Comparative study of SRS end-to-end QA processes of a diode array device and an anthropomorphic phantom loaded with GafChromic XD film.

PURPOSE: End-to-end testing (E2E) is a necessary process for assessing the readiness of the stereotactic radiosurgery (SRS) program and annual QA of an SRS system according to the AAPM MPPG 9a. This study investigates the differences between using a new SRS MapCHECK (SRSMC) system and an anthropomorphic phantom film-based system in a large network with different SRS delivery techniques. METHODS AND MATERIALS: Three SRS capable Linacs (Varian Medical Systems, Palo Alto, CA) at three different regional sites were chosen to represent a hospital network, a Trilogy with an M120 multi-leaf collimator (MLC), a TrueBeam with an M120 MLC, and a TrueBeam Stx with an HD120 MLC. An anthropomorphic STEEV phantom (CIRS, Norfolk, VA) and a phantom/diode array: StereoPHAN/SRSMC (Sun Nuclear, Melbourne, FL) were CT scanned at each site. The new STV-PHANTOM EBT-XD films (Ashland, Bridgewater, NJ) were used. Six plans with various complexities were measured with both films and SRSMC in the StereoPHAN to establish their dosimetric correlations. Three SRS cranial plans with a total of sixteen fields using dynamic conformal arc and volumetric-modulated arc therapy, with 1-4 targets, were planned with Eclipse v15.5 treatment planning system (TPS) using a custom SRS beam model for each machine. The dosimetric and localization accuracy were compared. The time of analysis for the two systems by three teams of physicists was also compared to assess the throughput efficiency. RESULTS: The correlations between films and SRSMC were found to be 0.84 (p = 0.03) and 0.16 (p = 0.76) for γ (3%, 1 mm) and γ (3%, 2 mm), respectively. With film, the local dose differences (ΔD) relative to the average dose within the 50% isodose line from the three sites were found to be -3.2%-3.7%. The maximum localization errors (Elocal ) were found to be within 0.5 ± 0.2 mm. With SRSMC, the ΔD was found to be within 5% of the TPS calculation. Elocal were found to be within 0.7 to 1.1 ± 0.4 mm for TrueBeam and Trilogy, respectively. Comparing with film, an additional uncertainty of 0.7 mm was found with SRSMC. The delivery and analysis times were found to be 6 and 2 h for film and SRSMC, respectively. CONCLUSIONS: The SRS MapCHECK agrees dosimetrically with the films within measurement uncertainties. However, film dosimetry shows superior sub-millimeter localization resolving power for the MPPG 9a implementation.

Accuracy of surface-guided patient setup for conventional radiotherapy of brain and nasopharynx cancer.

PURPOSE: To evaluate the accuracy of surface-guided radiotherapy (SGRT) in cranial patient setup by direct comparison between optical surface imaging (OSI) and cone-beam computed tomography (CBCT), before applying SGRT-only setup for conventional radiotherapy of brain and nasopharynx cancer. METHODS AND MATERIALS: Using CBCT as reference, SGRT setup accuracy was examined based on 269 patients (415 treatments) treated with frameless cranial stereotactic radiosurgery (SRS) during 2018-2019. Patients were immobilized in customized head molds and open-face masks and monitored using OSI during treatment. The facial skin area in planning CT was used as OSI region of interest (ROI) for automatic surface alignment and the skull was used as the landmark for automatic CBCT/CT registration. A 6 degrees of freedom (6DOF) couch was used. Immediately after CBCT setup, an OSI verification image was captured, recording the SGRT setup differences. These differences were analyzed in 6DOFs and as a function of isocenter positions away from the anterior surface to assess OSI-ROI bias. The SGRT in-room setup time was estimated and compared with CBCT and orthogonal 2D kilovoltage (2DkV) setups. RESULTS: The SGRT setup difference (magnitude) is found to be 1.0 ± 2.5 mm and 0.1˚±1.4˚ on average among 415 treatments and within 5 mm/3˚ with greater than 95% confidence level (P < 0.001). Outliers were observed for very-posterior isocenters: 15 differences (3.6%) are >5.0mm and 9 (2.2%) are >3.0˚. The setup differences show minor correlations (|r| < 0.45) between translational and rotational DOFs and a minor increasing trend (<1.0 mm) in the anterior-to-posterior direction. The SGRT setup time is 0.8 ± 0.3 min, much shorter than CBCT (5 ± 2 min) and 2DkV (2 ± 1 min) setups. CONCLUSION: This study demonstrates that SGRT has sufficient accuracy for fast in-room patient setup and allows real-time motion monitoring for beam holding during treatment, potentially useful to guide radiotherapy of brain and nasopharynx cancer with standard fractionation.

Commissioning of optical surface imaging systems for cranial frameless stereotactic radiosurgery.

