Stereotactic radiosurgery and anti-PD-1 + CTLA-4 therapy, anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK inhibitors, BRAF inhibitors, or conventional chemotherapy for the management of melanoma brain metastases.

BACKGROUND: Immunotherapy and targeted BRAF/MEK inhibitors (i) have revolutionised the systemic management of advanced melanoma. Given the role of stereotactic radiosurgery (SRS) in the local management of brain metastases, we sought to evaluate clinical outcomes in patients with melanoma brain metastases (MBM) treated with SRS and various systemic therapies. METHODS: Patients were included if MBM were diagnosed and treated with SRS within 3 months of receiving anti-PD-1+CTLA-4 therapy, anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK-i, BRAF-i, or conventional chemotherapy. Comparisons between groups were made for overall survival (OS), distant MBM control, local MBM, systemic progression-free survival (sPFS), and neurotoxicity. RESULTS: In total, 257 patients with 1048 MBM treated over 368 SRS sessions between 2011 and 2020 were identified. On MVA, treatment with anti-PD1+anti-CTLA-4, anti-PD-1, and BRAF/MEK-i improved distant intracranial control over conventional chemotherapy. No significant differences were noted in local control (LC) between groups (p = 0.78). Kaplan-Meier OS at 12 months for anti-PD-1 + CTLA-4 therapy, anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK-i, BRAF-i, and conventional chemotherapy was 68%, 59%, 45%, 62%, 21%, and 15%, respectively (p = <0.0001). The sPFS rates at 12 months were 57%, 53%, 42%, 45%, 14%, and 6% (p = <0.0001). No significant differences were noted in rates of radiation necrosis (p = 0.93). CONCLUSIONS: This is among the largest series evaluating MBM treated with SRS and various systemic therapy regimens. Our analysis noted significant differences in OS, distant MBM control, and sPFS by systemic therapy. No differences in LC or radiation necrosis risk were noted.

Methodology for computed tomography characterization of commercially available 3D printing materials for use in radiology/radiation oncology.

3D printing in medical physics provides opportunities for creating patient-specific 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 10o 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/cm3 ) 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.

Dosimetric feasibility of hippocampal avoidance whole brain radiotherapy with an MRI-guided linear accelerator.

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-MRI-guided 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.