Randomized prospective trial of fractionated stereotactic radiosurgery with chemotherapy versus chemotherapy alone for bevacizumab-resistant high-grade glioma.

PURPOSE: Outcomes for patients with recurrent high-grade glioma (HGG) progressing on bevacizumab (BEV) are dismal. Fractionated stereotactic radiosurgery (FSRS) has been shown to be feasible and safe when delivered in this setting, but prospective evidence is lacking. This single-institution randomized trial compared FSRS plus BEV-based chemotherapy versus BEV-based chemotherapy alone for BEV-resistant recurrent malignant glioma. MATERIALS AND METHODS: HGG patients on BEV with tumor progression after 2 previous treatments were randomized to 1) FSRS plus BEV-based chemotherapy or 2) BEV-based chemotherapy with irinotecan, etoposide, temozolomide, or carboplatin. FSRS was delivered as 32 Gy (8 Gy × 4 fractions within 2 weeks) to the gross target volume and 24 Gy (6 Gy × 4 fractions) to the clinical target volume (fluid-attenuated inversion recovery abnormality). The primary endpoints were local control (LC) at 2 months and progression-free survival (PFS). RESULTS: Of the 35 patients enrolled, 29 had glioblastoma (WHO IV) and 6 had anaplastic glioma (WHO III). The median number of prior recurrences was 3. Patients treated with FSRS had significantly improved PFS (5.1 vs 1.8 months, P < .001) and improved LC at 2 months (82% [14/17] vs 27% [4/15], P = .002). The overall median survival was 6.6 months (7.2 months with FSRS vs 4.8 months with chemotherapy alone, P = .11). CONCLUSIONS: FSRS combined with BEV-based chemotherapy in recurrent HGG patients progressing on BEV is feasible and improves LC and PFS when compared to treatment with BEV-based chemotherapy alone.

Evaluation and verification of the QFix EncompassTM couch insert for intracranial stereotactic radiosurgery.

The QFix EncompassTM stereotactic radiosurgery (SRS) immobilization system consists of a thermoplastic mask that attaches to the couch insert to immobilize patients treated with intracranial SRS. This study evaluates the dosimetric impact and verifies a vendor provided treatment planning system (TPS) model in the Eclipse TPS. A thermoplastic mask was constructed for a Lucy 3D phantom, and was scanned with and without the EncompassTM system. Attenuation measurements were performed in the Lucy phantom with and without the insert using a pinpoint ion chamber for energies of 6xFFF, 10xFFF and 6X, with three field sizes (2 × 2, 4 × 4, and 6 × 6 cm2 ). The measurements were compared to two sets of calculations. The first set utilized the vendor provided Encompass TPS model (EncompassTPS ), which consists of two structures: the Encompass and Encompass base structure. Three HU values for the Encompass (200, 300, 400) and Encompass Base (-600, -500, -400) structures were evaluated. The second set of calculations consists of the Encompass insert included in the external body contour (EncompassEXT ) for dose calculation. The average measured percent attenuation in the posterior region of the insert ranged from 3.4%-3.8% for the 6xFFF beam, 2.9%-3.4% for the 10xFFF, and 3.3%-3.6% for the 6X beam. The maximum attenuation occurred at the region where the mask attaches to the insert, where attenuation up to 17% was measured for a 6xFFF beam. The difference between measured and calculated attenuation with either the EncompassEXT or EncompassTPS approach was within 0.5%. HU values in the EncompassTPS model that provided the best agreement with measurement was 400 for the Encompass structure and -400 for the Encompass base structure. Significant attenuation was observed at the area where the mask attaches to the insert. Larger differences can be observed when using few static beams compared to rotational treatment techniques.

Overlapping Electronic States with Nearly Parallel Transition Dipole Moments in Reduced Anionic Flavin Can Distort Photobiological Dynamics.

Chromophoric biomolecules are exploited as reporters of a diverse set of phenomena, acting as internal distance monitors, environment and redox sensors, and endogenous imaging probes. The extent to which they can be exploited is dependent on an accurate knowledge of their fundamental electronic properties. Arguably of greatest importance is a precise knowledge of the direction(s) of the absorption transition dipole moment(s) (TDMs) in the molecular frame of reference. Such is the case for flavins, fluorescent redox cofactors utilized for ground- and excited-state redox and photochemical processes. The directions of the TDMs in oxidized and semiquinone flavins were characterized decades ago, and the details of charge redistribution in these forms have also been studied by Stark spectroscopy. The electronic structure of the fully reduced hydroquinone anionic state, FlH-, however, has been the subject of unfounded assumptions and estimates about the number and direction of TDMs in FlH-, as well the electronic structure changes that occur upon light absorption. Here we have used Stark spectroscopy to measure the magnitude and direction of charge redistribution in FlH- upon optical excitation. These data were analyzed using TD-DFT calculations. The results show unequivocally that not one but two nearly orientation-degenerate electronic transitions are required to explain the 340-500 nm absorption spectral range, demolishing the commonly held assumption of a single transition. The difference dipole moments for these states show that electron density shifts toward the xylene ring for both transitions. These measurements force a reappraisal of previous studies that have used erroneous assumptions and unsubstantiated estimates of these quantities. The results put future optical studies of reduced flavins/flavoproteins on a firm photophysical footing.