PURPOSE: This study aimed to evaluate and compare different system calibration methods from a large cohort of systems to establish a commissioning procedure for surface-guided frameless cranial stereotactic radiosurgery (SRS) with intrafractional motion monitoring and gating. Using optical surface imaging (OSI) to guide non-coplanar SRS treatments, the determination of OSI couch-angle dependency, baseline drift, and gated-delivered-dose equivalency are essential. METHODS: Eleven trained physicists evaluated 17 OSI systems at nine clinical centers within our institution. Three calibration methods were examined, including 1-level (2D), 2-level plate (3D) calibration for both surface image reconstruction and isocenter determination, and cube phantom calibration to assess OSI-megavoltage (MV) isocenter concordance. After each calibration, a couch-angle dependency error was measured as the maximum registration error within the couch rotation range. A head phantom was immobilized on the treatment couch and the isocenter was set in the middle of the brain, marked with the room lasers. An on-site reference image was acquired at couch zero, the facial region of interest (ROI) was defined, and static verification images were captured every 10° for 0°-90° and 360°-270°. The baseline drift was assessed with real-time monitoring of the motionless phantom over 20 min. The gated-delivered-dose equivalency was assessed using the electron portal imaging device and gamma test (1%/1mm) in reference to non-gated delivery. RESULTS: The maximum couch-angle dependency error occurs in longitudinal and lateral directions and is reduced significantly (P < 0.05) from 1-level (1.3 ± 0.4 mm) to 2-level (0.8 ± 0.3 mm) calibration. The MV cube calibration does not further reduce the couch-angle dependency error (0.8 ± 0.2 mm) on average. The baseline drift error plateaus at 0.3 ± 0.1 mm after 10 min. The gated-delivered-dose equivalency has a >98% gamma-test passing rate. CONCLUSION: A commissioning method is recommended using the 3D plate calibration, which is verified by radiation isocenter and validated with couch-angle dependency, baseline drift, and gated-delivered-dose equivalency tests. This method characterizes OSI uncertainties, ensuring motion-monitoring accuracy for SRS treatments.

Implementation and validation of an in-house geometry optimization software for SRS VMAT planning of multiple cranial metastases.

PURPOSE: The implementation and evaluation of an in-house developed geometry optimization (GO) software are described. The GO script provides optimal lesion clustering, isocenter placement, and collimator angle of each arc for cranial multi-lesion stereotactic radiosurgery (SRS) volumetric modulated arc therapy (VMAT) planning. MATERIALS AND METHODS: An Eclipse-plugin program was developed to facilitate automatic plan geometry generation for multiple metastases SRS VMAT plans. A mixed, semi-supervised exhaustive and k-means clustering method is used to group lesions and place isocenters. The sum of squared euclidean distance (SSED) and the boundaries of lesions' projection from beams' eye view are used as supervised parameters to determine the optimal isocenter numbers. The collimator angle is optimized by minimizing the sum of the MLC opening area from all gantry angles for each arc. In all, 10 clinical cases treated during 2016-2017 were compared to plan quality of GO script generated plans. Paddick gradient index (GI), conformity index (CI), and local brain volume receiving 12 Gy (local V12 Gy) around each lesion were compared. RESULT: For four cases, the number of isocenters was reduced in the GO plans. For four other cases, the GO plans had the same number of isocenters as their corresponding clinical plans but with different lesion grouping. The GO plans had significantly lower GI (4.1 ± 1.0 vs 4.4 ± 0.9, P < 0.0001) and local V12 Gy (5.1 ± 4.2 vs 5.5 ± 4.3 in cm3 , P < 0.0001), but not significantly different mean normal brain dose or CI. The volume of normal brain receiving ≥6 Gy was significantly lower in the GO plans. The total time to run the GO script for each case was <2 min. CONCLUSION: The GO software automates lesion grouping, isocenter placement, and the collimator angles for SRS VMAT planning. When tested on 10 cases, the GO script resulted in improved plan quality and shorter planning time when compared to the clinical SRS VMAT plans.

A phantom study to evaluate three different registration platform of 3D/3D, 2D/3D, and 3D surface match with 6D alignment for precise image-guided radiotherapy.

PURPOSE: To evaluate two three-dimensional (3D)/3D registration platforms, one two-dimensional (2D)/3D registration method, and one 3D surface registration method (3DS). These three technologies are available to perform six-dimensional (6D) registrations for image-guided radiotherapy treatment. METHODS: Fiducial markers were asymmetrically placed on the surfaces of an anthropomorphic head phantom (n = 13) and a body phantom (n = 8), respectively. The point match (PM) solution to the six-dimensional (6D) transformation between the two image sets [planning computed tomography (CT) and cone beam CT (CBCT)] was determined through least-square fitting of the fiducial positions using singular value decomposition (SVD). The transformation result from SVD was verified and was used as the gold standard to evaluate the 6D accuracy of 3D/3D registration in Varian's platform (3D3DV), 3D/3D and 2D/3D registration in the BrainLab ExacTrac system (3D3DE and 2D3D), as well as 3DS in the AlignRT system. Image registration accuracy from each method was quantitatively evaluated by root mean square of target registration error (rmsTRE) on fiducial markers and by isocenter registration error (IRE). The Wilcoxon signed-rank test was utilized to compare the difference of each registration method with PM. A P < 0.05 was considered significant. RESULTS: rmsTRE was in the range of 0.4 mm/0.7 mm (cranial/body), 0.5 mm/1 mm, 1.0 mm/1.5 mm, and 1.0 mm/1.2 mm for PM, 3D3D, 2D3D, and 3DS, respectively. Comparing to PM, the mean errors of IRE were 0.3 mm/1 mm for 3D3D, 0.5 mm/1.4 mm for 2D3D, and 1.6 mm/1.35 mm for 3DS for the cranial and body phantoms respectively. Both of 3D3D and 2D3D methods differed significantly in the roll direction as compared to the PM method for the cranial phantom. The 3DS method was significantly different from the PM method in all three translation dimensions for both the cranial (P = 0.003-P = 0.03) and body (P < 0.001-P = 0.008) phantoms. CONCLUSION: 3D3D using CBCT had the best image registration accuracy among all the tested methods. 2D3D method was slightly inferior to the 3D3D method but was still acceptable as a treatment position verification device. 3DS is comparable to 2D3D technique and could be a substitute for X-ray or CBCT for pretreatment verification for treatment of anatomical sites that are rigid.

