Less Time Is Less Motion: Analysis of Practical Efficiencies Gained With a Modified Workflow Integrating Planar kV Midimaging With CBCT for Spine Stereotactic Body Radiation Therapy.

Purpose: Our purpose was to optimize an image guided radiation therapy (IGRT) workflow to achieve practical setup accuracy in spine stereotactic body radiation therapy (SBRT). We assessed the time-saving efficiencies gained from incorporating planar kV midimaging as a surrogate for cone beam computed tomography (CBCT) for intrafraction motion monitoring. Methods and Materials: We selected 5 thoracic spine SBRT patients treated in 5 fractions and analyzed patient shifts captured by a modified IGRT workflow using planar kV midimaging integrated with CBCT to maintain a tolerance of 1 mm and 1°. We determined the frequency at which kV midimaging captured intrafraction motion as validated on repeat CBCT and assessed the potential time and dosimetric advantages of our modified IGRT workflow. Results: Patient motion, detected as out-of-tolerance shifts on planar kV midimaging, occurred during 6 of 25 fractions (24%) and were validated on repeat CBCT 100% of the time. Observed intrafraction absolute shifts (mean ± standard deviation) for the 25 fractions were 0.39 ± 0.21, 0.56 ± 0.22, and 0.45 ± 0.21 mm for lateral-longitude-vertical translations and 0.38 ± 0.12°, 0.32 ± 0.09°, and 0.47 ± 0.14° for pitch-roll-yaw rotation, which if uncorrected, could have significantly affected target coverage and increased spinal cord dose. The average times for pretreatment imaging, midtreatment verification, and total treatment time were 8.94, 2.81, and 16.21 minutes. Our modified IGRT workflow reduced the total number of CBCTs required from 120 to 35 (70%) and imaging dose from 126.2 to 43.4 cGy (65.6%) while maintaining high fidelity for our patient population. Conclusions: Accurate patient positioning was effectively achieved with use of multiple 2-dimensional-3-dimensional kV images and an average of 1 verification CBCT scan per fraction. Integration of planar kV midimaging can effectively reduce treatment time associated with spine SBRT delivery and minimize the potential dosimetric effect of intrafraction motion on target coverage and spinal cord dose.

Development and Implementation of an Online Adaptive Stereotactic Body Radiation Therapy Workflow for Treatment of Intracardiac Metastasis.

Cardiac metastases pose clinical challenges for radiation oncologists given the need to balance the benefit of local therapy against the risks of cardiac toxicity in the setting of cardiac motion, respiratory motion, and nearby organs at risk. Stereotactic magnetic resonance-guided adaptive radiation therapy has recently become more commonly used, conferring benefits in tumor visualization for setup, real-time motion management monitoring, and enabling plan adaptation for daily changes in tumor and/or normal tissues. Given these benefits, we developed and implemented a workflow for local treatment of metastatic disease within the heart using stereotactic magnetic resonance-guided adaptive radiation therapy.

Feasibility of hippocampal avoidance whole brain radiation in patients with hippocampal involvement: Data from a prospective study.

PURPOSE: Among patients with brain metastases, hippocampal avoidance whole brain radiation (HA-WBRT) preserves neurocognitive function relative to conventional WBRT but the feasibility of hippocampal sparing in patients with metastases in/near the hippocampus is unknown. We identified the incidence of hippocampal/perihippocampal metastases and evaluated the feasibility of HA-WBRT in such patients. MATERIALS/METHODS: Dosimetric data from 34 patients randomized to HA-WBRT (30 Gy/10 fractions) in a phase III trial (NCT03075072) comparing HA-WBRT to stereotactic radiation in patients with 5 to 20 brain metastases were analyzed. Patients with metastases in/near the hippocampi received HA-WBRT with prioritization of tumor coverage over hippocampal avoidance. Target coverage and hippocampal sparing metrics were compared between patients with targets in/near the hippocampus versus not. RESULTS: In total, 9 of 34 (26%) patients had targets in the hippocampus and an additional 5 of 34 (15%) patients had targets in the hippocampal avoidance zone (HAZ, hippocampus plus 5 mm expansion) but outside the hippocampus. Patients with targets within the hippocampus and those with targets in the HAZ but outside the hippocampus were spared 34% and 73% of the ipsilateral mean biologically equivalent prescription dose, respectively. Of the latter cohort, 88% and 25% met conventional hippocampal sparing metrics of Dmin ≤ 9 Gy and Dmax ≤ 16 Gy, respectively. Among 11 patients with unilateral hippocampal/perihippocampal involvement, the uninvolved/contralateral hippocampus was limited to Dmin ≤ 9 Gy and Dmax ≤ 17 Gy in all cases. CONCLUSIONS: In this study, a substantial percentage of patients with 5 to 20 brain metastases harbored metastases in/near the hippocampus. In such cases, minimizing hippocampal dose while providing tumor coverage was feasible and may translate to neurocognitive protection.