Initial clinical experience with a radiation oncology dedicated open 1.0T MR-simulation.

The purpose of this study was to describe our experience with 1.0T MR-SIM including characterization, quality assurance (QA) program, and features necessary for treatment planning. Staffing, safety, and patient screening procedures were developed. Utilization of an external laser positioning system (ELPS) and MR-compatible couchtop were illustrated. Spatial and volumetric analyses were conducted between CT-SIM and MR-SIM using a stereotactic QA phantom with known landmarks and volumes. Magnetic field inhomogeneity was determined using phase difference analysis. System-related, in-plane distortion was evaluated and temporal changes were assessed. 3D distortion was characterized for regions of interest (ROIs) 5-20 cm away from isocenter. American College of Radiology (ACR) recommended tests and impact of ELPS on image quality were analyzed. Combined ultrashort echotime Dixon (UTE/Dixon) sequence was evaluated. Amplitude-triggered 4D MRI was implemented using a motion phantom (2-10 phases, ~ 2 cm excursion, 3-5 s periods) and a liver cancer patient. Duty cycle, acquisition time, and excursion were evaluated between maximum intensity projection (MIP) datasets. Less than 2% difference from expected was obtained between CT-SIM and MR-SIM volumes, with a mean distance of < 0.2 mm between landmarks. Magnetic field inhomogeneity was < 2 ppm. 2D distortion was < 2 mm over 28.6-33.6 mm of isocenter. Within 5 cm radius of isocenter, mean 3D geometric distortion was 0.59 ± 0.32 mm (maximum = 1.65 mm) and increased 10-15 cm from isocenter (mean = 1.57 ± 1.06 mm, maximum = 6.26 mm). ELPS interference was within the operating frequency of the scanner and was characterized by line patterns and a reduction in signal-to-noise ratio (4.6-12.6% for TE = 50-150 ms). Image quality checks were within ACR recommendations. UTE/Dixon sequences yielded detectability between bone and air. For 4D MRI, faster breathing periods had higher duty cycles than slow (50.4% (3 s) and 39.4% (5 s), p < 0.001) and ~fourfold acquisition time increase was measured for ten-phase versus two-phase. Superior-inferior object extent was underestimated 8% (6 mm) for two-phase as compared to ten-phase MIPs, although < 2% difference was obtained for ≥ 4 phases. 4D MRI for a patient demonstrated acceptable image quality in ~ 7 min. MR-SIM was integrated into our workflow and QA procedures were developed. Clinical applicability was demonstrated for 4D MRI and UTE imaging to support MR-SIM for single modality treatment planning.

Characteristics of a novel treatment system for linear accelerator-based stereotactic radiosurgery.

The purpose of this study is to characterize the dosimetric properties and accuracy of a novel treatment platform (Edge radiosurgery system) for localizing and treating patients with frameless, image-guided stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT). Initial measurements of various components of the system, such as a comprehensive assessment of the dosimetric properties of the flattening filter-free (FFF) beams for both high definition (HD120) MLC and conical cone-based treatment, positioning accuracy and beam attenuation of a six degree of freedom (6DoF) couch, treatment head leakage test, and integrated end-to-end accuracy tests, have been performed. The end-to-end test of the system was performed by CT imaging a phantom and registering hidden targets on the treatment couch to determine the localization accuracy of the optical surface monitoring system (OSMS), cone-beam CT (CBCT), and MV imaging systems, as well as the radiation isocenter targeting accuracy. The deviations between the percent depth-dose curves acquired on the new linac-based system (Edge), and the previously published machine with FFF beams (TrueBeam) beyond D(max) were within 1.0% for both energies. The maximum deviation of output factors between the Edge and TrueBeam was 1.6%. The optimized dosimetric leaf gap values, which were fitted using Eclipse dose calculations and measurements based on representative spine radiosurgery plans, were 0.700 mm and 1.000 mm, respectively. For the conical cones, 6X FFF has sharper penumbra ranging from 1.2-1.8 mm (80%-20%) and 1.9-3.8 mm (90%-10%) relative to 10X FFF, which has 1.2-2.2mm and 2.3-5.1mm, respectively. The relative attenuation measurements of the couch for PA, PA (rails-in), oblique, oblique (rails-out), oblique (rails-in) were: -2.0%, -2.5%, -15.6%, -2.5%, -5.0% for 6X FFF and -1.4%, -1.5%, -12.2%, -2.5%, -5.0% for 10X FFF, respectively, with a slight decrease in attenuation versus field size. The systematic deviation between the OSMS and CBCT was -0.4 ± 0.2 mm, 0.1± 0.3mm, and 0.0 ± 0.1 mm in the vertical, longitudinal, and lateral directions. The mean values and standard deviations of the average deviation and maximum deviation of the daily Winston-Lutz tests over three months are 0.20 ± 0.03 mm and 0.66 ± 0.18 mm, respectively. Initial testing of this novel system demonstrates the technology to be highly accurate and suitable for frameless, linac-based SRS and SBRT treatment.

