Hypofractionated stereotactic radiosurgery (HSRS) as a salvage treatment for brain metastases failing prior stereotactic radiosurgery (SRS).

INTRODUCTION: Various treatment options exist to salvage stereotactic radiosurgery (SRS) failures for brain metastases, including repeat SRS and hypofractionated SRS (HSRS). Our objective was to report outcomes specific to salvage HSRS for brain metastases that failed prior HSRS/SRS. METHODS: Patients treated with HSRS to salvage local failures (LF) following initial HSRS/SRS, between July 2010 and April 2020, were retrospectively reviewed. The primary outcomes were the rates of LF, radiation necrosis (RN), and symptomatic radiation necrosis (SRN). Univariable (UVA) and multivariable (MVA) analyses using competing risk regression were performed to identify predictive factors for each endpoint. RESULTS: 120 Metastases in 91 patients were identified. The median clinical follow up was 13.4 months (range 1.1-111.1), and the median interval between SRS courses was 13.1 months (range 3.0-56.5). 115 metastases were salvaged with 20-35 Gy in 5 fractions and the remaining five with a total dose ranging from 20 to 24 Gy in 3-fractions. 67 targets (56%) were postoperative cavities. The median re-treatment target volume and biological effective dose (BED10) was 9.5 cc and 37.5 Gy, respectively. The 6- and 12- month LF rates were 18.9% and 27.7%, for RN 13% and 15.6%, and for SRN were 6.1% and 7.0%, respectively. MVA identified larger re-irradiation volume (hazard ratio [HR] 1.02, p = 0.04) and shorter interval between radiosurgery courses (HR 0.93, p < 0.001) as predictors of LF. Treatment of an intact target was associated with a higher risk of RN (HR 2.29, p = 0.04). CONCLUSION: Salvage HSRS results in high local control rates and toxicity rates that compare favorably to those single fraction SRS re-irradiation experiences reported in the literature.

Evaluation of lens dose from anterior electron beams: comparison of Pinnacle and Gafchromic EBT3 film.

Lens dose is a concern during the treatment of facial lesions with anterior electron beams. Lead shielding is routinely employed to reduce lens dose and minimize late complications. The purpose of this work is twofold: 1) to measure dose pro-files under large-area lead shielding at the lens depth for clinical electron energies via film dosimetry; and 2) to assess the accuracy of the Pinnacle treatment planning system in calculating doses under lead shields. First, to simulate the clinical geometry, EBT3 film and 4 cm wide lead shields were incorporated into a Solid Water phantom. With the lead shield inside the phantom, the film was positioned at a depth of 0.7 cm below the lead, while a variable thickness of solid water, simulating bolus, was placed on top. This geometry was reproduced in Pinnacle to calculate dose profiles using the pencil beam electron algorithm. The measured and calculated dose profiles were normalized to the central-axis dose maximum in a homogeneous phantom with no lead shielding. The resulting measured profiles, functions of bolus thickness and incident electron energy, can be used to estimate the lens dose under various clinical scenarios. These profiles showed a minimum lead margin of 0.5 cm beyond the lens boundary is required to shield the lens to ≤ 10% of the dose maximum. Comparisons with Pinnacle showed a consistent overestimation of dose under the lead shield with discrepancies of ~ 25% occur-ring near the shield edge. This discrepancy was found to increase with electron energy and bolus thickness and decrease with distance from the lead edge. Thus, the Pinnacle electron algorithm is not recommended for estimating lens dose in this situation. The film measurements, however, allow for a reasonable estimate of lens dose from electron beams and for clinicians to assess the lead margin required to reduce the lens dose to an acceptable level.

Conventionally fully fractionated Gamma Knife Icon re-irradiation of primary recurrent intracranial tumors: the first report indicating feasibility and safety.