Use of a healthy volunteer imaging program to optimize clinical implementation of stereotactic MR-guided adaptive radiotherapy.

PURPOSE: MR-linacs (MRLs) have enabled the use of stereotactic magnetic resonance (MR) guided online adaptive radiotherapy (SMART) across many cancers. As data emerges to support SMART, uncertainty remains regarding optimal technical parameters, such as optimal patient positioning, immobilization, image quality, and contouring protocols. Prior to clinical implementation of SMART, we conducted a prospective study in healthy volunteers (HVs) to determine optimal technical parameters and to develop and practice a multidisciplinary SMART workflow. METHODS: HVs 18 years or older were eligible to participate in this IRB-approved study. Using a 0.35 T MRL, simulated adaptive treatments were performed by a multi-disciplinary treatment team in HVs. For each scan, image quality parameters were assessed on a 5-point scale (5 = extremely high, 1 = extremely poor). Adaptive recontouring times were compared between HVs and subsequent clinical cases with a t-test. RESULTS: 18 simulated treatments were performed in HVs on MRL. Mean parameters for visibility of target, visibility of nearby organs, and overall image quality were 4.58, 4.62, and 4.62, respectively (range of 4-5 for all measures). In HVs, mean ART was 15.7 min (range 4-35), comparable to mean of 16.1 (range 7-33) in the clinical cases (p = 0.8963). Using HV cases, optimal simulation and contouring guidelines were developed across a range of disease sites and have since been implemented clinically. CONCLUSIONS: Prior to clinical implementation of SMART, scans of HVs on an MRL resulted in acceptable image quality and target visibility across a range of organs with similar ARTs to clinical SMART. We continue to utilize HV scans prior to clinical implementation of SMART in new disease sites and to further optimize target tracking and immobilization. Further study is needed to determine the optimal duration of HV scanning prior to clinical implementation.

Optimization of MLC parameters for TPS calculation and dosimetric verification: application to single isocenter radiosurgery of multiple brain lesions using VMAT.

Linac and MLC-based stereotactic radiosurgery (SRS) using single-isocenter-multiple-target (SIMT) VMAT has become increasingly popular in the management of multi-focal cranial metastases. However, significant geometrical and dosimetric challenges exist due to the typically small target volumes and in most cases, non-isocentric locations. To the best of our knowledge, there hasn't been a study in the optimization of MLC parameters, in the context of SIMT SRS, to ensure TPS calculation accuracy. In this work, we set out to optimize the dosimetric leaf gap (DLG) for the HD MLC installed on dedicated stereotactic Varian STx systems using a diverse group of 21 clinical SRS and SBRT plans. These plans featured a broad range of target sizes and target-to-isocenter distances that are typical of the stereotactic cases treated on these systems. Dose discrepancies between TPS calculations and verification measurements using a previously validated diode array Delta4 (ScandiDos) were minimized in a balanced manner to accommodate the variety of stereotactic plans. A DLG of 0.6 mm was found to be 'optimal' for the HD MLC and for the 'typical' plans treated on our STx systems. The finding was independently verified using commercially available 3D polymer gel dosimeter CrystalBallTM (MGS Research Inc.). 3D verification for 6 SIMT SRS plans, consisted of 5 to 15 targets, achieved an average gamma score of 97.3% (σ = 2.0%) on 3%/2 mm criteria with a cutoff isodose level of 20%. We further examined the practice of routine dosimetric verifications including the selection of appropriate detectors and optimal gamma parameters. We found that the commonly used standard 3%/3 mm criteria would have resulted in all but 4 (out of 2840) clinical plans achieving a gamma score of 95% or better, and therefore, losing sensitivity to detect potential dosimetric discrepancies. Based on the characteristics of stereotactic plans, a more stringent distance-to-agreement parameter is needed.