Dosimetric comparison of glioblastoma radiotherapy treatment plans on a low-field MRI-guided linear accelerator compared to conventional C-arm linear accelerator.

INTRODUCTION: Magnetic resonance imaging (MRI)-guided radiation therapy has proven to provide many benefits such as real-time tracking, dose escalation, and the ability to perform online adaptive therapy. The objective of this study is to compare curative treatment plans for glioblastoma tumors on a low-field MR-guided linac vs a C-arm linac and evaluate if they are comparable in terms of coverage, organ at risk sparing, delivery time, and deliverability. METHODS: This is a retrospective study that consisted of 15 previously treated patients who received radiation therapy for glioblastoma on a C-arm linac. The CT simulation data used for the original clinical plans was imported into the MR-linac treatment planning system (TPS) and utilized for MR-linac plan generation. The plans were evaluated utilizing the dose volumetric histogram (DVH) and isodose lines, then compared in terms of plan quality consisting of PTV coverage, dose distributions, and OAR constraints. Statistical analysis was performed to compare differences between the two planning techniques. QA was performed on a subset of the plans to verify deliverability. RESULTS: Plans generated on the MR-linac were more heterogenous compared to C-arm linac plans. A statistically significant difference was found in the homogeneity index (HI) and the PTV V105% volume (cc) values. The volume of the normal brain receiving 30 Gy also showed a statistically significant (p = 0.0479) difference, where on average an additional 41.5 cc's of the normal brain tissue received 30 Gy in the MR-linac plans. The maximum dose to the normal brain structure also increased in the MR-linac plans on average by 2.6 Gy (p = 0.0002). Similarly, the average maximum dose to the scalp 4 mm structure was 6.5 Gy higher in the MR-linac plans compared to C-arm linac plans (p = 0.0103). The total MU's were higher in the MR-linac plans compared to the C-arm linac plans (p = 0.0015). CONCLUSIONS: Both MR-linac and C-arm linac plans met constraints for PTV coverage and OAR sparing, were deliverable, and resulted to be clinically acceptable. However, our study showed that MR-linac plans were not as conformal or as homogenous as C-arm linac plans utilizing noncoplanar beams.

Stereotactic Radiosurgery vs Conventional Radiotherapy for Localized Vertebral Metastases of the Spine: Phase 3 Results of NRG Oncology/RTOG 0631 Randomized Clinical Trial.

Importance: Spine metastasis can be treated with high-dose radiation therapy with advanced delivery technology for long-term tumor and pain control. Objective: To assess whether patient-reported pain relief was improved with stereotactic radiosurgery (SRS) as compared with conventional external beam radiotherapy (cEBRT) for patients with 1 to 3 sites of vertebral metastases. Design, Setting, and Participants: In this randomized clinical trial, patients with 1 to 3 vertebral metastases were randomized 2:1 to the SRS or cEBRT groups. This NRG 0631 phase 3 study was performed as multi-institutional enrollment within NRG Oncology. Eligibility criteria included the following: (1) solitary vertebral metastasis, (2) 2 contiguous vertebral levels involved, or (3) maximum of 3 separate sites. Each site may involve up to 2 contiguous vertebral bodies. A total of 353 patients enrolled in the trial, and 339 patients were analyzed. This analysis includes data extracted on March 9, 2020. Interventions: Patients randomized to the SRS group were treated with a single dose of 16 or 18 Gy (to convert to rad, multiply by 100) given to the involved vertebral level(s) only, not including any additional spine levels. Patients assigned to cEBRT were treated with 8 Gy given to the involved vertebra plus 1 additional vertebra above and below. Main Outcomes and Measures: The primary end point was patient-reported pain response defined as at least a 3-point improvement on the Numerical Rating Pain Scale (NRPS) without worsening in pain at the secondary site(s) or the use of pain medication. Secondary end points included treatment-related toxic effects, quality of life, and long-term effects on vertebral bone and spinal cord. Results: A total of 339 patients (mean [SD] age of SRS group vs cEBRT group, respectively, 61.9 [13.1] years vs 63.7 [11.9] years; 114 [54.5%] male in SRS group vs 70 [53.8%] male in cEBRT group) were analyzed. The baseline mean (SD) pain score at the index vertebra was 6.06 (2.61) in the SRS group and 5.88 (2.41) in the cEBRT group. The primary end point of pain response at 3 months favored cEBRT (41.3% for SRS vs 60.5% for cEBRT; difference, -19 percentage points; 95% CI, -32.9 to -5.5; 1-sided P = .99; 2-sided P = .01). Zubrod score (a measure of performance status ranging from 0 to 4, with 0 being fully functional and asymptomatic, and 4 being bedridden) was the significant factor influencing pain response. There were no differences in the proportion of acute or late adverse effects. Vertebral compression fracture at 24 months was 19.5% with SRS and 21.6% with cEBRT (P = .59). There were no spinal cord complications reported at 24 months. Conclusions and Relevance: In this randomized clinical trial, superiority of SRS for the primary end point of patient-reported pain response at 3 months was not found, and there were no spinal cord complications at 2 years after SRS. This finding may inform further investigation of using spine radiosurgery in the setting of oligometastases, where durability of cancer control is essential. Trial Registration: ClinicalTrials.gov Identifier: NCT00922974.