OBJECTIVE: With the incorporation of real-time image guidance on the Gamma Knife system allowing for mask-based immobilization (Gamma Knife Icon [GKI]), conventionally fully fractionated (1.8-3.0 Gy/day) GKI radiation can now be delivered to take advantage of an inherently minimal margin for delivery uncertainty, sharp dose falloff, and inhomogeneous dose distribution. This case series details the authors' preliminary experience in re-irradiating 7 complex primary intracranial tumors, which were considered to have been previously maximally radiated and situated adjacent to critical organs at risk. METHODS: The authors retrospectively reviewed all patients who received fractionated re-irradiation using GKI at the Sunnybrook Health Sciences Centre, University of Toronto, Ontario, Canada, between 2016 and 2021. Patients with brain metastases, and those who received radiotherapy courses in 5 or fewer fractions, were excluded. All radiotherapy doses were converted to the equivalent total dose in 2-Gy fractions (EQD2), with the assumption of an α/ß ratio of 2 for late normal tissue toxicity and 10 for the tumor. RESULTS: A total of 7 patients were included in this case series. Three patients had recurrent meningiomas, as well as 1 patient each with ependymoma, intracranial sarcoma, pituitary macroadenoma, and papillary pineal tumor. Six patients had undergone prior linear accelerator-based conventional fractionated radiotherapy and 1 patient had undergone prior proton therapy. Patients were re-irradiated with a median (range) total dose of 50.4 (30-63.4) Gy delivered in a median (range) of 28 (10-38) fractions with GKI. The median (range) target volume was 6.58 (0.2-46.3) cm3. The median (range) cumulative mean EQD2 administered to the tumor was 121.1 (107.9-181.3) Gy, and the median (range) maximum point EQD2 administered to the brainstem, optic nerves, and optic chiasm were 91.6 (74.0-111.5) Gy, 58.9 (6.3-102.9) Gy, and 59.9 (36.7-127.3) Gy, respectively. At a median (range) follow-up of 15 (6-42) months, 6 of 7 patients were alive with 4 having locally controlled disease. Only 3 patients experienced treatment-related toxicities, which were self-limited. CONCLUSIONS: Fractionated radiotherapy using GKI may be a safe and effective method for the re-irradiation of complex progressive primary intracranial tumors, where the aim is to minimize the potential for serious late effects.

Skull phantom-based methodology to validate MRI co-registration accuracy for Gamma Knife radiosurgery.

PURPOSE: Target localization, for stereotactic radiosurgery (SRS) treatment with Gamma Knife, has become increasingly reliant on the co-registration between the planning MRI and the stereotactic cone-beam computed tomography (CBCT). Validating image registration between modalities would be particularly beneficial when considering the emergence of novel functional and metabolic MRI pulse sequences for target delineation. This study aimed to develop a phantom-based methodology to quantitatively compare the co-registration accuracy of the standard clinical imaging protocol to a representative MRI sequence that was likely to fail co-registration. The comparative methodology presented in this study may serve as a useful tool to evaluate the clinical translatability of novel MRI sequences. METHODS: A realistic human skull phantom with fiducial marker columns was designed and manufactured to fit into a typical MRI head coil and the Gamma Knife patient positioning system. A series of "optimized" 3D MRI sequences-T1 -weighted Dixon, T1 -weighted fast field echo (FFE), and T2 -weighted fluid-attenuated inversion recovery (FLAIR)-were acquired and co-registered to the CBCT. The same sequences were "compromised" by reconstructing without geometric distortion correction and re-collecting with lower signal-to-noise-ratio (SNR) to simulate a novel MRI sequence with poor co-registration accuracy. Image similarity metrics-structural similarity (SSIM) index, mean squared error (MSE), and peak SNR (PSNR)-were used to quantitatively compare the co-registration of the optimized and compromised MR images. RESULTS: The ground truth fiducial positions were compared to positions measured from each optimized image volume revealing a maximum median geometric uncertainty of 0.39 mm (LR), 0.92 mm (AP), and 0.13 mm (SI) between the CT and CBCT, 0.60 mm (LR), 0.36 mm (AP), and 0.07 mm (SI) between the CT and T1 -weighted Dixon, 0.42 mm (LR), 0.23 mm (AP), and 0.08 mm (SI) between the CT and T1 -weighted FFE, and 0.45 mm (LR), 0.19 mm (AP), and 1.04 mm (SI) between the CT and T2 -weighted FLAIR. Qualitatively, pairs of optimized and compromised image slices were compared using a fusion image where separable colors were used to differentiate between images. Quantitatively, MSE was the most predictive and SSIM the second most predictive metric for evaluating co-registration similarity. A clinically relevant threshold of MSE, SSIM, and/or PSNR may be defined beyond which point an MRI sequence should be rejected for target delineation based on its dissimilarity to an optimized sequence co-registration. All dissimilarity thresholds calculated using correlation coefficients with in-plane geometric uncertainty would need to be defined on a sequence-by-sequence basis and validated with patient data. CONCLUSION: This study utilized a realistic skull phantom and image similarity metrics to develop a methodology capable of quantitatively assessing whether a modern research-based MRI sequence can be co-registered to the Gamma Knife CBCT with equal or less than equal accuracy when compared to a clinically accepted protocol.