Ventricular Tachycardia: A Treatment Comparison Study of the CyberKnife with Conventional Linear Accelerators.

The work described here compared the available technical solutions for the treatment of ventricular tachycardia with stereotactic body radiation therapy. Due to the complexity of target motion during cardiac and pulmonary motion as well as the several proximate radio-sensitive structures of the tracheobronchial tree and esophagogastrointestinal tract, four potential candidates for this treatment were identified: Accuray CyberKnife (Accuray Incorporated, Sunnyvale, California, United States), Varian TrueBeam (Varian Medical Systems, Palo Alto, California, USA), Elekta Infinity (Elekta, Stockholm, Sweden), and Varian Edge (Varian Medical Systems, Palo Alto, California, USA). All four treatment modalities were evaluated for their ability to deliver a conformal, homogeneous dose to most of the target volume, to spare nearby and distant critical and sensitive anatomical structures as well as for treatment efficiency. It was found that conventional linear accelerator technology was superior in their ability to spare distant critical structures and deliver treatments efficiently while the CyberKnife showed superiority in sparing nearby critical structures more aggressively by creating larger dose gradients at the periphery of the target volume. Both treatment modalities were similar in their ability to cover the entire target with the prescription dose, conform that dose to the target volume, and deliver a homogeneous dose.

Clinical Outcomes After Lung Stereotactic Body Radiation Therapy in Patients With or Without a Prior Lung Resection.

OBJECTIVES: Tumor control (TC), toxicity and survival, following stereotactic body radiation therapy (SBRT) were compared between patients with and without a prior lung resection (PLR). MATERIALS AND METHODS: The study is comprised of 130 patients with 141 peripheral tumors treated with SBRT at our institution from 2009 to 2013. Primary TC and lobar control (LC) were defined per RTOG 0236. Toxicity was scored using Common Terminology Criteria for Adverse Events version 4.0. Survival/TC and toxicity were compared between patients with and without PLR using the Kaplan-Meier method and cumulative incidence, respectively. Fine and Gray regression was used for univariable/multivariable analysis for radiation pneumonitis (RP). RESULTS: Of the 130 patients with median age 70 years (range, 42 to 93 y), 50 had undergone PLR (median time between PLR and SBRT: 33 mo; range, 1 to 206), including pneumonectomy (12%), lobectomy (46%), wedge resection (42%). With a median follow-up of 21 months in survivors, the PLR group had better TC (1-y 100% vs. 93%; P<0.01) and increased grade ≥2 (RP; 1-y 12% vs. 1%; P<0.01). OS was not significantly different between the 2 groups (1-y 91% vs. 85%; P=0.24). On univariable/multivariable analyses, biologically effective dose was associated with TC (hazard ratios, 0.97; 95% confidence interval, 0.94-0.999; P=0.04). Chemotherapy use was associated with grade ≥2 RP for all patients (hazard ratios, 14.92; 95% confidence interval, 5.68-39.21; P<0.0001) in multivariable analysis. PLR was not associated with increased RP in multivariable analysis. CONCLUSIONS: Patients with PLR who receive lung SBRT for lung tumors have high local control and relatively low toxicity. SBRT is an excellent option to treat second lung tumors or pulmonary metastases in patients with PLR.

Two-argument total scatter factor for small fields simultaneously collimated by MLC and jaws: application to stereotactic radiosurgery and radiotherapy.

Direct use of the total scatter factor (S tot) for independent monitor unit (MU) calculations can be a good alternative approach to the traditional separate treatment of head/collimator scatter (S c) and phantom scatter (S p), especially for stereotactic small fields under the simultaneous collimation of secondary jaws and tertiary multileaf collimators (MLC). We have carried out the measurement of S tot in water for field sizes down to 0.5 × 0.5 cm2 on a Varian TrueBeam STx medical linear accelerator (linac) equipped with high definition MLCs. Both the jaw field size (c) and MLC field size (s) significantly impact the linac output factors, especially when c [Formula: see text] s and s is small (e.g. s < 5 cm). The combined influence of MLC and jaws gives rise to a two-argument dependence of the total scatter factor, S tot(c,s), which is difficult to functionally decouple. The (c,s) dependence can be conceived as a set of s-dependent functions ('branches') defined on domain [s min, s max = c] for a given jaw size of c. We have also developed a heuristic model of S tot to assist the clinical implementation of the measured S tot data for small field dosimetry. The model has two components: (i) empirical fit formula for the s-dependent branches and (ii) interpolation scheme between the branches. The interpolation scheme preserves the characteristic shape of the measured branches and effectively transforms the measured trapezoidal domain in (c,s) plane to a rectangular domain to facilitate easier two-dimensional interpolation to determine S tot for arbitrary (c,s) combinations. Both the empirical fit and interpolation showed good agreement with experimental validation data.