Practical methods for improving dose distributions in Monte Carlo-based IMRT planning of lung wall-seated tumors treated with SBRT.

Current commercially available planning systems with Monte Carlo (MC)-based final dose calculation in IMRT planning employ pencil-beam (PB) algorithms in the optimization process. Consequently, dose coverage for SBRT lung plans can feature cold-spots at the interface between lung and tumor tissue. For lung wall (LW)-seated tumors, there can also be hot spots within nearby normal organs (example: ribs). This study evaluated two different practical approaches to limiting cold spots within the target and reducing high doses to surrounding normal organs in MC-based IMRT planning of LW-seated tumors. First, "iterative reoptimization", where the MC calculation (with PB-based optimization) is initially performed. The resultant cold spot is then contoured and used as a simultaneous boost volume. The MC-based dose is then recomputed. The second technique uses noncoplanar beam angles with limited path through lung tissue. Both techniques were evaluated against a conventional coplanar beam approach with a single MC calculation. In all techniques the prescription dose was normalized to cover 95% of the PTV. Fifteen SBRT lung cases with LW-seated tumors were planned. The results from iterative reoptimization showed that conformity index (CI) and/or PTV dose uniformity (UPTV) improved in 12/15 plans. Average improvement was 13%, and 24%, respectively. Nonimproved plans had PTVs near the skin, trachea, and/or very small lung involvement. The maximum dose to 1cc volume (D1cc) of surrounding OARs decreased in 14/15 plans (average 10%). Using noncoplanar beams showed an average improvement of 7% in 10/15 cases and 11% in 5/15 cases for CI and UPTV, respectively. The D1cc was reduced by an average of 6% in 10/15 cases to surrounding OARs. Choice of treatment planning technique did not statistically significantly change lung V5. The results showed that the proposed practical approaches enhance dose conformity in MC-based IMRT planning of lung tumors treated with SBRT, improving target dose coverage and potentially reducing toxicities to surrounding normal organs.

An Analysis of Clinical Toxic Effects and Quality of Life as a Function of Radiation Dose and Volume After Lung Stereotactic Body Radiation Therapy.

PURPOSE: To analyze clinical toxicity and quality-of-life (QOL) outcomes among patients with stage I non-small cell lung cancer (NSCLC) after stereotactic body radiation therapy (SBRT) as a function of radiation dose and volume parameters. METHODS AND MATERIALS: In this institutional review board-approved study, 55 patients with stage I NSCLC who received SBRT (12 Gy × 4) and completed QOL forms were analyzed. Clinical symptoms and QOL outcomes were measured at baseline and at 3, 6, 12, 18, 24, and 36 months after SBRT. Clinical toxicity was graded using the Common Terminology Criteria for Adverse Events, version 4.0. Quality of life was followed using the validated Functional Assessment of Cancer Therapy-Lung-Trial Outcome Index (FACT-L-TOI) instrument. Dosimetric parameters including the mean lung radiation dose and the volume of normal lung receiving greater than 5, 10, 13, or 20 Gy (V5, V10, V13, and V20) were measured from the radiation treatment plan. Student t tests and Pearson correlation analyses were used to examine the relationships between radiation lung metrics and clinically meaningful changes in QOL and/or clinical toxic effects. The Kaplan-Meier method was used to estimate rates of local control (LC), disease-free survival (DFS), and overall survival (OS). RESULTS: With a median follow-up of 24 months, the 3-year LC, DFS, and OS were 93%, 65%, and 84%, respectively, with a 5.5% rate of grade-3 toxic effects and no grade 4 or 5 toxic effects. Clinically meaningful declines in patient-reported QOL (FACT-L-TOI, lung cancer subscale, physical well-being, and/or functional well-being) posttreatment significantly correlated with increased dosimetric parameters such as V10, V13, and V20. CONCLUSION: Although lung SBRT was associated with excellent LC and minimal clinical toxic effects for early-stage NSCLC, clinically meaningful declines in QOL were significantly correlated with increasing lung dose and volume parameters.

