. The median time between treatment courses was 13.7 months (IQR 10.88). With a median follow up of 34.9 months (interquartile range [IQR] 25-41.9), the 1 and 2-year overall survival rates were 59.8% (95% confidence interval [95% CI] 50.4-70.9) and 36.2% (95% CI, 27.2-48.2), respectively. The risk of local failure at 1 and 2 years was 26.2% (95%CI, 18.5-34) and 28% (95%CI, 20.1-35.9), respectively. MVA identified increasing target volume (hazard ratio [HR] 1.03; 95% CI, 1.02-1.04), and a shorter time-interval between radiosurgery courses (HR 0.29; 95% CI, 0.19-0.45) to be associated with worse local control. The crude incidence of RN was 18.5% (N = 24), of which 8 events (6.15%) were symptomatic. The 1 and 2-year rates of RN were 17.6% (95% CI, 10.9-34) and 19.3% (95%CI, 12.3-35.9), respectively. Repeat radiosurgery for locally recurrent brain metastases results in good local control with a moderate risk of RN. Larger target volume and a shorter timeframe between radiosurgery treatments are associated with worse control. [ABSTRACT FROM AUTHOR]

Stereotactic body radiotherapy (SBRT) for spine metastases improves pain response rates and local control 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, using an established treatment technique, was reviewed to identify those treated with 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 159 patients (301 segments, 31.8%) received 28 Gy and 323 patients (646 segments, 68.2%) received 24 Gy in 2 fractions. Median follow-up 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 local failure were 3.5%, 5.4% and 11.1%, respectively, vs. 6.0%, 12.5% and 17.6% in the 24 Gy cohort, respectively (p=0.0075). On multivariable analysis, 24 Gy (HR: 1.572, 95%CI: 1.08-2.30, p=0.0196), epidural disease (HR: 1.522, 95%CI: 1.10-2.10, p=0.0108), and paraspinal extension (HR: 1.517, 95%CI: 1.08-2.12, p=0.0151) predicted for greater rates of local failure. Risk of VCF was 5.5%, 7.6% and 10.7% at 6-, 12- and 24-months, respectively, and similar between the two cohorts (p=0.573). Spinal malalignment (p<0.001), baseline vertebral body collapse (p=0.0027), junctional spine location (p=0.0296), and a greater PTVD90 predicted for greater rates of VCF. 28 Gy in 2 daily fractions was associated with improved local control without increasing the risk of VCF, and the 2-year local control rates fit the HYTEC spine tumor control probability model. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): The development of high-field strength MR-guided radiotherapy systems enables daily MR imaging, the opportunity for adaptive radiotherapy, and functional imaging acquisition. This study reports the workflow implementation, treatment times, and initial experience of glioma radiotherapy on the 1.5T MR-Linac (MRL).Materials/methods: Selected glioma patients treated with concurrent chemoradiation (chemoRT) between October 2019 and August 2020 were identified from a prospective database. All patients were treated on the MRL with backup plans on conventional Linac if the MRL was unavailable. Workflow timings were recorded and online adaptive plans were generated using the Adapt-To-Position (ATP) workflow derived from a pre-beam T1-weighted MRI. Temporal variation within the FLAIR hyperintense region (FHR) was assessed by the Dice similarity coefficient (DSC) and relative FHR volumes, compared to the initial FLAIR contour at the first MRL fraction. Multi-parametric images were acquired on the MR-Linac during radiation treatment, including diffusion-weighted imaging (DWI), chemical exchange saturation transfer (CEST), magnetization transfer (MT), and blood oxygenation level dependent (BOLD) resting-state fMRI. The behavior of selected functional parameter values was investigated within the FHR at the imaged fractions.Results: Ten high grade glioma patients completed chemoRT to a median dose of 60 Gy (range, 54-60 Gy) in 30 fractions (range, 30-33), receiving a total of 287 fractions on the MRL. The mean in-room time per fraction was 37.3 minutes (range, 24-51 minutes), and 42.9 minutes if including post-beam research imaging. Three patients (30%) required re-planning between fractions 15 to 19 due to progression of tumor and/or edema identified on daily MRL imaging. At the 10, 20, and 30 day post-first fraction time points, 3, 3, and 4 patients had a FLAIR volume that changed by at least 20% relative to the first MRL fraction, respectively. Multi-parametric images including DWI, CEST, MT, and BOLD resting-state fMRI were successfully acquired on the MR-Linac. The median apparent diffusion coefficients (ADC) within the FHR and volumes of FLAIR were significantly correlated when the data from all patients and time points were pooled (r = 0.68, P < 10-3).Conclusion: We report the first clinical series of glioma patients treated with