Characterization of linear accelerator X-ray source size using a laminated beam-spot camera.

A laminated beam-spot camera of length 20 cm and effective cross-sectional area 2.5 cm × 3 cm was designed and constructed for the measurement of X-ray beam-spot sizes on different models of Siemens accelerators. With the accelerator gantry at 180° and camera positioned on an accessory tray holder, an XV film placed in contact with the camera at the distal end of it detected those X-rays that were transmitted through the camera. The FWHM of the detected X-ray intensity profile in the gun-target (G-T) direction or the orthogonal A-B direction was used as a measure of the beam-spot size in that direction. Siemens Mevatron MXEs exhibited a beam-spot size of 1.7 ± 0.2 mm in both the in-plane and cross-plane directions for 6 MV photon beams. The beam-spot size observed for a Mevatron MDX-2 was larger by up to 1 mm, and also was different for the in-plane and cross-plane directions. For Siemens PRIMUS accelerators, the beam-spot size in the in-plane direction was found to fall in the range 2.0-2.2 ± 0.2 mm, whereas the beam-spot size in the cross-plane direction fell within 1.7-1.9 ± 0.2 mm for 6, 10, and 18 MV photon beams. Assessment of long-term stability of the beam-spot size shows the spot size remains fairly stable over time.

Quantification and reduction of peripheral dose from leakage radiation on Siemens Primus accelerators in electron therapy mode.

In this work, leakage radiation from EA200 series electron applicators on Siemens Primus accelerators is quantified, and its penetration ability in water and/or the shielding material Xenolite-NL established. Initially, measurement of leakage from 10 x 10 - 25 x 25 cm2 applicators was performed as a function of height along applicator and of lateral distance from applicator body. Relative to central-axis ionization maximum in solid water, the maximum leakage in air observed with a cylindrical ion chamber with 1 cm solid water buildup cap at a lateral distance of 2 cm from the front and right sidewalls of applicators were 17% and 14%, respectively; these maxima were recorded for 18 MeV electron beams and applicator sizes of >or=20 x 20 cm2. In the patient plane, the applicator leakage gave rise to a broad peripheral dose off-axis distance peak that shifted closer to the field edge as the electron energy increases. The maximum peripheral dose from normally incident primary electron beams at a depth of 1 cm in a water phantom was observed to be equal to 5% of the central-axis dose maximum and as high as 9% for obliquely incident beams with angles of obliquity

Clinical Image Coregistration Variability on a Dedicated Radiosurgery Unit.

BACKGROUND: On a new dedicated radiosurgery unit enabling frameless treatments, a cone-beam computed tomography (CBCT) can be used for stereotactic definition. Since magnetic resonance imaging (MRI) is used to delineate target, reproducible MRI-to-CBCT coregistration is vital for accurate target localization. OBJECTIVE: To evaluate reproducibility of image coregistration in patient images. METHODS: Three types of coregistration (source-to-target) were analyzed: (1) MRI-to-CT; (2) MRI-to-CBCT; and (3) CT-to-CBCT. For each patient (n = 15), each coregistration type was independently performed 5 to 30 times (total: 465 coregistrations). Each coregistration yielded a transformation matrix, which was subsequently applied to transform every point in the source image to stereotactic coordinates. Two metrics were measured: (1) target registration error (TRE): mean distance between the registered position of each target point and the average registration position of that point; (2) compound registration error (CRE): mean spatial difference between stereotactic coordinates using (A) MRI-to-CT-to-CBCT and (B) MRI-to-CBCT. RESULTS: The median (range) of TRE was 0.11 mm (0.06-0.22 mm), 0.17 mm (0.10-0.36 mm), and 0.12 mm (0.08-0.21 mm) for MRI-to-CT, MRI-to-CBCT, and CT-to-CBCT, respectively. The TRE for MRI-to-CBCT was statistically higher than the other 2 methods (P < .01). The median (range) of CRE was 0.44 mm (0.22-0.59 mm). The maximum point CRE between patients ranged from 0.37-1.15 mm when considering all MRI points, but reduced to 0.31-0.90 mm within the central 16 cm. The CRE varied across the image volume, and typically was minimized near the center. CONCLUSION: The variation in image coregistration is within 0.2 mm, indicating a high degree of reproducibility. The CRE varies throughout the head but is submillimeter in the central 16 cm region.