A Grade I Intracranial Meningioma with Metastasis to Multiple Vertebral Bodies: A Case Report and Literature Review.

World Health Organization (WHO) grade I meningiomas are slow-growing and typically benign brain tumors that can often be easily removed by surgery and rarely become malignant. We report the case of a WHO grade I meningioma in a 67-year-old man with multiple extracranial metastases.

FMEA of MR-Only Treatment Planning in the Pelvis.

PURPOSE: To evaluate the implementation of a magnetic resonance (MR)-only workflow (ie, implementing MR simulation as the primary planning modality) using failure mode and effects analysis (FMEA) in comparison with a conventional multimodality (MR simulation in conjunction with computed tomography simulation) workflow for pelvis external beam planning. METHODS AND MATERIALS: To perform the FMEA, a multidisciplinary 9-member team was assembled and developed process maps, identified potential failure modes (FMs), and assigned numerical values to the severity (S), frequency of occurrence (O), and detectability (D) of those FMs. Risk priority numbers (RPNs) were calculated via the product of S, O, and D as a metric for evaluating relative patient risk. An alternative 3-digit composite number (SOD) was computed to emphasize high-severity FMs. Fault tree analysis identified the causality chain leading to the highest-severity FM. RESULTS: Seven processes were identified, 3 of which were shared between workflows. Image fusion and target delineation subprocesses using the conventional workflow added 9 and 10 FMs, respectively, with 6 RPNs >100. By contrast, synthetic computed tomography generation introduced 3 major subprocesses and propagated 46 unique FMs, 15 with RPNs >100. For the conventional workflow, the largest RPN scores were introduced by image fusion (RPN range, 120-192). For the MR-only workflow, the highest RPN scores were from inaccuracies in target delineation resulting from misinterpretation of MR images (RPN = 240) and insufficient management of patient- and system-level distortions (RPN = 210 and 168, respectively). Underestimation (RPN = 140) or overestimation (RPN = 192) of bone volume produced higher RPN scores. The highest SODs for both workflows were related to changes in target location because of internal anatomy changes (conventional = 961, MR-only = 822). CONCLUSIONS: FMEA identified areas for mitigating risk in MR-only pelvis RTP, and SODs identified high-severity process modes. Efforts to develop a quality management program to mitigate high FMs are underway.

Electronic transition dipole moment directions of reduced anionic flavin in stretched poly(vinyl alcohol) films.

The IR and UV/vis linear dichroic spectra of reduced anionic flavin mononucleotide (FMNH-) partially oriented in poly(vinyl alcohol) (PVA) films have been measured to determine the direction of the major electronic transition dipole moments. The IR linear dichroism (LD) was measured in the 1750-1350 cm(-1) region to provide the overall molecular orientation of the FMNH- in the stretched films. Time-dependent density functional theory using the B3LYP functional was used to calculate the normal modes and the transition dipole moments of reduced lumiflavin. The calculated normal modes assisted in IR band assignments and in the determination of the IR transition dipole moment directions which were required for the determination of the orientation parameters for FMNH- in PVA films. The UV/vis LD spectrum was measured over the 200-700 nm region and was resolved into contributions from three pi-->pi* transitions. The directions of the transitions are 90 degrees+/-4 degrees at 440 nm, 79 degrees+/-4 degrees at 350 nm, and 93 degrees+/-4 degrees at 290 nm with counterclockwise rotations with respect to the N5-N10 axis. Comparison of the calculated and experimentally determined transition dipole moments allowed for refined assignment of the transition dipole moment directions. To our knowledge, this is the first experimental evidence that the 350-450 nm absorption arises from two unique transitions. Remarkably, the two lowest energy transition dipole moments for FMNH- are nearly parallel to those obtained in prior studies for both oxidized and semiquinone flavin.

Retroperitoneal Metastasis Abutting Small Bowel: A Novel Magnetic Resonance-Guided Radiation Approach.