Inter-scan and inter-observer tumour volume delineation variability on cone beam computed tomography in patients treated with stereotactic body radiation therapy for early-stage non-small cell lung cancer.

INTRODUCTION: Quantification of volume changes on cone beam computed tomography (CBCT) during lung stereotactic body radiation therapy (SBRT) for non-small cell lung cancer (NSCLC) may provide a useful radiological marker for radiation response and for adaptive treatment planning. This study quantifies inter-scan and inter-observer variability in tumour volume delineation on CBCT. METHODS: Three clinicians independently contoured the primary gross tumour volume (GTV) manually on CBCTs taken immediately before SBRT treatment (pre) and after the same SBRT treatment (post) for 19 NSCLC patients. Relative volume differences (RVD) were calculated between the pre- and post-CBCTs for a given treatment and between any two of three observers for a given CBCT. Coefficient of variation (CV) was used to quantitatively measure and compare the extent of variability. RESULTS: Inter-observer variability had a significantly higher CV of 0.15 ± 0.13 compared to inter-scan CV of 0.03 ± 0.04 with P < 0.0001. The greatest variability was observed with tumours (<2 cm in diameter) versus larger tumours with 95% limit of agreement (LOA) (Mean ± Standard Deviation) of 1.90% ± 19.55% vs. -0.97% ± 12.26% for inter-scan RVD and 29.99% ± 73.84% vs. 9.37% ± 29.95% for inter-observer RVD respectively. CONCLUSIONS: Inter-observer variability was greater than inter-scan variability for tumour volume delineation on CBCT with greatest variability for small tumours (<2 cm in diameter). LOA for inter-scan variability (~12%) helps defines a threshold for clinically meaningful tumour volume change during SBRT treatment for tumours with diameter greater than 2 cm, with larger thresholds needed for smaller tumours.

Evaluation of initial setup accuracy and intrafraction motion for spine stereotactic body radiation therapy using stereotactic body frames.

PURPOSE: The purposes of this study were (1) to evaluate the initial setup accuracy and intrafraction motion for spine stereotactic body radiation therapy (SBRT) using stereotactic body frames (SBFs) and (2) to validate an in-house-developed SBF using a commercial SBF as a benchmark. METHODS AND MATERIALS: Thirty-two spine SBRT patients (34 sites, 118 fractions) were immobilized with the Elekta and in-house (BHS) SBFs. All patients were set up with the Brainlab ExacTrac system, which includes infrared and stereoscopic kilovoltage x-ray-based positioning. Patients were initially positioned in the frame with the use of skin tattoos and then shifted to the treatment isocenter based on infrared markers affixed to the frame with known geometry relative to the isocenter. ExacTrac kV imaging was acquired, and automatic 6D (6 degrees of freedom) bony fusion was performed. The resulting translations and rotations gave the initial setup accuracy. These translations and rotations were corrected for by use of a robotic couch, and verification imaging was acquired that yielded residual setup error. The imaging/fusion process was repeated multiple times during treatment to provide intrafraction motion data. RESULTS: The BHS SBF had greater initial setup errors (mean±SD): -3.9±5.5mm (0.2±0.9°), -1.6±6.0mm (0.5±1.4°), and 0.0±5.3mm (0.8±1.0°), respectively, in the vertical (VRT), longitudinal (LNG), and lateral (LAT) directions. The corresponding values were 0.6±2.7mm (0.2±0.6°), 0.9±5.3mm (-0.2±0.9°), and -0.9±3.0mm (0.3±0.9°) for the Elekta SBF. The residual setup errors were essentially the same for both frames and were -0.1±0.4mm (0.1±0.5°), -0.2±0.4mm (0.0±0.4°), and 0.0±0.4mm (0.0±0.4°), respectively, in VRT, LNG, and LAT. The intrafraction shifts in VRT, LNG, and LAT were 0.0±0.4mm (0.0±0.3°), 0.0±0.5mm (0.0±0.4°), and 0.0±0.4mm (0.0±0.3°), with no significant difference observed between the 2 frames. CONCLUSIONS: These results showed that the combination of the ExacTrac system with either SBF was highly effective in achieving both setup accuracy and intrafraction stability, which were on par with that of mask-based cranial radiosurgery.