Institutional experience with SRS VMAT planning for multiple cranial metastases.

BACKGROUND AND PURPOSE: This study summarizes the cranial stereotactic radiosurgery (SRS) volumetric modulated arc therapy (VMAT) procedure at our institution. MATERIALS AND METHODS: Volumetric modulated arc therapy plans were generated for 40 patients with 188 lesions (range 2-8, median 5) in Eclipse and treated on a TrueBeam STx. Limitations of the custom beam model outside the central 2.5 mm leaves necessitated more than one isocenter pending the spatial distribution of lesions. Two to nine arcs were used per isocenter. Conformity index (CI), gradient index (GI) and target dose heterogeneity index (HI) were determined for each lesion. Dose to critical structures and treatment times are reported. RESULTS: Lesion size ranged 0.05-17.74 cm3 (median 0.77 cm3 ), and total tumor volume per case ranged 1.09-26.95 cm3 (median 7.11 cm3 ). For each lesion, HI ranged 1.2-1.5 (median 1.3), CI ranged 1.0-2.9 (median 1.2), and GI ranged 2.5-8.4 (median 4.4). By correlating GI to PTV volume a predicted GI = 4/PTV0.2 was determined and implemented in a script in Eclipse and used for plan evaluation. Brain volume receiving 7 Gy (V7 Gy ) ranged 10-136 cm3 (median 42 cm3 ). Total treatment time ranged 24-138 min (median 61 min). CONCLUSIONS: Volumetric modulated arc therapy provide plans with steep dose gradients around the targets and low dose to critical structures, and VMAT treatment is delivered in a shorter time than conventional methods using one isocenter per lesion. To further improve VMAT planning for multiple cranial metastases, better tools to shorten planning time are needed. The most significant improvement would come from better dose modeling in Eclipse, possibly by allowing for customizing the dynamic leaf gap (DLG) for a special SRS model and not limit to one DLG per energy per treatment machine and thereby remove the limitation on the Y-jaw and allow planning with a single isocenter.

Long-term risk of radionecrosis and imaging changes after stereotactic radiosurgery for brain metastases.

Radionecrosis is a well-characterized effect of stereotactic radiosurgery (SRS) and is occasionally associated with serious neurologic sequelae. Here, we investigated the incidence of and clinical variables associated with the development of radionecrosis and related radiographic changes after SRS for brain metastases in a cohort of patients with long-term follow up. 271 brain metastases treated with single-fraction linear accelerator-based SRS were analyzed. Radionecrosis was diagnosed either pathologically or radiographically. Univariate and multivariate Cox regression was performed to determine the association between radionecrosis and clinical factors available prior to treatment planning. After median follow up of 17.2 months, radionecrosis was observed in 70 (25.8%) lesions, including 47 (17.3%) symptomatic cases. 22 of 70 cases (31.4%) were diagnosed pathologically and 48 (68.6%) were diagnosed radiographically. The actuarial incidence of radionecrosis was 5.2% at 6 months, 17.2% at 12 months and 34.0% at 24 months. On univariate analysis, radionecrosis was associated with maximum tumor diameter (HR 3.55, p < 0.001), prior whole brain radiotherapy (HR 2.21, p = 0.004), prescription dose (HR 0.56, p = 0.02) and histology other than non-small cell lung, breast or melanoma (HR 1.85, p = 0.04). On multivariate analysis, only maximum tumor diameter (HR 3.10, p < 0.001) was associated with radionecrosis risk. This data demonstrates that with close imaging follow-up, radionecrosis after single-fraction SRS for brain metastases is not uncommon. Maximum tumor diameter on pre-treatment MR imaging can provide a reliable estimate of radionecrosis risk prior to treatment planning, with the greatest risk among tumors measuring >1 cm.

Clinical experience with two frameless stereotactic radiosurgery (fSRS) systems using optical surface imaging for motion monitoring.

