Chemoradiotherapy is the standard treatment after maximal safe resection for glioblastoma (GBM). Despite advances in molecular profiling, surgical techniques, and neuro-imaging, there have been no major breakthroughs in radiotherapy (RT) volumes in decades. Although the majority of recurrences occur within the original gross tumor volume (GTV), treatment of a clinical target volume (CTV) ranging from 1.5 to 3.0 cm beyond the GTV remains the standard of care. Over the past 15 years, the incorporation of standard and functional MRI sequences into the treatment workflow has become a routine practice with increasing adoption of MR simulators, and new integrated MR-Linac technologies allowing for daily pre-, intra- and post-treatment MR imaging. There is now unprecedented ability to understand the tumor dynamics and biology of GBM during RT, and safe CTV margin reduction is being investigated with the goal of improving the therapeutic ratio. The purpose of this review is to discuss margin strategies and the potential for adaptive RT for GBM, with a focus on the challenges and opportunities associated with both online and offline adaptive workflows. Lastly, opportunities to biologically guide adaptive RT using non-invasive imaging biomarkers and the potential to define appropriate volumes for dose modification will be discussed.

Background: 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).Purpose: To use saturation transfer MRI methods including chemical exchange saturation transfer (CEST) and magnetization transfer (MT) to distinguish RN from TP.Study Type: Prospective cohort study.Subjects: Seventy patients (median age 60; 73% females) with BM (75 lesions) post‐SRS.Field Strength/Sequence: 3‐T, CEST imaging using low/high‐power (saturation B₁ = 0.52 and 2.0 μT), quantitative MT imaging using B₁ = 1.5, 3.0, and 5.0 μT, WAter Saturation Shift Referencing (WASSR), WAter Shift And B₁ (WASABI), T₁, and T₂ mapping. All used gradient echoes except T₂ mapping (gradient and spin echo).Assessment: Voxel‐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 T₁ and T₂. Regions of interests (ROIs) were manually contoured on the post‐Gd T₁w. The mean (of median ROI values) was compared between groups. Clinical outcomes were determined by clinical and radiologic follow‐up or histopathology.Statistical Tests: t‐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.Results: 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.Data Conclusion: Significant differences between RN and TP were observed based on saturation transfer MRI.Evidence Level: 3Technical Efficacy: Stage 2

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.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is used to deliver ablative dose of radiation to spinal metastases. OBJECTIVE: To report the first dedicated series of spine SBRT specific to prostate cancer (PCa) metastases with outcomes reported according to hormone sensitivity status. METHODS: A prospective database was reviewed identifying patients with PCa treated with spine SBRT. This included those with hormone-sensitive PCa (HSPC) and castrate-resistant PCa (CRPC). The primary end point was MRI-based local control (LC). RESULTS: A total of 183 spine segments in 93 patients were identified; 146 segments had no prior radiation and 37 had been previously radiated; 27 segments were postoperative. The median follow-up was 31 months. At the time of SBRT, 50 patients had HSPC and the remaining 43 had CRPC. The most common fractionation scheme was 24-28 Gy in 2 SBRT fractions (76%). LC rates at 1 and 2 years were 99% and 95% and 94% and 78% for the HSPC and CRPC cohorts, respectively. For patients treated with de novo SBRT, a higher risk of local failure was observed in patients with CRPC (P = .0425). The 1-year and 2-year overall survival rates were significantly longer at 98% and 95% in the HSPC cohort compared with 79% and 65% in the CRPC cohort (P = .0005). The cumulative risk of vertebral compression fracture at 2 years was 10%. CONCLUSION: Favorable LC rates were observed after spine SBRT for PCa metastases; strategies to improve long-term LC in patients with CRPC require further investigation.

To describe the implementation and initial results of using Chemical Exchange Saturation Transfer (CEST) for monitoring patients with central nervous system (CNS) tumours treated using a 1.5 tesla MR-guided radiotherapy system. CNS patients were treated with up to 30 fractions (total dose up to 60 Gy) using a 1.5 T Elekta Unity MR-Linac. CEST scans were obtained in 54 subjects at one or more time points during treatment. CEST metrics, including the amide magnetization transfer ratio (MTRAmide), nuclear Overhauser effect (NOE) MTR (MTRNOE) and asymmetry, were quantified in phantoms and CNS patients. The signal was investigated between tumour and white matter, across time, and across disease categories including high- and low-grade tumours. The gross tumour volume (GTV) exhibited lower MTRAmide and MTRNOE and higher asymmetry compared to contralateral normal appearing white matter. Signal changes in the GTV during fractionated radiotherapy were observed. There were differences between high- and low-grade tumours, with higher CEST asymmetry associated with higher grade disease. CEST MRI using a 1.5 T MR-Linac was demonstrated to be feasible for in vivo imaging of CNS tumours. CEST images showed tumour/white-matter contrast, temporal CEST signal changes, and associations with tumour grade. These results show promise for the eventual goal of using metabolic imaging to inform the design of adaptive radiotherapy protocols.