Salvage whole brain radiotherapy or stereotactic radiosurgery after initial stereotactic radiosurgery for 1-4 brain metastases.

Patients with limited brain metastases are often candidates for stereotactic radiosurgery (SRS) or whole brain radiotherapy (WBRT). Among patients who receive SRS, the likelihood and timing of salvage WBRT or SRS remains unclear. We examined rates of salvage WBRT or SRS among 180 patients with 1-4 newly diagnosed brain metastases who received index SRS from 2008-2013. Competing risks multivariable analysis was used to examine factors associated with time to WBRT. Patients had non-small cell lung (53 %), melanoma (23 %), breast (10 %), renal (6 %), or other (8 %) cancers. Median age was 62 years. Patients received index SRS to 1 (60 %), 2 (21 %), 3 (13 %), or 4 (7 %) brain metastases. Median survival after SRS was 9.7 months (range, 0.3-67.6 months). No further brain-directed radiotherapy was delivered after index SRS in 55 % of patients. Twenty-seven percent of patients ever received salvage WBRT, and 30 % ever received salvage SRS; 12 % of patients received both salvage WBRT and salvage SRS. Median time to salvage WBRT or salvage SRS were 5.6 and 6.1 months, respectively. Age ≤60 years (adjusted hazard ratio [AHR] = 2.80; 95 % CI 1.05-7.51; P = 0.04) and controlled/absent extracranial disease (AHR = 6.76; 95 % CI 1.60-28.7; P = 0.01) were associated with shorter time to salvage WBRT. Isolated brain progression caused death in only 11 % of decedents. In summary, most patients with 1-4 brain metastases receiving SRS never require salvage WBRT or SRS, and the remainder do not require salvage treatment for a median of 6 months.

Outcomes by tumor histology and KRAS mutation status after lung stereotactic body radiation therapy for early-stage non-small-cell lung cancer.

BACKGROUND: We analyzed outcomes after lung stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung-carcinoma (NSCLC) by histology and KRAS genotype. PATIENTS AND METHODS: We included 75 patients with 79 peripheral tumors treated with SBRT (18 Gy × 3 or 10 to 12 Gy × 5) at our institution from 2009 to 2012. Genotyping for KRAS mutations was performed in 10 patients. Outcomes were analyzed by the Kaplan-Meier method/Cox regression, or cumulative incidence method/Fine-Gray analysis. RESULTS: The median patient age was 74 (range, 46 to 93) years, and Eastern Cooperative Oncology Group performance status was 0 to 1 in 63%. Tumor histology included adenocarcinoma (44%), squamous cell carcinoma (25%), and NSCLC (18%). Most tumors were T1a (54%). Seven patients had KRAS-mutant tumors (9%). With a median follow-up of 18.8 months among survivors, the 1-year estimate of overall survival was 88%, cancer-specific survival (CSS) 92%, primary tumor control 94%, and freedom from recurrence (FFR) 67%. In patients with KRAS-mutant tumors, there was a significantly lower tumor control (67% vs. 96%; P = .04), FFR (48% vs. 69%; P = .03), and CSS (75% vs. 93%; P = .05). On multivariable analysis, histology was not associated with outcomes, but KRAS mutation (hazard ratio, 10.3; 95% confidence interval, 2.3-45.6; P = .0022) was associated with decreased CSS after adjusting for age. CONCLUSION: In this SBRT series, histology was not associated with outcomes, but KRAS mutation was associated with lower FFR on univariable analysis and decreased CSS on multivariable analysis. Because of the small sample size, these hypothesis-generating results need to be studied in larger data sets.

Local control after fractionated stereotactic radiation therapy for brain metastases.