The purpose of this study was to compare two clinical immobilization systems for intracranial frameless stereotactic radiosurgery (fSRS) under the same clinical procedure using cone-beam computed tomography (CBCT) for setup and video-based optical surface imaging (OSI) for initial head alignment and intrafractional motion monitoring. A previously established fSRS procedure was applied using two intracranial immobilization systems: PinPoint system (head mold and mouthpiece) and Freedom system (head mold and open face mask). The CBCT was used for patient setup with four degrees of freedom (4DOF), while OSI was used for 6DOF alignment prior to CBCT, post-CBCT setup verification at all treatment couch angles (zero and nonzero), and intrafractional motion monitoring. Quantitative comparison of the two systems includes residual head rotation, head restriction capacity, and patient setup time in 25 patients (29 lesions) using PinPoint and 8 patients (29fractions) using Freedom. The maximum possible motion was assessed in nine volunteers with deliberate, forced movement in Freedom system. A consensus-based comparison of patient comfort level and clinical ease of use is reported. Using OSI-guided corrections, the maximum residual rotations in all directions were 1.1° ± 0.5° for PinPoint and 0.6° ± 0.3° for Freedom. The time spent performing rotation corrections was 5.0 ± 4.1 min by moving the patient with PinPoint and 2.7 ± 1.0min by adjusting Freedom couch extension. After CBCT, the OSI-CBCT discrepancy due to different anatomic landmarks for alignment was 2.4 ± 1.3 mm using PinPoint and 1.5 ± 0.7 mm using Freedom. Similar results were obtained for setup verification at couch angles (< 1.5 mm) and for motion restriction: 0.4± 0.3 mm/0.2° ± 0.2° in PinPoint and 0.6 ± 0.3 mm/0.3° ± 0.1° in Freedom. The maximum range of forced head motion was 2.2 ± 1.0 mm using Freedom. Both intracranial fSRS immobilization systems can restrict head motion within 1.5 mm during treatment as monitored by OSI. Setting a motion threshold for beam-hold ensures that head motion is constrained within the treatment margin during beam-on periods. The capability of 6D setup is useful to improve treatment accuracy. Patient comfort and clinical workflow should play a substantial role in system selection, and Freedom system outperforms PinPoint system in these two aspects.

Artificial-intelligence-driven measurements of brain metastases' response to SRS compare favorably with current manual standards of assessment.

Background: Evaluation of treatment response for brain metastases (BMs) following stereotactic radiosurgery (SRS) becomes complex as the number of treated BMs increases. This study uses artificial intelligence (AI) to track BMs after SRS and validates its output compared with manual measurements. Methods: Patients with BMs who received at least one course of SRS and followed up with MRI scans were retrospectively identified. A tool for automated detection, segmentation, and tracking of intracranial metastases on longitudinal imaging, MEtastasis Tracking with Repeated Observations (METRO), was applied to the dataset. The longest three-dimensional (3D) diameter identified with METRO was compared with manual measurements of maximum axial BM diameter, and their correlation was analyzed. Change in size of the measured BM identified with METRO after SRS treatment was used to classify BMs as responding, or not responding, to treatment, and its accuracy was determined relative to manual measurements. Results: From 71 patients, 176 BMs were identified and measured with METRO and manual methods. Based on a one-to-one correlation analysis, the correlation coefficient was R2 = 0.76 (P = .0001). Using modified BM response classifications of BM change in size, the longest 3D diameter data identified with METRO had a sensitivity of 0.72 and a specificity of 0.95 in identifying lesions that responded to SRS, when using manual axial diameter measurements as the ground truth. Conclusions: Using AI to automatically measure and track BM volumes following SRS treatment, this study showed a strong correlation between AI-driven measurements and the current clinically used method: manual axial diameter measurements.

Automatically tracking brain metastases after stereotactic radiosurgery.

Background and purpose: Patients with brain metastases (BMs) are surviving longer and returning for multiple courses of stereotactic radiosurgery. BMs are monitored after radiation with follow-up magnetic resonance (MR) imaging every 2-3 months. This study investigated whether it is possible to automatically track BMs on longitudinal imaging and quantify the tumor response after radiotherapy. Methods: The METRO process (MEtastasis Tracking with Repeated Observations was developed to automatically process patient data and track BMs. A longitudinal intrapatient registration method for T1 MR post-Gd was conceived and validated on 20 patients. Detections and volumetric measurements of BMs were obtained from a deep learning model. BM tracking was validated on 32 separate patients by comparing results with manual measurements of BM response and radiologists' assessments of new BMs. Linear regression and residual analysis were used to assess accuracy in determining tumor response and size change. Results: A total of 123 irradiated BMs and 38 new BMs were successfully tracked. 66 irradiated BMs were visible on follow-up imaging 3-9 months after radiotherapy. Comparing their longest diameter changes measured manually vs. METRO, the Pearson correlation coefficient was 0.88 (p < 0.001); the mean residual error was -8 ± 17%. The mean registration error was 1.5 ± 0.2 mm. Conclusions: Automatic, longitudinal tracking of BMs using deep learning methods is feasible. In particular, the software system METRO fulfills a need to automatically track and quantify volumetric changes of BMs prior to, and in response to, radiation therapy.

Risk of tract recurrence with stereotactic biopsy of brain metastases: an 18-year cancer center experience.