Stereotactic body radiation therapy (SBRT) is an option for selected patients with metastatic disease. However, sometimes these lesions are located in such close proximity to critical normal structures that the use of safe tumoricidal SBRT doses is not achievable. Here we present a case in which real-time imaging and tracking with a magnetic resonance linear accelerator (MR-LINAC) provided a novel treatment approach and enabled safe treatment of the tumor using SBRT. Our case is a 69-year-old female who presented with localized recurrent small cell lung cancer with a retroperitoneal (FDG-avid) soft tissue lesion measuring 2.4 x 4.1 cm that was causing pain and right hydronephrosis. A Food and Drug Administration (FDA)-approved MR-LINAC system was utilized for planning and the delivery of 21 Gy in three fractions to the retroperitoneal lesion planning target volume (PTV), limited by the neighboring small bowel tolerance. The gross tumor volume (GTV) itself received 27 Gy (9 Gy per fraction). Simulation was performed using a volumetric MR imaging study in treatment position co-registered to a 4D-computed tomography (CT) image set for contouring of the target and organs at risk (OAR). Treatment planning was performed using the primary CT dataset. We developed a reasonable SBRT treatment plan to deliver the prescribed dose without exceeding tolerance doses to the right kidney, the small bowel and all other OAR's. Real-time MR imaging and tracking during treatment delivery enabled assessment of respiratory-induced target movement in relation to the small bowel and kidney. Gating was performed to halt treatment when PTV movement exceeded the 2-mm range as specified by the treating physician. The treatment course was concluded successfully. The patient denied any acute gastrointestinal or genitourinary toxicity. The pain was significantly improved within a short time following treatment. Follow-up CT showed a near complete response of the mass with total restoration of renal functions, allowing the ureteric stent to be removed. This response has been maintained for five months till the last follow-up. In conclusion, MR-guided planning and delivery using real-time MR imaging and tracking facilitated the treatment of the retroperitoneal mass accurately and efficiently with excellent clinical and radiological response and minimal to no toxicity. We would not discern it safe to treat this mass utilizing SBRT without this ability to accurately visualize the tumor boundary using magnetic resonance imaging (MRI), and offer tracking of the target within the millimeter of surrounding critical OAR's.

Using synthetic CT for partial brain radiation therapy: Impact on image guidance.

PURPOSE: Recent advancements in synthetic computed tomography (synCT) from magnetic resonance (MR) imaging data have made MRI-only treatment planning feasible in the brain, although synCT performance for image guided radiation therapy (IGRT) is not well understood. This work compares geometric equivalence of digitally reconstructed radiographs (DRRs) from CTs and synCTs for brain cancer patients and quantifies performance for partial brain IGRT. METHODS AND MATERIALS: Ten brain cancer patients (12 lesions, 7 postsurgical) underwent MR-SIM and CT-SIM. SynCTs were generated by combining ultra-short echo time, T1, T2, and fluid attenuation inversion recovery datasets using voxel-based weighted summation. SynCT and CT DRRs were compared using patient-specific thresholding and assessed via overlap index, Dice similarity coefficient, and Jaccard index. Planar IGRT images for 22 fractions were evaluated to quantify differences between CT-generated DRRs and synCT-generated DRRs in 6 quadrants. Previously validated software was implemented to perform 2-dimensional (2D)-2D rigid registrations using normalized mutual information. Absolute (planar image/DRR registration) and relative (differences between synCT and CT DRR registrations) shifts were calculated for each axis and 3-dimensional vector difference. A total of 1490 rigid registrations were assessed. RESULTS: DRR agreements in anteroposterior and lateral views for overlap index, Dice similarity coefficient, and Jaccard index were >0.95. Normalized mutual information results were equivalent in 75% of quadrants. Rotational registration results were negligible (<0.07°). Statistically significant differences between CT and synCT registrations were observed in 9/18 matched quadrants/axes (P < .05). The population average absolute shifts were 0.77 ± 0.58 and 0.76 ± 0.59 mm for CT and synCT, respectively, for all axes/quadrants. Three-dimensional vectors were <2 mm in 77.7 ± 10.8% and 76.5 ± 7.2% of CT and synCT registrations, respectively. SynCT DRRs were sensitive in postsurgical cases (vector displacements >2 mm in affected quadrants). CONCLUSIONS: DRR synCT geometry was robust. Although statistically significant differences were observed between CT and synCT registrations, results were not clinically significant. Future work will address synCT generation in postsurgical settings.

Stereotactic radiosurgery for primary tumors of the spine and spinal cord†.

PURPOSE: The purpose of this study was to evaluate the role of stereotactic radiosurgery in the treatment of primary tumors of the spine and spinal cord. METHODS: An Institutional Review Board approved retrospective analysis of 30 patients with primary spine tumors treated at a single institution was performed. Post-treatment pain, neurological, and radiographic responses were the endpoints. RESULTS: Nine patients were treated for benign tumors, and 21 patients were treated for malignant tumors. The median dose delivered was 16 Gy in one fraction. Median follow up was 13.13 months (range, 1 month-84 months). Pain relief was 88% initially. Pain recurred in five patients with a median time to recurrence of 5 months (range, 3.6 months - 80 months). Neurological improvement was achieved in 65% of patients. Three patients experienced a recurrence in their neurological deficit (at 3.6 months, 1.6 years, and 3.7 years after SRS). Radiographic control was achieved in 77% of sites treated with SRS. Thirteen of the treated sites recurred with a median time of 9.9 months. Two long-term toxicities were observed (asymptomatic radio-necrosis of the erector spinae muscle and foot drop). CONCLUSIONS: Our results suggest that SRS is a safe and effective treatment option for primary tumors of the spine and spinal cord.

Evaluation of a magnetic resonance guided linear accelerator for stereotactic radiosurgery treatment.