Single-Fraction Stereotactic Radiosurgery Versus Hippocampal-Avoidance Whole Brain Radiation Therapy for Patients With 10 to 30 Brain Metastases: A Dosimetric Analysis.

PURPOSE: To compare normal tissue dosimetry between hippocampal-avoidance whole brain radiation therapy (HA-WBRT) and stereotactic radiosurgery (SRS) in patients with 10 to 30 brain metastases, and to describe a novel SRS strategy we term Spatially Partitioned Adaptive RadiosurgEry (SPARE). METHODS AND MATERIALS: A retrospective review identified SRS treatment plans with >10 brain metastases located >5 mm from the hippocampi. Our Gamma Knife Icon (GKI) SPARE (GKI-Spr) technique treats multiple metastases with single-fraction SRS partitioned over consecutive days while limiting the total treatment time to ≤60 minutes per day. Hippocampal and normal brain dosimetry were compared among GKI-Spr, single-fraction single-day GKI (GKI-Sfr), and 30 Gy in 10 fractions HA-WBRT. Dose metrics were converted to equivalent dose in 2 Gy fractions. RESULTS: Ten cases were analyzed. Compared with HA-WBRT, GKI-Spr significantly reduced the median equivalent dose in 2 Gy fractions hippocampal maximum point dose, mean dose, and dose to 40% of the hippocampi (D40%) by 86%, 93%, and 93%, respectively, and similarly for GKI-Sfr by 81%, 92%, and 91%, respectively. The normal brain median mean dose was reduced by 95% with GKI-Spr and 94% with GKI-Sfr. Compared with GKI-Sfr, GKI-Spr further reduced all normal brain and hippocampal dose metrics (P ≤ .014). CONCLUSIONS: GKI yields superior hippocampal and normal brain dosimetry compared with HA-WBRT, and GKI-Spr results in further dosimetric advantages.

Dosimetric verification of micro-MLC based intensity modulated radiation therapy.

A methodology for the dosimetric verification of micro-multileaf collimator MMLC) based intensity modulated radiation therapy (IMRT) plans intended for stereotactic applications is described. The procedure is similar to that of conventional IMRT patient-specific quality assurance with some notable exceptions. Relative dosimetry measurements are performed with radiographic film, a commercial film-scanning system and a dose-image registration program. Film dosimetry results are within +/- 3.0% of calculated distributions or within 2.0 mm distance to agreement. Absolute dosimetry measurements are performed with a small volume ion-chamber and a commercially available stereotactic phantom. The cumulative dose from all beams is within +/- 2.0 % of the prescribed dose. Large deviations may be observed from individual beams since the smaller IMRT fields tend to have very few high-dose and low-gradient regions. An independent program that examines the treatment MLC file is used to estimate the central axis dose from each beam and provide a dose image that can be assessed alongside the intended fluence distribution prior to treatment. Tolerances for relative and absolute dosimetry of MMLC-based IMRT treatments are tighter than what is typically reported for conventional MLC-based IMRT. Also, the time commitment for the IMRT QA is slightly longer than of conventional MLC-based IMRT due to QA processes which check the mechanical alignment of the MMLC device with the laser and radiation isocentre.

Performance characterization of an integrated cone-beam CT system for dedicated gamma radiosurgery.