OBJECTIVE: Stereotactic biopsy is increasingly performed on brain metastases (BrMs) as improving cancer outcomes drive aggressive multimodality treatment, including laser interstitial thermal therapy (LITT). However, the tract recurrence (TR) risk is poorly defined in an era defined by focused-irradiation paradigms. As such, the authors aimed to define indications and adjuvant therapies for this procedure and evaluate the BrM-biopsy TR rate. METHODS: In a single-center retrospective review, the authors identified stereotactic BrM biopsies performed from 2002 to 2020. Surgical indications, radiographic characteristics, stereotactic planning, dosimetry, pre- and postoperative CNS-directed and systemic treatments, and clinical courses were collected. Recurrence was evaluated using RANO-BM (Response Assessment in Neuro-Oncology Brain Metastases) criteria. RESULTS: In total, 499 patients underwent stereotactic intracranial biopsy for any diagnosis, of whom 25 patients (5.0%) underwent biopsy for pathologically confirmed viable BrM, a proportion that increased over the time period studied. Twelve of the 25 BrM patients had ≥ 3 months of radiographic follow-up, of whom 6 patients (50%) developed new metastatic growth along the tract at a median of 5.0 months post-biopsy (range 2.3-17.1 months). All of the TR cases had undergone pre- or early post-biopsy stereotactic radiosurgery (SRS), and 3 had also undergone LITT at the time of initial biopsy. TRs were treated with resection, reirradiation, or observation/systemic therapy. CONCLUSIONS: In this study the authors identified a nontrivial, higher than previously described rate of BrM-biopsy tract recurrence, which often required additional surgery or radiation and justified close radiographic surveillance. As BrMs are commonly treated with SRS limited to enhancing tumor margins, consideration should be made, in cases lacking CNS-active systemic treatments, to include biopsy tracts in adjuvant radiation plans where feasible.

Motion monitoring for cranial frameless stereotactic radiosurgery using video-based three-dimensional optical surface imaging.

PURPOSE: To establish a new clinical procedure in frameless stereotactic radiosurgery (SRS) for patient setup verification at treatment couch angles as well as for head-motion monitoring during treatment using video-based optical surface imaging (OSI). METHODS: A video-based three-dimensional (3D) OSI system with three ceiling-mounted camera pods was employed to verify setup at treatment couch angles as well as to monitor head motion during treatment. A noninvasive head immobilization device was utilized, which includes an alpha head mold and a dental mouthpiece with vacuum suction; both were locked to the treatment couch. Cone beam computed tomography (CBCT) was used as the standard for image-guided setup. Orthogonal 2D-kV imaging was applied for setup verification before treatment, between couch rotations, and after treatment at zero couch angle. At various treatment couch angles, OSI setup verification was performed, relative to initial OSI setup verification at zero couch angle after CBCT setup through a coordinate transformation. For motion monitoring, the setup uncertainty was decoupled by taking an on-site surface image as new reference to detect motion-induced misalignment in near real-time (1-2 frames per second). Initial thermal instability baseline of the real-time monitoring was corrected. An anthropomorphous head phantom and a 1D positioning platform were used to assess the OSI accuracy in motion detection in longitudinal and lateral directions. Two hypofractionated (9 Gy x 3 and 6 Gy x 5) frameless stereotactic radiotherapy (SRT) patients as well as two single-fraction (21 and 18 Gy) frameless SRS patients were treated using this frameless procedure. For comparison, 11 conventional frame-based SRS patients were monitored using the OSI to serve as clinical standards. Multiple noncoplanar conformal beams were used for planning both frameless and frame-based SRS with a micromultileaf collimator. RESULTS: The accuracy of the OSI in 1D motion detection was found to be 0.1 mm with uncertainty of +/- 0.1 mm using the head phantom. The OSI registration against simulation computed tomography (CT) external contour was found to be dependent on the CT skin definition with -0.4 mm variation. For frame-based SRS patients, head-motion magnitude was detected to be <1.0 mm (0.3 +/- 0.2 mm) and <1.0 degree (0.2 degrees +/- 0.2 degrees) for 98% of treatment time, with exception of one patient with head rotation <1.5 degrees for 98% of the time. For frameless SRT/SRS patients, similar motion magnitudes were observed with an average of 0.3 +/- 0.2 mm and 0.2 degrees +/- 0.1 degree in ten treatments. For 98% of the time, the motion magnitude was <1.1 mm and 1.0 degree. Complex head-motion patterns within 1.0 mm were observed for frameless SRT/SRS patients. The OSI setup verification at treatment couch angles was found to be within 1.0 mm. CONCLUSIONS: The OSI system is capable of detecting 0.1 +/- 0.1 mm 1D spatial displacement of a phantom in near real time and useful in head-motion monitoring. This new frameless SRS procedure using the mask-less head-fixation system provides immobilization similar to that of conventional frame-based SRS. Head-motion monitoring using near-real-time surface imaging provides adequate accuracy and is necessary for frameless SRS in case of unexpected head motion that exceeds a set tolerance.

Magnetic resonance spectroscopy imaging in radiotherapy planning for recurrent glioma.