INTRODUCTION: The purpose of this study was to investigate the systematic localization accuracy, treatment planning capability, and delivery accuracy of an integrated magnetic resonance imaging guided Linear Accelerator (MR-Linac) platform for stereotactic radiosurgery. MATERIALS AND METHODS: The phantom for the end-to-end test comprises three different compartments: a rectangular MR/CT target phantom, a Winston-Lutz cube, and a rectangular MR/CT isocenter phantom. Hidden target tests were performed at gantry angles of 0, 90, 180, and 270 degrees to quantify the systematic accuracy. Five patient plans with a total of eleven lesions were used to evaluate the dosimetric accuracy. Single-isocenter IMRT treatment plans using 10-15 coplanar beams were generated to treat the multiple metastases. RESULTS: The end-to-end localization accuracy of the system was 1.0 ±â€¯0.1 mm. The conformity index, homogeneity index and gradient index of the plans were 1.26 ±â€¯0.22, 1.22 ±â€¯0.10, and 5.38 ±â€¯1.44, respectively. The average absolute point dose difference between measured and calculated dose was 1.64 ±â€¯1.90%, and the mean percentage of points passing the 3%/1 mm gamma criteria was 96.87%. CONCLUSIONS: Our experience demonstrates that excellent plan quality and delivery accuracy was achievable on the MR-Linac for treating multiple brain metastases with a single isocenter.

Investigating the dosimetric effects of grid size on dose calculation accuracy using volumetric modulated arc therapy in spine stereotactic radiosurgery.

PURPOSE: Sharp dose gradients between the target and the spinal cord are critical to achieve dose constraints in spine stereotactic radiosurgery (SRS), however the accuracy of the doses to the spinal cord at these high dose gradients is sensitive to the how the dose is sampled across the structure using a discretized isotropic calculation grid. In this study, the effect of the grid size (GS) on the dosimetric accuracy of volumetric modulated arc therapy (VMAT) spine SRS plans was investigated. METHODS: The Eclipse v11.0 Anisotropic Analytical Algorithm (AAA) algorithm was used for dose calculation. Plan qualities of fifty treatment plans were evaluated with a GS of 2.5 (AAA's default value), 1.5 and 1mm. All plans were prescribed to the 90% isodose line in 1 fraction. Parameters used for plan comparison included the distance-to-fall-off (DTF) between the 90% and 50% isodose levels in the axial plane, planning tumor volume (PTV) coverage to 99%, 95%, 5% and 0.03cc, dose to 10% (Cord_D10%) and 0.03cc (Cord_D0.03cc) of the spinal cord sub volume. The dosimetric accuracy was evaluated based on film dosimetry percent gamma pass rate, line profile through the cord. Calculation times between different grid sizes as well as DVH algorithm differences between two treatment planning systems (Eclipse vs Velocity) were compared. Paired t-test was used to investigate the statistical significance. RESULTS: The DTF decreased for all plans with 1mm compared to 1.5mm and 2.5mm GS (2.52±0.54mm, 2.83±0.58mm, 3.30±0.64, p<0.001). Relative to the 1mm GS, Cord_D0.03cc and Cord_D10% increased by 6.24% and 7.81% with the 1.5mm GS, and 9.80% and 13% with the 2.5mm GS. Film analysis demonstrated higher gamma pass rates for 1.5mm GS compared to 1 and 2.5mm GS (95.9%±5.4%, 94.3%±6.0%, 93.6%±5.4%, p<0.001), however 1mm GS showed better agreement in the high dose gradient near the cord. Calculation times for 1mm GS plans increased for 1.5 and 2.5mm GS (61% and 84%, p<0.001). The average difference between the two treatment planning systems was approximately 0-1.2%. A maximum difference of 5.9% occurred for Cord_D0.03cc for the 1mm GS. CONCLUSION: Plans calculated with a 1mm grid size resulted in the most accurate representation of the dose delivered to the cord, however resulted in less uniform dose distributions in the high dose region of the PTV. The use of a 1.5mm grid size may balance accurate cord dose and PTV coverage, while also being more practical with respect to computation time.

Reirradiation of the spine with stereotactic radiosurgery: Efficacy and toxicity.