chemoRT on the MRL. The workflow and treatment times were clinically acceptable, and daily online MRL imaging triggered adaptive re-planning for selected patients. Acquisition of multi-parametric imaging sequences was feasible on the MRL during routine treatment workflow. ADC parameter changes could be reliably tracked during chemoRT, and mature clinical outcomes data is anticipated to define the role of functional imaging in adaptive radiotherapy.Author Disclosure: C. Tseng: Advisory Board; Sanofi. H. Chen: Employee; North York General Hospital. J. Stewart: None. A. Lau: None. R. Chan: None. L.S. Lawrence: Student affiliated with University of Toronto; Sunnybrook Research Institute. M. Campbell: None. S.D. Myrehaug: Advisory Board; Novartis AG.H. Soliman: None. Z.A. Husain: Independent Contractor; RadOncQuestions LLC. Research Grant; Merck. Travel Expenses; Elekta; NIH Head and neck PULA task force. J. Detsky: None. P. Maralani: None. B.M. Keller: None. M.E. Ruschin: Patent/License Fees/Copyright; Elekta AB.A. Sahgal: Research Grant; Elekta. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Magnetic resonance image guided brain radiotherapy (MRIgRT) is a promising advance to maximize the therapeutic ratio. An unexplored uncertainty in this approach is the residual setup uncertainty after translation-only MR based patient setup. This work quantified this uncertainty, including intrafraction motion, and determined the impact on planning target volume (PTV) margins.Materials/methods: Sixty-six patients treated on a 1.5T-based MR-Linac were included. Of these, 49 and 17 patients received conventional (15-30 fractions for glioblastoma) and hypofractionated (5 fractions for post-operative brain metastases) treatments, respectively; 1,329 total patient fractions were analyzed. At each fraction, patients were setup using online MR guidance by translation-only (T) fusion of the T1 volumetric MR to the planning image set to determine the treatment isocenter shift. These fusions were independently validated offline with translational and rotational (T+R) fusion of bony anatomy. The difference between the T and T+R co-registrations was applied to the original clinical target volume (CTV) to yield the CTV at each fraction (CTVtreat). The set of all CTV and CTVtreat volumes was incorporated in a population-based model parameterized by the relative thresholds (CTVmin, Fxmin, Ptmin). This model determined the minimum planning target volume (PTV) margin such that the PTV encompassed CTVmin of the CTVtreat volume in ≥ Fxmin of fractions in ≥ Ptmin of patients. In this work, we determined the PTV margin that for two sets of thresholds: A) (CTVmin, Fxmin, Ptmin) = (98%, 95%, 90%) and B) (CTVmin, Fxmin, Ptmin) = (95%, 95%, 90%). In a subset of 412 fractions, intrafraction motion was determined as the spatial registration difference between a post-treatment acquired MRI and the pre-treatment MRI.Results: Residual setup uncertainty (difference between T+R and T registrations) and intrafraction motion results are summarized in Table 1. Across all patient fractions, the vector magnitude of the setup uncertainty and intrafraction motion was 1.3 ± 0.8 mm (mean ± SD) and 0.6 ± 0.5 mm, respectively. To accommodate the setup uncertainty, PTV margins of 2.5 and 1.8 mm were required to meet criteria sets A and B, respectively.Conclusion: We have quantified residual setup and motion uncertainties for a large series of treated MR-Linac brain tumor patients, generated a model for a population-based PTV, and recommend a minimum PTV of 2-3 mm for this indication. This work is a crucial step towards developing an adaptive brain treatment based on dynamic tumor changes and tumor response. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): The Magnetic Resonance Imaging (MRI)-Linac (MRL) is a hybrid machine integrating a high field strength 1.5T MRI with a linear accelerator, providing superior soft tissue visualization of tumors and organs-at-risk (OARs) during treatment delivery. A special consideration for MRL radiotherapy is accounting for interactions of secondary electrons generated within the magnetic field, which can alter dose deposition at air-tissue interfaces. We evaluated dosimetric outcomes in clinically treated malignant glioma patients who received at least one fraction of radiotherapy on both the MRL and a conventional Linac.Materials/methods: Thirty-seven glioma patients treated on both the MRL and a conventional Linac for adjuvant chemoradiotherapy between July 2019 and February 2021 were analyzed. Planning was completed on treatment planning systems (TPS) using a Monte-Carlo algorithm that accounts for magnetic field effects (Monaco v5.40) for the MRL, and a convolution-superposition algorithm (Pinnacle v9.8) for the conventional Linac. Dosimetric parameters