PURPOSE: This work describes the performance characterization of a cone-beam CT-guided radiosurgery device, the Gamma Knife® Icon™. METHODS: The performance tests have been categorized into: (a) image quality and mechanical integrity; (b) image coregistration fidelity; (c) adaptive treatment delivery quality; (d) high definition motion management performance characterization; (e) software communication performance testing of the integrated cone-beam CT (CBCT) system. RESULTS: All image quality performance characterization satisfied or exceeded manufacturer specifications. The image quality and mechanical stability of the CBCT system over a 3-month period was within tolerance with negligible (<0.1°) detector tilt angle. The CBCT definition of the stereotactic space had a measured average discrepancy of 0.15-0.16 mm in x, y, and z directions. On average, the high definition motion management system performance was within 0.05 mm with a residual offset of 0.15 mm when large displacements in a given direction were taken. The adaptive treatment delivery component as measured with CBCT coregistration of daily setups against reference setup images was accurate to within 0.2°. Comprehensive end-to-end testing showed a total uncertainty of better than 0.2 mm in positioning and 0.4% in dosimetry for treatment of centrally located lesions. CONCLUSIONS: A set of system performance characterization tests spanning all aspects of the Gamma Knife Icon are presented. Overall, the system performance was in line with manufacturer specifications.

Investigation of irradiated volume in linac-based brain hypo-fractionated stereotactic radiotherapy.

BACKGROUND: Emerging techniques such as brain hypo-fractionated radiotherapy (HF-RT) involve complex cases with limited guidelines for plan quality and normal tissue tolerances. The purpose of the present study was to statistically parameterize irradiated volume independently of dose prescription, or margin to determine what spread in achievable irradiated volume one may expect for a given case. METHODS: We defined EXT as the total tissue within the external contour of the patient (including the target) and we defined BMP as the contour of the brain minus PTV. Irradiated volumes of EXT and BMP at specific doses (i.e. 50, 60%, etc., of the prescribed dose) were extracted from 135 single-target HF-RT clinical cases, each planned with a single-arc, homogeneous (SAHO) approach in which target maximum dose (Dmax) was constrained to <130% of the prescribed dose. Irradiated volumes were subsequently measured for cases involving 2 targets (N = 29), 3 targets (N = 7) and >3 targets (N = 10) to investigate the effect of target number. We also examined the effect of shape complexity. A series of best fit curves with confidence and prediction intervals were generated for irradiated volume versus total target volume and the resulting model was subsequently validated on a subsequent set of 23 consecutive prospective cases not originally used in curve-fitting. A subset of 30 HF-RT cases were re-planned with a well-published four-arc, heterogeneous (FAHE) radiosurgery planning approach (Dmax could exceed 130%) to demonstrate how technique affects irradiated volume. RESULTS: For SAHO, strong correlation (R2 > 0.98) was found for predicting irradiated volumes. For a given total target volume, irradiated-volume increased by a range of 1.4-2.9× for >3 versus single-targets depending on isodose level. Shape complexity had minor impact on irradiated volume. There was no statistical difference in irradiated volumes between validation and input data (p > 0.2). The FAHE-generated irradiated volumes yielded curves and prediction and confidence bands that agreed well with published data indicating that the proposed approach is feasible for cross-institutional comparisons. CONCLUSIONS: A description of irradiated volume for linac-based HF-RT is proposed based on population data. We have demonstrated that the proposed approach is feasible for inter and intra-institutional comparisons.

Investigation of Dose Falloff for Intact Brain Metastases and Surgical Cavities Using Hypofractionated Volumetric Modulated Arc Radiotherapy.