PURPOSE: To determine the potential benefits and adverse effects associated with reirradiating the spinal cord when at least 1 course of radiation therapy (RT) is stereotactic radiosurgery (SRS). METHODS AND MATERIALS: This institutional review board-approved retrospective review included 162 patients (237 reirradiated spine lesions). All patients received SRS at our institution between 2001 and 2013. Electronic medical records were reviewed for clinical exams and radiologic tests (computed tomography/magnetic resonance imaging). Primary endpoints were pain, neurological, radiographic responses, and the development of adverse effects. RESULTS: A total of 120 patients (74.1%) were deceased with a median survival of 13 months. Time between courses of RT was a median of 10.2 months. Median SRS dose was 16 Gy in 1 fraction, whereas the median conventional external beam radiation therapy (cEBRT) dose was 30 Gy in 10 fractions. The median tumor equivalent dose in 2-Gy fractions (EQD2) for SRS doses was 34.7 Gy, whereas the median tumor EQD2 for cEBRT was 32.5 Gy, providing a median total tumor EQD2 of 69.3 Gy (22-145.6 Gy). The median critical nervous tissue EQD2 for SRS and cEBRT was 56 Gy and 37.5 Gy, respectively, resulting in a median total critical nervous tissue EQD2 of 93.5 Gy. Overall pain, neurological, and radiographic response rates were 81%, 82%, and 71%, respectively. Adverse effects occurred in 11 (6.8%) patients. Seventy-seven vertebral compression fractures were observed, 22 (9.3%) of which may be attributed to RT. CONCLUSIONS: Our results demonstrate that reirradiation achieves favorable response rates with minimal toxicity if recommended dose constraints to the spinal cord with SRS are carefully observed. To the best of our knowledge, this is the largest reported single-institution experience analyzing the efficacy and toxicity of reirradiation of the spine when at least 1 course of RT is stereotactic radiosurgery.

A prediction model of radiation-induced necrosis for intracranial radiosurgery based on target volume.

PURPOSE: This study aims to extend the observation that the 12 Gy-radiosurgical-volume (V12Gy) correlates with the incidence of radiation necrosis in patients with intracranial tumors treated with radiosurgery by using target volume to predict V12Gy. V12Gy based on the target volume was used to predict the radiation necrosis probability (P) directly. Also investigated was the reduction in radiation necrosis rates (ΔP) as a result of optimizing the prescription isodose lines for linac-based SRS. METHODS: Twenty concentric spherical targets and 22 patients with brain tumors were retrospectively studied. For each case, a standard clinical plan and an optimized plan with prescription isodose lines based on gradient index were created. V12Gy were extracted from both plans to analyze the correlation between V12Gy and target volume. The necrosis probability P as a function of V12Gy was evaluated. To account for variation in prescription, the relation between V12Gy and prescription was also investigated. RESULTS: A prediction model for radiation-induced necrosis was presented based on the retrospective study. The model directly relates the typical prescribed dose and the target volume to the radionecrosis probability; V12Gy increased linearly with the target volume (R2  > 0.99). The linear correlation was then integrated into a logistic model to predict P directly from the target volume. The change in V12Gy as a function of prescription was modeled using a single parameter, s (=-1.15). Relatively large ΔP was observed for target volumes between 7 and 28 cm3 with the maximum reduction (8-9%) occurring at approximately 18 cm3 . CONCLUSIONS: Based on the model results, optimizing the prescription isodose line for target volumes between 7 and 28 cm3 results in a significant reduction in necrosis probability. V12Gy based on the target volume could provide clinicians a predictor of radiation necrosis at the contouring stage thus facilitating treatment decisions.

Analysis of the Factors Contributing to Vertebral Compression Fractures After Spine Stereotactic Radiosurgery.

PURPOSE: To determine our institutional vertebral compression fracture (VCF) rate after spine stereotactic radiosurgery (SRS) and determine contributory factors. METHODS AND MATERIALS: Retrospective analysis from 2001 to 2013 at a single institution was performed. With institutional review board approval, electronic medical records of 1905 vertebral bodies from 791 patients who were treated with SRS for the management of primary or metastatic spinal lesions were reviewed. A total of 448 patients (1070 vertebral bodies) with adequate follow-up imaging studies available were analyzed. Doses ranging from 10 Gy in 1 fraction to 60 Gy in 5 fractions were delivered. Computed tomography and magnetic resonance imaging were used to evaluate the primary endpoints of this study: development of a new VCF, progression of an existing VCF, and requirement of stabilization surgery after SRS. RESULTS: A total of 127 VCFs (11.9%; 95% confidence interval [CI] 9.5%-14.2%) in 97 patients were potentially SRS induced: 46 (36%) were de novo, 44 (35%) VCFs progressed, and 37 (29%) required stabilization surgery after SRS. Our rate for radiologic VCF development/progression (excluding patients who underwent surgery) was 8.4%. Upon further exclusion of patients with hematologic malignancies the VCF rate was 7.6%. In the univariate analyses, females (hazard ratio [HR] 1.54, 95% CI 1.01-2.33, P=.04), prior VCF (HR 1.99, 95% CI 1.30-3.06, P=.001), primary hematologic malignancies (HR 2.68, 95% CI 1.68-4.28, P<.001), thoracic spine lesions (HR 1.46, 95% CI 1.02-2.10, P=.02), and lytic lesions had a significantly increased risk for VCF after SRS. On multivariate analyses, prior VCF and lesion type remained contributory. CONCLUSIONS: Single-fraction SRS doses of 16 to 18 Gy to the spine seem to be associated with a low rate of VCFs. To the best of our knowledge, this is the largest reported experience analyzing SRS-induced VCFs, with one of the lowest event rates reported.