PURPOSE: The purpose of this study was to investigate how incorporation of magnetic resonance spectroscopy imaging (MRSI) into radiotherapy planning would increase the target volume for patients with recurrent glioma. METHODS: After prior standard radiotherapy, 25 patients with recurrent glioma were treated with bevacizumab and concurrent hypofractionated stereotactic radiotherapy (HFSRT), delivering 30 Gy in five fractions. MRSI were acquired for 12 patients. Areas with markedly higher choline levels relative to the levels of total creatine and N-acetylaspartate were identified and referred to as MRSI voxels with elevated metabolite ratios (EMR). Gross tumor volume (GTV) consisted of contrast-enhancing tumor on T1-weighted magnetic resonance images (MRI) and computed tomography. Clinical target volume (CTV) was GTV + 5 mm margin and MRSI voxels with EMR. Overall survival (OS) and 6-month progression free survival (PFS) for these patients were reported in a prior publication [Gutin et al., Int. J. Radiat. Oncol., Biol., Phys. 75(1), 156-163 (2009)], and the outcome was correlated with the GTV and the volume of MRSI voxels with EMR in this study. RESULTS: Seven of the 12 patients had MRSI voxels with EMR. If none of the MRSI voxels with EMR were included, the CTV would range from 9.2 to 73.0 cm3 with a median of 31.0 cm3, whereas if all voxels were included, the CTV would range from 27.4 to 74.4 cm3 with a median of 35.0 cm3. For three of the seven patients, including the voxels with EMR, would have increased the CTV by 14%-23%. For one patient, where the MRSI voxels with EMR did not overlap the GTV, including these voxels would increase the CTV by 198%. No correlation could be found between the OS and PFS and the GTV or the volume of MRSI voxels with EMR. CONCLUSIONS: Seven of 12 patients with recurrent glioma had MRSI voxels with EMR. For four of these seven patients, including the MRSI voxels with EMR, significantly increased the CTV. This study does not have statistical power to conclude on the importance of including areas with MRSI-suspect disease into the radiation target volume.

Automatic segmentation of brain metastases using T1 magnetic resonance and computed tomography images.

An increasing number of patients with multiple brain metastases are being treated with stereotactic radiosurgery (SRS). Manually identifying and contouring all metastatic lesions is difficult and time-consuming, and a potential source of variability. Hence, we developed a 3D deep learning approach for segmenting brain metastases on MR and CT images. Five-hundred eleven patients treated with SRS were retrospectively identified for this study. Prior to radiotherapy, the patients were imaged with 3D T1 spoiled-gradient MR post-Gd (T1 + C) and contrast-enhanced CT (CECT), which were co-registered by a treatment planner. The gross tumor volume contours, authored by the attending radiation oncologist, were taken as the ground truth. There were 3 ± 4 metastases per patient, with volume up to 57 ml. We produced a multi-stage model that automatically performs brain extraction, followed by detection and segmentation of brain metastases using co-registered T1 + C and CECT. Augmented data from 80% of these patients were used to train modified 3D V-Net convolutional neural networks for this task. We combined a normalized boundary loss function with soft Dice loss to improve the model optimization, and employed gradient accumulation to stabilize the training. The average Dice similarity coefficient (DSC) for brain extraction was 0.975 ± 0.002 (95% CI). The detection sensitivity per metastasis was 90% (329/367), with moderate dependence on metastasis size. Averaged across 102 test patients, our approach had metastasis detection sensitivity 95 ± 3%, 2.4 ± 0.5 false positives, DSC of 0.76 ± 0.03, and 95th-percentile Hausdorff distance of 2.5 ± 0.3 mm (95% CIs). The volumes of automatic and manual segmentations were strongly correlated for metastases of volume up to 20 ml (r=0.97,p<0.001). This work expounds a fully 3D deep learning approach capable of automatically detecting and segmenting brain metastases using co-registered T1 + C and CECT.

Durable 5-year local control for resected brain metastases with early adjuvant SRS: the effect of timing on intended-field control.

BACKGROUND: Adjuvant stereotactic radiosurgery (SRS) improves the local control of resected brain metastases (BrM). However, the dependency of long-term outcomes on SRS timing relative to surgery remains unclear. METHODS: Retrospective analysis of patients treated with metastasectomy-plus-adjuvant SRS at Memorial Sloan Kettering Cancer Center (MSK) between 2013 and 2016 was conducted. Kaplan-Meier methodology was used to describe overall survival (OS) and cumulative incidence rates were estimated by type of recurrence, accounting for death as a competing event. Recursive partitioning analysis (RPA) and competing risks regression modeling assessed prognostic variables and associated events of interest. RESULTS: Two hundred and eighty-two patients with BrM had a median OS of 1.5 years (95% CI: 1.2-2.1) from adjuvant SRS with median follow-up of 49.8 months for survivors. Local surgical recurrence, other simultaneously SRS-irradiated site recurrence, and distant central nervous system (CNS) progression rates were 14.3% (95% CI: 10.1-18.5), 4.9% (95% CI: 2.3-7.5), and 47.5% (95% CI: 41.4-53.6) at 5 years, respectively. Median time-to-adjuvant SRS (TT-SRS) was 34 days (IQR: 27-39). TT-SRS was significantly associated with surgical site recurrence rate (P = 0.0008). SRS delivered within 1 month resulted in surgical site recurrence rate of 6.1% (95% CI: 1.3-10.9) at 1-year, compared to 9.2% (95% CI: 4.9-13.6) if delivered between 1 and 2 months, or 27.3% (95% CI: 0.0-55.5) if delivered >2 months after surgery. OS was significantly lower for patients with TT-SRS >~2 months. Postoperative length of stay, discharge to a rehabilitation facility, urgent care visits, and/or disease recurrence between surgery and adjuvant SRS associated with increased TT-SRS. CONCLUSIONS: Adjuvant SRS provides durable local control. However, delays in initiation of postoperative SRS can decrease its efficacy.

