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Background: Simultaneous involvement of multiple distinct brain regions occurs in 2-5% of all high-grade gliomas (HGG) and is associated with poor prognosis. Whereas radiotherapy (RT) is an important and well-established treatment for high-grade glioma, the role of dose-escalated radiotherapy has yet to be established. In this case series, we report upon the dosimetry, adverse effects, and response in patients with multiple un-methylated high-grade gliomas receiving dose-escalated radiation. Materials and methods: We reviewed charts of patients with multifocal high grade glioma treated at our institution since January 2022. All patients had stereotactic biopsies after an magnetic resonance imaging (MRI) contrast-enhanced with T1, T2, FLAIR sequences and were discussed in a multidisciplinary oncology team. MGMT-positive patients received either TMZ alone or RT with TMZ and were excluded from this analysis. Un-methylated patients received dose-escalated RT without temezolamide (TMZ). Following computed tomography (CT) and MR simulation, the gros tumor volume (GTV) was delineated and prescribed 52.5 Gy in 15 fractions within the standard 40.05 Gy planning treatment volume (PTV). Treatment planning was volumetric modulated arc therapy. Results: A total of 20 patients with multiple un-methylated MGMT glioblastoma multiforme were treated with dose-escalated radiation therapy between January 2022 and June 2023. All patients completed dose escalated radiotherapy without acute adverse effects. Progression-free survival at six months was 85%, as defined by the RANO criteria. Conclusion: In this case series, we showed that un-methylated multiple high-grade glioma could be safely treated with dose escalation. Results of progression-free survival should be validated in a larger prospective clinical trial. [ABSTRACT FROM AUTHOR]

Five fraction salvage stereotactic body radiation therapy (SBRT) is a Delphi consensus recommendation for prostate re-irradiation, yet remains debatable and underutilized, and is associated with higher risk of treatment-related adverse events compared to primary radiotherapy. We hypothesized that intensification of hypo-fractionation delivering 2 fractions of 9 GY would be advantageous and here report the feasibility, toxicity, and preliminary outcomes of 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) directed salvage focal re-irradiation with this regimen. From July 2022 to November 2023, 17 Men with isolated prostate cancer recurrence after definitive radiation were treated at single institution. All patients underwent 68Ga-PSMA PET/CT following biochemical recurrence by the phoenix criteria or a repeated PSA increase. Confirmation of recurrence was performed by prostate biopsy and multiparametric MRI in 53% and 35% of patients, respectively. Focal SBRT of 18 Gy in two fractions was delivered to the PSMA-avid disease and a 3-5mm margin in the prostate on alternate days with image guidance by fiducial markers. Placement of hydrogel spacer (29%) or endorectal balloon (71%) was mandated. Androgen deprivation therapy was given concurrently in 88% of patients for a median duration of six months (range = 4-21). Toxicity was assessed according to Common Terminology Criteria for Adverse Events version 5. Median follow-up was 11.9 months (range = 3-18) with a median time between primary radiation treatment and salvage SBRT of 4.3 years (range = 0.6- 15.6). Median age was 73.1 (range = 66-89) and Prostate-specific antigen (PSA) level at reirradiation was 1.87 ng/ml (range = 0.02-7.1). At the end of follow up only one patient had a biochemical recurrence, which was confirmed by 68Ga-PSMA PET/CT. No patient developed acute or late gastrointestinal toxicity, and four patients (23.5%) did not have any adverse events. Rates of acute genitourinary (GU) toxicity grade 1 and 2 were 41.2% and 11.8%, respectively. Late grade 1 and 2 GU toxicity occurred in 41% and 35%, with cystitis as the leading toxicity followed by urinary incontinence. No grade 3 or 4 toxicities were reported. With a short follow-up, PSMA-directed salvage focal reirradiation to the prostate using SBRT of 18 Gy in two fractions is feasible and has acceptable toxicity. No gastrointestinal toxicity was reported, as well as no high-grade toxicity of any type, with very favorable short term biochemical control in a selected cohort of patients. [ABSTRACT FROM AUTHOR]