INTRODUCTION: Intact brain metastases tend to be small and spherical compared to postsurgery brain cavities, which tend to be large and irregular shaped and, as a result, a challenge with respect to treatment planning. The purpose of the present study is to develop guidelines for normal brain tissue dose and to investigate whether there is a dependence on target type for patients treated with hypofractionated volumetric modulated arc radiotherapy (HF-VMAT). METHODS: Treatment plans from a total of 100 patients and 136 targets (55 cavity and 81 intact) were retrospectively reviewed. All targets were treated with HF-VMAT with total doses ranging between 20 and 30 gray (Gy) in 5 fractions. All plans met institutional objectives for organ-at-risk constraints and were clinically delivered. Dose falloff was quantified using gradient index (GI) and distance between the 100% and 50% isodose lines (R50). Additionally, the dose to normal brain tissue (brain contour excluding all gross tumor or clinical target volumes) was assessed using volume receiving specific doses (Vx) where x ranged from 5 to 30 Gy. Best-fit curves using power law relationships of the form y = ax(b) were generated for GI, R50, and Vx (normal brain tissue) versus target volume. RESULTS: There was a statistically significant difference in planning target volume (PTV) for cavities versus intact metastases with mean volumes of 37.8 cm(3) and 9.5 cm(3), respectively (P < .0001). The GI and R50 were statistically different: 3.4 and 9.8 mm for cavities versus 4.6 and 8.3 mm for intact metastases (P < .0001). The R50 increased with PTV with power law coefficients (a, b) = (6.3, 0.12) and (5.9, 0.15) for cavities and intact, respectively. GI decreased with PTV with coefficients (a, b) = (5.9, -0.18) and (5.7, -0.14) for cavities and intact, respectively. The normal brain tissue Vx also exhibited power law relationships with PTV for x = 20 to 28.8 Gy. In conclusion, target volume is the main predictor of dose falloff. The results of the present study can be used for determining target volume-based thresholds for dose falloff and normal brain tissue dose-volume constraints.

Quality Assurance Results for a Commercial Radiosurgery System: A Communication.

The purpose of this communication is to inform the radiosurgery community of quality assurance (QA) results requiring attention in a commercial FDA-approved linac-based cone stereo-tactic radiosurgery (SRS) system. Standard published QA guidelines as per the American Association of Physics in Medicine (AAPM) were followed during the SRS system's commissioning process including end-to-end testing, cone concentricity testing, image transfer verification, and documentation. Several software and hardware deficiencies that were deemed risky were uncovered during the process and QA processes were put in place to mitigate these risks during clinical practice. In particular, the present work focuses on daily cone concentricity testing and commissioning-related findings associated with the software. Cone concentricity/alignment is measured daily using both optical light field inspection, as well as quantitative radiation field tests with the electronic portal imager. In 10 out of 36 clini-cal treatments, adjustments to the cone position had to be made to align the cone with the collimator axis to less than 0.5 mm and on two occasions the pre-adjustment measured offset was 1.0 mm. Software-related errors discovered during commissioning included incorrect transfer of the isocentre in DICOM coordinates, improper handling of non-axial image sets, and complex handling of beam data, especially for multi-target treatments. QA processes were established to mitigate the occurrence of the software errors. With proper QA processes, the reported SRS system complies with tolerances set out in established guidelines. Discussions with the vendor are ongoing to address some of the hardware issues related to cone alignment.

Intensity and energy modulated radiotherapy with proton beams: variables affecting optimal prostate plan.

Inverse planning for intensity- and energy-modulated radiotherapy (IEMRT) with proton beams involves the selection of (i) the relative importance factors to control the relative importance of the target and sensitive structures, (ii) an appropriate energy resolution to achieve an acceptable depth modulation, (iii) an appropriate beamlet width to modulate the beam laterally, and (iv) a sufficient number of beams and their orientations. In this article we investigate the influence of these variables on the optimized dose distribution of a simulated prostate cancer IEMRT treatment. Good dose conformation for this prostate case was achieved using a constellation of I factors for the target, rectum, bladder, and normal tissues of 500, 50, 15, and 1, respectively. It was found that for an active beam delivery system, the energy resolution should be selected on the basis of the incident beams' energy spread (sigmaE) and the appropriate energy resolution varied from 1 MeV at sigmaE = 0.0 to 5 MeV at sigmaE= 2.0 MeV. For a passive beam delivery system the value of the appropriate depth resolution for inverse planning may not be critical as long as the value chosen is at least equal to one-half the FWHM of the primary beam Bragg peak. Results indicate that the dose grid element dimension should be equal to or no less than 70% of the beamlet width. For this prostate case, we found that a maximum of three to four beam ports is required since there was no significant advantage to using a larger number of beams. However for a small number (< or = 4) of beams the selection of beam orientations, while having only a minor effect on target coverage, strongly influenced the sensitive structure sparing and normal tissue integral dose.