Frequency of Large Intrafractional Target Motions During Spine Stereotactic Body Radiation Therapy.

Spine stereotactic body radiation therapy frequently involves the delivery of high doses to targets in proximity to the spinal cord; thus, the radiation must be delivered with great spatial accuracy. Monitoring for large shifts in target and cord position that might occur during dose delivery is a challenge for clinics equipped with a conventional C-arm Linac. Treatment must be halted, then imaging and registration must be done to determine whether a significant shift has occurred. In this retrospective study of 1019 spine SBRT treatments, we investigated the number of target shifts >2 mm in any direction that occurred in carefully immobilized patients. Orthogonal kV images were acquired 3 to 5 times during each session using in an in-room imaging system. Although the likelihood of large intrafractional shifts was found to be very low, they did occur in 6 treatment sessions. Intrafractional monitoring was found to be an important safety component of treatment delivery.

A pilot study of 13N-ammonia cardiac PET imaging to assess subacute cardiotoxicity following adjuvant intensity-modulated radiotherapy for locally advanced breast cancer.

OBJECTIVE: (1) Assess the feasibility of 13 N-ammonia cardiac PET (13 N-ammonia-PET) imaging in radiotherapy (RT) treatment position in locally-advanced breast cancer (LABC) patients. (2) Correlate pre-/post-RT changes in myocardial flow reserve (MFR) with the corresponding radiation heart dose. METHODS: Ten left-sided LABC patients undergoing Volumetric Modulated-Arc-Therapy (VMAT) to chest wall and regional lymph nodes underwent a rest/stress 13 N-ammonia-PET at baseline and (median) 13 months post-RT. Changes in cardiac functions and coronary artery Ca2+ scoring between baseline and follow-up were correlated with average RT dose to the myocardium,3 coronary territories, and 17 myocardial segments. RESULTS: Eight (of 10) patients successfully completed the study. The average rest (stress) global MBF (ml.g-1.min-1) for baseline (follow-up) were 0.83 ± 0.25 (2.4 ± 0.79) and 0.92 ± 0.30 (2.76 ± 0.71), respectively. Differences in MBF, heart rate, blood pressure, and rate-pressure product (RPP) between baseline and follow-up were insignificant (P > 0.1).Strong (R = 0.79; P < 0.01) and moderate (R = 0.53; P = 0.37) correlation existed between MBF Rest and MBF Stress, and RPP respectively. Four patients showed a reduction in MFR of up to ~41% in follow-up studies, increasing to ~52% in myocardial segments close to high-radiation isodose lines in 5/8 patients. Agatston Ca + 2 scoring were zero in both baseline and follow-up in six patients; two patients exhibited mild increase in Ca + 2 on follow-ups (range:10-20).Rest and stress LVEF's were normal (>50) for all patients in both studies. CONCLUSION: The feasibility of 13 N-ammonia-PET imaging in treatment position of LABC patients was demonstrated. MFR at 1-year post-irradiation of the heart decreased in 50% of the patients. MFR may be a potential index for early detection of cardiotoxicity in BC patients receiving RT to the chest wall.

A VMAT planning technique for locally advanced breast cancer patients with expander or implant reconstructions requiring comprehensive postmastectomy radiation therapy.

Locally advanced breast cancer patients with expander or implant reconstructions who require comprehensive postmastectomy radiotherapy (PMRT) can pose unique treatment planning challenges. Traditional 3D conformal radiation techniques often result in large dose inhomogeneity throughout the treatment volumes, inadequate target coverage, or excessive normal tissue doses. We have developed a volumetric modulated arc therapy (VMAT) planning technique without entering through the ipsilateral arm that produced adequate target volume coverage, excellent homogeneity throughout the target volume, and acceptable doses to the normal structures. Twenty left-sided and 10 right-sided patients with either ipsilateral or bilateral permanent implants or tissue expanders who received comprehensive PMRT between October 2014 and February 2016 were included in this study. Ten left-sided cases used deep inspiration breath hold (DIBH) technique, and others used free breathing (FB). Planning target volume (PTV) included chestwall, internal mammary nodes (IMNs), supraclavicular, and axillary lymph nodes. A VMAT plan using 4 or 5 partial arcs with 6 MV photon beam avoiding entering through the ipsilateral arm was generated for each patient. Prescription dose was 50 Gy in 25 fractions. PTV coverage, maximum depth of IMNs, dose homogeneity and dose to the heart, lungs, thyroid, contralateral intact breast or implant, liver, stomach, left anterior descending artery, ipsilateral brachial plexus, esophagus, spinal cord, and total MU were evaluated. PTV D95% (Gy) was 49.6 ± 0.9, 48.7 ± 0.9, and 49.5 ± 1.1; PTV D05% (Gy) was 55.7 ± 0.6, 55.1 ± 1.4, and 55.0 ± 0.7; maximum depth of IMNs (cm) was 4.3 ± 0.9, 4.6 ± 1.1, and 4.9 ± 2.3; ipsilateral lung, V20Gy (%) was 29.0 ± 2.1, 28.8 ± 2.5, and 27.5 ± 3.4; heart mean dose (Gy) was 4.2 ± 0.4, 7.5 ± 1.1, and 6.6 ± 0.8 for right-sided FB, left-sided FB, and left-sided DIBH cases, respectively. D95% of IMNs all received 100% prescription dose. The maximum dose (Gy) to the left anterior descending artery was 33.8 ± 11.7 for left-sided FB and 31.4 ± 7.3 for left-sided DIBH. VMAT technique avoiding ipsilateral arm can produce acceptable clinical plans for locally advanced breast cancer patients with expander or implant reconstructions receiving comprehensive PMRT.