of interest from the target, OARs, and air-tissue interface volumes for each patients' clinical treatment plans were extracted and compared. For 10 representative patients, in vivo skin doses during a single fraction of MRL and conventional Linac treatment were obtained using an Optically Stimulated Luminescent Dosimeter (OSLD) placed in a defined location on the patient's skin near the Planning Target Volume (PTV). Student's t-test and Wilcoxon signed-rank test were used to compare parameters between Monaco and Pinnacle. Spearman's correlation was used to assess the relationship between in vivo OSLD measurements and TPS skin dose. Threshold for statistical significance was P < 0.05.Results: Most patients were treated for high grade glioma (76% Grade III or IV, 24% Grade II), and median PTV was 257.4 cm3 (range, 37.1-570.3 cm3). MRL and conventional Linac had similar V100, V95, D98, and D95 for PTV, and D3cc for optic chiasm, optic nerves, and each cochlea (P = NS). However, clinically delivered Monaco plans had significantly greater doses within air cavities (mean Dmean higher by 1.3 Gy, P < 0.0001) and skin (mean Dmean higher by 1.9 Gy, P < 0.0001; mean D2cc higher by 8.1 Gy, P < 0.0001; mean V20 Gy higher by 7.2 cm3, P < 0.0001), compared to clinically delivered Pinnacle plans. In vivo OSLD skin readings were 14.5% greater for treatments delivered on the MRL (P = 0.0027), and were more accurately predicted by Monaco (r = 0.95, P < 0.0001) vs. Pinnacle (r = 0.80, P = 0.0096).Conclusion: In this prospective study of clinically treated glioma patients on both MRL and conventional Linac, the dosimetric impact of the magnetic field was minimal for the target and standard OARs. However, higher doses to skin and air cavities were observed. In vivo correlation of dose to skin was more accurately predicted with Monaco. Future MRL planning processes are being designed to account for skin dosimetry and treatment delivery. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Stereotactic radiosurgery (SRS) is an important treatment modality in the management of breast cancer-related brain metastases (BrM). Recent research has found Trastuzumab emtansine (T-DM1) to be effective against Her2+ BrM. However, the risk of radionecrosis (RN) with T-DM1 in combination with SRS is unclear. The objective of this study was to investigate factors associated with RN post-SRS in patients with Her2+ BrM.Materials/methods: Patients with Her2+ BrM treated with SRS at the Sunnybrook Odette Cancer Centre between 2010 and 2020 were retrospectively identified. The incidence of RN was determined on a lesion-by-lesion basis using serial brain imaging with or without histological confirmation. Clinical factors associated with RN, such as age, RT dose, lesion volume, intracranial location, total number of BrM, along with history of whole brain RT, and T-DM1 treatment were investigated with univariable and multivariable competing risks regression (MVR) using death from any cause as a competing risk factor. A P-value of < 0.05 in MVR following backward selection was considered statistically significant.Results: 67 patients with Her2+ BrM (223 lesions) treated with SRS were identified; among them, 21 (31.3%) were treated with T-DM1 post-SRS, including 14 (20.9%) who received T-DM1 within 12 months of SRS. The median follow-up was 15.6 (IQR 5.4-35.3) months. The 1-year, and 2-year risk of RN post-SRS was 6.7% (95% CI 2.7-10.7%), and 15.2% (95% CI 9.2-21.3%), respectively. MVR identified T-DM1 treatment post-SRS (HR 2.5, 95% CI 1.2-5.3, P = 0.02) and RT dose with a biologically effective dose (BED) > 50.4 Gy (HR 2.4, 95% CI 1.1-5.1, P = 0.02) as independent risk factors of RN. Patients treated with T-DM1 and SRS had a 25.2% (95% CI 12.8-37.6%) risk of RN at both 1- and 2-years post-T-DM1. The median time to RN after T-DM1 among the affected was 4.8 (95% CI: 3.8-25.6) months with 80% of all RN cases occurring within 12 months of T-DM1 treatment.Conclusion: This study demonstrates that T-DM1 exposure post-SRS was independently associated with a higher risk of RN in Her2+ BrM patients. The potential side effects of brain-penetrating agents post-SRS merit greater awareness.Author Disclosure: B. Id Said: None. H. Chen: None. K. Jerzak: Research Grant; Astra Zeneca, Eli Lilly. Consultant; Amgen, AstraZeneca, Apo Biologix, Eli Lilly, Esai, Genomic Health, Knight Therapeutics, Merck, Myriad Genetics Inc, Pfizer, Roche, Novartis, Purdue Pharma. S.D. Myrehaug: Advisory Board; Novartis AG.C. Tseng: Consultant; Sanofi. Travel Expenses; Elekta. Member; Elekta MR-LINAC.J. Detsky: None. Z.A. Husain: None. A. Sahgal: Research Grant; Elekta AB. Honoraria; Elekta AB, Varian, BrainLAB, Medtronic Kyphon. Consultant; Varian. Travel Expenses; Elekta AB, Varian. H. Soliman: None. [ABSTRACT FROM AUTHOR]