Stereotactic radiosurgery (SRS) is frequently used in the management of brain metastases, but concerns over potential toxicity limit applications for larger lesions or those in eloquent areas. Fractionated stereotactic radiation therapy (SRT) is often substituted for SRS in these cases. We retrospectively analyzed the efficacy and toxicity outcomes of patients who received SRT at our institution. Seventy patients with brain metastases treated with SRT from 2006-2012 were analyzed. The rates of local and distant intracranial progression, overall survival, acute toxicity, and radionecrosis were determined. The SRT regimen was 25 Gy in 5 fractions among 87 % of patients. The most common tumor histologies were non-small cell lung cancer (37 %), breast cancer (20 %) and melanoma (20 %), and the median tumor diameter was 1.7 cm (range 0.4-6.4 cm). Median survival after SRT was 10.7 months. Median time to local progression was 17 months, with a local control rate of 68 % at 6 months and 56 % at 1 year. Acute toxicity was seen in 11 patients (16 %), mostly grade 1 or 2 with the most common symptom being mild headache. Symptomatic radiation-induced treatment change was seen on follow-up MRIs in three patients (4.3 %). SRT appears to be a safe and reasonably effective technique to treat brain metastases deemed less suitable for SRS, though dose intensification strategies may further improve local control.

Low incidence of chest wall pain with a risk-adapted lung stereotactic body radiation therapy approach using three or five fractions based on chest wall dosimetry.

PURPOSE: To examine the frequency and potential of dose-volume predictors for chest wall (CW) toxicity (pain and/or rib fracture) for patients receiving lung stereotactic body radiotherapy (SBRT) using treatment planning methods to minimize CW dose and a risk-adapted fractionation scheme. METHODS: We reviewed data from 72 treatment plans, from 69 lung SBRT patients with at least one year of follow-up or CW toxicity, who were treated at our center between 2010 and 2013. Treatment plans were optimized to reduce CW dose and patients received a risk-adapted fractionation of 18 Gy×3 fractions (54 Gy total) if the CW V30 was less than 30 mL or 10-12 Gy×5 fractions (50-60 Gy total) otherwise. The association between CW toxicity and patient characteristics, treatment parameters and dose metrics, including biologically equivalent dose, were analyzed using logistic regression. RESULTS: With a median follow-up of 20 months, 6 (8.3%) patients developed CW pain including three (4.2%) grade 1, two (2.8%) grade 2 and one (1.4%) grade 3. Five (6.9%) patients developed rib fractures, one of which was symptomatic. No significant associations between CW toxicity and patient and dosimetric variables were identified on univariate nor multivariate analysis. CONCLUSIONS: Optimization of treatment plans to reduce CW dose and a risk-adapted fractionation strategy of three or five fractions based on the CW V30 resulted in a low incidence of CW toxicity. Under these conditions, none of the patient characteristics or dose metrics we examined appeared to be predictive of CW pain.

Quantifying ITV instabilities arising from 4DCT: a simulation study using patient data.

Treatment planning for patients undergoing radiation therapy is often performed based on four-dimensional computed tomography (4DCT) when respiratory motion is present, as in lung cancer patients. 4DCT is used to define the internal target volume (ITV) that, ideally, incorporates all potential locations of the tumour. In this work, we use the locations of gold fiducial markers implanted in lung tumours of eight patients to represent tumour motion. These fiducial locations are used in a simulation of a four-slice CT scanner to generate the ITV for 10, 20 and 30 mm diameter model tumours. To demonstrate instabilities in the ITV definition based on 4DCT, the ITV calculation was repeated for the same patients for consecutive scan start times, staggered by 1 s. The volumetric difference in the ITV and the per cent of time that the ITV contains in the tumour are both evaluated. The ITV from a single patient was found to vary by 46%-127% for a tumour diameter of 10 mm. The ITV did not cover the entirety of the tumour 11%-74% of the time for a 10 mm tumour diameter.

Stereotactic irradiation of the postoperative resection cavity for brain metastasis: a frameless linear accelerator-based case series and review of the technique.