Long-Term Pulmonary Outcomes of a Feasibility Study of Inverse-Planned, Multibeam Intensity Modulated Radiation Therapy in Node-Positive Breast Cancer Patients Receiving Regional Nodal Irradiation.

PURPOSE: Multibeam intensity modulated radiation therapy (IMRT) enhances the therapeutic index by increasing the dosimetric coverage of the targeted tumor tissues while minimizing volumes of adjacent organs receiving high doses of RT. The tradeoff is that a greater volume of lung is exposed to low doses of RT, raising concern about the risk of radiation pneumonitis (RP). METHODS AND MATERIALS: Between July 2010 and January 2013, patients with node-positive breast cancer received inverse-planned, multibeam IMRT to the breast or chest wall and regional nodes, including the internal mammary nodes (IMNs). The primary endpoint was feasibility, predefined by dosimetric treatment planning criteria. Secondary endpoints included the incidence of RP grade 3 or greater and changes in pulmonary function measured with the Common Terminology Criteria for Adverse Events version 3.0 scales, pulmonary function tests and community-acquired pneumonia questionnaires, obtained at baseline and 6 months after IMRT. Clinical follow-up was every 6 months for up to 5 years. RESULTS: Median follow-up was 53.4 months (range, 0-82 months). Of 113 patients enrolled, 104 completed follow-up procedures. Coverage of the breast or chest wall and IMN was comprehensive (median 48.1 Gy and 48.9 Gy, respectively). The median volume of lung receiving a high dose (V20Gy) and a low dose (V5) was 29% and 100%, respectively. The overall rate of respiratory toxicities was 10.6% (11/104), including 1 grade 3 RP event (0.96%). No differences were found in pulmonary function test or community-acquired pneumonia scores after IMRT. The 5-year rates of locoregional recurrence-free, disease-free, and overall survival were 93.2%, 63.6%, and 80.3%, respectively. CONCLUSIONS: Multibeam IMRT in patients with breast cancer receiving regional nodal irradiation was dosimetrically feasible, based on early treatment planning criteria. Despite the large volume of lung receiving low-dose RT, the incidence of grade 3 RP was remarkably low, justifying inverse-planned IMRT as a treatment modality for patients with high-risk breast cancer in whom conventional RT techniques prove inadequate.

Electron postmastectomy chest wall plus comprehensive nodal irradiation technique using Electron Monte Carlo dose algorithm.

For left-sided postmastectomy patients requiring chest wall plus comprehensive nodal irradiation, sometimes traditional techniques such as partial wide tangents or electron/tangents combination are not feasible due to abnormal chest wall contour or heart position or unusually wide excision scar. We developed electron chest wall irradiation technique using Electron Monte Carlo (EMC) dose algorithm that will achieve heart sparing with acceptable ipsilateral lung dose, minimal contralateral lung, and breast dose. Ten left-sided postmastectomy patients with very challenging anatomy were selected for this dosimetry study. The en face electron fields were designed from a single isocenter and gantry angle with different energy beams using different cutouts that matched on the skin. Smaller energy was used in the central thin chest wall part and higher energy in the medial internal mammary nodes (IMN) area, superior part of the thick chest wall, and/or axillary nodal area. The electron fields were matched to the photon supraclavicular field in the superior region. Daily field junctions were used to feather the match lines between all the fields. Electron field dose calculations were done with Monte Carlo. Five patients' chest wall fields were planned with 6/9MeVcombination, 1 with 6/12 MeV, 2 with 9/12 MeV, 1 with 9/16 MeV, and 1 with 6/9/12 MeV. Institutional criteria of prescription dose of 50 Gy for target volumes and normal tissue dose were met with this technique in spite of the challenging anatomy. Mean heart dose averaged 3.0 Gy ± 0.8 Gy. For ipsilateral lung, V20Gy and V5Gy averaged 33.2% ± 4.5% and 64.6% ± 9.6%, respectively. For contralateral lung, V5Gy averaged 5.1% ± 5.0%. For contralateral breast, V5Gy averaged 3.3% ± 3.1%. The electron chest wall irradiation technique using EMC dose algorithm can provide adequate dose coverage to the chest wall, IMNs, and/or axillary nodes while achieving heart sparing with acceptable ipsilateral lung dose, minimal contralateral lung, and breast dose.