Purpose/Objective(s): Whole brain radiotherapy with hippocampal avoidance (HA-WBRT) is a technique utilized to treat metastatic brain disease while preserving memory and neurocognitive function. We hypothesized that the treatment planning and delivery of HA-WBRT plans is feasible with an MRI-guided linear accelerator (linac) and compared plan results with clinical non-MRIguided C-Arm linac plans. Materials/Methods: Twelve HA-WBRT patients treated on a non-MRI-guided C-Arm linac were selected for retrospective analysis. Treatment plans were developed using a 0.35T MRI-guided linac system for comparison to clinical plans. Treatment planning goals were defined as provided in the Phase II Trial NRG CC001. MRI-guided radiotherapy (MRgRT) treatment plans were developed by a dosimetrist and compared with clinical plans. quality assurance (QA) plans were generated and delivered on the MRI-guided linac to a cylindrical diode detector array. Planning target volume (PTV) coverage was normalized to ∼95% to provide a control point for comparison of dose to the organs at risk. Results: MRgRT plans were deliverable and met all clinical goals. Mean values demonstrated that the clinical plans were less heterogeneous than MRgRT plans with mean PTV V37.5 Gy of 0.00% and 0.03% (p = 0.013), respectively. Average hippocampi maximum doses were 14.19 ± 1.29 Gy and 15.00 ± 1.51 Gy, respectively. The gamma analysis comparing planned and measured doses resulted in a mean of 99.9% ± 0.12% of passing points (3%/2mm criteria). MRgRT plans had an average of 38.33 beams with average total delivery time and beam-on time of 13.7 (11.2-17.5) min and 4.1 (3.2-5.4) min, respectively. Clinical plan delivery times ranged from 3 to 7 min depending on the number of noncoplanar arcs. Planning time between the clinical and MRgRT plans was comparable. Conclusion:This study demonstrates that HA-WBRT can be treated using an MRI-guided linear accelerator with comparable treatment plan quality and delivery accuracy.
BACKGROUND Anti-PD-1+CTLA-4 therapy has revolutionized melanoma brain metastases (MBM) treatment. Prospective trials show higher response in asymptomatic versus symptomatic patients. We evaluated clinical outcomes in MBM treated with stereotactic radiosurgery (SRS) and anti-PD-1+CTLA-4. METHODS Patients were included if MBM were diagnosed and treated with SRS within 3 months of anti-PD-1+CTLA-4, and this was their last course of systemic treatment. Endpoints of this study were distant MBM control, MBM local control (LC) defined as less than 20% volume increase on follow-up MRI, and overall survival (OS) from SRS. Adverse advents were evaluated using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. RESULTS 29 patients with 122 MBM treated over 40 SRS sessions between 2015-2020 were identified. Median SRS dose: 24 Gy (range: 15-24). Median MBM diameter: 0.6 cm (range: 0.3-2.9). Median follow-up using reverse Kaplan-Meier (KM) method: 19.3 months (interquartile range: 14.6-38.4).Six-, twelve-, and eighteen-month KM distant MBM control rates were 51%, 42%, 42%, respectively. LC rates: 90%, 86%, 85%. OS rates: 76%, 68%, 56%. 17 patients (59%) were asymptomatic and 12 (41%) symptomatic. KM distant MBM control and OS for asymptomatic and symptomatic patients were not significant; p=0.61 and p=0.67, respectively.On univariate analysis (UVA), Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) 0-1 was associated with increased risk of distant MBM failure versus DS-GPA 3.5-4 (hazard ratio (HR): 9.8, 95% confidence interval (CI) 1.9-51.5, p=0.007). UVA showed decreased OS with increased number of organs with metastases at diagnosis (HR:12, 95% CI 2.0-83.1, p=0.0075).2 lesions (1.6%) developed symptomatic radiation necrosis requiring steroids; 10 lesions developed grade 3 edema (8%); 13 patients experienced grade 1-2 fatigue and/or headache (45%); no patients experienced grade >3 events. CONCLUSION Combination SRS and anti-PD-1+CTLA-4 in MBM shows durable intracranial control with similar outcomes between asymptomatic and symptomatic patients with acceptable toxicity. Further study is warranted.
3D printing in medical physics provides opportunities for creating patientspecific treatment devices and in-house fabrication of imaging/dosimetry phantoms. This study characterizes several commercial fused deposition 3D printing materials with some containing nonstandard compositions. It is important to explore their similarities to human tissues and other materials encountered in patients. Uniform cylinders with infill from 50 to 100% at six evenly distributed intervals were printed using 13 different filaments. A novel approach rotating infill angle 10 o between each layer avoids unwanted patterns. Five materials contained high-Z/metallic components. A clinical CT scanner with a range of tube potentials (70, 80, 100, 120, 140 kVp) was used. Density and average Hounsfield unit (HU) were measured.A commercial GAMMEX phantom mimicking various human tissues provides a comparison. Utility of the lookup tables produced is demonstrated. A methodology for calibrating print materials/parameters for a desired HU is presented. Density and HU were determined for all materials as a function of tube voltage (kVp) and infill percentage. The range of HU (−732.0-10047.4 HU) and physical densities (0.36-3.52 g/cm 3 ) encompassed most tissues/materials encountered in radiology/radiotherapy applications with many overlapping those of human tissues. Printing filaments doped with high-Z materials demonstrated increased attenuation due to the photoelectric effect with decreased kVp, as found in certain endogenous materials (e.g., bone). HU was faithfully reproduced (within one standard deviation) in a 3D-printed mimic of a commercial anthropomorphic phantom section. Characterization of commercially available 3D print materials facilitates custom object fabrication for use in radiology and radiation oncology, including human tissue and common exogenous implant mimics. This allows for cost reduction and increased flexibility to fabricate novel phantoms or patient-specific devices imaging and dosimetry purposes. A formalism for calibrating to specific CT scanner, printer, and filament type/batch is presented. Utility is demonstrated by printing a commercial anthropomorphic phantom copy. Jasmine A. Graham and Gage Redler contributed equally to this work.
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