PURPOSE: Whole-brain radiation therapy (WBRT) is the standard of care after resection of a brain metastasis. However, concern regarding possible neurocognitive effects and the lack of survival benefit with this approach has led to the use of stereotactic radiosurgery (SRS) to the resection cavity in place of WBRT. We report our initial experience using an image-guided linear accelerator-based frameless stereotactic system and review the technical issues in applying this technique. METHODS AND MATERIALS: We retrospectively reviewed the setup accuracy, treatment outcome, and patterns of failure of the first 18 consecutive cases treated at Brigham and Women's Hospital. The target volume was the resection cavity without a margin excluding the surgical track. RESULTS: The median number of brain metastases per patient was 1 (range, 1-3). The median planning target volume was 3.49 mL. The median prescribed dose was 18 Gy (range, 15-18 Gy) with normalization ranging from 68% to 85%. In all cases, 99% of the planning target volume was covered by the prescribed dose. The median conformity index was 1.6 (range, 1.41-1.92). The SRS was delivered with submillimeter accuracy. At a median follow-up of 12.7 months, local control was achieved in 16/18 cavities treated. True local recurrence occurred in 2 patients. No marginal failures occurred. Distant recurrence occurred in 6/17 patients. Median time to any failure was 7.4 months. No Grade 3 or higher toxicity was recorded. A long interval between initial cancer diagnosis and the development of brain metastasis was the only factor that trended toward a significant association with the absence of recurrence (local or distant) (log-rank p = 0.097). CONCLUSIONS: Frameless stereotactic irradiation of the resection cavity after surgery for a brain metastasis is a safe and accurate technique that offers durable local control and defers the use of WBRT in select patients. This technique should be tested in larger prospective studies.

Total dural irradiation: RapidArc versus static-field IMRT: a case study.

The purpose of this study was to compare conventional fixed-gantry angle intensity-modulated radiation therapy (IMRT) with RapidArc for total dural irradiation. We also hypothesize that target volume-individualized collimator angles may produce substantial normal tissue sparing when planning with RapidArc. Five-, 7-, and 9-field fixed-gantry angle sliding-window IMRT plans were generated for comparison with RapidArc plans. Optimization and normal tissue constraints were constant for all plans. All plans were normalized so that 95% of the planning target volume (PTV) received at least 100% of the dose. RapidArc was delivered using 350° clockwise and counterclockwise arcs. Conventional collimator angles of 45° and 315° were compared with 90° on both arcs. Dose prescription was 59.4 Gy in 33 fractions. PTV metrics used for comparison were coverage, V(107)%, D1%, conformality index (CI(95)%), and heterogeneity index (D(5)%-D(95)%). Brain dose, the main challenge of this case, was compared using D(1)%, Dmean, and V(5) Gy. Dose to optic chiasm, optic nerves, globes, and lenses was also compared. The use of unconventional collimator angles (90° on both arcs) substantially reduced dose to normal brain. All plans achieved acceptable target coverage. Homogeneity was similar for RapidArc and 9-field IMRT plans. However, heterogeneity increased with decreasing number of IMRT fields, resulting in unacceptable hotspots within the brain. Conformality was marginally better with RapidArc relative to IMRT. Low dose to brain, as indicated by V5Gy, was comparable in all plans. Doses to organs at risk (OARs) showed no clinically meaningful differences. The number of monitor units was lower and delivery time was reduced with RapidArc. The case-individualized RapidArc plan compared favorably with the 9-field conventional IMRT plan. In view of lower monitor unit requirements and shorter delivery time, RapidArc was selected as the optimal solution. Individualized collimator angle solutions should be considered by RapidArc dosimetrists for OARs dose reduction. RapidArc should be considered as a treatment modality for tumors that extensively involve in the skull, dura, or scalp.

Linear accelerator-based stereotactic radiosurgery for brainstem metastases: the Dana-Farber/Brigham and Women's Cancer Center experience.

To review the safety and efficacy of linear accelerator-based stereotactic radiosurgery (SRS) for brainstem metastases. We reviewed all patients with brain metastases treated with SRS at DF/BWCC from 2001 to 2009 to identify patients who had SRS to a single brainstem metastasis. Overall survival and freedom-from-local failure rates were calculated from the date of SRS using the Kaplan-Meier method. Prognostic factors were evaluated using the log-rank test and Cox proportional hazards model. A total of 24 consecutive patients with brainstem metastases had SRS. At the time of SRS, 21/24 had metastatic lesions elsewhere within the brain. 23/24 had undergone prior WBRT. Primary diagnoses included eight NSCLC, eight breast cancer, three melanoma, three renal cell carcinoma and two others. Median dose was 13 Gy (range, 8-16). One patient had fractionated SRS 5 Gy ×5. Median target volume was 0.2 cc (range, 0.02-2.39). The median age was 57 years (range, 42-92). Follow-up information was available in 22/24 cases. At the time of analysis, 18/22 patients (82%) had died. The median overall survival time was 5.3 months (range, 0.8-21.1 months). The only prognostic factor that trended toward statistical significance for overall survival was the absence of synchronous brain metastasis at the time of SRS; 1-year overall survival was 31% with versus 67% without synchronous brain metastasis (log rank P = 0.11). Non-significant factors included primary tumor histology and status of extracranial disease (progressing vs. stable/absent). Local failure occurred in 4/22 cases (18%). Actuarial freedom from local failure for all cases was 78.6% at 1 year. RTOG grade 3 toxicities were recorded in two patients (ataxia, confusion). Linac-based SRS for small volume brainstem metastases using a median dose of 13 Gy is associated with acceptable local control and low morbidity.

A clinical comparison of patient setup and intra-fraction motion using frame-based radiosurgery versus a frameless image-guided radiosurgery system for intracranial lesions.

BACKGROUND AND PURPOSE: A comparison of patient positioning and intra-fraction motion using invasive frame-based radiosurgery with a frameless X-ray image-guided system utilizing a thermoplastic mask for immobilization. MATERIALS AND METHODS: Overall system accuracy was determined using 57 hidden-target tests. Positioning agreement between invasive frame-based setup and image-guided (IG) setup, and intra-fraction displacement, was evaluated for 102 frame-based SRS treatments. Pre and post-treatment imaging was also acquired for 7 patients (110 treatments) immobilized with an aquaplast mask receiving fractionated IG treatment. RESULTS: The hidden-target tests demonstrated a mean error magnitude of 0.7mm (SD=0.3mm). For SRS treatments, mean deviation between frame-based and image-guided initial positioning was 1.0mm (SD=0.5mm). Fusion failures were observed among 3 patients resulting in aberrant predicted shifts. The image-guidance system detected frame slippage in one case. The mean intra-fraction shift magnitude observed for the BRW frame was 0.4mm (SD=0.3mm) compared to 0.7mm (SD=0.5mm) for the fractionated patients with the mask system. CONCLUSIONS: The overall system accuracy is similar to that reported for invasive frame-based SRS. The intra-fraction motion was larger with mask-immobilization, but remains within a range appropriate for stereotactic treatment. These results support clinical implementation of frameless radiosurgery using the Novalis Body Exac-Trac system.

Automatic marker detection and 3D position reconstruction using cine EPID images for SBRT verification.

In previous studies, an electronic portal imaging device (EPID) in cine mode was used for validating respiratory gating and stereotactic body radiation therapy (SBRT) by tracking implanted fiducials. The manual marker tracking methods that were used were time and labor intensive, limiting the utility of the validation. The authors have developed an automatic algorithm to quickly and accurately extract the markers in EPID images and reconstruct their 3D positions. Studies have been performed with gold fiducials placed in solid water and dynamic thorax phantoms. In addition, the authors have examined the cases of five patients being treated under an SBRT protocol for hepatic metastases. For each case, a sequence of images was created by collecting the exit radiation using the EPID. The markers were detected and recognized using an image processing algorithm based on the Laplacian of Gaussian function. To reduce false marker detection, a marker registration technique was applied using image intensity as well as the geometric spatial transformations between the reference marker positions produced from the projection of 3D CT images and the estimated marker positions. An average marker position in 3D was reconstructed by backprojecting, towards the source, the position of each marker on the 2D image plane. From the static phantom study, spatial accuracies of <1 mm were achieved in both 2D and 3D marker locations. From the dynamic phantom study, using only the Laplacian of the Gaussian algorithm, the marker detection success rate was 88.8%. However, adding a marker registration technique which utilizes prior CT information, the detection success rate was increased to 100%. From the SBRT patient study, intrafractional tumor motion (3.1-11.3 mm) in the SI direction was measured using the 2D images. The interfractional patient setup errors (0.1-12.7 mm) in the SI, AP, and LR directions were obtained from the average marker locations reconstructed in 3D and compared to the reference planning CT image. The authors have developed an automatic algorithm to extract marker locations from MV images and have evaluated its performance. The measured intrafractional tumor motion and the interfractional daily patient setup error can be used for off-line retrospective verification of SBRT.